Textbook of stereotactic and functional neurosurgery [1 ed.] 9780070236042, 0070236046

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NATIONAL INSTITUTES 0 HE NTH LIBRARY PR - 4 IS98

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I_J BLDG 10, 10 CENTER DR. BETHESDA, MD 20892-1150

TEXTBOOK

O

F

STEREOTACTIC AND

FUNCTIONAL NEUROSURGERY

NOTICE Medicine is an ever-changing science. As new research and clinical experience broaden our knowledge, changes in treatment and drug therapy are required. The editors and the publisher of this work have checked with sources believed to be reliable in their efforts to provide information that is complete and generally in accord with the stan¬ dards accepted at the time of publication. However, in view of the possibility of human error or changes in medical sciences, neither the editors nor the publisher nor any other party who has been involved in the preparation or publication of this work warrants that the informa¬ tion contained herein is in every respect accurate or complete, and they are not responsible for any errors or omissions or for the results obtained from use of such information. Readers are encouraged to confirm the information contained herein with other sources. For ex¬ ample and in particular, readers are advised to check the product in¬ formation sheet included in the package of each drug they plan to ad¬ minister to be certain that the information contained in this book is accurate and that changes have not been made in the recommended dose or in the contraindications for administration. This recommen¬ dation is of particular importance in connection with new or infre¬ quently used drugs.

TEXTBOOK

OF

STEREOTACTIC AND

FUNCTIONAL NEUROSURGERY EDITORS

PHILIP L. GILDENBERG, M.D., Ph.D. Clinical Professor of Neurosurgery and Radiology Baylor College of Medicine Houston, Texas

RONALD R.TASKER, M.D., M.A., ER.C.S.(C.) Professor, Division of Neurosurgery The Toronto Hospital Western Division Department of Surgery, and Institute of Medical Science University of Toronto Toronto, Canada

PATRICIA O. FRANKLIN MANAGING EDITOR Houston Stereotactic Center Houston, Texas

McGraw-Hill Health Professions Division New York St. Louis San Francisco Auckland Bogota Caracas Lisbon London Madrid Mexico City Milan Montreal New Delhi San Juan Singapore Sydney Tokyo Toronto

RP McGraw-Hill A Division of Vie McGraw-Hill Companies

Cl 2-

TEXTBOOK OF STEREOTACTIC AND FUNCTIONAL NEUROSURGERY Copyright ©1998 by The McGraw-Hill Companies, Inc. All rights reserved. Printed in the United States of America. Except as permitted under the United States copyright Act of 1976, no part of this publication may be reporduced or distributed in a any form or by any means, or stored in a data base or retrieval system, without the prior written permission of the publisher. 1234567890/QPK/QPK/9987 ISBN 0-07-023604-6 This book was set in Times Roman by Monotype Composition Co., Inc. The editors were James T. Morgan III and Lester A. Sheinis. The production supervisors were Clare Stanley and Helene G. Landers. The cover designer was Parallelogram/Marsha Cohen. The index was prepared by Jerry Ralya. Quebecor Printing/Kingsport was printer and binder. This book is printed on acid-free paper.

Library of Congress Cataloging-in-Publication Data Textbook of stereotactic and functional neurosurgery / Philip L. Gildenberg, Ronald R. Tasker, editors, p. cm. Includes bibliographical references and index. ISBN 0-07-023604-6 1. Nervous system—Surgery. I. Gildenberg, Philip L.

2. Stereoencephalotomy.

II. Tasker, Ronald R.

(DNLM: 1. Neurosurgery—methods. 3. Nervous System Diseases—surgery. RD593.T475

2. Stereotaxic Techniques. WL 368 T355 1996]

1996

617.4'8—dc20 DNLM/DLC for Library of Congress

96-2939

CONTENTS Contributors

xvii

I

Preface

PART

xxix

I

STEREOTACTIC PRINCIPLES / 1 Section

1

12.

The Gouda Apparatus

113

Kasim I Gouda / Stephen R. Freidberg

Frame-Based Systems / 3 1.

The History of Stereotactic and Functional Neurosurgery

13.

The Mathematics of Cartesian Coordinates

14.

5

Historical Development of Stereotactic Frames

15.

21

The Leksell Stereotactic System

16.

The brw/crw Stereotactic Apparatus

29

17.

The Riechert/Mundinger Apparatus

51 18.

The Talairach System Alim-Louis Benabid / Dominique Hoffmann /

The Guiot-Gillingham Apparatus

139

The utec Stereotactic System

145

151

The Compass System Stephan J. Goerss

19.

65

Reapplication of Head Frames

163

David G. T. Thomas /Neil D. Kitchen

20. 73

The Gildenberg-Laitinen Adapter Device (glad): A Noninvasive Reapplication System for Stereotactic Head Rings

79

Philip L. Gildenberg

Fritz Mundinger / Robert Boesecke

7.

131

Rudi Verbeeck / Bart Nuttin / Jan M. Gybels / Dirk Vandermeulen / Paul Suetens / Guy Marchal

Theodore S. Roberts

6.

The Sugita Apparatus

John Gillingham

L. Dade Lunsford / Douglas Kondziolka / Dan Leksell

5.

127

Kenichiro Sugita /Naomi Mutsuga

Eric M. Gabriel / Blaine S. Nashold, Jr.

4.

The Narabayashi Apparatus Hirotaro Narabayashi

David W. Roberts

3.

119

William D. Tobler

Philip L. Gildenberg

2.

The Pelorus Apparatus

169

Jean-Francois LeBas / Claudio Munari

8.

The Laitinen Apparatus

87

Section

2

Marwan I. Hariz / Laurie V. Laitinen

9.

10.

The Todd-Wells Apparatus Trent H. Wells, Jr. / Edwin M. Todd The Hitchcock Apparatus

Frameless Systems / 175

95

21. 101

Colin Shieff

11.

The Patil Apparatus

Frameless Stereotactic Systems

177

Robert L. Galloway, Jr.

22. 105

A run Angelo Patil

Image-Guided Neurosurgery: The Operating Arm System Eric R. Cosman

v

183

viii

Contents

PART

3

STEREOTACTIC RADIOTHERAPY / 557 Section

Section

8

Technical Radiosurgery / 639

Brachytherapy / 559 64.

Radioisotopes and Radiophysics of Brachytherapy

76.

77.

67.

Stereotactic Interstitial Brachytherapy

William A. Friedman 577

78.

Brachytherapy Boost in the Adjuvant Treatment of

Ladislau Steiner 581

79.

687

Philip H. Gutin / Penny K. Sneed

Hanne M. Kooy / Marc R. Bellerive / Jay S. Loeffter

Interstitial Radiosurgery of 589

80

Gold Seed Brachytherapy

599

705

Stephen B. Tatter / William E. Butler/ Paul H. Chapman

603

81.

Technical Aspects of Dynamic 71 1

COLLIMATION

Mark P. Carol

Low-Dose Brachytherapy in the 607

82.

Dynamic Stereotactic Irradiation: Physical Aspects, Treatment

Lucia Zamorano / Laurie Caspar

Planning, and Clinical Applications

Fractionated High-Dose-Rate Brachytherapy for Glioma

Proton-Beam

Stereotactic Radiosurgery

Barry M. Berner

Treatment of Malignant Gliomas

Technical and Clinical Aspects

of

Philip L. Gildenberg / Shiao Y. Woo /

72.

LINAC

Radiosurgery Dosimetry

Mark Bernstein

11.

Technical Concepts of

Stephen L. Huhn / Michael D. Prados /

Indications for Brachytherapy

669

Christer Lindquist / Dheerendra Prasad /

Christoph B. Ostertag

70.

Technical Aspects of Gamma Knife Stereotactic Radiosurgery

Brain Tumors

69.

649

Sanford L. Meeks / Frank J. Bova /

David M. Bellezza / Barry M. Berner

Malignant Glioma

68.

Technical Aspects of Radiation Physics

569

Normand J. Laperriere

66.

641

Federico Colombo / Paolo Francescon

John C. Flickinger / Geoffrey Levine /

Radiobiology of Brachytherapy

Introduction and Overview of Stereotactic Radiosurgery

561

Ann Maitz/L. Dade Lunsford 65.

9

719

Ervin B. Podgorsak / Conrado Pla /

617

Luis Souhami

Shiao Y. Woo / Walter H. Grant III/ Philip L. Gildenberg / E. Brian Butler/

Section

Barry Berner/L. Steven Carpenter/

10

Hsin H. Lu / W. Sam Dennis /

Clinical Radiosurgery / 731

J. Kam Chiu / Lois Freedman 73.

Interstitial Radiosurgery

619

G. Rees Cosgrove / Nicholas T. Zervas 74.

Radiation Sensitizers: Protective Agents for the Brain

83.

The Use

of

John M. Buatti

84.

Hyperthermia in

Stereotactic Brachytherapy Michael Salcman

733

William A. Friedman / Frank J. Bova /

625

Michael Louis Goodman 75.

LINAC Stereotactic Radiosurgery: Clinical Experience at the University of Florida

629

Clinical Experience with LINAC Radiosurgery Eben Alexander III / Jay S. Loeffler

745

Contents

85.

Clinical Linear Accelerator Radiosurgery

90.

Gamma Knife Radiosurgery for

757

Acousic Neurinomas

Federico Colombo / Paolo Francescon 86.

835

Georg Noren

Clinical Aspects of Gamma Knife Stereotactic Radiosurgery

IX

91.

Radiosurgery for Pituitary

763

Tumors

Ladislau Steiner/Dheerendra Prasad/

845

Jeremy C. Ganz

Christer Lindquist / Melita Steiner 92. 87.

Linear Accelerator

Deep Brain Surgery Using the Gamma Knife

(LINAC)-Based Stereotactic 805

Spinal Radiosurgery

L. Dade Lunsford / Douglas Kondziolka /

857

Allan J. Hamilton

John C. Flickinger 93. 88.

Functional Radiosurgery Using

Radiosurgery for the

the Gamma Knife: Current and

Treatment of Metastases

817

Future Applications

Volker Sturm / Rolf Peter Muller 89.

871

Douglas Kondziolka / L. Dade Lunsford

Focused and Conventional Radiation Treatments for Acoustic Neurinomas

823

David W. Andrews / Benjamin W. Corn / William A. Buchheit

PART

4

FUNCTIONAL STEREOTAXIS / 879 Section

11

96.

Microelectrode Recording in Functional Neurosurgery

Recording in Functional Neurosurgery / 881 94.

Lance H. Rowland / Patrick M. Dougherty / Frederick A. Lenz

Subcortical and Thalamic

97.

Mapping in Functional Neurosurgery

935

Neural Noise Recording in Functional Neurosurgery

883

941

Chihiro Ohye

Ronald R. Tasker / Karen D. Davis / William D. Hutchison /

98.

Jonathan O. Dostrovsky 95.

Impedance Recording in Functional Neurosurgery

949

Dennis E. Bullard / Blaine S. Nashold, Jr.

Evoked Potential Recording in Functional Neurosurgery 99.

Part I: Use of Thalamic Evoked

Functional Mapping of Motor,

Potentials to Improve the

Sensory, and Language Cortex

Stereotactic Localization of

during Intracranial

Electrodes in the Human Brain

911

Tumor Removal

Denise Albe-Fessard

Michael M. Haglund/ George A. Ojemann/

Part II: Correlation of

Mitchel S. Berger

955

Microstimulation, Single-Unit Recording, and Averaged Evoked Potentials Katsumi Yamashiro / Jiro Mukawa

100. Chronic Stimulation of the 925

Central Nervous System Ross Davis

963

Contents

X

Section

114.

12

Cerebellar Stimulation for Movement Disorders

Lesioning Techniques / 971 101.

Radiofrequency Lesions

Ross Davis

973

115.

for Control of Involuntary

Eric R. Cosman 102.

Movements Caused by Stroke or Head Injury

Cryosurgery Lesions in Parkinson’s Disease

Takashi Tsubokawa / Takamitsu Yamamoto /

987

Yoichi Katayama

Robert W. Rand 116. Section

13

Central Nervous System Fred C. Junn/Andres M. Lozano 117.

Fetal Tissue Transplantation in Movement Disorders

Overview of the Surgical Treatment of Movement Disorders

Transplantation to Improve Functions in the Diseased

Functional Procedures for Movement Disorders / 993 103.

Chronic Thalamic Stimulation

Alan Fine / Renn O. Holness

995

Andrew G. Parrent 104.

Anatomy of Movement Disorders

1005

Section

14

Soledad Serrano Lopez 105.

Functional Procedures for Parkinson’s Disease / 1131

Surgical Treatment of the Dystonias

1015

Ronald R. Tasker 106.

118.

Functional Neurosurgery for

Parkinson’s Disease

Nontremulous Movement Disorders

Allen S. Mandir / Frederick A. Lenz

1033

Hirotaro Narabayashi 107.

119.

Pathophysiological Basis of Neurosurgical Treatment of

Intradural Rhizotomy for the Treatment of Torticollis

Clinical Pathophysiology in

Parkinson’s Disease

1039

Mahlon R. DeLong / Thomas Wichmann

Alan T. Villavicencio / Allan H. Friedman

/

Jerrold L. Vitek 108.

Overview of the Surgical 120.

Treatment of Spasmodic Torticollis

1053

Parkinson’s Disease Andre Parent/Pierre-Yves Cote

Ronald R. Tasker 109.

Botulinum Toxin for the Treatment

121.

of Spasmodic Torticollis and Other Movement Disorders

Treatment of Hemifacial Spasm

Pallidotomy for Parkinson’s Disease

1059

Part I: The New York University/

Tim Anderson / C. David Marsden 110.

Animal Models of

University of California at Irvine Experience

1071

Peter J. Jannetta / Hae Dong Jho

Jeffrey D. Gross / Michael Dogali

Hemifacial Spasm Treated with

Experience

Part 111.

Microvascular Decompression in 486 Chinese Patients

II:

The Toronto Hospital

Andres M. Lozano / Anthony E. Lang 1077 122.

Cho Shun Li

Thalamotomy for Parkinson’s Disease and Other Types of Tremor

112.

Deep Brain Stimulation for Movement Disorders

Part 1081

Jean Siegfried 113.

Joseph M. Waltz

Historical Background

Chihiro Ohye Part 11: The Outcome of

Chronic Stimulation for Motor Disorders

I:

and Technique

1087

Thalamotomy for Tremor Ronald R. Tasker

Contents

123.

Chronic Stimulation for

135.

Parkinson’s Disease and Other Movement Disorders

Evaluation of Results of Pain Surgery

1199

xi

1311

Ron C. Kupers / Jan M. Gybels

Alim-Louis Benabid / Pierre Poliak / 136.

Dominique Hoffmann / Patricia Limousin /

General Principles and Selection of Techniques in the

Dong Ming Gao / Jean-Franqois LeBas /

Management of Pain of Benign

Abdelhamid Benazzouz /

Origin

Christoph Segebarth / Sylvie Grand

1321

Philip L. Gildenberg 124.

Adrenal Medullary Grafting in the Treatment of Parkinsonism

1213

137.

The Importance of Neural Plasticity in Functional

Claudio A. Feler

Neurosurgery 125.

Genetically Modified Cell

1337

Zelma H. T. Kiss

Therapy in Cerebral Transplantation

1217

Section

17

Allan B. Levin Section

Cancer Pain /1343

15

Functional Procedures for Spasticity / 1221

138.

The Nature and Management of Cancer Pain

1345

Ehud Arbit 126. Historical Ablative Intracranial Procedures for Spasticity

1223

139.

General Principles of Cancer Pain Management

Jean Siegfried

1353

Suellen M. Walker / Michael J. Cousins 127.

The Neurosurgical Treatment of Spasticity

1227

140.

Various Functional Procedures for Pain

Richard D. Penn

Part I: Cancer Pain 128.

The History of Stereotactic and Functional Neurosurgery

Part

Techniques

1381

John P. Gorecki 1233

II:

Facial Pain

1389

Manoel Jacobsen Teixeira

Albrecht Struppler 141. 129.

Destructive Neurosurgical Procedures for Spasticity

Percutaneous Lower Cervical Cordotomy

1245

1403

Paul M. Lin

Marc P. Sindou / Patrick Mertens

142. 130.

Spinal Entry Zone Interruption for Spasticity

Spinal Cord Surgery for Pain Management

1257

1411

Philip L. Gildenberg

Marc P. Sindou 143. 131.

Chronic Spinal Cord Stimulation for Spasticity

Persistent Pain 1267

Part I: An Overview

Milan R. Dimitrijevic 132.

Part

Use of Intrathecal Drugs

II:

Outcome

1425

Keiichi Amano

1275

Robert J. Coffey

144.

Thalamotomy for Cancer Pain

Intrathecal Baclofen for Spasticity

Part

1281

I:

An Overview

1431

John P. Gorecki

Richard D. Penn

Part Section

1417

John P. Gorecki

for Spasticity

133.

Destructive Central Lesions for

16

II:

Outcome

1443

Keiichi Amano 145.

Pain / 1287

Pulvinotomy for Cancer Pain

1445

Lauri V. Laitinen

134. Anatomy

and Physiology of Pain

William D. Willis, Jr. / Karin N. Westlund

1289

146.

ClNGULOTOMY FOR CANCER PAIN

Samuel J. Hassenbusch

1447

xii

147.

Contents

161.

Stimulation and Coagulation of

Syndrome

the Posterior Hypothalamus for Intractable Pain

Overview of the Failed Back 1601

Donlin M. Long

1453

Yoshiaki Mayanagi / Keiji Sano 162. 148.

The Pituitary Gland and Pain Relief

1457

Failed Back Surgery Syndrome

John Miles 149.

Continuous Delivery of Opiates

163. 1463

Deep Brain Stimulation for Failed Back Syndrome

Burton M. Onofrio / Tony L. Yaksh

1621

Ronald F. Young

INTRACEREBROVENTRICULAR

164.

Administration of Morphine Cancer Pain

1477

John P. Gorecki

Jean-Claude Verdie

165.

Evaluation and Management of Central and Peripheral

18

Deafferentation Pain

1631

Mario Meglio

Persistent Pain Syndromes / 1483 166. Percutaneous Cervical Cordotomy for Persistent Pain

1627

Janice Ovelmen-Levitt / Melvin Levitt /

Yves Lazorthes / Brigitte Sallerin /

Section

Pathophysiology of Central/ Neuropathic Pain

for Control of Irreducible

151.

1611

Richard B. North

for Persistent Pain States

150.

Spinal Cord Stimulation for the

Nonsurgical Considerations in Neuropathic Pain

1485

C.

1637

Peter N. Watson

Yiicel Kanpolat 152.

167.

Percutaneous Cordotomy for Persistent Pain

Neuropathic Pain

1491

Stereotactic Hypothalamotomy

1645

Andrew G. Shetter

Ronald R. Tasker 153.

Peripheral Nerve Stimulation for

1507

168.

Stereotactic Midbrain Tractotomy

Samuel E. Hunter

1651

John P. Gorecki 154.

Spinal Cord Stimulation for Persistent Pain Management

1519

169.

Giancarlo Barolat 155.

156.

Hyperhidrosis

1539

The Pathophysiology of Trigeminal Neuralgia

Motor Cortex Stimulation in

William H. Sweet 1547

Takashi Tsubokawa / Yoichi Katayama 157.

170.

Bernard Bendok / Robert M. Levy

Persistent Pain Management

1661

Harold A. Wilkinson

Brain Stimulation for Persistent Pain Management

Sympathectomy for Pain and

171.

Overview of the Treatment of Cranial Neuralgias

Chronic Trigeminal

1667

1683

Ian M. Turnbull

Nerve Stimulation for the Relief of Persistent Pain

1557

172.

Radiofrequency Rhizotomy for Trigeminal and Other

Ulrich Steude

Cranial Neuralgias 158.

Spinal Entry Zone Interruption for Persistent Pain

Jamal M. Taha / John M. Tew, Jr. 1565

173.

Marc P. Sindou 159.

Lesions

of Trigeminal Neuralgia

1573 174.

Radiofrequency Lesions in the Treatment of Pain of Spinal Origin Maarten van Kleef/ Menno E. Sluijter

1585

1697

Sten Hdkanson / Bengt Linderoth

Bermans J. Iskandar / Blaine S. Nashold, Jr. 160.

Injection of Glycerol into the Gasserian Cistern for Treatment

Spinal and Trigeminal

DREZ

1687

Trigeminal Nerve Compression for Neuralgia Arthur M. Gerber /Sean F. Mullan

1707

Contents

175.

Microvascular Decompression for Trigeminal Neuralgia

188. 1715

xiii

Cerebral Localization Mapping in Neurosurgery

1839

Jorge Roberto Pagura /

Jose C. Martin del Campo / Ethan Taub /

Jader Pacheco Rabello /

Andres M. Lozano

Wanderley Cerqueira de Lima 189. 176.

Treatment of Facial Pain

1723

in the Evaluation of Epilepsy

Kim J. Burchiel

111.

1849

Raul Marino, Jr. / Gary Gronich /

Treatment of Occipital Neuralgia

Arthur Cukiert

1729

Andres M. Lozano 178.

The Role of Electrocorticography

190.

Treatment of Headache

The Role of Intraoperative Monitoring in the Surgical

1735

Management of Epilepsy

Ninan T. Mathew

1857

George A. Ojemann

Section

Section

19

Medical Management of Epilepsy / 1865

Evaluation of Epilepsy /1751 179.

Introduction to Epilepsy

1753

191.

Classification of Epileptic Seizures and Epileptic Syndromes

1775

192.

Epilepsy Surgery

Eduardo Garcia-Almaguer

Mounir N. Abou-Madi

The Role of

193.

194. Electroencephalography

Michael Dogali

Monitoring in the

Management of Epilepsy

1793

195.

196. 1801

1903

Robert E. Maxwell

The Role of Psychological

197. 1809

Hemispherectomy for Surgical Management of Epilepsy

M. Jones-Gotman

1913

Jean-Guy Villemure

The Role of Imaging in the Evaluation of Epilepsy

Corpus Callosotomy for Surgical Management of Epilepsy

Brenda Koska / Juhn A. Wada

Testing in Epilepsy

1893

Jeffrey D. Gross/Michael Dogali

The Role of the Wada Test— Current Perspectives

1889

Subpial Transections for the Surgical Management of Epilepsy

Hiroshi Otsubo / Paul A. Hwang

186.

Cortical and Lesion Resection in the Control of Epilepsy

EEG

1883

Gian Franco Rossi / Gabriella Colicchio

The Role of and

1875

Temporal Lobectomy for Surgical Management of Epilepsy

1781

Peter Kellaway

185.

Anesthesia Considerations in

Eduardo Garda-Flores / Rodolfo Farias /

in the Diagnosis of Epilepsy

184.

21

Surgical Management of Epilepsy / 1873

Electroencephalography

183.

1867

Epidemiology of Epilepsy in North America

182.

Section

1763

Soheyl Noachtar / Hans Otto Liiders 181.

Medical Management of Epilepsy Michael E. Newmark / Stephanie Dubinsky

Jerome Engel, Jr. 180.

.20

198. 1815

The Role of Radiosurgery in the Treatment of Epilepsy

Jose E. Cavazos / Cheng-Jen Wang /

1925

Juan L. Barcia-Salorio / Juan A. Barcia

Robert D. Tien 199. 187. The Role of Depth Electrode

Stimulation in the Control of

Recording in the Evaluation of Epilepsy

The Role of Thalamic Electrical Seizures

1823

Francisco Velasco / Marcos Velasco /

Ralph A. W. Lehman / Dennis D. Spencer /

Fiacro Jiminez / Ana Luisa Velasco /

Susan S. Spencer

Francisco Brito / Mark Rise

1933

Contents

XIV

200.

205.

Vagal Nerve Stimulation for the Treatment of Refractory Seizures

Persistent Vegetative State

1941

Elinor Ben-Menachem

206.

Seizure Control

207. o

n

2

1987

R. Graham Vanderlinden

1945

Ross Davis i

Phrenic Nerve Stimulation (Diaphragmatic Pacing)

Cerebellar Stimulation for

t

1979

Takashi Tsubokawa / Takamitsu Yamamoto

Lars-Erik Augustinsson /

201.

Deep Brain Stimulation in the

Modulation of Bladder Function through Electrical Stimulation

2

1991

Magdy M. Hassouna

Psychosurgery / 1953

208.

Visual Prosthesis

1999

John P. Girvin/Harold Fodstad

202.

Neurosurgical Treatment of

209.

Mental Disorders: Introduction Bjorn A. Meyerson 203.

210.

ClNGULOTOMY IN PSYCHOSURGERY

c

t

o

n

2

Sympathetic Procedures for Treatment of Persistent

1965

Pain Syndromes

G. Rees Cosgrove / H. Thomas Ballantine e

2005

Gerald E. Loeb

1955

and Indications

Auditory Prosthesis

2009

Carlos R. Telles-Ribeiro / Luiz F. de Oliveira

3

Other Stimulation Procedures / 1971 204.

Spinal Cord Stimulation in Peripheral Vascular Disease and Angina Pectoris

1973

Lars-Erik Augustinsson / Bengt Linderoth / Tore Eliasson / Clas Mannheimer

PART

future technological advances / 2015 211.

From the Past into the Future

2017

216.

Trends in Computer and Imaging Technology

217. 2025

218.

Computers for Map Generation 2031

CNS 2073

Richard D. Penn 219.

The Future of Frameless Stereotaxy

The Future of

Infusion Systems

Jonathan O. Dostrovsky 214.

2057

Ross Davis

The Use of Inexpensive Personal and Data Analysis

Future Possibilities for Neural Stimulation

Bruce A. Kail 213.

2053

Paul W. Sperduto

Manuel Velasco-Sudrez 212.

The Future of Radiosurgery

Neuro-Oncology Advances in the Management of Brain Tumors:

2037

Today and Tomorrow

David W. Roberts

2077

Raymond Sawaya / B. Lee Ligon 215.

The Future of Robotics in Stereotactic Surgery

2047

220.

The Future of Central Nervous

James M. Drake / James T. Rutka /

System Tissue Transplantation

Harold J. Hoffman

Roy A. E. Bakay / Kevin L. Boyer

2091

Contents

221.

The Future of Degenerative Disease Treatment

Index 2103

Erik-Olaf Backlund 222.

The Future of Molecular Neuro-Oncology in Stereotactic Neurosurgery Abhijit Guha / Matthias M. Feldkamp

2107

xv

2127

CONTRIBUTORS

Contributors

xx

William A. Buchheit, M.D.

G. Rees Cosgrove, M.D., F.R.C.S.

Professor and Vice Chairman, Department of Neurosurgery, Thomas Jefferson Medical College. Philadelphia, Pennsylvania (Chapter 89)

Associate Professor of Neurosurgery, Harvard Medical School, Department of Neurosurgery, Massachusetts General Hospital, Boston, Massachusetts (Chapters 73, 203)

Richard D. Buchoi.z, M.D. Professor, Division of Neurosurgery, St. Louis University School of Medicine, St. Louis, Missouri ( Chapter 40)

Dennis E. Bullard, M.D. Associate Clinical Professor of Neurosurgery, University of North Carolina, Raleigh Neurosurgical Clinic, Raleigh, North Carolina (Chapter 98)

Kim J. Burchiel, M.D. John Raaf Professor and Head, Division of Neurological Surgery, University of Oregon, Portland, Oregon (Chapter 176)

E. Brian Butler, M.D. (Chapter 72)

William E. Butler, M.D. Assistant Professor, Neurosurgical Service, Massachusetts General Hospital, Boston, Massachusetts (Chapter 80)

Mark P. Carol, M.D. Melford, New York (Chapter 81)

L. Steven Carpenter,M.D. (Chapter 72)

Jose E. Cavazos, M.D., Ph.D. Epilepsy Fellow T, Division of Neurology, Duke University Medical Center, Durham, North Carolina (Chapter 186)

Parakrama T. Chandrasoma, M.D.

Eric R. Cosman, Ph.D. Professor of Physics, Massachusetts Institute of Technology Radionics, Inc., Burlington, Massachusetts (Chapters 22, 101)

Pierre-Yves Cote, Ph.D. (Chapter 120)

Michael J. Cousins, M.D., F.R.C.A. Professor and Head. Department of Anaesthesiology, University of Sydney, St. Leonards, Australia (Chapter 139)

Arthur Cukiert Division of Neurosurgery, University of Sao Paulo Medical School, Sao Paulo, Brazil (Chapter 189)

Karen D. Davis, Ph.D. Assistant Professor, Division of Neurosurgery, University of Toronto, Toronto, Ontario, Canada (Chapter 94)

Ross Davis, M.D. Director, Clinical Neuroscience Center, Neural Engineering Clinic, Augusta, Maine (Chapters 100, 114, 201, 217)

Jose C. Martin del Campo, M.D. Lecturer. Department of Neurology, Toronto Western Hospital, Toronto, Ontario, Canada (Chapter 188)

Department of Pathology, LSC/USC Medical Center, Los Angeles, California (Chapter 48)

Wanderley Cerqueira de Lima

Paul H. Chapman, M.D.

Timmie Professor and Chairman, Department of Neurology, Emory University School of Medicine, Atlanta, Georgia (Chapter 119)

Associate Professor of Surgery, Harvard Medical School, Neurosurgical Service, Massachusetts General Hospital. Boston, Massachusetts (Chapter 80)

Thomas C. Chen, M.D., Ph.D. Assistant Professor, Department of Neurosurgery, LAC-USC Medical Center, Los Angeles, California (Chapter 47)

J. Kam Chiu (Chapter 72)

Chang Rak Choi, M.D., Ph.D. Professor and Director, Department of Neurological Surgery, Catholic University Medical College, Seoul, Korea (Chapter 31)

Robert J. Coffey, M.D. New Rochelle, New York (Chapters 29. 132)

Gabriklla Colicchio (Chapter 193)

Federico Colombo, M.D.

(Chapter 175)

Mahlon R. DeLong, M.D.

W. Sam Dennis (Chapter 72)

Luiz F.

de Oliveira, M.D. Associate Professor of Anesthesiology and Pharmacology, Faculdade Ciencias Medicas, University of State of Rio de Janeiro, Rio de Janeiro, Brazil (Chapter 210) Antonio A. F. De Salles, M.D. Associate Professor, Division of Neurosurgery, UCLA Medical Center. Los Angeles, California (Chapter 34)

Milan R. Dimitrijevic, M.D. Vivian L. Smith Professor and Head, Division of Restorative Neurology. Baylor College of Medicine, Houston. Texas (Chapter 131)

Michael Dogali, M.D.

Professor, Department of Neurological Surgery. Ospedale Civile, Vicen/.a. Italy (Chapters 76. 85)

Professor of Neurosurgery. Department of Neurosurgery, LAC/USC Medical Center, Los Angeles, California (Chapters 121, 194, 195)

Benjamin W. Corn, M.D.

Jonathan O. Dostrovsky, Ph.D.

Associate Professor and Vice Chairman. Department of Radiation Oncology. Thomas Jefferson Medical College, Philadelphia, Pennsylvania (Chapter 89)

Professor. Department of Physiology, University of Toronto, Toronto, Ontario. Canada (Chapters 94, 213)

Contributors

xxt

Patrick M. Dougherty, Ph.D.

Stephen R. Freidberg, M.D.

Assistant Professor, Department of Neurosurgery, The Johns Hopkins University, Baltimore, Maryland (Chapter 96)

Professor and Chairman, Department of Neurosurgery, Lahey Hitchcock Clinic, Burlington, Massachusetts (Chapter 12)

James

M.

Drake,

M.D.

Allan H. Friedman, M.D.

Division of Neurosurgery, Hospital for Sick Children, Toronto, Ontario, Canada (Chapters 44, 215)

Stephanie Dubinsky

William A. Friedman,

(Chapter 191)

Manuel Dujovny,

Professor and Chief, Division of Neurosurgery, Duke University Medical Center, Durham, North Carolina (Chapter 107)

M.D.

Department of Neurosurgery, University of Illinois, Chicago, Illinois (Chapters 43, 53)

M.D.

Professor, Department of Neurosurgery, University of Florida, Gainesville, Florida (Chapters 77, 83)

Eric

M.

Gabriel,

M.D.

Senior Resident, Division of Neurosurgery, Duke University Medical Center, Durham, North Carolina (Chapter 3)

Nadav Dujovny (Chapter 45)

Tore Eliasson

L.

Robert

Jerome Engel, Jr.,

Department of Neurosurgery, Vanderbilt University Medical Center, Nashville, Tennessee (Chapters 21, 24, 39)

M.D.

Professor, Department of Neurology, Reed Neurological Research Center, Los Angeles, California (Chapter 179)

Rodolfo Farias Department of Neurology, Centro Medico Osier, Monterrey, Mexico (Chapter 181)

Galloway, Jr.,

Ph.D.

(Chapter 204)

Jeremy C. Ganz, M.D. Honorary Professor, University of Graz (Austria) School of Medicine, Hong Kong, China (Chapter 91J

Dong Ming Gao Matthias M. Feldkamp, M.D.

(Chapter 123)

Division of Neurosurgery, The Toronto Western Hospital, Toronto, Ontario, Canada (Chapter 222)

Eduardo Garcia-Almaguer Department of Neurology, Centro Medico Osier, Monterrey, Mexico (Chapter 181)

Claudio A. Feler, M.D. Assistant Professor, Department of Neurosurgery, University of Tennessee, Memphis, Tennessee (Chapter 124)

Patricia

M.

Fernandez,

M.D.

Visiting Professor, Department of Neurosurgery, University of Illinois, Chicago, Illinois (Chapter 43)

Eduardo Garcia-Flores,

M.D.

Director, Centro Medico Osier, Col. Miravalle, Monterrey, Mexico (Chapter 181)

Laurie Gaspar, M.D. Department of Radiation Oncology, Wayne State University, Detroit, Michigan (Chapter 71)

M.

Arthur

Clinical Assistant Professor of Physical Medicine and Rehabilitation, Medical College of Ohio, Department of Neurosurgery, St. Vincent’s Mercy Medical Center, Toledo, Ohio (Chapter 174)

J.

Michael Fitzpatrick,

Ph.D.

Department of Neurosurgery, Vanderbilt Medical Center, Nashville, Tennessee (Chapter 24)

John C. Flickinger, M.D. Professor of Radiation Oncology and Neurosurgery, Department of Radiation Oncology, University of Pittsburgh, Pittsburgh, Pennsylvania (Chapters 64, 87)

Harold Fodstad,

M.D., Ph.D.

Division of Neurosurgery, New York Methodist Hospital, Brooklyn, New York (Chapter 208)

Paolo Francescon, Ph.D. (Chapters 76, 85)

Angelo Franzini,

M.D.

Department of Neurosurgery, Instituto Neurologico C. Besta, Milano, Italy (Chapter 37)

Lois

Freedman

(Chapter 72)

Gerber,

M.D.

Alan Fine, M.D. Professor, Department of Physiology and Biophysics, Dalhousie University, Halifax, Nova Scotia, Canada (Chapter 117)

Philip L. Gildenberg, M.D., Ph.D. Clinical Professor of Neurosurgery and Radiology, Baylor College of Medicine, Houston Stereotactic Center, Houston. Texas (Chapters 1, 20, 46, 55, 70, 72, 136, 142)

John Gillingham Las Colinas, L’Algueria Gassent, Alicante, Spain (Chapter 16)

John

P.

Girvin,

M.D.

Chairman, Division of Neurosurgery, London Health Science Centre University Campus, London, Ontario, Canada (Chapter 208)

Stephen J. Goerss Neurosurgical Research Associate, Department of Neurologic Surgery, Mayo Clinic, Rochester. Minnesota (Chapter 18)

John G. Golfinos, M.D. Department of Neurosurgery, Barrow Neurological Institute, Phoenix, Arizona (Chapter 57)

XXII

Contributors

Michael Louis Goodman, M.D.

Samuel J. Hassenbusch, M.D., Ph.D.

Atlanta, Georgia (Chapter 74)

Associate Professor, Department of Neurosurgery, M. D. Anderson Cancer Center, Houston, Texas (Chapter 146)

John P. Gorecki, M.D., F.R.C.S. (C.) Assistant Professor of Surgery (Neurosurgery), Department of Neurosurgery, Duke University, Durham, North Carolina (Chapters 140, 143, 144, 164, 168)

Kasim I. Gouda, M.D. Millis. Massachusetts (Chapter 12)

Sylvie Grand (Chapter 123)

Magdy M. Hassouna, M.D., Ph.D. Associate Professor, Division of Urology, The Toronto Hospital-Western Division, Toronto, Ontario, Canada (Chapter 207)

M. Peter Heilbrun, M.D. Department of Neurosurgery, University of Utah School of Medicine. Salt Lake City, Utah (Chapter 56)

Walter H. Grant III, Ph.D.

Harold J. Hoffman, M.D.

(Chapter 72)

Professor, Division of Pediatric Neurosurgery, Hospital for Sick Children. Toronto, Ontario, Canada (Chapter 215)

Gary Gronich EEG Service, Institute of Psychiatry, University of Sao Paulo Medical School, Sao Paulo, Brazil (Chapter 189)

Jeffrey D. Gross, M.D. Senior Resident, Department of Neurological Surgery, UC-Irvine Medical Center, Orange. California (Chapters 121, 195)

John Grossmith, M.D. Chief Resident, Department of Neurosurgery, Henry Ford Hospital, Detroit, Michigan (Chapter 50)

Abhuit Guha, M.Sc., M.D., F.R.C.S.(C.) Associate Professor, Division of Neurosurgery, The Toronto Hospital, University of Toronto, Scientist at Lunenfeld Research Centre, Mt. Sinai Hospital, University of Toronto, Toronto, Ontario, Canada (Chapter 222)

Dominique Hoffmann Staff Neurosurgeon, Department of Neurological Surgery, Universite de Grenoble, Grenoble, France (Chapters 7, 123)

R. Edward Hogan, M.D. Assistant Professor, Division of Neurosurgery, St. Louis University School of Medicine, St. Louis, Missouri (Chapter 40)

Renn O. Holness, M.D. Professor, Department of Neurosurgery, Dalhousie University, Halifax, Nova Scotia, Canada (Chapter 117)

Hideki Hondo, M.D.

Philip H. Gutin, M.D.

Associate Professor, Department of Neurological Surgery, Tokushima University Medical School, Tokushima, Japan (Chapter 61)

Memorial Sloan Kettering Hospital, New York, New York (Chapter 67)

Gerhard A. Horstmann, M.D.

Jan M. Gybels, M.D., Ph.D.

Department of Neurosurgery, Gamma Knife Praxis, Munchen, Germany (Chapter 27)

Department of Neurosurgery, Katholieke Universiteit Leuven, Leuven, Belgium (Chapters 17, 135)

Michael M. Haglund, M.D., Ph.D. Assistant Professor. Division of Neurosurgery, Duke University Medical Center, Durham, North Carolina (Chapter 99)

Sten Hakanson, M.D., Dr. Med. Sci. Professor, Department of Neurosurgery. Karolinska Hospital, Stockholm, Sweden (Chapter 173)

Lance H. Howland, B.S. Research Associate, Department of Neurosurgery, The Johns Hopkins University, Baltimore, Maryland (Chapter 96)

Stephen L. Huhn, M.D. Department of Neurosurgery, University of California Medical Center. San Francisco, California (Chapter 67)

Samuel E. Hunter, M.D.’

Allan J. Hamilton, M.D.

Houston Stereotactic Center, Houston, Texas . (Chapter 153)

Associate Professor and Chief, Division of Neurosurgery, University of Arizona Health Sciences Center, Tucson, Arizona (Chapter 92)

W. D. Hutchison, Ph.D.

Peter A. Hardy, Ph.D. Department of Radiology, Cleveland Clinic Foundation, Cleveland, Ohio (Chapter 33)

Tyrone L. Hardy, M.D., F.A.C.S. El Cajon, California ( Chapter 54)

Assistant Professor, Division of Neurosurgery, Toronto Western Hospital. Toronto, Ontario, Canada (Chapter 94)

PaulA. Hwang, M.D. Department of Paediatrics. The Hospital for Sick Children. Toronto, Ontario, Canada (Chapter 183)

Marvvan I. Hariz, M.D., Ph.D.

Bermans J. Iskandar, M.D.

Associate Professor, Department of Neurosurgery, University Hospital, Umea, Sweden (Chapters 8, 32)

Chief Resident, Department of Neurosurgery. Duke University, Division of Pediatric Neurosurgery, Children's Hospital, Birmingham, Alabama (Chapter 159)

*Deceased.

Contributors

Peter J. Jannetta, M.D., D.Sc. Walter E. Dandy Professor and Chairman, Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania (Chapter 110)

Hae Dong Jho, M.D., Ph.D. Associate Professor, Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania (Chapter 110)

Fiacro Jiminez, M.D. UMR Neurophysiology, Biomedical Research Department, Mexico City, Mexico (Chapter 199)

M. Jones-Gotman, Ph.D. Associate Professor, Department of Neurology and Neurosurgery, Montreal Neurological Institute, Montreal, Quebec, Canada (Chapter 185)

xxiii

Epilepsy Program, Vancouver Hospital, Vancouver, British Columbia, Canada (Chapter 184)

Ron C. Kupers, M.D. Research Associate, Department of Clinical Neurophysiology, Karolinska Institute, Huddinge, Sweden (Chapter 135)

Jeffrey Labuz, Ph.D. Radionics, Inc., Burlington, Massachusetts (Chapter 55)

Daniel Lacerte, M.D. Associate Professor, Department of Neurological Sciences, Enfant-Jesus Hospital, Quebec, Quebec, Canada (Chapter 23)

Lauri V. Laitinen, M.D.

Fred C. Junn, M.D.

Associate Professor, Department of Neurosurgery, Sophiahemmet, Stockholm, Sweden (Chapters 8, 145)

Department of Neurosurgery, Henry Ford Hospital, Detroit, Michigan (Chapter 116)

Anthony E. Lang (Chapter 121)

Bruce A. Kall, M.S. Lead Analyst, Department of Neurological Surgery, Mayo Clinic, Rochester, Minnesota (Chapters 41, 212)

Lauren A. Langford, M.D. Assistant Professor, Department of Neuropathology, M. D. Anderson Cancer Center, Houston, Texas (Chapter 49)

Yucel Kanpolat, M.D.

Normand J. Laperriere, M.D.

Department of Neurosurgery, University of Ankara Faculty of Medicine, Ankara, Turkey (Chapter 151)

Assistant Professor, Department of Radiation Oncology, Princess Margaret Hospital, Toronto, Ontario, Canada (Chapter 65)

Yoichi Katayama, M.D.

Yves Lazorthes

Professor, Department of Neurological Surgery, Nihon University, Tokyo, Japan (Chapters 115, 156)

Professor, Department of Neurological Surgery, CHU Rangueil, Toulouse, France (Chapter 150)

Peter Kellaway, Ph.D.

Jean-Franqois LeBas

Professor, Department of Neurology, Baylor College of Medicine, Houston, Texas (Chapter 182)

Professor, Department of Radiology, Universite de Grenoble, Grenoble, France (Chapters 7, 123)

Patrick J. Kelly, M.D. Professor and Chairman, Department of Neurosurgery, New York University Medical Center, New York, New York (Chapter 58)

Jae-Hyoo Kim, M.D., Ph.D. Associate Professor, Department of Neurosurgery, Chonnam National University Medical School, Kwangju, Korea (Chapter 46)

Zelma H. T. Kiss, M.D. University of Toronto, Toronto Western Hospital, Toronto, Ontario, Canada (Chapter 137)

Neil D. Kitchen, F.R.C.S. (Chapters 19, 60)

Douglas Kondziolka, M.D., M. University of Pittsburgh, Department of Neurological Surgery, Pittsburgh, Pennsylvania (Chapters 4, 63, 87, 93)

Robert J. Ledoux, Ph.D. Bedford, Massachusetts (Chapter 38)

Ralph A. W. Lehman, M.D. Division of Neurosurgery, The Milton S. Hershey Medical Center, Hershey, Pennsylvania (Chapter 187)

Dan Leksell, M.D. Elekta Instruments, Stockholm, Sweden (Chapter 4)

Frederick A. Lenz, M.D., Ph.D., F.R.C.S. Associate Professor, Department of Neurosurgery, The Johns Hopkins University, Baltimore, Maryland (Chapters 96, 118)

Daniel Levi, M.D. Department of Neurosurgery, Institute Neurologico C. Besta, Milano, Italy (Chapter 37)

Allan B. Levin, M.D.

Hanne M. Kooy, Ph.D.

Professor, Division of Neurosurgery, University of Wisconsin Hospital, Madison, Wisconsin (Chapter 125)

Associate Professor. Joint Center for Radiation Therapy, Harvard Medical School, Boston, Massachusetts (Chapter 79)

(Chapter 64)

Brenda Koska, Ph.D.

Geoffrey Levine, Ph.D.

XXIV

Contributors

Melvin Levitt, Ph.D.

Robert J. Maciunas, M.D.

Professor Emeritus. Bowman Gray School of Medicine, Winston-Salem, North Carolina (Chapter 164)

Professor of Neurological Surgery and Biomedical Engineering, Department of Neurological Surgery, Vanderbilt University Medical Center, Nashville, Tennessee (Chapters 24, 52)

Robert M. Levy, M.D. Associate Professor of Neurosurgery and Physiology, Department of Neurosurgery, Northwestern Medical School, Chicago, Illinois (Chapter 155)

Cho Shun Li, M.D. Clinical Assistant Professor and Chief, Division of Neurosurgery, Kuang Tien General Hospital, Taichung, Taiwan, Republic of China (Chapter 111)

B. Lee Ligon, Ph.D. Department of Neurosurgery, University of Arkansas for Medical Sciences, Little Rock, Arkansas (Chapter 219)

Ann Maitz, M.S. ( Chapter 64)

Allen S. Mandir, M.D., Ph.D. Assistant Professor, Neurosurgery, The Johns Hopkins Hospital, Baltimore, Maryland (Chapter 118)

Clas Mannheimer (Chapter 204)

Guy Marchal, M.D. (Chapter 17)

Patricia Limousin

Raul Marino, Jr., M.D.

Department of Neurology, Universite de Grenoble, Grenoble, France (Chapter 123)

Professor and Chairman, Department of Neurosurgery, Instituto Neurologico de Sao Paulo, Sao Paulo, Brazil (Chapter 189)

Paul M. Lin, M.D., F.A.C.S. Clinical Professor of Neurosurgery, Rydal, Pennsylvania (Chapter 141)

Bengt Linderoth, M.D., Ph.D. Professor, Department of Neurosurgery, Karolinska Hospital, Stockholm, Sweden (Chapters 173, 204)

Christer Lindquist, M.D., Ph.D. Professor, Department of Neurosurgery, Karolinska Hospital, Stockholm, Sweden (Chapters 78, 86)

C. David Marsden, M.D. (Chapter 109)

Ninan T. Mathew, M.D. Clinical Professor of Restorative Neurology, Baylor College of Medicine, Houston Headache Clinic, Houston, Texas (Chapter 178)

Keizo Matsumoto, M.D. Professor Emeritus, Department of Neurological Surgery, Tokushima University Medical School, Tokushima, Japan (Chapter 61)

Gerald E. Loeb, M.D. Chief Scientist, Advanced Bionics, Sylmar, California (Chapter 209)

Jay S. Loeffler, M.D.

Robert E. Maxwell, M.D. Professor and Head, Department of Neurosurgery, University of Minnesota Medical School, Minneapolis, Minnesota (Chapter 196)

(Chapters 79, 84)

Donlin M. Long, M.D. Professor and Chairman, Department of Neurosurgery, The Johns Hopkins Hospital, Baltimore. Maryland (Chapter 161)

Soledad Serrano L6pez, M.D. S. Neurologia, Hospital General de Merida, Merida. Spain (Chapter 104)

Andres M. Lozano, M.D., Ph.D. Associate Professor, Division of Neurosurgery, The Toronto Hospital, Western Division, University of Toronto, Toronto, Ontario, Canada (Chapters 59, 116, 121. 177, 188)

Hsin H. Lu (Chapter 72)

Yoshiaki Mayanagi, M.D., D.M. Professor, Department of Neurosurgery, Tokyo Metro. Police. Hospital, Tokyo,Japan (Chapter 147)

Sanford L. Meeks, Ph.D. Assistant Professor, Department of Radiation Oncology, University of Florida. Gainesville, Florida (Chapter 77)

Mario Meglio, M.D. Associate Professor, Department of Neurosurgery, Universita Cattolica S. Cuore, Rome, Italy (Chapter 165)

Patrick Mertens (Chapter 129)

J. Luber, M.D. (Chapter 42)

Bjorn A. Meyerson, M.D., Ph.D.

Hans Otto LCiders, M.D., Ph.D.

Department of Neurosurgery, Karolinska Sjukhuset, Stockholm, Sweden (Chapter 202)

Professor, Department of Neurology, Cleveland Clinic Foundation, Cleveland. Ohio (Chapter 180)

J. Michiels, M.S.

L. Dade Lunsford, M.D. Lars Leksell Professor of Neurosurgery, Department of Neurological Surgery, University of Pittsburgh. Pittsburgh, Pennsylvania (Chapters 4, 63. 64, 87, 93)

John K. Macfarlane, M.D. Department of Neurosurgery. Neurosurgical Associates. Salt Lake City, Utah (Chapter 56)

Laboratory for Experimental Neurosurgery, U.Z. Gasthuisberg, Leuven, Belgium (Chapter 35)

John Miles, M.B.B.Ch. Department of Medical and Surgical Neurology, Walton Hospital, Liverpool, England (Chapter 148)

JlRO MUKAWA (Chapter 95)

Contributors

Sean F. Mullan, M.D.

Hiroshi Otsubo, M.D.

Professor Emeritus, Department of Neurosurgery, University of Chicago, Chicago, Illinois (Chapter 174)

Assistant Professor, Department of Paediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada (Chapter 183)

Rolf Peter Muller Department of Radiation Oncology, University of Koln, Koln, Germany ( Chapter 88)

C. Munari (Chapter 7)

Fritz Mundinger, M.D. Professor, Freiburg, Germany (Chapter 6)

Naomi Mutsuga Department of Neurosurgery, Handa City Hospital, Handa, lapan (Chapter 15)

Hirotaro Narabayashi, M.D. Professor Emeritus, Juntendo University Medical College, Department of Neurosurgery, Neurological Clinic, Tokyo, Japan (Chapters 14, 106)

Blaine S. Nashold, Jr., M.D. Professor Emeritus, Division of Neurosurgery, Duke University Medical Center, Durham, North Carolina (Chapters 3, 28, 98, 159)

Michael E. Newmark, M.D. Clinical Associate Professor, Department of Neurology, Baylor College of Medicine, Houston, Texas (Chapter 191)

Soheyl Noachtar, M.D. Department of Neurology, University of Munich, Munchen, Germany (Chapter 180)

Georg Noren Associate Professor, Brown University School of Medicine, New England Gamma Knife Center at Brown University, Rhode Island Hospital, Providence, Rhode Island (Chapter 90)

Richard B. North, M.D. Professor, Department of Neurological Surgery, Johns Hopkins Hospital, Baltimore, Maryland (Chapter 162)

Bart Nuttin, M.D., Ph.D. Departments of Neurology and Neurosurgery, Katholieke Universiteit Leuven, Leuven, Belgium (Chapters 17, 35)

Chihiro Ohye, M.D. Professor, Department of Neurosurgery. Gunma University School of Medicine, Maebashi, Gunma, Japan (Chapters 97, 122)

George A. Ojemann, M.D. Professor, Department of Neurological Surgery, University of Washington School of Medicine, Seattle, Washington (Chapters 99, 190)

Andre Olivier, M.D. Department of Neurosurgery, McGill University, Montreal, Quebec, Canada (Chapter 23)

xxv

Janice Ovelmen-Levitt, Ph.D. Research Associate, Department of Neurosurgery, Duke University, Durham, North Carolina (Chapter 164)

Jorge Roberto Pagura, M.D. Professor Titular, Department of Neurosurgery, Hospital I. Albert Einstein, Morumbi-Sao Paulo, Brazil (Chapter 175)

Andre Parent, M.D., Ph.D. Professor of Anatomy and Neuroscience, Centre de Recherche, Universite Laval Robert-Biffard, Beauport, Quebec, Canada (Chapter 120)

Andrew G. Parrent, M.D. Assistant Professor, Division of Neurosurgery, University of Western Ontario, London, Ontario, Canada (Chapter 103)

Arun Angelo Patil, M.D. Professor, Division of Neurological Surgery, University of Nebraska Medical Center. Omaha, Nebraska (Chapter 11)

Richard D. Penn, M.D. Professor, Department of Neurosurgery, Rush-Presbyterian Medical Center, Chicago, Illinois (Chapters 127, 133, 218)

Prem K. Pillay, M.D. Asian Brain-Spine-Nerve Center, Mount Elizabeth Medical Center, Singapore, Republic of Singapore (Chapter 42)

Conrado Pla, Ph.D. Associate Professor, Department of Medical Physics, McGill University, Montreal. Quebec, Canada (Chapter 82)

Ervin B. Podgorsak, Ph.D. Professor, Department of Medical Physics, McGill University, Montreal, Quebec, Canada (Chapter 82)

Pierre Pollak Professor, Department of Neurology, Universite de Grenoble, Grenoble, France (Chapter 123)

Michael D. Prados, M.D. Professor, Department of Neurosurgery, University of California at San Francisco, San Francisco, California (Chapter 67)

Dheerendra Prasad, M.D. Department of Neurosurgery, University of Virginia, Charlottesville, Virginia (Chapters 78, 86)

Jader Pacheco Rabello

Burton M. Onofrio, M.D.

(Chapter 175)

Professor, Department of Neurosurgery, Mayo Clinic, Rochester, Minnesota (Chapter 149)

(Chapter 53)

Vicente Ramirez, M.D.

Christoph B. Ostertag, M.D.

Robert W. Rand, M.D.

Professor, Department of Stereotaxic Neurosurgery, University Neurosurgery Clinic, Freiburg, Germany (Chapter 68)

Associate Director, John Wayne Cancer Institute, Saint John’s Hospital and Health Center, Santa Monica, California (Chapter 102)

xxvi

Contributors

Hans F. Reinhardt, M.D.

Konstantin V. Slavin, M.D.

Professor Dr. Med., Neurosurgical University Clinic, Kantonsspital, Basel, Switzerland (Chapter 27)

(Chapters 45, 53)

Mark Rise (Chapter 199)

Menno E. Sluijter, M.D. Professor of Anesthesiology. Department of Anesthesiology, Pain Relief Unit, Maastricht, Netherlands (Chapter 160)

David W. Roberts, M.D.

Penny K. Sneed, M.D.

Professor of Surgery (Neurosurgery), Dartmouth Medical School, Department of Neurosurgery. Dartmouth-Hitchcock Medical Center, Lebanon. New Hampshire (Chapters 2, 214)

(Chapter 67)

Theodore S. Roberts, M.D. Professor, Department of Neurosurgery, University of Washington Medical Center, Seattle, Washington (Chapter 5)

Mark L. Rosenblum, M.D. Professor and Chairman, Department of Neurosurgery, Henry Ford Hospital, Detroit, Michigan (Chapter 50)

Gian Franco Rossi Professor Emeritus, Department of Neurosurgery, Universita Cattolica, Rome, Italy (Chapter 193)

Lance H. Rowland, B.S. Research Associate. Department of Neurosurgery, The Johns Hopkins University, Baltimore, Maryland (Chapter 96)

James T. Rutka, M.D. Associate Professor, Division of Pediatric Neurosurgery, Hospital for Sick Children. Toronto, Ontario, Canada (Chapter 215)

Michael Salcman, M.D. Clinical Professor of Neurosurgery, George Washington University. Towson, Maryland (Chapter 75)

Brigitte Sallerin (Chapter 150)

Keiji Sano, M.D., D.M. Professor Emeritus, Department of Neurosurgery, University of Tokyo, Tokyo,Japan (Chapter 147)

Raymond Sawaya, M.D. Professor and Chairman, Department of Neurosurgery, M. D. Anderson Hospital, Houston, Texas (Chapter 219)

Luis Souhami, M.D. Professor, Department of Oncology, McGill University, Montreal, Quebec, Canada (Chapter 82)

Dennis D. Spencer, M.D. Department of Neurological Surgery, Yale University School of Medicine, New Haven, Connecticut (Chapter 187)

Susan S. Spencer, M.D. Department of Neurology, Yale University School of Medicine, New Haven, Connecticut (Chapter 187)

Paul W. Sperduto, M.D. Director, Stereotactic Radiosurgery, Health System Minnesota. Methodist Hospital Cancer Center, St. Louis Park, Minnesota (Chapter 216)

Robert F. Spetzler, M.D. Professor, University of Arizona College of Medicine, Department of Neurosurgery, Barrow Neurological Institute, Phoenix, Arizona (Chapter 57)

Michael Stanley, M.D. (Chapter 62)

Richard A. Stea, M.D. Clinical Professor of Neurosurgery. University of Rochester, Fingerlakes Neurosurgical Group, Rochester, New York (Chapter 36)

Charles P. Steiner, B.S. Department of Neurosurgery, Cleveland Clinic Foundation, Cleveland. Ohio (Chapter 26)

Ladislau Steiner, M.D., Ph.D. Department of Neurosurgery, University of Virginia, Charlottesville. Virginia (Chapters 78, 86)

Melita Steiner, M.D. (Chapter 86)

Ulrich Steude, M.D. Christoph Segebarth (Chapter 123)

Andrew G. Shetter, M.D. Chief. Division of Stereotactic Surgery. Department of Neurosurgery, Barrow Neurological Institute, Phoenix, Arizona (Chapter 167)

Colin Shieff Consultant Neurosurgeon, Department of Neurosurgery. The Royal Free Hospital. London, England (Chapter 10)

Jean Siegfried, M.D. Professor, AMI Klinik im Park, Neurochirurgie FMH, Zurich, Switzerland (Chapters 112, 126)

Marc P. Sindou, M.D., D.Sc. Professor and Chairman, Department of Neurological Surgery, Hopital Neurologique P. Wertheimer, Lyon, France (Chapter 129)

Priv. Doz„ Department of Neurosurgery, University of Munich Klin. Gosshadern, Munich, Bavaria, Germany (Chapter 157)

Albrecht Struppler Professor, Department of Neurosurgery, Klinikum rechts der Isar der TU, Munchen. Germany (Chapter 128)

Christopher D. Sturm, M.D. Resident, Department of Neurosurgery, St. Louis University School of Medicine. St. Louis, Missouri (Chapter 40)

Volker Sturm Professor, Department of Stereotactic and Functional Neurosurgery, University of Koln, Koln, Germany (Chapter 88)

Paul Suetens, Ph.D. (Chapters 17. 35)

Contributors

xxvii

Kenichiro Sugita, M.D., Ph.D.*

Takashi Tsubokawa, M.D.

Department of Neurosurgery, Nagoya University School of Medicine, Nagoya, Japan (Chapter 15)

Professor of Research Center, Department of Neurological Surgery, Nihon University School of Medicine, Tokyo, Japan (Chapters 115, 156, 205)

William H. Sweet, M.D., D.Sc.

Ian M. Turnbull, M.D.

Professor Emeritus, Harvard University Medical School, Department of Neurological Surgery, Massachusetts General Hospital, Boston, Massachusetts (Chapter 170)

Associate Professor, Department of Neurosurgery, University of British Columbia, Vancouver. British Columbia, Canada (Chapter 171)

Jamal M. Taha, M.D. Department of Neurosurgery, University of Cincinnati, Cincinnati, Ohio (Chapter 172)

Takaaki Takizawa, M.D. Professor and Chief, Fujieda Heisei Memorial Hospital, Stereotactic and Gamma Unit Center, Shizuka, Japan (Chapter 25)

Ronald R. Tasker, M.D. Professor, Division of Neurosurgery, The Toronto Hospital, Western Division, University of Toronto, Toronto, Ontario, Canada (Chapters 94, 105, 108, 122, 152)

Stephen B. Tatter, M.D., Ph.D. Assistant Professor, Department of Neurosurgery, Bowman Gray School of Medicine, Winston-Salem, North Carolina (Chapter 80)

Ethan Taub, M.D. Fellow in Functional Neurosurgery, Division of Neurosurgery, The Toronto Hospital, Western Division, Toronto, Ontario, Canada (Chapters 59, 188)

Manoel Jacobsen Teixeira Professor, Department of Neurology, University of Sao Paulo, Sao Paulo, Brazil (Chapter 140)

Carlos R. Telles-Ribeiro, M.D. Associate Professor and Chairman, Department of Neurological Surgery, University of State of Rio De Janeiro-Faculdade Ciencias Medicas, Rio de Janeiro, Brazil (Chapter 210)

John M. Tew, Jr., M.D. Frank H. Mayfield Professor and Chairman, Department of Neurosurgery, University of Cincinnati College of Medicine, Cincinnati, Ohio (Chapter 172)

David G. T. Thomas, F.R.C.S. Professor, Gough-Cooper Department of Neurological Surgery, National Hospital, London, England (Chapters 19, 60)

F. Deaver Thomas (Chapter 36)

Robert D. Tien, M.D., M.P.H. Associate Professor, Department of Radiology, Duke University Medical Center, Durham, North Carolina (Chapter 186)

William D. Tobler, M.D. Associate Professor of Clinical Neurosurgery, University of Cincinnati, Department of Neurosurgery, Mayfield Clinic, Cincinnati, Ohio (Chapters 13, 62)

Edwin M. Todd, M.D. Clinical Professor of Neurosurgery, University of Southern California, Arcadia, California (Chapter 9)

Michael Trippel, M.D. Neurosurgical University Clinik, Basel, Switzerland (Chapter 27) *Deceased.

Maarten van Kleef, M.D., Ph.D. Department of Anesthesiology, Pain Relief Unit, Maastricht, Netherlands (Chapter 160)

R. Graham Vanderlinden, M.D., F.R.C.S.(C.) Associate Professor of Neurosurgery, University of Toronto, Mississauga, Ontario, Canada (Chapter 206)

Dirk Vandermeulen, Ph.D. Professor, Laboratory for Medical Imaging Research, University Hospital Gasthuisberg, Leuven, Belgium (Chapters 17, 35)

Ana Luisa Velasco (Chapter 199)

Francisco Velasco Professor, Division of Neurophysiology, UMR Neurophysiology, Mexico City, Mexico (Chapter 199)

Marcos Velasco, M.D., Ph.D. UMR Neurophysiology, Biomedical Research Department, Mexico City, Mexico (Chapter 199)

Manuel Velasco-Suarez, M.D. Professor of Neurology and Neurosurgery, U.N.A.M., Department of Neurosurgery, National Institute of Neurology and Neurosurgery, Mexico City, Mexico (Chapter 211)

Rudi Verbeeck, M.Sc., Ph.D. Laboratory for Medical Imaging, Katholieke Universiteit Leuven, Leuven, Belgium (Chapters 17, 35)

Jean-Claude Verdie (Chapter 150)

Alan T. Villavicencio, M.D. Resident, Division of Neurosurgery, Duke University Hospital, Durham, North Carolina (Chapter 107)

Jean-Guy Villemure, M.D. Professor, Department of Neurosurgery, Montreal Neurological InstituteMcGill University, Montreal, Quebec, Canada (Chapter 197)

Jerrold L. Vitek, M.D. Associate Professor, Department of Neurology, Emory University Medical School, Atlanta, Georgia (Chapter 119)

Juhn A. Wada, M.D. Professor, Division of Neurology and Neurological Sciences, University of British Columbia, Vancouver, British Columbia, Canada (Chapter 184)

Suellen M. Walker, M.D., B.S. Clinical Lecturer and Staff Specialist, University of Sydney, Pain Management and Research Center, Royal North Shore Hospital, St. Leonards, Australia (Chapter 139)

xxviii

Contributors

Alain Waltregny, M.D., Ph.D.

William D. Willis, Jr., Ph.D.

Agrege de Faculte, Stereotactic Department, Universite de Liege, Liege, Belgium (Chapter 51)

Director, Marine Biomedical Institute, University of Texas Medical Branch, Galveston, Texas (Chapter 134)

Joseph M. Waltz, M.D.

James T. Wilson, M.D.

Director, Department of Neurosurgery, St. Barnabas Hospital, Bronx, New York (Chapter 113)

Southern Maine Neurosurgical Associates, Portland, Maine (Chapter 44)

Cheng-Jen Wang

Professor, Department of Radiation Oncology, Baylor College of Medicine, Houston, Texas (Chapters 70, 72)

(Chapter 186)

E. Sidney Watkins, M.D., F.R.C. Professor Emeritus, Department of Neurosurgery, The London Independent Hospital, London, England (Chapter 28)

C. Peter N. Watson, M.D., F.R.C. Assistant Professor, Department of Medicine, University of Toronto, Toronto, Ontario, Canada (Chapter 166)

Vance Watson, M.D.

Shiao Y. Woo, M.D.

Tony L. Yaksh Department of Anesthesiology, University of Califomia-San Diego, LaJolla, California (Chapter 149)

Takamitsu Yamamoto, M.D., D.Sc. Assistant Professor, Department of Neurological Surgery, Nihon University, Tokyo, Japan (Chapters 115, 205)

(Chapter 34)

Katsumi Yamashiro, M.D.

Trent H. Wells, Jr.

Department of Neurosurgery, Ryukyu University, Okinawa, Japan (Chapter 95)

Senior Consultant, TrentWells, Inc., Coulterville, California (Chapter 9)

Masafumi Yoshida, M.D.

Birgit Westermann (Chapter 27)

Vice Chairman. Department of Neurosurgery, Baba Hospital, Fukuokaken, Japan (Chapter 30)

Karin N. Westlund

Ronald F. Young, M.D.

Marine Biomedical Institute. University of Texas Medical Branch, Galveston, Texas (Chapter 134)

Medical Director, Gamma Knife Center, Northwest Hospital, Seattle, Washington (Chapter 163)

Thomas Wichmann, M.D.

Lucia Zamorano, M.D., Ph.D.

Assistant Professor, Department of Neurology, Emory University Medical School. Atlanta, Georgia (Chapter 119)

Professor of Neurosurgery and Radiation Oncology, Department of Neurosurgery, Wayne State University Health Center, Detroit, Michigan (Chapter 71)

Harold A. Wilkinson, M.D.

Nicholas T. Zervas, M.D.

Professor of Neurosurgery, Department of Neurosurgery, University of Massachusetts Medical Center, Worcester, Massachusetts (Chapter 169)

Higgins Professor and Chief, Neurosurgical Service, Massachusetts General Hospital. Harvard Medical School, Boston. Massachusetts (Chapter 73)

PREFACE Why write a Textbook of Stereotactic and Functional Neurosurgeryl And why at this particular time when so many other neurosurgical texts are appearing on the market? There are many reasons. Never before has there been so much progress and conse¬ quent activity in stereotactic and functional neurosurgery re¬ sulting in so many neurosurgeons using the techniques. Stereotactic surgery has changed from an esoteric subspecialty to a technique that is being incorporated into nearly every neu¬ rosurgical practice. This has come about because of rapidly in¬ creasing knowledge in the neurosciences and because of tech¬ nological developments in many fields, especially imaging and computer graphics. Particularly, the marriage of stereotactic techniques and imaging has opened the door to both framebased and frameless stereotactic approaches to mass lesions of the brain ordinarily in the realm of the general neurosurgeon. These developments have in turn spawned renewed interest in all aspects of functional neurosurgery to treat epilepsy, pain, and movement disorders. Thus, stereotactic surgery is at the crossroads. Since it de¬ pends jointly upon what has been done in the past and current advances, a reference is needed that reviews the former and de¬ tails the latter, presenting the current wealth of available tech¬ niques in their broadest terms. It is also important to try to discern in what direction this ac¬ tive field is progressing. As the necessary equipment becomes more complex and expensive, decisions about making capital outlays increasingly depend on information comparing systems and defining their capabilities. Moreover, modern advances have made stereotactic and functional neurosurgery a multidis¬ ciplinary endeavor in which each involved specialist, whether neurosurgeon or not, must have access to a broad information base. This renaissance of stereotactic and functional neuro¬ surgery, essentially amounting to the birth of a new specialty, comes at a time when all of medicine is seeking minimally in¬ vasive means to treat disease and to do so more precisely— goals that stereotactic surgery has always been in the forefront of achieving. This, then, is a propitious time to present a Textbook of Stereotactic and Functional Neurosurgery. This in¬ tensity of activity in stereotactic and functional neurosurgery coincides with the fiftieth anniversary of the field. In 1947, Spiegel and Wycis performed the first human stereotactic oper¬ ation on a patient using a device that was a modification of the Horsley-Clarke apparatus that had already been in use in exper¬ imental animals for 40 years. The introduction of human stereotactic surgery was made possible by the use of internal cerebral landmarks for finding the target, a technique made possible by advances in intraoperative radiology. There has never before been an encyclopedic work in this field. There has never been a source to which the medical stu¬ dent, resident, neurosurgeon, and neuroscientist alike could be referred for orientation in and detailed information about the underlying basic sciences and the involved techniques. In putting this book together we have included reviews not only of well-known subjects in common use but also of techniques

used in the past that may have limited application today, as well as of current techniques that may have enjoyed thus far very limited exploitation, since it is felt that those to whom future development is entrusted should have access to what others have experienced. We have been fortunate in the generous response of experts in the stereotactic and functional community in providing con¬ tributions in their fields of interest. The authors are well known and respected by virtue of expertise, presentations, and publi¬ cations in the fields in which they write. They have offered their own opinions and conclusions, which may or may not be shared by the editors, and their contributions round out an international view of the field. Both of us (Tasker and Gildenberg) have worked and attended conferences with many of the authors around the world and edited or written other publica¬ tions in the field. Gildenberg has for the last 22 years been edi¬ tor of the journal now known as Stereotactic and Functional Neurosurgery, providing close contact with scientists in func¬ tional and image-based stereotactic neurosurgery, including many of the contributors to this volume. Both have been Presi¬ dents of the American and World Societies for Stereotactic and Functional Neurosurgery, and Gildenberg is the current Presi¬ dent of the World Society. Special thanks are due to Patricia O. Franklin for her work as managing editor of this large project. It has required dedica¬ tion, diligence, and organization to track so many manuscripts and illustrations and to keep a productive correspondence with so many authors, as well as to maintain a complex database as publication proceeded and to preserve a river of information between Toronto and Houston. She has handled many editorial questions and problems with aplomb and has negotiated sched¬ ules of busy clinicians to try to satisfy as promptly as possible the needs of the publishers. This book would not have been possible without her. We also recognize the efficiency and hard work of Anne Chiacchieri who maintained the other end of the information pipeline in Toronto. Particularly the editors wish to recognize the diligence, hard work, and common sense of the editors at McGraw-Hill. James Morgan has led us through a long and complicated editorial process. Martin Wonsiewicz has represented our interests well in smoothing out the difficulties encountered in publishing a book. Lester Sheinis has worked long and hard to polish all the manuscripts and to bring them to a more uniform format. We must, of course, thank the many authors to whom we dedicate this book; their devotion to the completion of this work in the form of astounding numbers of hours spent with meticulous attention to detail is the greatest single contribution. They have provided their best, sharing with the reader their opinions and vast experience not ordinarily available under one cover. We are also indebted to our colleagues at home who have tolerated the long hours devoted to working on this publication. We are particularly grateful to our wives, Patricia Franklin and Mary Tasker, for their understanding and encouragement. Finally, we are grateful to the readers whom we hope will find this volume of interest and value as they lead stereotactic and functional neurosurgery into the next millennium. xxtx

PART

1

STEREOTACTIC PRINCIPLES

CHAPTER

1

THE HISTORY OF STEREOTACTIC AND FUNCTIONAL NEUROSURGERY

Philip L. Gildenherg

it also was necessary to produce the first stereotaxic atlas, which appeared as part of the same article but also was pub¬ lished independently later7,8 and which consisted of illustra¬ tions of sections of the monkey brain at calibrated intervals. A scale provided measurements of each slice; the height of each slice above the base of the apparatus was indicated. The atlas sections were registered by a cartesian coordinate system to landmarks on the monkey’s skull—the external auditory canals and the inferior orbital rim—which also constituted the fixation points of the stereotactic apparatus. When the animal’s head was secured by earplugs and tabs that held the inferior orbit, the head was automatically positioned so that the horizontal plane intersected the ear canals and the inferior orbit (similar to the Frankfort plane used by anthropologists), the midsagittal plane was automatically identified, and the coronal plane passed through the ear canals at right angles to the other two planes. The third part of the report concerned the production of electrolytic lesions with direct current, a description that has not been surpassed since that time. The fourth section reported the physiological observations of the cerebellum, which were based on the production of lesions with the stereotaxic

The first technique for the spatial localization of intracranial structures in the modern scientific era can be credited to Dittmar,1 who in 1873 used a guided probe to insert a blade into the medulla oblongata of the rat to perform physiological studies of that structure. The technique was not stereotactic, however, since it did not relate to a cartesian coordinate system, that is, employ a mathematical concept that identifies a point in space by its relationship to three planes intersecting at right an¬ gles to each other and intersecting at a common point; this con¬ cept forms the basis for identifying a stereotactic target by the three coordinates: anteroposterior (AP), lateral, and vertical.2 In the Russian perspective,3 the beginnings of human stereotac¬ tic surgery are traced to Zernov’s work4 in 1889, with the de¬ scription of an encephalometer that helped localize surface ar¬ eas of the brain, and the demonstration of its clinical use by Altukhov5 2 years later. However, none of those systems meets the modern criteria for stereotactic surgery; that is, they were not based on a three-dimensional cartesian coordinate system. The history of stereotactic surgery actually begins with the use of cartesian principles by Horsley and Clarke,6 who de¬ scribed the first animal stereotaxic* apparatus in a seminal pub¬ lication in 1908. Sir Victor Horsley was a neurophysiologist and neurosurgeon who looked for a technique to insert an elec¬ trode reliably into the dentate nucleus to study the cerebellum of the monkey. He invited Clarke, a mathematician, to help him design a device that would insert an electrode into any desired target in a controlled fashion. Not only is the technique they reported a milestone in neurological research and a model of scientific genius, their report is a paragon of scientific commu¬ nication.6 The article begins with a description of the apparatus used to hold an electrode and guide it to a target defined in three dimensions; this is the best remembered part of the re¬ port. To find the target, as well as other targets within the brain,

apparatus. Although Clarke suggested to Horsley that the technique might be useful in humans and even patented the idea for a hu¬ man apparatus,9 the pair separated because of disagreements about other matters and did not develop that idea.10 In about 1918, however, Mussen, an engineer who had worked with the Horsley-Clarke stereotaxic apparatus, designed a similar device for the human skull.11 He could not persuade his neurosurgical colleagues to use it, however, so he wrapped it in newspaper and stored it in his attic, where it was not discovered until after his death. The year when he stored it was determined by the date of the newspaper, since he never reported the device in the literature. It was perhaps best that it was not used. The variabil¬ ity between the human skull and the intracerebral structures is so great that it would have proved grossly inaccurate, and the field of human stereotaxis might not have recovered. In addi¬ tion, it was not until 30 years later that concepts of human neu¬ rophysiology advanced enough to make this technique clini¬

*Horsley and Clarke called their technique stereotaxic from the Greek stereo for “three-dimensional” and taxic for “an arrangement.” When this technique was later applied to human surgery, some workers started to use the term stereotactic. At the organizational meeting of the World Society for Stereotactic and Functional Neurosurgery in Tokyo in 1973, it was agreed to use the latter term for human surgery, and that convention has been accepted by most publications. It was felt that tactic, from the Latin “to touch,” was more descriptive of the technique. Today stereotaxic gener¬ ally is reserved for animal techniques, stereotactic is used for human surgery, and stereotaxis applies to both.

cally useful. The problem of establishing an accurate reference system for human stereotaxis was solved by Ernest A. Spiegel and Henry T. Wycis. Spiegel was a neurologist who fled the Nazis

5

6

Part 1/Stereotactic Principles

in Vienna for Philadelphia in 1936, where he served as pro¬ fessor of experimental neurology at Temple Medical School. Wycis began to work in Spiegel’s laboratory as a medical student, and their collaboration developed as Wycis became a neurosurgeon. In 1947, they reported a human stereotactic ap¬ paratus that allowed intraoperative x-rays to be taken so that landmarks in the brain could be visualized.12 Anatomic struc¬ tures could be targeted by referring to a human stereotactic at¬ las, which they designed and later published.13 They originally called this new science stereoencephalotomy, meaning a threedimensional technique with landmarks in the brain itself. The timing was right for such a development. Prefrontal lobotomy was a popular procedure in the days before adequate psychotropic medication.14 The impetus for the development of stereotactic surgery was that Spiegel had hoped to refine that procedure to avoid the many complications and deficits that it often involved; once the technique was available, however, it was not used for psychosurgery for several years. The stage had been set for the development of human cere¬ bral functional neurosurgery. The understanding of neurophysi¬ ology had advanced to the point where the concept of the extrapyramidal system and the pathways involved with pain and movement disorders were defined, to a large extent because of animal experimentation that involved stereotactic techniques. X-ray technology had evolved so that intraoperative films could be taken. The landmarks they first used were calcifications in the pineal gland and the foramen of Monro defined by lumbar instillation of air, but soon the intercommissural line, as recom¬ mended by Talairach and associates,15 became the standard. There was a growing understanding that interruption of the extrapyramidal system might benefit patients with movement disorders, but existing craniotomy techniques had unacceptable mortality and morbidity. Much of the pioneering surgery for movement disorders had been developed by Russel Meyers16-17 at the University of Iowa. His name is perhaps not as familiar to present-day stereotactic surgeons because his major contribu¬ tions occurred before 1946, and he never became comfortable with conventional stereotactic techniques. However, he devised ingenious craniotomy approaches to interrupt the extrapyrami¬ dal system, such as an interhemispheric approach to interrupt the ansa lenticularis at the base of the globus pallidus and a transventricular approach to the head of the caudate nucleus. There were no effective drugs for Parkinson’s disease, and so adventurous surgery was often indicated. Meyers1617 attempted to control tremor and rigidity of Parkinson’s disease by a non¬ stereotactic transventricular approach, which, however, carried a mortality rate of 15.7 percent. Although he admitted that the morbidity and mortality rates were prohibitive, he set the stage for less invasive stereotactic procedures. In contrast, within a decade after the introduction of stereotactic surgery, Spiegel and Wycis18 reported a stereotactic operative mortality of 2 per¬ cent, and Riechert and Mundinger19 soon reported mortality of less than 1 percent, where it remains today. There also had been attempts to interrupt pathways in the brain for the treatment of pain. Many of these techniques in¬ volved surgical interruption of conveniently superficial path¬ ways and are still in use.20-23 There was a good understanding of the primary pain pathway as it ascended through the brain stem, and the concept of the participation of the limbic system in pain perception was well developed.24-25

THE ORIGINS OF STEREOTACTIC SURGERY Although logic suggests that a historical topic be developed chronologically, various aspects of stereotactic surgery devel¬ oped at different rates, and so it is easier for the reader to fol¬ low if the chronology of each topic is developed separately. The references are cited as examples and usually are not the sole references for most subjects. There is no line between his¬ tory and current events, and the details of most recent topics are presented in much more detail in other chapters in this book. The evolution of stereotactic apparatus after the initial de¬ sign period was to a great extent dependent on developments in technologies in other fields that were later incorporated into stereotaxis. The original Spiegel-Wycis Model I Stereoencephalotome, which is now in the Smithsonian Institution, bore a more than coincidental resemblance to the original HorsleyClarke apparatus (Fig. 1-1). It was anchored to a ring that cir¬ cled the patient’s head and was aligned by earplugs and orbital tabs. The ring was held in place by a plaster sling that was made to order for each patient. A microdrive was mounted on the ring so that it could be moved anterior-posteriorly or later¬ ally and could advance an electrode along a vertical tract. The operation was preceded by a lumbar puncture with the installa¬ tion of air, and measurements were based on an intraoperative pneumoencephalogram.'3-26 The original philosophy, which was maintained throughout Spiegel and Wycis’s career and adopted by many other stereotacticians, was that every time an electrode was inserted into the human brain, it provided a unique research opportunity, and so the initial part of the proce-

Figure 1-1. The original Spiegel-Wycis Stereoencephalotome, Model I.

Chapter 1/The History of Stereotactic and Functional Neurosurgery

dure included both physiological confirmation of the elec¬ trode’s position and neurophysiological studies. This fortunate custom credits stereotactic surgery with significant advances in our understanding of the human brain, and this in turn has led to additional opportunities for stereotactic intervention. Lesions originally were made with the same electrolytic direct current used 40 years before,27 but other techniques were soon developed, such as oil-procaine or oil-procaine-wax injec¬ tion,28,29 alcohol injection with a balloon cannula or coagulating substance,30,31 mechanical damage with a leukotome,32 and later radiofrequency33 and cryoprobe34 methods. During the first 20 years of stereotactic surgery, Spiegel and Wycis (Fig. 1-2) sampled most of the indications and targets and pioneered almost every area of stereotactic functional neurosurgery.35 Inspired by Spiegel and Wycis, a number of neurosurgeons throughout the world soon reported on their own apparatuses in a flurry of scientific innovation. Lars Leksell36 returned to Sweden from a visit to Philadelphia and designed the first arccentered stereotactic apparatus in 1948 (Fig. 1-3). The follow¬ ing year, Talairach37 in Paris reported his apparatus, which in¬ volved the insertion of electrodes through a fixed grid system. In Germany, Riechert and Wolff38 reported in 1951 their arccentered apparatus, which included a phantom base to assess the settings mechanically. Bailey and Stein39 exhibited a burr hole-mounted apparatus in the United States that same year. The development of Narabayashi’s40,41 apparatus in Japan was curious. After the war, he was isolated from the western litera-

Figure 1-2. Spiegel and Wycis and their team during an early stereotactic surgical procedure.

7

ture but independently developed an apparatus under difficult circumstances. During the 1950s, at least 40 other stereotactic apparatuses were designed that were of three basic types.2,42 The HorsleyClarke and Spiegel-Wycis instruments were translational types of instruments; that is, the position of the electrode was changed by sliding the electrode carrier anterior-posteriorly and laterally along a base plate and a microdrive for vertical positioning to set each of the three coordinates separately. The predetermined trajectory might involve two separate angular settings. The Leksell36 and Riechert38 devices (and later the Todd-Wells43) were arc-centered; that is, the three coordinates indicated the center of a semicircular arc along which an elec¬ trode carrier moved, always pointing the electrode toward the isocenter. Since the target always lay at the center of the arc, in¬ sertion along any angle would bring the probe to the target. Burr hole-mounted systems had no transverse settings but con¬ sisted of a ball and socket to hold the electrode. Preinsertion AP and lateral x-rays allowed adjustments to point the electrode to the target and lock it into that trajectory.2,44,45 A fourth type of apparatus was introduced in 1980 as the Brown-Roberts-Wells (BRW) system, which is adjusted by a complicated system of interlocking arcs46 (Fig. 1-4). In the first decade, in addition to those already mentioned, a number of centers for stereotactic investigations were begun throughout the world: Talairach, and associates47 and Guiot and colleagues48 in Paris, Gillingham49 in Great Britain, Laitinen and Toivakka50 in Finland, Bertrand and coworkers51 in Canada, Velasco-Suarez and Escobedo52 in Mexico, Obrador53 in Spain, and Bechtereva and coauthors54 in Russia, among oth¬ ers. Within 20 years, stereotactic surgery was being practiced throughout the world.55 It is estimated that by 1965, more than 25,000 stereotactic treatments had been done worldwide,56 and 37,000 patients had been treated by 1969.57

Figure 1-3. Lars Leksell, shown here with an early model of his stereotactic apparatus, introduced the concept of arc-centered targeting and is recognized as the father of stereotactic radiosurgery.

8

Part 1/Stereotactic Principles

Figure 1-4. All frame-based stereotactic apparatus are of four basic designs: the translational system (Spiegel-Wycis model V) (A), the arc-centered devices (Leksell, Model B) (B), a burr hole-mounted device (C), and a system of interlocking arcs (BRW system) (D).

The first meeting of the International Society for Research in Stereoencephalotomy, (which became the World Society for Stereotactic and Functional Neurosurgery in 1973), was held in Philadelphia in 1966, 20 years after the first human stereotactic procedure. The emphasis was on instrumentation; everyone was invited to take his or her apparatus to the meeting to be dis¬ played. Over 40 types of apparatus were presented, most of which were variations of the three basic systems described above. Almost all were custom-made, since there were few commercially available devices at that time. The second meet¬ ing was held in Atlantic City the following year. As an example of how the science was progressing, the emphasis at that meet¬ ing was on reviewing the large number of indications for stereotactic surgery and sharing clinical experiences.

EVOLUTION OF STEREOTACTIC SURGICAL TECHNOLOGY During the 1960s and 1970s, the Todd-Wells system became the most popular in the United States and the Leksell and Riechert-Mundinger systems became the most popular in Europe, with the Leksell system later gaining ascendancy.51,59 There was little further modification in stereotactic appara¬ tus in the 1970s, when the emphasis was on indications and re¬

sults. However, with the introduction of computed tomography (CT) in the late 1970s, there was a rapid surge in the develop¬ ment of new stereotactic techniques. The ability to see and lo¬ calize a mass lesion expanded the indications for stereotaxis, and the field of image-based stereotactic surgery was born.60 This aspect of stereotactic surgery has advanced so rapidly that it now overshadows functional stereotactic surgery and eventu¬ ally will be incorporated into the armamentarium of every gen¬ eral neurosurgeon.61-62 However, it was necessary to develop techniques to marry stereotactic surgery and computerized imaging, which had much in common. CT scanning involved the display of a series of slices through the brain. Each slice presented a measurable two-dimensional picture from which AP and lateral coordinates could be defined readily. The relative position of each slice in space provided the third vertical coordinate. By reconstructing the head by laying the slices one on the other, one could define a three-dimensional structure in cartesian or stereotactic space.46-63-64 This concept could be used directly on the CT scanner console to define stereotactic coordinates, which then could be taken to the operating room, where a probe or biopsy cannula could be inserted with any stereotactic apparatus to the target visualized on CT, using the same intraoperative x-ray techniques that had been used for functional stereotaxis.64"66 A number of techniques were designed to establish the posi¬ tion of the CT slice relative to a stereotactic head frame, that is, to define the vertical coordinate. The Leksell apparatus was modified with a base plate that could be secured accurately to the scanner and then to the head frame in the operating room to transpose the coordinates from the scan to the stereotactic ap¬ paratus.67 One system used a series of wires of varying lengths incorporated into plastic plates attached to the stereotactic frame so that not all wires were intersected by each slice. The height of the plane of the target slice could be determined by counting the number of intersected wires visualized as white dots on that slice.68 One ingenious system employed three acrylic screws with lead markers that were secured to the pa¬ tient’s skull before scanning and were used to establish a refer¬ ence plane. The base ring of the apparatus was attached to the screws, and calculations were done by computer.69-70 A group of stereotactic apparatuses were developed espe¬ cially to be used with CT scanning. Some depended on the cal¬ ibrated movement of the CT scanner table between slices to de¬ fine the vertical coordinate.68-71 It was even suggested that a CT scanner that incorporated a stereotactic head holder be manu¬ factured.72 In some busy stereotactic services, the CT scanner was installed in the operating room.73 The breakthrough in marrying CT scanning (and later other imaging modalities as well) to stereotactic surgery involved the development in 1980 of a fiducial system that contains all the information for three-dimensional targeting on each single twodimensional slice ( Fig. 1-5). Three sets of three rods, with each set in an N-shaped configuration, are intersected by each slice. Since the center rod of each set is diagonal, the height of the slice can be determined by the position of the center rod rela¬ tive to the vertical rods on either side of it. Since there are three sets, three vertical coordinates are calculated to define the plane bearing the target point. This system was first incorporated into the BRW system, an apparatus involving a system of interlock¬ ing arcs,46 and similar systems have been used with other appa¬ ratuses as well.74 76

Chapter 1/The History of Stereotactic and Functional Neurosurgery

9

Figure 1-5. The use of N-shaped fiducials has facilitated the marriage of CT and MRI imaging with stereotactic surgery.

The availability of image-based stereotactic surgery has al¬ lowed the treatment of lesions that previously could be local¬ ized only indirectly and has drawn a large number of general neurosurgeons into the stereotactic fold. During the past 15 years, the most common stereotactic procedure has been the biopsy.58 Almost any lesion visualized on CT or later magnetic resonance (MR) scanning has become a target. In addition to biopsy, abscesses,77 hematomas,78,79 and cysts80,81 can be aspi¬ rated. A stereotactic frame can be used to direct the surgeon to a target at craniotomy. The approaches to and the boundaries of brain tumors can be defined before incision, and the stereotactic frame can be used to direct the neurosurgeon to resection.82 Cannulas83 or isotope seeds84 can be inserted into tumors to pro¬ vide brachytherapy, which originally was based on the use of a series of two-dimensional point-in-space targets. Kelly74,85 fathered the technology that made volumetric stereotactic guidance for tumor resection possible, a field of stereotactic surgery that was born between 1980 and 1983. The availability of three-dimensional data from CT scans again

Figure 1-6. Kelly introduced a practical method of registering computer-generated threedimensional volumetric images into the surgical field by using stereotactic techniques. (From Kelly PJ et al: Laso-resection of deep-seated tumors, chap 14, fig 3, in Heilbrun MP (ed'): Concepts in Neurosurgery, vol 2: Stereotactic Neurosurgery. Baltimore: Williams & Wilkins, 1988, p 235. Used with permission.)

opened new possibilities for stereotactic surgery. The data from a CT scan are fed into a computer workstation. The slices are restacked back into a three-dimensional configuration in the workstation, and so the target is defined as a volume in space rather than a point in space, as had been the practice until then. The volumetric image is then displayed in the operating room to guide the surgical resection. The original concept was devel¬ oped when computer graphics demanded a large and expensive facility.86 The stereotactic apparatus was similar to the ToddWells system, but incorporated a system of setting the three co¬ ordinates and two angles with servomotors that assured that the computer graphics and stereotactic apparatus were coordinated. The stereotactic arc held a cylindrical retractor aimed at the center of rotation, which was used to direct the surgeon’s view line along the same trajectory as the computer reconstruction. A heads-up display was added to the surgical microscope so that the surgeon could see the border or the tumor in his or her line of sight, and the resection usually was done with a CO, laser86-88 (Fig. 1-6). Later authors used similar techniques to

10

Part I/Stereotactic Principles

employ three-dimensional volumetric reconstruction to guide craniotomy and tumor resection.89-91 Subsequent developments by others as early as 1986 registered the microscope itself to stereotactic space without the intervention of a frame by means of ultrasound triangulation and identified the view of the CT slices on a monitor in the operating room.92 The introduction of graphic computer workstations into stereotaxis opened additional new possibilities. Complex tra¬ jectories and target points could be calculated and visual¬ ized,9394 even with a side-protruding electrode.95 Tumor vol¬ umes could be defined to direct resection stereotactically.90,96'97 Anatomic targets could be reconstructed in three dimensions to facilitate electrode exploration for functional stereotaxis98-100 or epilepsy surgery.101 After MR scanning was introduced in the mid-1980s, it soon was incorporated into stereotactic surgery, using tech¬ niques similar to those used in CT for tumor resection102103 and functional neurosurgery.1(14 Although MRI provides more infor¬ mation content than does CT scanning, although the ability to display the head in any of three planes is a significant advan¬ tage, and although MRI is acquired in three dimensions simul¬ taneously rather than requiring a reconstruction of slices, MRI introduced additional complexities. Patients may not tolerate the amount of time required in a claustrophobic environment. The usual stereotactic head rings are not compatible with MRI both because of their size and because many have ferromag¬ netic properties that may distort the magnetic field and intro¬ duce errors of localization. MR scanning has an innate risk that the magnetic field may be distorted, causing errors of localiza¬ tion, and an inherent distortion is created just by placing the pa¬ tient’s head in the magnetic field. Ordinarily, the error pro¬ duced is not large enough to compromise the surgery except for the smallest targets, but large errors may not be recognized and consequently may not be accommodated.105 106 One means of minimizing the risk of false localization is to calculate the tar¬ get on both CT and MRI whenever possible. Techniques intro¬ duced in 1994 were devised to fuse the MR and CT images, that is, to adjust the MR image to fit the CT image, thus cor¬ recting MRI spatial distortions.107 The introduction of computer workstations brought another advance: the development of so-called frameless stereotactic systems. In most of these systems, the surgeon holds an instru¬ ment or a pointer and the computer displays where the tip of the pointer is in relation to the head, usually as demonstrated by a series of CT or MRI slices or a three-dimensional picture derived from imaging. Frameless systems generally are used to guide the surgeon during craniotomy but are not employed for functional stereotaxis, in which the electrode must be immobi¬ lized securely and accurately. The first frameless systems, which were reported at the be¬ ginning of this decade, used a multiarticulated arm attached to the operating table or head holder.108 A pointer is attached to the end of the arm. The angles of each of the joints of the arm are accurately read by encoders, so the computer can calculate the precise position of the tip of the pointer in space. The head is scanned preoperatively, and the data are entered into a work¬ station, where a three-dimensional reconstruction is done. A minimum of three, and usually more, fiducial points or land¬ marks are used: these are specific features that can be identified accurately on both the patient and the computerized image. As the pointer touches each of these points, the position in space is registered to the stereotactic location in the computerized im¬

age. When all the points or surface contours are thus registered, the entire volume of the head and its contents has been regis¬ tered to the position of the pointer as it moves about the head. As the surgeon points, the position of the pointer on the appro¬ priate slice of the scan or a three-dimensional picture is dis¬ played, so the surgeon can see where the pointer is in relation to the displayed structures.109 Advances in frameless stereotactic surgery in this decade have been rapid, and newer systems use ultrasound,110 lightemitting diodes,111 or video “machine vision,”112 which use for localization in stereotactic space hand-held pointers or instru¬ ments not connected to an arm (see Chaps. 22 and 25).

HISTORY OF FUNCTIONAL STEREOTACTIC SURGERY The first functional stereotactic surgery was performed by Spiegel and Wycis early in 1946. Their patient had Huntington’s chorea and was treated with alcohol injection into the globus pallidus and medial thalamus. The rationale for the use of alcohol was to try to spare fibers en passage as much as possible. The reasons for using the two targets were to (1) in¬ terrupt the extrapyramidal circuit in the pallidum, since chor¬ eiform movements were known to involve that system, and (2) lessen the emotional tone of the patient, since it was recognized that stress made the chorea worse.26 The patient had moderate but only temporary improvement, but it was demonstrated that pathways could be interrupted without the loss of neurological function. Many of the earliest patients had intractable pain,113 since at that time the philosophy was to try to interrupt primary pain pathways when pain became disabling.114115 Dorsomedial thal¬ amotomy was recommended to relieve the emotional compo¬ nent of pain.113116 Lesions were made in the ventral posterome¬ dial nucleus and the center-median nucleus for thalamic pain.47 During the next few years, emotional disorders were treated by Spiegel and Wycis and others by making lesions in the dor¬ somedial nucleus.12 Dorsomedial lesions were combined with le¬ sions in the anterior nuclei for anxiety and aggressive disorders,117 and lesions of the internal medullary lamina were advocated for obsessive-compulsive disorders.118 Thalamic lesions were combined with hypothalamic lesions for aggressive behavior.119 Many different movement disorders were treated with func¬ tional and stereotactic surgery. Intention tremor was treated with lesions in the ventrolateral nucleus,120 as was hemiballismus.121 Lesions in the substantia nigra also were used for hemiballismus35,122 and hypertonus.123 Parkinson’s disease, however, became the main indication for stereotactic surgery, and the evolution of the various tech¬ niques merits elaboration. Even before the introduction of stereotactic techniques, surgery was attempted for parkinson¬ ism. Such surgery was adventurous not only because of the dif¬ ficulty and risk of the procedure itself but because many, such as Dandy,124 held that surgery on the basal ganglia would be universally lethal. As early as 1932, Bucy and Buchanan125 demonstrated that ablation of the primary motor cortex im¬ proved parkinsonian tremor, but not without loss of voluntary motor function. In 1932, Putnam interrupted the proprioceptive input by cervical posterolateral cordotomy to lessen tremor and rigidity.126 Meyers1617 reported transventricular extirpation of the head of the caudate nucleus in 1939 and ansotomy in 1942,

Chapter 1/The History of Stereotactic and Functional Neurosurgery

both with some benefit but with unacceptable risk (see above). In 1942, Walker22 reported mesencephalic tractotomy, which was extended to mesencephalic pedunculotomy in 1949,127 when it was reported also by Guiot and Pecker.128 These proce¬ dures, although not stereotactic, later became important in the history of stereotactic procedures for Parkinson’s disease. Although pallidotomy had been performed for Huntington’s chorea,26 Spiegel and Wycis were initially reluctant to lesion that structure for Parkinson’s disease for fear that the hypokine¬ sia of experimental pallidotomy might make the parkinsonian akinesia worse. Hassler and Riechert129 reported that they suc¬ cessfully treated Parkinson’s disease by ventrolateral thalamo¬ tomy as early as 1951. This encouraged Spiegel and Wycis the following year to lesion the ansa lenticular fibers as they emerged from the globus pallidus.130 At about the same time, Narabayashi and Okuma28 made a lesion with procaine-oil in¬ jected into the pallidum. Also in 1952, Cooper131 experienced a “surgical accident.” He was attempting a mesencephalic pedunculotomy, as de¬ scribed by Walker, when he accidentally sectioned the anterior choroidal artery. He aborted the procedure, but the patient awoke with significant contralateral improvement in his parkin¬ sonian tremor and no neurological deficit. This led Cooper to advocate litigation of that vessel to treat parkinsonism. Despite his initial glowing reports, the results proved to be variable, with significant risk to the internal capsule. In considering which structure was supplied by the anterior choroidal artery, the infarction of which might be responsible for the beneficial effect, he decided on the globus pallidus; this was consistent with reports from stereotactic surgeons. The distribution of the anterior choroidal artery is quite variable, however, and it often also supplies the internal capsule and the ventrolateral portion of the thalamus.132 Consequently, in 1955 Cooper133 advocated destruction of the pallidum by alcohol injection, but he still did not use stereotactic guidance. The trajectory through which the injection cannula was advanced passed through the temporal lobe, pointed medially and upward, in what happened to be a direct line with the thalamus. When one of his successful pa¬ tients died of other causes and the lesion was found to be in the thalamus, Cooper and associates134 advised in 1958 that the ventrolateral nucleus was the preferred target. In the meantime. Cooper devised an apparatus to help guide the injection can¬ nula. Again, this was consistent with what others had found stereotactically. By 1954, Hassler and Riechert129 had defined their targets more precisely, with the Vop recommended for tremor and the Voa recommended for rigidity. Spiegel and Wycis still preferred the pallidum as the target, and in 1958 they commented that the lesion would be more effective against rigidity if it were placed more posteriorly than the tremor target in the emerging ansa lenticularis fibers.18 In 1959, Svenilson and coauthors135 reviewed Leksell’s cases and also advocated a lesion more ventral and posterior than that used by other au¬ thors. (This ventral posterior pallidotomy has recently again become the preferred target for parkinsonian rigidity, bradykinesia, and dyskinesia.136137) In the late 1950s, however, most stereotacticians followed the lead of Hassler and Riechert to the thalamus, since the most dramatic effect of surgery for Parkinson’s disease was the prompt and usually complete abo¬ lition of tremor, which was the dominant symptom in the days before L-dopa. The optimal target for tremor was eventually ac¬ cepted to be the Vim nucleus,138'141 and the pallidum eventually

11

was abandoned as a target for parkinsonism in the early 1960s.142 There was still considerable disagreement, however, about where the ideal target lay.143 Spiegel and Wycis moved their target to Forel’s field, again to target the pallidofugal fibers.144-145 In 1964, microelectrode recording from the human brain was introduced as a surgical tool. The science of microelectrode recording has advanced to the point where many consider it a routine technique in stereotactic functional neurosurgery146-148 (see Chap. 96). A number of authors confirmed placement of the lesion in Vim by microelectrode recording.139-147-149-150 Things changed drastically in 1968, when L-dopa became generally available.60 Within a few months, the number of Parkinson’s disease patients presenting for surgery plummeted. Only a few patients with primarily tremor went to stereotactic surgeons during the next few years, even though surgery has al¬ ways been the most effective treatment for tremor. The number of surgeons doing stereotactic surgery declined, and the field was practiced mainly by the few neurosurgeons in academic centers who enjoyed the challenge. It was not until the intro¬ duction of CT-directed targeting that stereotactic surgery re¬ bounded, and it now is more active than ever. Eventually, it was recognized that L-dopa is not the perma¬ nent answer to Parkinson’s disease. As the disease progresses and with prolonged L-dopa administration, the symptoms be¬ come refractory to that drug. Dyskinesias may occur after each dose. The response to medication may vary significantly and abruptly, producing repeated on-off episodes during the day. Rigidity and akinesia may progress, and freezing episodes may intervene. By the early 1980s, a search was on for a surgical an¬ swer to those problems, and patients with tremor were referred more frequently for thalamotomy. In 1985, Backiund and associates151 reported the first clini¬ cal trials of autologous transplantation of adrenal medulla into the head of the caudate nucleus in two patients. They con¬ cluded that “the results merit further clinical trials.” Two years later, Madrazo and colleagues152 reported two additional pa¬ tients and cited more favorable results. Later that year, they reported that they had operated on 18 patients.153 This provoked great interest, and programs were begun at many institu¬ tions.154-156 However, the results were considered to be modest and of questionable duration,157 the surgery to retrieve one adrenal gland was stressful to a fragile group of patients, and the adrenal sometimes was found to be atrophic.158 In addition, there were a number of complications resulting from the cran¬ iotomy being placed in the tissue by open surgery159 but very few complications when stereotactic techniques were used.160 By 1991, the procedure was essentially abandoned. The enthusiasm generated by tissue transplantation, how¬ ever, provided an impetus to consider the transplantation of fetal nigral tissue. The experimental groundwork had already been done to a large extent in the late 1980s in rats161-162 or MPTP-injected monkeys.163 164 As early as 1984, a symposium was devoted to the potential neurosurgical uses of fetal cells.165 The scientific justification for fetal cell transplantation had been presented by ] 9 8 7.156166167 In 1989, the first two patients to receive fetal cell transplantation for the treatment of Parkinson’s disease were reported,168 and others followed soon afterward.156 Although research in this area continues, prob¬ lems are increasingly being recognized, including difficulty in obtaining fetal tissue at the proper age in the proper amounts, identification of the proper tissue, processing of the tissue, and

12

Part 1 /Stereotactic Principles

coordination between obtaining the tissue and arranging for the implantation surgery.154156 169 During the past 10 years, stereotactic pallidotomy has been revisited. Laitinen and coworkers136 recalled the review of Leksell’s pallidotomy that had been published in 1980 by Svennilson and associates,135 who had reported more improve¬ ment in bradykinesia and rigidity than had been noted by other authors. Laitinen attributed this observation to the fact that the lesion was slightly more ventral and posterior than the usual pallidoansotomy lesion that aimed for the pallidofugal fibers. After a cautious start in 1987, Laitinen and colleagues136-137 re¬ ported in 1992 a significant improvement in rigidity, brady¬ kinesia, and dopa-induced dyskinesia in Parkinson’s disease patients who had become disabled despite taking L-dopa, sometimes for many years. Other authors have confirmed these observations,170-172 and there is now increasing use of this pro¬ cedure.173 Further refinements suggest that microelectrode identification of the pallidum may improve targeting170 but may increase the risk, and so that issue is not resolved.174 Meanwhile, another promising field has emerged. In 1982, Siegfried and Lippitz175 noted improvement in tremor in a Parkinson’s disease patient who underwent implantation of a deep brain stimulating electrode into the thalamus for the treat¬ ment of pain. This observation encouraged him176 and Benabid and colleagues177 to implant chronic stimulating electrodes into the thalamus for the treatment of parkinsonian tremor, and oth¬ ers have followed since 1987. The results are often dramatic, with prompt suppression of tremor when the stimulator is turned on and a rapid return when it is turned off. There appear to be fewer complications than is the case when a permanent lesion is produced. The use of chronic thalamic stimulation is preferred if there is a risk factor for thalamotomy, as in older patients, or on the second side after a successful unilateral thal¬ amotomy.178 More recent studies have suggested that the globus pallidus175-177 and the subthalamic nucleus179 may be better tar¬ gets for chronic stimulation to treat rigidity and bradykinesia. Functional neurosurgical management of pain had been considered for almost a century before the introduction of stereotactic surgery.180 In 1853, Trousseau181 suggested that the paroxysmal activity of trigeminal neuralgia resembled epilepsy and suggested gasserian ganglionectomy, which was not for¬ mally reported until 1890 by Rose.182 Horsley and coauthors183 advocated epidural total retrogasserian rhizotomy by a transsphenoidal approach in 1891, but mortality rates of 20 to 25 percent were common. In 1900 Cushing184 modified the pro¬ cedure, and in 1920 he reported 298 consecutive ganglionec¬ tomy procedures without mortality.185 During the first half of this century, many modifications of the approach to the trige¬ minal nerve were described. Ramonede186 introduced the suboccipital approach in 1903, and Dandy187 modified it with great success in 1925. Of great interest from the stereotactic standpoint, in 1931 Kirshner188-189 introduced electrocoagulation of the gasserian ganglion. He developed an apparatus to guide the electrode through the foramen ovale that has sometimes been cited as the first stereotactic apparatus, but again, it was not a cartesianbased system. Although the first patient treated with stereotactic surgery by Spiegel and Wycis in 1947 had Huntington’s chorea, the second patient operated on that year had chronic pain.13 "3 Walker22 had earlier described the surgical technique of mesen¬

cephalic tractotomy and the involvement of secondary psychi¬ atric factors in chronic pain had become well recognized; this led to the decision to make lesions in both the spinothalamic tract in the mesencephalon and the dorsal medial nucleus.113-190 In 1949, Hecaen and associates37 reported using for the treatment of pain a thalamotomy that interrupted the diffuse projection system in the centrum medianum plus a lesion in the ventrobasal complex, demonstrating successful relief of pain without interruption of the neospinothalamic tract. Spiegel and Wycis113 reported similar findings in 1953 and refined the pro¬ cedure in 1964 by defining several distinct targets within the mediobasal thalamus.191 Nashold and associates192 also in 1969, observed that patients undergoing stereotactic interruption of the spinothalamic tract at the level of the mesencephalon had better pain relief if the lesion were extended more medially to include some of the central gray matter as well. This naturally led to the limbic system becoming a target for pain relief. Gybels and Sweet,193 who had considerable experi¬ ence in the use of cingulotomy for psychiatric disorders, began to use that target for chronic pain in 1964. Long-term relief was obtained in over half the patients with cancer pain and onethird of those with “failed back syndrome.” Although mesencephalotomy often provided excellent anal¬ gesia and pain relief to the head and face, it had the disadvan¬ tage of rendering the entire body half analgesic. As early as 1937, Sjoqvist194 presented a technique, later modified by White and Sweet,195 for surgical interruption of the descending trigeminal tract at the level of the medulla, limiting the anal¬ gesic area to the distribution of the trigeminal nerve. In 1970, Hitchcock196 made the procedure stereotactic by inserting an electrode through the foramen magnum, since his stereotactic apparatus allowed mounting of the electrode carrier below the head frame. He reported that trigeminal tractotomy was partic¬ ularly good for facial postherpetic neuralgia.197 Also in 1970, he used a similar stereotactic technique to modify percutaneous cervical cordotomy by passing the electrode dorsally through the uppermost spinal cord into the spinothalamic tract;198 this was similar to the procedure that had been reported by Crue and colleagues199 in 1968. That inadvertently set off a series of events that led to the discovery of a new pain pathway. One patient reportedly moved as the cordotomy electrode was inserted through the pia so that the electrode tip lay directly in the center of the spinal cord, and that patient reported immediate relief of pain. A small lesion at that site provided the patient with excellent, lasting pain relief without analgesia to pin stick testing. Hitchcock2™ theorized that a pain pathway had been interrupted and then re¬ ported a series of patients who obtained excellent relief of pain by having a lesion placed stereotactically at that target in a pro¬ cedure that he and later Schvarcz201 termed extralemniscal myelotomy. In an attempt to restrict the denervation to the lower body for patients who had only pelvic or perineal pain, Gildenberg and Hirshberg202-203 in 1981 exposed the spinal cord with laminectomy and made a similar lesion mechanically at the thoracolumbar spinal cord, achieving good relief of espe¬ cially visceral pain, a procedure they called a limited myelo¬ tomy. Study of the postmortem specimen of one patient who had had successful pain relief suggested the existence of a pre¬ viously unreported pathway, which prompted Al-Chaer and as¬ sociates’"4 to demonstrate that the transmission of visceral pain produced by rectocolonic distension in rats was carried by a

Chapter 1/The History of Stereotactic and Functional Neurosurgery

new pathway deep in the fissure on the medial surfaces of the dorsal columns. In the early 1960s, however, the major target for pain relief was still the spinothalamic tract. Spiller205 reported as early as 1905 a patient in whom pain and temperature sensation in the lower body were lost; that patient had a tuberculoma that had compromised the anterolateral quadrants of the thoracic spinal cord. Spiller persuaded his colleague Martin206 to treat the pain of a tumor by making a transverse cut in the anterolateral spinal cord in a patient he reported in 1912. The procedure for cordo¬ tomy was modified and popularized by Foerster207,208 in Europe and by Frazier209 in America and has become the most fre¬ quently performed neurosurgical operation for the treatment of pain since the early part of the century. In 1963, Mullan and colleagues210 reported a percutaneous technique in which they inserted a radioactive strontium seed into the spinal canal through the convenient opening at the C1-C2 level to rest against the anterolateral spinal cord. The procedure was simplified and popularized by Rosomoff and as¬ sociates,211 who performed percutaneous cervical cordotomy by making a radiofrequency lesion at the same site. The major disadvantage of making a lesion at that level was that the respi¬ ratory control pathways also were interrupted, making bilateral cordotomy or cordotomy after pneumonectomy particularly hazardous, with the risk of sleep-induced apnea.212 This led Lin and Gildenberg213,214 in 1966 to describe a procedure in which the electrode was inserted diagonally through the intervertebral disk at lower cervical levels, below the respiratory fibers; this made bilateral percutaneous cervical cordotomy much safer. One of the most significant concepts in pain perception was presented in 1965 by Melzack and Wall215 as the gate theory. This theory codified and coordinated previously investigated concepts and proposed an anatomic arrangement that might explain how pain information was processed and gated, to a large extent in the substantia gelatinosa, and sent via the neospinothalamic tract to higher cognitive centers and also to the motivational and affective centers. Not only did that help explain why procedures for chronic pain failed so often, it also opened a dialogue about how pain perception might be modi¬ fied by increasing the nonpainful somesthetic input. In 1967, Wall and Sweet216 reported that electrical stimula¬ tion of the infraorbital nerves produced analgesia in the distrib¬ ution of those nerves. In the same year, Shealy and coauthors217 reported that stimulation of the ascending dorsal columns not only projected sensation to the lower part of the body and limbs but provided relief of pain in those areas, and the field of spinal cord stimulation was born. The anatomic accident that gathered the large fibers that inhibit pain transmission in the dorsal spinal cord made it possible to stimulate those fibers selectively to close the pain gate. The following year. Sweet and Wepsic218 reported successful alleviation of pain by stimulating the pe¬ ripheral nerve supplying the painful area. As interest mounted in the use of stimulating techniques to treat chronic pain and as implantable devices were manufac¬ tured, this field grew rapidly. The emphasis changed from inter¬ ruption of pathways for the treatment of chronic pain to stimu¬ lation of pain-inhibiting pathways, although ablative procedures remained more popular for cancer pain.219 220 As experience in the use of implanted stimulators grew, chronic deep brain stimulation (DBS) began to emerge. In 1969, Reynolds221 observed that electrical stimulation of mid¬

13

brain structures in rats could provide profound analgesia, pre¬ sumably by activating an endorphin-dependent system that could inhibit pain perception. A series of animal studies led to the first reported clinical trial of the use of DBS for pain man¬ agement, and the hardware was available from developments in spinal cord stimulation. In 1977, Richardson and Akil219,222 re¬ ported a 70 percent success rate in cancer and chronic pain patients after chronic DBS of the periventricular and periaque¬ ductal gray matter. DBS at that site was particularly effective for neurogenic pain,223"226 but stimulation of the somatosensory thalamus was found to be more effective for deafferentation pain.227’228 The most important advance in the surgical management of cancer pain in the 1980s was the development of techniques to instill morphine directly into the cerebrospinal fluid.229 A pro¬ grammable pump made it possible to modify doses and admin¬ istration schedules easily.230 It is possible to obtain relief of pain anywhere below the upper extremities with a lumbar placement.231 Although much less frequently used, a ventricular catheter could be used to deliver morphine for patients with head or face pain with equal analgesia at a tenth of the dose of the spinal subarachnoid morphine pump.232’233

HISTORY OF STEREOTACTIC RADIOSURGERY The father of stereotactic radiosurgery is Lars Leksell. He coined the term and in 1951 described both the technical basis and many of the practical applications.234 Leksell had always been an advocate of the most minimally invasive surgery possi¬ ble and had devised the first arc-centered stereotactic instru¬ ment.36 He considered radiation to be less invasive than the in¬ sertion of electrodes and decided to develop an instrument that would produce a lesion stereotactically without inserting an in¬ strument into the brain. He mounted his apparatus on an ortho¬ voltage x-ray tube that could be directed at the arc-centered tar¬ get from many directions and from a variety of arc angles,234 but the technology of x-ray therapy at that time restricted the potential accuracy and applications. Although linear accelera¬ tors (LINACs) had been under development in both the United States and Great Britain since the 1950s, they were not accurate enough at that time to be used for radiosurgery. In the first radiosurgery patients, the gasserian ganglion was irradiated for trigeminal neuralgia with good long-term results.235 Leksell was not satisfied with the technique, and so he joined forces with Larsson at Uppsala University to investi¬ gate and develop an apparatus that would use a cyclotron to produce proton beams crossing at a point.236 Woodruff and coworkers237 used a similar cyclotron system to introduce ra¬ diosurgery into the United States in 1954, at which time they reported irradiation of the pituitary gland to control cancer pain. As the Berkeley program progressed, Fabrikant and col¬ leagues238 used a helium ion beam to treat arteriovenous mal¬ formations and reported comparable success in 1985. The cost and technical difficulties of cyclotron irradiation prompted Leksell to develop the Gamma Knife in 1967 the first equipment designed specifically to use radiation as a neurosur¬ gical tool.235’239 The original instrument consisted of 179 sources of cobalt 60 distributed in a dome, with collimators di¬ recting the beams to produce a small disk-shaped lesion the

14

Part 1/Stereotactic Principles

same size and shape Leksell had produced with radiofrequency electrodes. The original intention was to use the system to in¬ terrupt pathways for functional stereotaxis. The first patient treated, however, had a craniopharyngioma, and treatment of other tumors and vascular malformations followed quickly. I had the honor of visiting the first Gamma Knife center shortly after it opened at the Sophiahemmet in Stockholm. After I toured this typical nineteenth-century hospital, Leksell led me down a flight of stairs and opened the door to a bright modern room with an impressive apparatus dominating the scene. During its first 4 years, 21 tumors were treated,240 and in 1972, the radiosurgical treatment of arteriovenous malforma¬ tions was introduced by Steiner and associates.241 Despite its success, radiosurgery never displaced Leksell’s apparatus with its double electrode configuration for functional neurosurgery. The second Gamma Knife was designed in 1975 specifically for stereotactic radiosurgery, with a more spherical radiation field. The indications were expanded to include benign tumors such as acoustic neurinomas, craniopharyngiomas, and pitu¬ itary tumors as well as arteriovenous malformations. Leksell was reluctant to consider radiosurgical treatment of malignant tumors because the radiobiological effects were less favorable than those of fractionated radiation programs. In addition, the number of patients was growing, so that priority had to be given to patients with a better prognosis and chance of cure with radiosurgery.242 Additional Gamma Knife units were later installed in Buenos Aires and Sheffield, Great Britain.243 When they be¬ came commercially available, the first Gamma Knife in the United States was installed at the University of Pittsburgh in 1987. Lunsford shepherded the device through an unbelievably complicated and bureaucratic maze of regulatory reviews that took 3 years, but his perseverance opened the door to the instal¬ lation of many more Gamma Knife units in the United States.244 The use of the Gamma Knife has expanded rapidly (see Chaps. 86, 87, 90, and 93). Meanwhile, LINAC technology had advanced to the point where it could be considered for stereotactic radiosurgery, and computer science made practical treatment planning available. In 1972, both Betti and Derechinsky245 and Colombo and col¬ leagues246,247 reported modifications of LINACs to provide noncoplanar isocentered administration of radiation for intracranial lesions, and several other systems were described shortly after¬ ward.248"251 This technology was advanced further by Lutz and Winston,252,253 who developed the technology to quantify and calculate the dosimetry and assure the accuracy of the system. The development of most commercially available systems is based on their concepts. Dosimetry-planning software became sophisticated, user-friendly, and efficient enough to be made generally available.254,255 The development of LINAC-based stereotactic radiosurgery systems created a rapid expansion of the field, since such systems are more affordable and LINACs are generally available. The LINAC radiosurgery units at the Brigham and Women’s Hospital and the University of Florida254 began to treat patients in 1986.255 The combined out¬ put from Gamma Knife and LINAC-based radiosurgery centers has produced a flood of publications and clinical experience (see Chaps. 79. 83, 84. and 92). With current progress in image-based stereotactic surgery and radiosurgery, the current rejuvenation of functional neuro¬ surgery, an increased interest in epilepsy surgery, and contin¬

ued progress in pain management techniques, stereotactic neu¬ rosurgery and functional neurosurgery are more active than ever.

References 1.

Dittmar C: Ueber die Lage des sogenannten Gefaesszentrums in der Medulla oblongata. Bersaechs Ges Wiss Leipzig (Math Phys) 25:449-469, 1873.

2.

Gildenberg PL: General concepts of stereotactic surgery, in Lunsford LD (ed): Modern Stereotactic Neurosurgery. Boston: Martinus Nijhoff, 1988, pp 3-12. Kandel El: Functional and Stereotactic Neurosurgery. New York, London: Plenum, 1989. Zernov DN: Encephalometer: Device for estimation of parts of brain in human. Proc Soc Physicomed Moscow Univ 2:70-80, 1889. Altukhov NV: Encephalometric Investigations of the Brain Relative to the Sex, Age and Skull Indexes. Moscow: 1891. Horsley V, Clarke RH; The structure and functions of the cerebellum examined by a new method. Brain 31:45-124, 1908. Clarke RH: Part I: Investigation of the Central Nervous System, Methods and Instruments. Baltimore: Johns Hopkins, 1920. Clarke RH: Part II: Atlas of the Frontal Sections of the Cranium and Brain of the Rhesus Monkey. Baltimore: Johns Hopkins, 1920. Levy R: A Short History of Stereotactic Neurosurgery. Park Ridge, 1L: American Association of Neurological Surgeons, 1992. Schaltenbrand G: Personal observations on the development of stereotaxy. Confin Neurol 37:410-416, 1975. Olivier A. Bertrand G, Picard C: Discovery of the first human stereo¬ tactic instrument. Appl Neurophysiol 46:84—91, 1983. Spiegel EA, Wycis HT, Marks M, Lee AS: Stereotaxic apparatus for operations on the human brain. Science 106:349-350, 1947. Spiegel EA, Wycis HT: Stereoencephalotomy. Part I. New York: Grune & Stratton, 1952. Freeman W, Watts JW: Psychosurgery: Intelligence, Emotional and Social Behavior Following Prefrontal Lobotomy for Mental Disorders. Springfield, IL: Thomas, 1942. Talairach J, David M, Tournoux P, et al: Atlas d'anatomie stereotaxique. Paris: Masson, 1957. Meyers R: The modification of alternating tremors, rigidity and festination by surgery of the basal ganglia. Res Publ Assoc Res Nerv Ment Dis 21:602-665, 1942. Meyers R: Historical background and personal experiences in the surgical relief of hyperkinesia and hypertonus, in Fields W (ed): Pathogenesis and Treatment of Parkinsonism. Springfield, IL: Thomas. 1958, pp 229-270. Spiegel EA, Wycis HT, Baird HW III: Long range effects of electropallido-ansotomy in extrapyramidal and convulsive disorders. Neurology 8:734—740, 1958. Riechert T, Mundinger F: Indications, technique and results of the stereotactic operations upon the hypophysis using radio-isotopes. J Nerv Ment Dis 13:1 -9, 1960. Schwartz HG, O'Leary JL: Section of the spinothalamic tract in the medulla with observations on the pathways for pain. Surgery 9:183-193, 1941. Dogliotti M: First surgical sections, in man, of the leinniscal lateralis (pain-temperature path) at the brain stem, for the treatment of dif¬ fuse rebellious pain. Anesth Analg 17:143-145, 1938. Walker AE: Relief of pain by mesencephalic tractotomy. Arch Neurol Psychiatr48:865-883,1942. Janetta PJ, Gildenberg PL, Loeser J, et al: Operations on the brain and brain stem for chronic pain, in Bonica JJ (ed): The Management of Pain in Clinical Practice, 2d ed. Philadelphia: Lea & Febiger, 1990, pp 2082-2103. Keele KD: Anatomies of Pain. Baltimore: Williams & Wilkins, 1949. Livingston WK: Pain Mechanisms. New York: Macmillan, 1943. Spiegel EA, Wycis HT: Pallido-thalamotomy in chorea. Arch Neurol Psychiatr 64:495—496, 1950.

3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14.

15. 16.

17.

18.

19.

20.

21.

22. 23.

24. 25. 26.

Chapter 1/The History of Stereotactic and Functional Neurosurgery

27.

28.

29.

30.

31. 32. 33. 34.

Gildenberg PL: Studies in stereoencephalotomy: VII. Comparison of the variability of subcortical lesions produced by various proce¬ dures. Confin Neurol 17:299-301, 1957. Narabayashi H, Okuma T: Procaine oil blocking of the globus pallidus for the treatment of rigidity and tremor of parkinsonism. Proc Jpn Acad 29:310-318, 1953. Narabayashi H, Shimazu H, Fujita Y, et al: Procaine-oil-wax pallido¬ tomy for double athetosis and spastic states in infantile cerebral palsy. Neurology 10:61-69, 1960. Gildenberg PL: Variability of subcortical lesions produced by a heat¬ ing electrode and Cooper’s balloon cannula. Confin Neurol 20:53-65, 1960. Cooper IS: Chemopallidectomy and chemothalamectomy for parkinsonism and dystonia. Proc R Soc Med 52:47-60, 1959. Obrador S, Dierssen G: Cirurgia de la region palidal. Rev Clin Esp AnoXVII 61:229-237, 1956. Cosman ER, Nashold BS Jr, Bedenbaugh P: Stereotactic radiofre¬ quency lesion making. Appl Neurophysiol 46:160-166, 1983. Cooper IS, Lee AStJ: Cryostatic congelation. J Nerv Ment Dis 133:259-263, 1961.

55. 56.

15

Bullard DE, Nashold BS Jr: Evolution of principles of stereotactic neurosurgery. Neurosurg Clin North Am 6:27-41, 1995. Spiegel EA: Methodological problems in stereoencephalotomy. Confin Neurol 26:125-132, 1965.

57.

Spiegel EA: History of human stereotaxy (stereoencephalotomy), in Schaltenbrand G, Walker AE (eds): Stereotaxy of the Human Brain: Anatomical, Physiological and Clinical Applications. Stuttgart, New York: Georg Thieme, 1982, pp 3-10.

58.

Gildenberg PL, Franklin PO: Survey of CT-guided stereotactic surgery. Appl Neurophysiol 48:477^180, 1985. Gildenberg PL: Survey of stereotactic and functional neurosurgery in the United States and Canada. Appl Neurophysiol 38:31-37. 1975:

59.

60.

Gildenberg PL: Whatever happened to stereotactic surgery? Neurosurgery 20:983-987, 1987.

61.

Lunsford LD, Coffey RJ, Cojocaru T, Leksell D: Image-guided stereotactic surgery: A 10-year evolutionary experience. Stereotact Funct Neurosurg 54, 55:375-387, 1990.

62.

Gildenberg PL: Whatever happened to stereotactic surgery? Part II. Neurosurgery, in preparation.

35.

Spiegel EA, Wycis HT: Stereoencephalotomy. Part II: Clinical and Physiological Applications. New York: Grune & Stratton, 1962.

63.

Gildenberg PL: Computerized tomography and stereotactic surgery, in Spiegel EA (ed): Guided Brain Operations. Basel: Karger, 1982, pp 24-34.

36.

Leksell L: A stereotaxic apparatus for intracerebral surgery. Acta ChirScand 99:229-233, 1949. Hecaen H, Talairach T, David M, Dell MB: Memoires originaux: Coagulations limitees du thalamus dans les algies du syndrome thalamique. Rev Neurol (Paris) 81:917-931, 1949. Riechert T, Wolff M: Uber ein neues Zielgeraet zur intrakraniellen elektrischen Abteilung und Ausschaltung. Arch Psychiatr Z Neurol 186:225-230, 1951. Bailey P, Stein SN: A stereotaxic apparatus for use on the human brain. AMA scientific exhibit, Atlantic City, 1951. Narabayashi H: Stereotaxic instrument for operation on the human basal ganglia. Psychiatr Neurol Jpn 54:669-671, 1952. UchimuraY, Narabayashi H: Stereoencephalotom. Psychiatr Neurol Jpn 52:265, 1951.

64.

Gildenberg PL, Kaufman HH, Murthy KS: Calculation of stereotac¬ tic coordinates from the computed tomographic scan. Neurosurgery 10:580-586, 1982.

65.

Bullard DE, Osborne D, Burger PC, Nashold BSJ: Further experi¬ ence utilizing the Gildenberg technique for computed tomographyguided stereotactic biopsies. Neurosurgery 19:386-391, 1986. Bullard DE, Nashold BSJ, Osborne D, et al: CT-guided stereotactic biopsies using a modified frame and Gildenberg techniques. J Neurol Neurosurg Psychiatry 47:590-595, 1984. Leksell L, Jernberg B: Stereotaxis and tomography: A technical note with six figures. Acta Neurochir (Wien) 52:1-7, 1980. Barcia-Salorio JL, Broseta J, Hernandez G, et al: A new approach for directed CT localization in stereotaxis. Appl Neurophysiol 45:383-386, 1982.

37.

38.

39. 40. 41. 42.

43.

Gildenberg PL: Principles of stereotaxis and instruments, in De Salles AAF, Goetsch SJ (eds): Stereotactic Surgery and Radio¬ surgery. Madison, WI: Medical Physics, 1993, pp 17-28. Todd EM: Stereotaxic surgery of the basal ganglia, in Todd-Wells Manual of Stereotaxic Procedures. Randolph, MA: Codman and Shurtleff, 1967.

66.

67. 68.

69.

70.

44.

Austin B, Lee A: A plastic ball and socket type of stereotaxic detector. JNeurosurg 15:264—268, 1958.

71.

45.

Linskey ME, Lunsford LD, Flickinger JC: Neuroimaging of acoustic nerve sheath tumors after stereotaxic radiosurgery. AJNR Am J Neuroradiol 12:1165-1175, 1991. Brown RA, Roberts TS, Osborn AG: Stereotaxic frame and computer software for CT-directed neurosurgical localization. Invest Radiol 15:308-312, 1980. Talairach J, Hecaen M, David M, et al: Recherches sur la coagula¬ tion therapeutique des structures sous-corticales chez l’homme. Rev Neurol (Paris) 81:4-24, 1949. Guiot G, Brion S, Fardeau M, et al: Dyskinesie volitionelle d’atti¬ tude suppremee par la coagulation thalamo-capsulaire. Rev Neurol (Paris) 102:220-229, 1960. Gillingham FJ: Small localized lesions of the internal capsule in the treatment of the dyskinesias. Confin Neurol 22:385-392, 1962. Laitinen L. Toivakka E: Locating brain tumors through depth EEG probes. Confin Neurol 34:101-105, 1972. Bertrand G, Jasper H: Microelectrode recording of unit activity in the human thalamus. Confin Neurol 26:205-208, 1965. Velasco Suarez MM, Escobedo FR: Stereotaxic intracerebral instil¬ lation of dopa. Confin Neurol 32:149-157, 1970. Obrador S: A simplified neurosurgical technique for approaching and damaging the region of the globus paliidus in Parkinson’s dis¬ ease. J Neurol Neurosurg Psychiatry 20:47-49, 1957. Bechtereva NP, Bondartchuk AN, Smirnow VM, et al: Method of electrostimulation of the deep brain structures in treatment of some chronic diseases. Confin Neurol 37:136-140, 1975.

72.

46.

47.

48.

49. 50. 51. 52. 53.

54.

73. 74.

75.

76. 77.

78.

79.

80.

Colombo F, Angrilli F, Zanardo A, et al: A new method for utilizing CT data in stereotactic surgery: Measurement and transformation technique. Acta Neurochir (Wien) 57:195-203, 1981. Colombo F, Angrilli F, Zanardo A, et al: A universal method to em¬ ploy CT scanner spatial information in stereotactic surgery. Appl Neurophysiol 45:352-365, 1982. Patil AA: Computed tomography-oriented stereotactic system. Neurosurgery 10:370-374, 1982. Koslow M, Abele MG: A fully interfaced comuterized tomo¬ graphic-stereotactic surgical system. Appl Neurophysiol 43: 174-175. 1980. Lunsford LD: A dedicated CT system for the stereotactic operating room. Appl Neurophysiol 45:374-378, 1982. Kelly PJ, Kail B, Goerss S, Alker GJ: Precision resection of intra-axial CNS lesions by CT-based stereotactic craniotomy and computer monitored C02 laser. Acta Neurochir (Wien) 68:1-9. 1983. Alker G, Kelly PJ: An overview of CT based stereotactic systems for the localization of intracranial lesions. Coinput Radiol 8:193-196, 1984. Leksell L, Leksell D, Schwebel J: Stereotaxis and nuclear magnetic resonance. J Neurol Neurosurg Psychiatry 48:14-18, 1985. Broggi G, Franzini A, Peluchetti D, Servello D: Treatment of deep brain abscesses by stereotactic implantation of an intracavitary de¬ vice for evacuation and local application of antibiotics. Acta Neuro¬ chir (Wien) 76:94-98, 1985. Backlund EO, von Holst H: Controlled subtotal evacuation of intrac¬ erebral hematomas by stereotactic technique. Surg Neurol 9:99-101, 1978. Tanikawa T, Amano K. Kawamura H, et al: CT-guided stereotactic surgery for evacuation of hypertensive intracerebral hematoma. Appl Neurophysiol 48:431-439, 1985. Zamorano L, Chavantes C, Dujovny M, et al: Stereotactic endo¬ scopic interventions in cystic and intraventricular brain lesions. Acta Neurochir Suppl (Wien) 54:69-76, 1992.

16

81.

Part 1 /Stereotactic Principles

Musolino A, Merckaert P. Munari C. et al: Stereotactic endocavitary treatment of cysts and pseudocysts of glioma. Preliminary report.

105.

82.

J Neumsurg Sci 33:107-114, 1989. Whittle IR. Denholm SW, Elshunnar K: CT-guided stereotactic neu¬ rosurgery using the Brown-Roberts-Wells system: Experience with

106.

83.

125 procedures. Aust NZJ Surg 61:919-928. 1991. Gutin PH, Hosobuchi Y. Phillips TL, Stupar TA: Stereotactic inter¬ stitial irradiation for the treatment of brain tumors. Cancer Treat Rep

107.

84. 85.

86.

87.

88. 89. 90.

91.

92.

93.

94. 95.

96.

97.

98.

99.

100.

101.

102.

103.

104.

65:103-106, 1981. Gildenberg PL: The history of stereotactic neurosurgery. Neurosurg Clin North Am 1:765-780, 1990. Kelly PJ, Alker GJ Jr: A method for stereotactic laser microsurgery in the treatment of deep seated CNS neoplasms. Appl Neurophysiol 43:210-215, 1980. Kelly PJ. Kali BA, Goerss S: Transposition of volumetric informa¬ tion derived from computed tomography scanning into stereotactic space. Surg Neurol 21 465^471, 1984. Kail BA, Kelly PJ, Goerss SJ: Interactive stereotactic surgical sys¬ tem for the removal of intracranial tumors utilizing the C02 laser and CT-derived database. IEEE Trans Biomed Eng 32:112-116, 1985. Kelly PJ: Tumor Stereotaxis. Philadelphia: Saunders, 1991. Kelly PJ: Stereotactic technology in tumor surgery. Clin Neurosurg 35:215-253, 1989. Zamorano L, Dujovny M, Chavantes C, et al: Image-guided stereo¬ tactic centered craniotomy and laser resection of solid intracranial lesions. Stereotact Fund Neurosurg 54, 55:398—403, 1990. Gildenberg PL, Ledoux R, Cosman E, Labuz J: A frame-based video/graphics system for intraoperative guidance of surgical resec¬ tions. Stereotact Fund Neurosurg 63:23-25, 1994. Roberts DW, Strohbehn JW, Hatch JF, et al: A frameless stereotaxic integration of computerized tomographic imaging and the operating microscope. J Neurosurg 65:545-549, 1986. Gybels J, Kempen D. Peluso F, Vanbael M: Computer techniques for tracking penetrating electrodes, plotting two-target trajectories and performing two-stage stereotaxic surgery in humans. Confin Neurol 36:302-309, 1974. Peluso F, Gybels J: Calculation of position of electrode point during penetration in human brain. Confin Neurol 32:213—218, 1970. Peluso F, Gybels J: Computer calculation of the position of the sideprotruding electrode tip during penetration in human brain. Confin Neurol 34:94-100. 1972. Zamorano L. Dujovny M, Malik G, et al: Factors affecting measure¬ ments in computed-tomography-guided stereotactic procedures. Appl Neurophysiol 50:53-56, 1987. Giorgi C, Ongania E, Franzini A, Broggi G: Three-dimensional re¬ construction of neuroradiological data within a stereotactic frame of reference for surgery of visible targets. Appl Neurophysiol 50: 77-80, 1987. Tasker RR. Organ LW, Hawrylyshyn P: Investigation of the surgical target for alleviation of involuntary movement disorders. Appl Neurophysiol 45:261-274, 1982. Hardy TL, Koch J, Lassiter A: Computer graphics with computer¬ ized tomography for functional neurosurgery. Appl Neurophysiol 46:217-226. 1983. Giorgi C. Garibotto G, Cerchiari U, et al: Neuroanatomical digital image processing in CT-guided stereotactic operations. Appl Neuro¬ physiol 46:236-239. 1983. Spenser DD: Stereotactic methods in the management of epilepsy, in Heilbrun MP (ed): Stereotactic Neurosurgery. Baltimore: Williams & Wilkins, 1988. pp 161-178. Olivier A. Peters TM. Clark JA, et al: Integration of digital angiogra¬ phy. magnetic resonance, x-ray computed tomography and positron emission tomography in stereotaxy. Rev Eledroencephalogr Neurophysiol Clin 17:1987. Peters TM, Clark J, Pike B. et al: Stereotactic surgical planning with magnetic resonance imaging, digital subtraction angiography and computed tomography. Appl Neurophysiol 50:33-38. 1987. Hardy TL: A method for MR1 and CT mapping of diencephalic somatotopography. Stereotact Fund Neurosurg 52:242-249. 1989.

108. 109.

110.

111.

112.

113. 114. 115. 116.

117. 118. 119.

120. 121.

122. 123.

124. 125. 126. 127.

128. 129. 130. 131. 132.

133.

Gerdes JS, Hitchon PW, Neerangun W, Tomer JC: Computed to¬ mography versus magnetic resonance imaging in stereotactic local¬ ization. Stereotad Fund Neurosurg 63:124-129, 1994. Meuli RA, Verdun FR, Bochud FO, et al: Assessment of MR image deformation for stereotactic neurosurgery using a tagging sequence. Am J Neuroradiol 15:45—49, 1994. Kooy HM, van Herk M. Barnes PD, et al: Image fusion for stereo¬ tactic radiotherapy and radiosurgery treatment planning. Int J Radial Oncol Biol Phys 28:1229-1234. 1994. Guthrie BL, Kaplan R, Kelly PJ: Neurosurgical stereotactic operat¬ ing arm. Stereotad Fund Neurosurg 54, 55:497-500. 1990. Golfinos JG, Fitzpatrick BC, Smith LR, Spetzler RF: Clinical use of a frameless stereotactic arm: Results of 325 cases. J Neurosurg 83:197-205, 1995. Roberts DW, Strohbehn JW, Friets EM, et al: The stereotactic oper¬ ating microscope: Accuracy, refinement and clinical experience. Ada Neurochir Suppl (Wien) 46:112-114, 1989. Barnett GH, Kormos DW, Steiner CP. Weisenberger J: Use of a frameless, armless stereotactic wand for brain tumor localization with two-dimensional and three-dimensional neuroimaging. Neurosurgery 33:674-678, 1993. Heilbrun MP, McDonald P, Wiker C, et al: Stereotactic localization and guidance using a machine vision technique. Stereotad Fund Neurosurg 58:94—98, 1992. Spiegel EA, Wycis HT: Mesencephalotomy in the treatment of “in¬ tractable” facial pain. Arch Neurol 69:1-13, 1953. White JC, Sweet WH: Pain, Its Mechanism and Neurosurgical Control. Springfield. 1L: Charles C Thomas, 1955. Iskandar BJ. Nashold BS Jr: History of functional neurosurgery. Neurosurg Clin North Am 6:1-25, 1995. Spiegel EA, Wycis HT, Szekely EG. Gildenberg PL: Medial and basal thalamotomy in so-called intractable pain, in Knighton RS, Dumke PR (eds): Pain. Boston: Little, Brown, 1966. pp 503-517. Spiegel EA, Wycis HT: The central mechanism of emotions. Am J Psychiatry 109:426-431. 1951. Spiegel EA, Wycis HT, Reyes V: Diencephalic mechanisms in petit mal epilepsy. EEG Clin Neurophysiol 3:473—475, 1951. Spiegel EA, Wycis HT, Orchinik C: Thalamotomy and hypothalamotomy for the treatment of psychoses. Res Publ Assoc Res Nerv MentDis 31:379-391, 1953. Cooper IS: Neurosurgical alleviation of intention tremor of multiple sclerosis and cerebellar disease. N Engl J Med 263:441-444. 1960. Tsubokawa T, Moriyasu N: Lateral pallidotomy for relief of ballistic movement—its basic evidences and clinical application. Confin Neurol 37:10-15, 1975. Andy OJ: Diencephalic coagulation in the treatment of hemiballism. Confin Neurol 22:346-350. 1962. Meyers R, Fry WJ, Fry FJ, et al: Early experiences with ultrasonic irradiation of the pallidofugal and nigral complexes in hyperkinetic and hypertonic disorders. .1 Neurosurg 16:32-54, 1959. Dandy WE: Changes in our conceptions of localization of certain functions in the brain. Am J Physiol 93:643-647, 1930. Bucy PC, Buchanan DN: Athetosis,Brain 55:479-492, 1932. Putnam TJ: Paralysis agitans and athetosis: Manifestations and methods of treatment. Arch Neurol Psychiatr 43:170-171, 1940. Walker AE: Cerebral pedunculotomy for the relief of involuntary movements: Parkinsonian tremor. J Nerv Mem Dis 116:766-775, 1952. Guiot G. Pecker J: Tractotomie mesencephalique anterieure pour tremblement parkinsonien. Rev Neurol IParis) 81:387-388, 1949. Hassler R. Riechert T: Indikationen und Lokalisationsmethode der gezielten Hirnoperationen. Nervenarzt 25:441-447, 1954. Spiegel EA, Wycis HT: Ansolomy in paralysis agitans. Arch Neurol Psychiatr 71:598-614. 1954. Cooper IS: Ligation of the anterior choroidal artery for involuntary movements of parkinsonism. Psychiatr Q 27:317-319, 1953. Rand RW'. Brown WJ. Stern WE: Surgical occlusion of anterior choroidal arteries in parkinsonism: Clinical and neuropathologic findings. Neurology 6:390—401, 1956. Cooper IS: Chemopallidectomy. Science 121:217, 1955.

Chapter 1/The History of Stereotactic and Functional Neurosurgery

134.

135.

136.

137.

138.

139.

140. 141.

142.

143.

144. 145.

146.

147. 148.

149. 150. 151.

152.

153.

154.

155.

Cooper IS, Bravo G, Riklan M, et al: Chemopallidectomy and chemothalamectomy for parkinsonism. Geriatrics 13:127-147, 1958. Svennilson E, Torvik A, Lowe R: Treatment of parkinsonism by stereotactic thermolesions in the pallidal region: A clinical evaluation of 81 cases. Acta Psychiatr Neurol Scand 35:358-377, 1960. Laitinen LV, Bergenheim AT, Hariz MI: Ventroposterolateral pallidotomy can abolish all parkinsonian symptoms. Stereotact Fund Neurosurg 58:14-21, 1992. Laitinen LV, Bergenheim AT, Hariz MI: Leksell’s posteroventral pallidotomy in the treatment of Parkinson’s disease. J Neurosurg 76: 53-61, 1992. Tasker RR, Siqueira J, Hawrylshyn P, Organ LW: What happened to V.im thalamotomy for Parkinson’s disease? Appl Neurophysiol 46:68-83, 1983. Kelly PJ, Ahlskog JE, Goerss SJ, et al: Computer-assisted stereotac¬ tic ventralis lateralis thalamotomy with microelectrode recording control in patients with Parkinson’s disease. Mayo Clin Proc 62:655-664, 1987. Riechert T: Long term follow-up of results of stereotaxic treatment of extrapyramidal disorders. Confin Neurol 22:356-363, 1962. Mundinger F, Riechert T: Die stereotaktischen Himoperationen zur Behandlung extrapyramidaler Bewegungsstorungen (Parkinsonismus und Hyperkinesen) und ihre Resultate: Postoperative und Langzeitergebnisse der stereotaktischen Himoperationen bei extrapyramidalmotorischen Bewedunasstrorungen; Teil B. Fortschr Neurol Psychiatr 31:69-120, 1963. Levy A: Stereotaxic brain operations in Parkinson’s syndrome and related motor disorders: Comparison of lesions in the pallidum and thalamus with those in the internal capsule. Confin Neurol 29:1-70, 1967. ' Laitinen LV: Brain targets in surgery for Parkinson’s disease: Results of a survey of neurosurgeons. J Neurosurg 62:349-351, 1985. Spiegel EA, Wycis HT, Szekely EG, et al: Campotomy in various extrapyramidal disorders. J Neurosurg 20:871-881, 1963. Spiegel EA, Wycis HT, Szekely EG, et al: Stimulation of Forel’s field during stereotaxic operations in the human brain. EEG Clin Neurophysiol 16:537-548, 1964. Ohye C, Hirai T, Miyazaki M, et al: V.im thalamotomy for the treat¬ ment of various kinds of tremor. Appl Neurophysiol 45:275-280, 1982. Narabayashi H, Ohye C: Importance of microstereoencephalotomy for tremor alleviation. Appl Neurophysiol 43:222-227, 1980. Narabayashi H, Gildenberg PL, Franklin PO: Proceedings of the Meeting on the Use of Microphysiological Recordings during Stereotactic Neurosurgery. Stereotact Fund Neurosurg 52:77-261, 1989. Tasker RR, Dostrovsky JO: What goes on in the motor thalamus? Stereotact Fund Neurosurg 60:121-126, 1993. Bertrand G, Jasper H: Microelectrode recording of unit activity in the human thalamus. Confin Neurol 26:205-208, 1965. Backlund EO, Granberg PO, Hamberger B, et al: Transplantation of adrenal medullary tissue to striatum in parkinsonism: First clinical trials. J Neurosurg 62:169-173, 1985. Madrazo I, Drucker-Colin R, Diaz V, et al: Open microsurgical auto¬ graft of adrenal medulla to the right caudate nucleus in two patients with intractable Parkinson’s disease. N Engl J Med 316:831-834, 1987. Drucker-Colin R, Madrazo I, Shkurovich M, et al: Open microsurgi¬ cal autograft of adrenal medulla to caudate nucleus of patients with Parkinson’s disease. Schmitt Neurological Sciences Symposium, Rochester, NY, June 30-July 3, 1987. Bakay RAE, Herring CJ: Central nervous system grafting in the treatment of parkinsonism. Stereotact Fund Neurosurg 53:1-20, 1989. Goetz CG, Olanow CW, Roller WC, et al: Multicenter study of au¬ tologous adrenal medullary transplantation to the corpus striatum in patients with advanced Parkinson’s disease. N Engl J Med 320:337-341, 1989.

17

156.

Hitchcock ER, Clough CG, Hughes RC, Kenny BG: Transplantation in Parkinson’s disease: Stereotactic implantation of adrenal medulla and foetal mesencephalon. Acta Neurochir Suppl (Wien) 46:48-50, 1989.

157.

Goetz CG, De Long MR, Penn RD, Bakay RA: Neurosurgical hori¬ zons in Parkinson’s disease. Neurology 43:1-7, 1993. Stoddard SL, Tyce GM, Ahlskog JE, et al: Decreased catecholamine content in parkinsonian adrenal medullae. Exp Neurol 104:22-27, 1989.

158.

159.

Jankovic J, Grossman R, Goodman C, et al: Clinical, biochemical, and neuropathologic findings following transplantation of adrenal medulla to the caudate nucleus for treatment of Parkinson’s disease. Neurology 39:1227-1234, 1989.

160.

Gildenberg PL, Pettigrew 1C, Merrell R, et al: Transplantation of adrenal medullary tissue to caudate nucleus using stereotactic tech¬ niques. Stereotad Fund Neurosurg 54, 55:268-271, 1990. Dymecki J, Puciowski O, Dyr W, et al: Effects of intracerebral trans¬ plantation of immature substantia nigra in rats with experimentally induced Parkinson’s disease: III Results of behavioural and bio¬ chemical investigations. Neuropatol Pol 23:287-295, 1985. Brundin P, Nilsson OG, Strecker RE, et al: Behavioural effects of human fetal dopamine neurons grafted in a rat model of Parkinson’s disease. Exp Brain Res 65:235-240, 1986. Bakay RA, Fiandaca MS, Barrow DL, et al: Preliminary report on the use of fetal tissue transplantation to correct MPTP-induced Parkinson-like syndrome in primates. Appl Neurophysiol 48: 358-361, 1985. Redmond DE, Sladek JR Jr, Roth RH, et al: Fetal neuronal grafts in monkeys given methylphenyltetrahydropyridine. Lancet 1:1125-1127, 1986. Gildenberg PL, Mark VH, Regelson W: Use of embryonic cell trans¬ plantation for correction of CNS disorders. Appl Neurophysiol 47:5-8, 1984. Perlow MJ: Brain grafting as a treatment for Parkinson’s disease. Neurosurgery 20:335-342, 1987. Bakay RA: Neurotransplantation: A clinical update (review). Acta Neurochir Suppl (Wien) 58:8-16, 1993. Lindvall O, Rehncrona S, Brundin P, et al: Human fetal dopamine neurons grafted into the striatum in two patients with severe Parkinson’s disease: A detailed account of methodology and a 6month follow-up. Arch Neurol 46:615-631, 1989. Bakay RA, Barrow DL: Neural transplantation for Parkinson’s dis¬ ease. J Neurosurg 69:807-810, 1988. Lozano A, Hutchison W, Kiss Z, et al: Methods for microelectrodeguided posteroventral pallidotomy. J Neurosurg 84:194-202, 1996. Goetz CG, Diederich NJ: There is a renaissance of interest in palli¬ dotomy for Parkinson’s disease. Nature Med 2:510-514, 1996. Iacono RP, Shima F, Lonser RR, et al: The results, indications, and physiology of posteroventral pallidotomy for patients with Parkinson’s disease. Neurosurgery 36:1118-1125, 1995. Laitinen LV: Pallidotomy for Parkinson’s disease. Neurosurg Clin

161.

162.

163.

164.

165.

166. 167. 168.

169. 170. 171. 172.

173. 174. 175.

176.

177.

178.

179.

North Am 6:105-112, 1995. Favre J, Taha JM, Nguyen TT, et al: Pallidotomy: A survey of cur¬ rent practices in North America. Neurosurgery 39:883-891, 1996. Siegfried J, Lippitz B: Chronic electrical stimulation of the VL-VPL complex and of the pallidum in the treatment of movement disor¬ ders: Personal experience since 1982. Stereotad Fund Neurosurg 62:71-75, 1994. Siegfried J, Lippitz B: Bilateral chronic electrostimulation of ventro¬ posterolateral pallidum: A new therapeutic approach for alleviating all parkinsonian symptoms. Neurosurgery 35:1126-1129, 1994. Benabid AL, Poliak P, Gervason C, et al: Long-term suppression of tremor by chronic stimulation of the ventral intermediate thalamic nucleus. Lancet 337:403^106, 1991. Benabid AL, Poliak P, Louveau A, et al: Combined thalamotomy and stimulation by stereotactic surgery of the VIM thalamic nucleus for bilateral Parkinson disease. Appl Neurophysiol 50:344—346, 1987. Benabid AL, Poliak P, Gross C, et al: Acute and long-term effects of subthalamic nucleus stimulation in Parkinson’s disease. Stereotad Fund Neurosurg 62:76-84, 1994.

18

180.

181. 182. 183.

184. 185.

186. 187. 188. 189. 190.

191.

192.

193. 194.

195. 196. 197. 198. 199.

200. 201. 202.

203. 204.

205. 206.

207.

208.

Part 1/Stereotactic Principles

Gildenberg PL: History of pain management, in Greenblatt SH (ed): A History of Neurosurgery in Its Scientific and Cultural Contexts. Park Ridge, 1L: American Association of Neurological Surgeons Press, 1993. Trousseau A: De la nevralgie epileptiforme. Arch Gen Med 1:33^14, 1853. Rose W: Removal of the gasserian ganglion for severe neuralgia. Trans Med Soc Land 14:35-40. 1890. Horsley V, Taylor J, Colman WS: Remarks on the various surgical procedures devised for the relief or cure of trigeminal neuralgia (tic douloureaux). Br Med J 2:1139-1143, 1891. Cushing H: A method for total extirpation of the Gasserian ganglion for trigeminal neuralgia. JAMA 34:1035-1041, 1900. Cushing H: The major trigeminal neuralgias and their surgical treatment based on experiences with 332 Gasserian operations: I. Varieties of facial neuralgia. Am J Med Sci 160:157-184, 1920. Ramonede L: Exerese de trijumeau. Presse Med 11:789-791, 1903. Dandy WE: Section of the sensory root of the trigeminal nerve at the pons. Bull Johns Hopkins Hosp 36:105-106, 1925. Kirschner M: Die Punktionstechnik u. Elektrokoagulation des Ganglion Gasseri. Arch Klin Chir 176:581-620, 1933. Kirschner M: Zur Electrochirurgie. Arch Klin Chir 161:761-768. 1931. Wycis HT, Spiegel EA: Long-range results in the treatment of in¬ tractable pain by stereotaxic midbrain surgery. J Neurosurg 19:101-107. 1962. Spiegel EA, Wycis HT, Szekely EG, et al: Combined dorsomedial, intralaminar and basal thalamotomy for relief of so-called intractable pain. J Int Coll Surg 42:160-168, 1964. Nashold BS, Wilson WP, Slaughter DG: Stereotaxic midbrain le¬ sions for central dysesthesia and phantom pain: Preliminary report. J Neurosurg 30:116-126, 1969. Gybels JM, Sweet WH: Neurosurgical Treatment of Persistent Pain. Pain and Headache. 11. Basel: Karger. 1989. Sjoqvist O: Eine neue Operationsmethode bei Trigeminus-neuralgie: Durchschneidung des Tractus spinalis trigemini. Zentralhl Neurochir 2:274-281, 1937. White JC, Sweet WH: Pain and the Neurosurgeon: A Forty Year Experience. Springfield, IL: Charles C Thomas. 1969. Hitchcock ER: Stereotactic trigeminal tractotomy. Ann Clin Res 2:131-135, 1970. Hitchock ER, Schvarcz JR: Stereotaxic trigeminal tractotomy for post-herpetic facial pain. J Neurosurg 37:412-417, 1972. Hitchcock ER: Stereotactic cervical myelotomy. J Neurol Neurosurg Psychiatry 33:224—230, 1970. Crue BL, Todd EM, Carrega! EJA: Posterior approach for high cer¬ vical percutaneous radiofrequency cordotomy. Confin Neurol 30:41-52, 1968. Hitchcock ER: Stereotactic myelotomy. JR Soc Med 67:771, 1974. Schvarcz JR: Stereotactic extralemniscal myelotomy. J Neurol Neurosurg Psychiatry 39:53-57, 1976. Gildenberg PL, Hirshberg RM: Limited myelotomy for the treat¬ ment of intractable cancer pain. J Neurol Neurosurg Psychiatry 47:94-96, 1984. Gildenberg PL. Hirshberg RM: Treatment of cancer pain with lim¬ ited myelotomy. Med J St Jos Hosp (Houston J 16:199-204. 1981. Al-Chaer ED, Lawand NB. Westlund KN, Willis WD: Visceral noci¬ ceptive input into the ventral posterolateral nucleus of the thalamus: A new function for the dorsal column pathway. J Neurophysiol 76:2661-2674,1996. Spiller WG: The location within the spinal cord of the fibers for tem¬ perature and pain sensations. J Ner\’ Ment Dis 32:318-320, 1905. Spiller WG, Martin E: The treatment of persistent pain of organic origin in the lower part of the body by division of the anterolateral column of the spinal cord. JAMA 58:1489-1490, 1912. Foerster O: Vorderseitenstrangdurchschneidung im Ruuckenmark zur Beseitigung von Schmerzen. Berlin Klin Wochnscltr 50:1499, 1913. Foerster O. Gagel O: Die Vorderseitenstrangdurchschneidung beim Menschen: Eine Klinische. pathophysiologisch, anatomische Studio. Zl Ges Neurol Psychiatr 138:1-92, 1932.

209. 210.

211.

212.

213. 214.

215. 216. 217.

218.

219.

220.

221. 222.

223.

224. 225.

226.

227.

228. 229. 230. 231. 232.

233.

234. 235.

Frazier CH: Section of the anterolateral columns of the spinal cord for the relief of pain. Arch Neurol Psychiatry 4:137-147, 1920. Mullan S, Harper PV, Hekmatpanah J, et al: Percutaneous interrup¬ tion of spinal pain tracts by means of a strontium-90 needle. J Neurosurg 20:931-939, 1963. Rosomoff HL, Carrol F, Brown J, Sheptak P: Percutaneous radio¬ frequency cervical cordotomy: Technique. J Neurosurg 23:639-644, 1965. Rosomoff HL, Krieger AJ, Kuperman AS: Effects of percutaneous cervical cordotomy on pulmonary function. J Neurosurg 31: 620-627, 1969. Lin PM. Gildenberg PL, Polakoff PPL: An anterior approach to per¬ cutaneous lower cervical cordotomy. J Neurosurg 25:553-560, 1966. Gildenberg PL, Lin PM, Polakoff PP, Flitter MA: Anterior percuta¬ neous cervical cordotomy: Determination of target point and calcu¬ lation of angle of insertion: Technical note. J Neurosurg 28: 173-177, 1968. Melzack R, Wall PD: Pain mechanisms: A new theory. Science 150:971-979, 1965. Wall PD, Sweet WH: Temporary abolition of pain in man. Science 155:108-109, 1967. Shealy CN, Mortimer JT, Reswick JB: Electrical inhibition of pain by stimulation of the dorsal columns: Preliminary clinical report. Anesth Analg 46:489^191, 1967. Sweet WH, Wepsic JG: Treatment of chronic pain by stimulation of fibers of primary afferent neuron, Trans Am Neurol Assoc 93:103-107, 1968. Richardson DE, Akil H: Pain reduction by electrical brain stimula¬ tion in man: 1. Acute administration in periaqueductal and periven¬ tricular sites. J Neurosurg 47:178-183, 1977. Long DM, Hagfors N: Electrical stimulation in the nervous system: The current status of electrical stimulation of the nervous system for relief of pain. Pain 1:109-123, 1975. Reynolds DV: Surgery in the rat during electrical analgesia induced by focal brain stimulation. Science 164:444^145. 1969. Richardson DE, Akil H: Pain reduction by electrical brain stimula¬ tion in man: II. Chronic self-administration in the periventricular grey matter. J Neurosurg 47:184-194, 1977. Hosobuchi Y, Adams JE, Rutkins B: Chronic thalamic stimulation for the control of facial anesthesia dolorosas. Arch Neurol 29:158-161, 1973. Gybels J: Electrical stimulation of the brain for pain control in hu¬ man. Verh Dtsch Ges Inn Med 86:1553-1559, 1980. Gybels J, Cosyns P: Modulation of clinical and experimental pain in man by electrical stimulation of thalamic periventricular gray, in Zotterman (ed): Sensory Functions of the Skin. Oxford: Pergamon Press, 1976, pp 521-530. Lazorthes Y: European study on deep brain stimulation. Third European Workshop on Electrical Neurostimulation. Paris: Medtronic, 1979. Hosobuchi Y: Combined electrical stimulation of the periaqueductal gray matter and sensory thalamus. Appl Neurophysiol 46:112-115, 1983. Mazars G, Merienne L, Cioloca C: Effects of so-called periaqueduc¬ tal gray substance stimulation. Neurochirurgie 25:96-100. 1979. Penn RD, Paice JA: Chronic intrathecal morphine for intractable pain. J Neurosurg 67:182-186. 1987. Penn RD: Drug pumps for treatment of neurologic diseases and pain. Neurol Clin 3:439-451, 1985. Onofrio BM. Yaksh TL: Long-term pain relief produced by intrathecal morphine infusion in 53 patients. Neurosurgery 72:200-209, 1990. Lazorthes Y: Intracerebroventricular administration of morphine for control of irreducible cancer pain. Ann N Y Acad Sci 531:123-132, 1988. Brazenor GA: Long term intrathecal administration of morphine: A comparison of bolus injection via reservoir with continuous infusion by implanted pump. Neurosurgery 21:484-491, 1987. Leksell L: The stereotaxic method and radiosurgery of the brain. Acta Chir Stand 102:316-319, 1951. Leksell L: Stereotaxis and Radiosurgery: An Operative System. Springfield. II,: Charles C Thomas, 1971.

Chapter 1/The History of Stereotactic and Functional Neurosurgery

236. 237. 238.

239. 240.

241.

242.

243.

244.

245.

Larsson B, Leksell L, Rexed B: The high energy proton beam as a neurosurgical tool. Nature 182:1222-1223, 1958. Woodruff KH, Lyman JT, Lawrence JH, et al: Delayed sequelae of pituitary irradiation. Hum Pathol 15:48-54, 1984. Fabrikant JI, Lyman JT, Frankel KA: Heavy charged-particle Bragg peak radiosurgery for intracranial vascular disorders. Radiat Res 8(suppl):S244—S258, 1985. Leksell L: Stereotactic radiosurgery. J Neurol Neurosurg Psychiatry 46:797-803, 1983. Larsson B: The history of radiosurgery: The early years (1950-1970), in Kondziolka D (ed): Radiosurgery 1995. Basel: Karger, 1996, pp 1-10. Steiner L, Leksell L, Greitz J, et al: Stereotaxic radiosurgery for cerebral arteriovenous malformations. Acta Chir Scand 138: 459-464, 1972. Lunsford LD, Alexander E HI, Loeffler JS: General introduction: History of radiosurgery, in Alexander E III, Loeffler JS, Lunsford LD (eds): Stereotactic Radiosurgery. New York: McGraw-Hill, 1993, pp 1-4. Walton L, Bomford CK, Ramsden D: The Sheffield stereotactic ra¬ diosurgery unit: Physical characteristics and principles of operation. BrJ Radiol 60:897-906, 1987. Lunsford LD, Flickinger J, Lindner G, Maitz A: Stereotactic radiosurgery of the brain using the first United States 201 cobalt-60 source gamma knife. Neurosurgery 24:151-159, 1989. Betti O, Derechinsky V: Hyperselective encephalic irradiation with a linear accelerator. Acta Neurochir Suppl (Wien) 33:385-390, 1984.

246.

247. 248.

249.

250.

251. 252.

253. 254. 255.

19

Colombo F, Benedetti A, Pozza F, et al: Radiosurgery using a 4MV linear accelerator: Technique and radiobiologic implications. Acta Radiol Suppl (Stockh) 369:603-607, 1986. Colombo F, Benedetti A, Pozza F, et al: External stereotactic irradia¬ tion by linear accelerator. Neurosurgery 16:154-160, 1985. Sturm V, Kober B, Hover KH, et al: Stereotactic percutaneous single dose irradiation of brain metastases with a linear accelerator. Int J Radiat Oncol Biol Phys 13:279-282, 1987. Pastyr O, Hartmann GH, Schlegel W, et al: Stereotactically guided convergent beam irradiation with a linear accelerator: Localization technique. Acta Neurochir (Wien) 99:61-64, 1989. Hartmann GH, Schlegel W, Sturm V: Cerebral radiation surgery us¬ ing moving field irradiation at a linear accelerator facility. Int J Radiat Oncol Biol Phys 11:1185-1192, 1985. Podgorsak EB, Olivier A, Pla M, et al: Physical aspects of dynamic stereotactic radiosurgery. Appl Neurophysiol 50:263-268, 1987. Lutz W, Winston KR, Maleki N: A system for stereotactic radio¬ surgery with a linear accelerator. Int J Radiat Oncol Biol Phys 14:373-381, 1988. Winston KR, Lutz W: Linear accelerator a$ a neurosurgical tool for stereotactic radiosurgery. Neurosurgery 22:454-464, 1988. Friedman WA, Bova F: The University of Florida radiosurgery sys¬ tem. Surg Neurol 32:334-342, 1989. Kooy HM, Nedzi LA, Loeffler JS, et al: Treatment planning for stereotactic radiosurgery of intra-cranial lesions. Int J Radiat Oncol Biol Phys 21:683-693, 1991

CHAPTER

2

THE MATHEMATICS OF CARTESIAN COORDINATES

David W. Roberts

Stereotaxy achieves accuracy by quantifying spatial informa¬ tion mathematically; that information can then be manipulated, enabling one to relate one set of data to another. Certain bene¬ fits derive from the establishment of such relationships, includ¬ ing the identification of anatomic structure from an atlas on an imaging study and the delivery of a surgical instrument to such a structure.

application; the errors that arise may be better appreciated. An equally compelling rationale derives from the impetus and di¬ rection such surgical understanding can provide to the develop¬ ment of the field. This chapter reviews the mathematical principles of stereo¬ tactic coordinate systems and their manipulation. It is directed to the surgeon rather than the engineer, mathematician, or pro¬ grammer; while a small number of equations and formulas are included, a mathematical background on the part of the reader is not required.

In the early days of classical stereotaxy—before the advent of computed tomography (CT) imaging and the adaptation of computing workstations to clinical neurosurgery—practitioners of this specialty were a self-selected small subset of individuals with a common interest in neurophysiology and precise me¬ chanical instrumentation. The instrumentation required of the stereotactician a modest but essential mathematical back¬ ground, intuition, and comfort. Determining the intraoperative central beam of a radiograph, scaling an atlas, accounting for parallax, and grasping the spiral diagram are examples of the manipulation of geometric space that clever devices and techniques made reasonably easy and reliable for a neurosur¬ geon who was willing to learn their fundamental concepts and principles.

COORDINATE SPACES The location of a point in n-dimensional space may be uniquely defined by the assignment of n coordinates to that point. Pierre de Fermat and Rene Descartes, two early seventeenth-century Frenchmen, independently recognized that a system composed of two perpendicular lines could be used to identify any point within a plane.1 The distances along each of these lines (what may be called the X and Y axes) from the origin (the axes’ inter¬ section, where each axis is usually assigned a value of 0) to a given point provide an ordered pair of numbers, or coordinates, unique to that point. Such a rectangular coordinate system is commonly called cartesian in honor of Descartes and may be extended to three dimensions with X, Y, and Z axes. There are obviously other ways in which a point’s location in space can be described. For example, the lines representing the coordinate system’s axes need not be perpendicular to each other (although for each to provide independent information about each point, they must be nonparallel). Alternatively, a point in a plane may be described by specifying its distance and direction from an origin, that is, a radius (r) and angle (com¬ monly labeled 0), using a polar coordinate system. This may be extended into three dimensions using a cylindrical coordinate system by specifying a distance along an additional (Z) axis perpendicular to the original plane, or one may use a spherical coordinate system, specifying a radius and two angles (perpen¬ dicular with respect to each other) describing the direction from the origin. All these systems achieve the same end of defining uniquely the location of a point in space, and all are mathemat¬ ically equivalent. One may readily convert the coordinates of one system to those of another. It is an elementary exercise to

The availability of computing resources in the operating room environment altered this in as significant a way as the technology of CT scanning broadened stereotaxy’s indications and facilitated its application. Inexpensive computational power provided a more efficient algebraic solution to many of the registration tasks required by stereotactic frame systems. Fairly simple programs could eliminate the geometric diagrams and paper and pencil calculations of surgeons. Very quickly, it was appreciated that this computational resource also could provide an efficient graphic representation of reformatted atlas information. Today’s software efficiently manipulates large volumes of individualized imaging and atlas and operative field data, and computer graphics provide us with unlimited refor¬ mations in two, three, and, with temporal information, four di¬ mensions. All this software is undergoing commercial develop¬ ment and distribution to a broad spectrum of neurosurgeons, many of whom may regularly use such instrumentation and technology without a stereotactic or mathematical background. While increasingly intuitive interfaces facilitate the technol¬ ogy’s deployment without the need for an understanding of the mathematical basis of its operation, there are reasons why such an understanding is advantageous to neurosurgeons. Foremost is the safeguard such an understanding provides during clinical

21

22

Part 1/Stereotactic Principles

show that the coordinates of a point (r, 0) in two-dimensional polar coordinate space may be converted to X, Y coordinates in two-dimensional cartesian coordinate space by using the formulas2 x = r cos0 y = r sin0 and a similar conversion from three-dimensional spherical co¬ ordinates is represented by the formulas2 x — r sin0 cos0 y = r sin0 sin0 Z = r cos0 A variety of two- and three-dimensional coordinate spaces may be employed in a stereotactic procedure. As was noted earlier, spatial information from imaging studies, atlases, stereotactic frames, and other intraoperative digitizers must be encoded in the parameters of such coordinate spaces. Consid¬ ering imaging studies first, the coordinates inherent in a single CT slice are most intuitive. The computer graphic representa¬ tion of such a slice is generated by using coordinates inherent to the scanner, and these machine-specific or gantry coordi¬ nates are usually readily accessible at the scanner console. By convention, an X coordinate is assigned along the right-left axis of the image, and a Y coordinate along the posterior-anterior axis. (It will be noted by pre-CT stereotacticians but is not a practical concern today that this convention differs from that of earlier stereotaxy, in which the X coordinate designated dis¬ tance along the anterior-posterior dimension on a lateral radi¬ ograph, the Y coordinate designated distance along the inferiorsuperior dimension, and the Z coordinate designated distance along the right-left dimension.) Thus, on any given two-dimen¬ sional CT image [or similarly represented magnetic resonance imaging (MR1), positron emission tomography (PET), or sin¬ gle photon emission computed tomography (SPECT) image], one may specify a given pixel’s location in terms of an X and a Y coordinate; it is immaterial at this point in the discussion whether this is in gantry coordinate space or some other space based on part of a stereotactic frame that may also be in the scan, but this issue will be revisited in the discussion about transformations, below. As neurosurgeons, we are interested in the three-dimen¬ sional space of the intracranial volume, and additional imaging information must account for this third dimension. The location of the target-bearing slice with respect to a frame or to other slices in the study may be determined in several ways, the most common of which is to monitor the position of the scanner table relative to the gantry or to use the geometry of frame components visible in the scanner that enable unique determi¬ nation of the slice plane relative to the frame (the various Nshaped fiducial plates). A coordinate incorporating this third dimension may be added to the coordinates already derived in two dimensions to provide a three-dimensional address for any location within the imaging study. Keeping in mind traps such as gantry tilt that introduce skew into the stack of slices (which can be accounted for), the cartesian coordinate system of CT and MR imaging is intuitive, tractable, and convenient. There are two possible configurations of a three-dimen¬ sional orthogonal coordinate system. Given X and Y axes in the plane of a page or monitor, the positive Z axis may extend ei¬

ther away from or toward the viewer. In the former instance, it is described as a left-handed coordinate system; in the latter, it is called a right-handed system (Fig. 2-1). Right-handed sys¬ tems may be more familiar, but the convenience of increasing Z values extending deep into the plane of the monitor has often favored left-handed systems in computer graphics.3 Various imaging devices, computer graphics displays, and stereotactic systems may use one or the other, but as long as the convention is recognized, this is not a problem. The projection geometry of conventional radiographs, in¬ cluding pneumoencephalography, ventriculography, and con¬ ventional (non-MRI) angiography, is not as simple (accounting in no small part for early stereotaxy’s esoteric mystique) but is directly solvable as well. In this instance, spatial information is obtained from two-dimensional images, and to derive threedimensional information, one must incorporate data from at least two images obtained from different perspectives, identify the same object(s) in each image, and account for magnifica¬ tion and parallax. All these issues have been worked out mathe¬ matically in general and in terms of multiple stereotactic sys¬ tems in particular.4 Geometric methods using plotting graphs (or a spiral diagram) provided nonalgebraic working solutions before computer availability. Analytic solutions for biplanar angiography, however, have been developed for multiple stereotactic frame systems using fiducial-embedded plates at¬ tached to the frame.5-6 Scalp-based fiducial markers in a frame¬ less adaptation have also been described.7 The incorporation of atlas-derived anatomic information of stereotactic interest is dependent on similar organization of its information into coordinate space. Nearly all stereotactic at¬ lases are cartesian and, from a mathematical perspective, differ primarily in terms of the selection of the coordinate system’s origin, the orientation of its axes (what other natural reference points are used to align one or more axes), the methodology of scaling, the (sometimes irregular) intervals of data sampling, and the occasional incorporation of statistical methodology. Independent of these issues, each atlas assigns a unique threedimensional address (the stack of anatomic slices compiled into a three-dimensional volume in a manner analogous to that of stacking CT slices) to each anatomic point of interest, en¬ abling subsequent manipulation and incorporation of that infor¬ mation into a stereotactic procedure.

y

y

Figure 2-1. Left: a right-handed coordinate system. Right: a lefthanded coordinate system.

Chapter 2/The Mathematics of Cartesian Coordinates

Stereotactic frames serve multiple functions, including the definition of a coordinate space that includes the relevant por¬ tion of a particular patient’s intracranial volume, means by which coregistration of that coordinate space with information from imaging studies or anatomic atlases can be accomplished, and the delivery of an operative instrument to a selected coor¬ dinate address (advantageous stabilization of that instrument is a convenient but nonstereotactic added benefit). The first task can be achieved using any type of coordinate system, and the various stereotactic frame systems utilize a variety. The Leksell, Talairach, and Hitchcock frames, to cite a few, are all cartesian-based. Target coordinates on these frames are speci¬ fied as ordered triplets (X, Y, Z). Arc-centered systems (such as the Leksell system) have the attractive and convenient feature of enabling free adjustment of the angles of the arc and probe carrier (and thus the trajectory), with the target point always re¬ maining centered. For applications of point targeting, however, these parameters need not be stereotactically defined. If a spe¬ cific trajectory is to be stereotactically defined (for example, one passing through more than one designated point), these an¬ gles of course are specified; there are more than three parame¬ ters to such a localization, and information in addition to the cartesian coordinates of the target is necessary. Other stereotactic frame systems are based on noncartesian coordinate systems. The Reichert-Mundinger frame uses two angles on an arc, an additional two angles on the probe carrier, and a dimension of depth.8 The determination of this combina¬ tion of spherical coordinates was originally performed noncomputationally by mechanically adjusting the trajectory probe until it reached the simulated target on a phantom. (The posi¬ tioning of this phantom target would already have been set by using radiographically determined cartesian rectangular coor¬ dinates derived through projection geometry from multiple two-dimensional image rectangular coordinates.) The inconve¬ nience and potential contamination of this step using a phan¬ tom were eventually replaced by mathematical calculation of the frame angles and length, exemplifying the integration of in¬ creasingly accessible computational power. The coordinate space of the Brown-Roberts-Wells (BRW) stereotactic system, in which targets and trajectories are de¬ fined by four angles and the length, is similarly noncartesian.9'10 Its development at a time when the available computational re¬ sources (initially using the CT scanner’s computer and later us¬ ing a programmable calculator) allowed computational conver¬ sion from cartesian scanner coordinates to spherical coordinates, and its phantom base was necessary only for me¬ chanical confirmation or to define a specific trajectory such as that from an entry point. The coordinate system established by a stereotactic frame defines the operative coordinate space. More recently devel¬ oped stereotactic systems that do not require a mechanical frame nevertheless require an operative coordinate space, and this requirement is fulfilled through the use of a three-dimen¬ sional digitizer in the operating room. Such a device can locate a point within its working volume and assign it a coordinate ad¬ dress (usually within whatever kind of coordinate space is de¬ sired, with the interconversion being straightforward, as was noted earlier). A variety of digitizing technologies can be em¬ ployed to accomplish this localization task, including those based on ultrasound emitters and microphone arrays, articu¬ lated arms with potentiometers or optical encoders at the joints

23

between links, light-emitting diodes (LEDs) and linear charged coupled device (CCD) camera arrays, stereo video or electronic cameras, and electromagnetic field transmitters and detecting coils. The software running these devices calculates from the one or more sensors of the digitizer the location of a selected point, and this information usually is passed directly to further software, determining coregistration, driving appropriate graphic displays, or interfacing with robotic instrumentation (the actual coordinate system and numeric coordinates for a se¬ lected point in operating room space is otherwise of no direct importance to the procedure). A good example of how such a digitizer might define an operating room stereotactic space is found in the description by Friets and colleagues of a sonic dig¬ itizer used to track an operating microscope."

REGISTRATION STRATEGIES At the heart of a stereotactic procedure is the linking of the multiple coordinate spaces defined by imaging studies and by the intraoperative stereotactic system. If two coordinate spaces are concordant, with corresponding points in the imaging study and the intracranial working space having identical coordi¬ nates, coregistration will in effect already have been accom¬ plished and no further manipulation or computation will be re¬ quired. With the goal of minimizing calculation, particularly when computational aids were less available, most frame-based methodologies were developed to incorporate some degree of mechanical alignment of frame and imaging studies. The prob¬ lem of determining the relationship between coordinate spaces is in this manner at least partially constrained and made more tractable. Using a central beam a given distance from or or¬ thogonal to a frame’s side is an example in working with pro¬ jection geometry; placing a frame in a scanner perpendicular to the gantry and without rotation is another. In the latter example, the elimination of rotation along any of three coordinate axes reduces the transformation from cartesian scanner space to cartesian frame space to a calculation with only three transla¬ tions (Fig. 2-2). As computation becomes increasingly fast and inexpensive, however, more of the task of determining the rela¬ tionship between different coordinate spaces can be shifted from the mechanical realm to the software realm. An example of this is the registration process underlying the BRW frame, in which a full three-dimensional transformation is derived for the registration step; positioning of the frame within a CT scanner is thus less constrained at the expense of more elaborate but still reasonably efficient calculation. Conceptually, this shift toward the computational derivation of necessary transfor¬ mations has led to the elimination of the stereotactic frame altogether. At its most fundamental level, correspondence between one cartesian coordinate space and another consists of the defini¬ tion of six parameters. These are three angles of rotation by which the X, Y, and Z coordinate axes can be made parallel to one another, and there are the three distances (along each of these axes) by which the origins of the two coordinate systems can be superimposed. An additional parameter of scale must, of course, also be explicitly or implicitly accounted for as well. It is not difficult to intuitively appreciate the rotations, transla¬ tions, and scaling (Fig. 2-3). In the common instance of regis¬ tering a patient’s imaging study with the patient’s head in the

24

Part 1/Stereotactic Principles

required (for example, registering a stereotactic atlas to an indi¬ vidual patient); such algorithms have not been well developed. This process of moving between different coordinate spaces is often represented mathematically by transformation mat¬ rices.3,4 Such a matrix for rotation about the X axis has the form

Rx(0) =

1

0

0

0

0

cos0

sin0

0

0

-sin0

cos0

0

0

0

0

1_

and multiplication of the coordinates of a point by this matrix generates the new coordinates for that point:

P’= P ■ Rx(0)

Figure 2-2. The generation of stereotactic frame coordinates at the CT or MRI console can be done by constraining the problem to one of straightforward translations, as in this case of a stereotactic biopsy using the Leksell stereotactic frame. The leftright (X) and posterior-anterior (Y) distances between the center of the frame (as determined by the intersection of diagonal lines passing through symmetrical landmarks on the frame’s imaged superstructure) and the target are measured by using the scanner console’s measure-distance function. The superior-inferior (Z) coordinate is calculated from the distance between a vertical fiducial rod (posteriorly) and a diagonal fiducial rod whose geometric relationship to the frame’s coordinate system is known.

operating room, it usually is assumed that the brain’s morphol¬ ogy is unchanged in both coordinate systems, and the method of registration is that of determining a rigid-body transforma¬ tion. Alternatively, there are instances in which one cannot make this assumption, and so an elastic transformation may be

1

0

0

0

0

COS0

sin0

0

0

-sin0

COS0

0

0

0

0

1

= [xyzl}-

= [*

(ycos0—zsin0)

(ysin0+zcos0)

1]

Conceptually, the new coordinates may be considered as either the movement of the point to a new location within a single co¬ ordinate space or the representation of an analogous point in a new coordinate system; the two are functionally equivalent. A matrix may be derived for each of the other rotations, translations, and scaling as follows:3 Rotation about the Y axis

Ry(0)

=

COS0

0

-sin0

0

0

1

0

0

sin0

0

cos0

0

0

0

0

1

Rotation about the Z axis

Rz{0) —

COS0

sin0

0

0

-sin0

COS0

0

0

0

0

1

0

0

0

0

1

Translation along all three axes

T(I)x, Dy, Dz) Figure 2-3. A rigid-body transformation from one coordinate space to another involves the designation of three angles of rotation and three translations.

1

0

0

0

0

1

0

0

0

0

1

0

Dx

Dy

Dz

1

=

Chapter 2/The Mathematics of Cartesian Coordinates

Scaling

Sx

0

0

0

0

Sy

0

0

0

0

ft

0

0

0

0

1

S(Sx, Sy, ft) =

In converting from one coordinate space to another, it is common for multiple processes to be required and for the vari¬ ous matrix transformations to be performed sequentially. It can be observed that translation is an additive process and that rota¬ tion and scaling are multiplicative. If one uses what are called homogeneous coordinates (as given above), it is possible to treat all three operations as multiplications, and in this way one can combine sequential transformations in a process referred to as concatenation or composition. A rigid-body transformation combining all the above operations is thus represented as

T = Rx Ry Rz -Txyz •Sxyz and registration across multiple coordinate spaces may be per¬ formed similarly:

Given a point whose coordinates are known in coordinate space A, the coordinates for that point in coordinate space C may be derived by matrix multiplaction:

Though this formulation has the appeal of formulaic sim¬ plicity, in the actual computation of transformational processes, the mathematical operations are sometimes broken back down into addition and multiplication for the sake of greater effi¬ ciency in terms of the number of operations required. It should also be pointed out in this regard that there are alternative methodologies for such operations, such as the use of the direc¬ tion cosines that were employed in early software for the Dartmouth microscope," but these methods are mathematically equivalent. The ability to move in the reverse direction be¬ tween coordinate spaces—a desirable process in any truly in¬ teractive form of stereotaxy—is facilitated by the inverse trans¬ formation, which is represented symbolically by T-1:

P2

=

25

frameless stereotactic systems is that of matching a set of or¬ dered points visible to both the imaging study and the intraop¬ erative digitizer."-16 A minimum of three such pairs of points is required for determination of the transformation, although many systems employ or allow additional pairs of points to im¬ prove registration accuracy. Such points may be markers that have been attached to the scalp before imaging (glass beads, staples, vitamin E capsules, skull-embedded screws). Alternatively, such algorithms may be used with natural fea¬ tures, such as the tragus, lateral canthi, or nasion. The less dis¬ crete nature of an anatomic feature may compromise accuracy, although this approach has the advantage of not requiring a special imaging study. In either instance, the algorithms used are the same. Rather than matching readily apparent analogous points, one may derive a transformation by using other features, such as the intrinsic curvatures of the scalp surface, to achieve align¬ ment. By calculating from both imaging studies and an intraop¬ erative digitizer the mathematically defined curvatures over a sufficient portion of the scalp, one can then align either points of maximum curvature or related features (such as ridge lines and saddle points) in a similar manner17-19 (Fig. 2-4). Given a set of ordered points whose coordinates are known in two different coordinate spaces, there are a number of ap¬ proaches to the problem of determining the parameters of the rigid-body transformation relating those spaces. These ap¬ proaches include closed-form solutions such as singular value decomposition of a matrix, eigenvalue-eigenvector decomposi¬ tion of a matrix, and unit quaternions as well as iterative solu¬ tion techniques.20 Given a set of reference features as described above, an iter¬ ative registration process requires two conceptual steps. The first step is to define a disparity function by which a measure of

P}-T

P 1 = P2Tl Derivation of the transformation matrix required to move between patient-specific imaging coordinate spaces and stereo¬ tactic operating space can be achieved in a number of ways. The known geometry of specific stereotactic frame superstruc¬ tures visible in imaging space allows a convenient determina¬ tion of the necessary transformation. As was previously alluded to, the simple hand calculation of Leksell X and Y coordinates from a CT or MRI console represents such a calculation, albeit a fairly constrained one: similarly, identification in image space of the so-called fiducial rods (or, in a two-dimensional image, points) of a BRW frame enables formulaic calculation of se¬ lected targets in stereotactic operating space. At the present time, the simplest and most commonly used method of achieving coregistration of coordinate spaces with

Figure 2-4. The inherent maximum and minimum curvatures at multiple points on the scalp, as determined by intraoperative digitizer data ( a sonic digitizer in this instance) and by CT or MR imaging, are represented by intersecting lines whose lengths are proportional to their curvature. The resulting feature maps, whose unique topography can be readily appreciated, can then be matched. (From Friets et al, 17 with permission.)

26

Part 1/Stereotactic Principles

the correspondence between two sets of corresponding features can be determined. The most common such function is a leastsquares criterion of the type 21 D = Iw i {distance [FAi,T(Fgi,/)]}2 i

In this function, D is equal to the sum of squares of the dis¬ tances between each of i corresponding points (w is a weight¬ ing factor related to the noise of the measurements). The sec¬ ond step is optimization of the disparity function, by which is meant the adjustment of various transformation parameters so that a usable value of the function is achieved. In the above ex¬ ample, minimization of the function is desired, and when this is achieved, the registration process is complete. There are nu¬ merous optimization strategies, and when there is no direct so¬ lution, nonlinear iterative methods are required. A frequently used method is gradient descent.21 In the registration strategy using three or more reference points, the ordering of those corresponding points in both coor¬ dinate spaces is known. There are alternative strategies, how¬ ever, in which unordered sets of points may be used, as in matching the surface of the head as imaged by CT, MRI, or PET with the surface of the scalp as digitized in the operating room. This surface-to-surface matching has the advantage of using a natural feature of the head (so that additional prospec¬ tive imaging is not required) whose segmentation can be auto¬ mated. A number of techniques have been developed, the best known of which is the hat-and-head matching algorithm of Pelizarri and Chen (Fig. 2-5).22'24 In this method, the distance between intraoperatively digitized surface points and the preoperatively imaged surface along rays extending from the cen¬ troid of that surface to each point is computed, and the sum of

Figure 2-5. The algorithm of Pelizarri and associates2’ matches two surfaces with one another. (From Pelizarri el al,23 with permission.)

these squared distances is then minimized. An iterative opti¬ mization process may inopportunely appear to have become optimized when it actually has not (the problem of local min¬ ima), and either initial guidance or user intervention may be re¬ quired to reduce this possibility. Numerous other surface-tosurface matching methodologies25'27 have advantages and disadvantages in terms of ease of automation and computa¬ tional efficiency, and though they vary in the details of their al¬ gorithms, all conceptually share the component steps of the de¬ finition of a disparity function and the optimization of that function.21 The accuracy, efficiency, and speed of various strategies employing different functions and optimizations are current areas of considerable attention.28,29 (Fig. 2-6). The fur¬ ther development of these more sophisticated registration strategies based on inherent anatomic features (not requiring the placement of artificial fiducial markers on special scans) and fully automated segmentation and matching algorithms will make coregistration of multimodality and sequential imag¬ ing studies of a given patient a standard practice. The extension of these methods into the operating room using three-dimen¬ sional digitizers will render nearly all procedures stereotactic in a manner that is transparent to the operating surgeon.

CONCLUSIONS Stereotactic operating systems achieve accurate integration of multiple data bases into the operative field through quantifica¬ tion of anatomic location, using coordinate systems that may then be related to one another through the process of coregis¬ tration. These requisite steps can be accomplished with wellunderstood, well-established mathematical methods. The avail¬ ability of powerful computational resources in the operating room allows the use of more sophisticated algorithms that have eliminated the need for a stereotactic frame, have become increasingly more efficient and more accurate, and have the potential to increasingly automate coregistration. While the mathematical and computer skills that allow these latter devel¬ opments have become more sophisticated and foreign to prac-

Figure 2-6. This graph from the work of Cuchet and colleagues29 shows the shapes of various cost functions using simulated data; only variation in rotation with the Zaxis is shown. (From Cuchet el al,2* with permission.)

Chapter 2/The Mathematics of Cartesian Coordinates

ticing neurosurgeons, the fundamental mathematical principles underlying stereotaxy are accessible to all. Out of a desire to facilitate further development of the field, reduce potential er¬ rors in clinical practice, and satisfy intellectual curiosity, an un¬ derstanding of these principles can be rewarding to all.

surgery, in Maciunas RJ (ed): Interactive Image-Guided Surgery. Park Ridge, IL: AANS, 1993, pp 259-270. 15.

16.

References 1.

West BH, Griesbach EN, Taylor JD, Taylor LT: The Prentice-Hall

17.

Encyclopedia of Mathematics. Englewood Cliffs, NJ: Prentice-Hall, 1982, pp 119-126. 2.

Clapham C: A Concise Dictionary of Mathematics. Oxford: Oxford University Press, 1990.

3.

Foley JD, Van Dam A: Fundamentals of Interactive Computer Graphics. Reading, MA: Addison-Wesley, 1984, pp 245-266. Lemieux L, Henri CJ, Wootton R, et al: The mathematics of stereo¬ tactic localization, in Thomas DGT (ed): Stereotactic and Image Directed Surgery of Brain Tumors. Edinburgh: Churchill Livingstone, 1993, pp 193-216. Kelly PJ, Goerss SJ, Kail BA: Modification of Todd-Wells system for imaging data acquisition, in Lunsford LD (ed): Modem Stereotactic Neurosurgery. Boston: Martinus Nijhoff, 1988, pp 79-97. Lunsford LD, Kondziolka D, Flickinger JC, et al: Stereotactic radio¬

4.

5.

6.

surgery for arteriovenous malformations of the brain. J Neurosurg 75:512-524, 1991.

27

18.

Day R, Heilbrun MP, Koehler S, et al: Three-point transformation for integration of multiple coordinate systems: Applications to tumor, functional, and fractionated radiosurgery stereotactic planning. Stereotact Fund Neurosurg 63:76-79, 1994. Heilbrun MP, Koehler S, MacDonald P, et al: Preliminary experience using an optimized three-point transformation algorithm for spatial registration of coordinate systems: A method of noninvasive localiza¬ tion using frame-based stereotactic guidance systems. J Neurosurg 81:676-682, 1994. Friets EM, Strohbehn JW, Roberts DW: Curvature-based nonfiducial registration for the frameless stereotactic operating microscope. IEEE Trans Biomed Eng 42:867-878, 1995. Gueziec A, Ayache N: Smoothing and matching of 3-D space curves: Visualization in biomedical computing 1992. Proc SPIE 1808: 259-273, 1992.

19.

Balter JM, Pelizzari CA, Chen GTY: Correlation of projection radi¬ ographs in radiation therapy using open curve segments and points. MedPhys 19:329-334, 1992.

20.

Maurer CR, Fitzpatrick JM: A review of medical image registration, in Maciunas RJ (ed): Interactive Image-Guided Surgery. Park Ridge, IL: AANS, 1993, pp 17^14. Lavallee S: Registration for computer-integrated surgery: Methodol¬ ogy, state of the art, in Taylor RH, Lavallee S, Burdea GC, Mosges R (eds): Computer-Integrated Surgery. Cambridge, MA: MIT Press, 1996, pp 77-97.

21.

22.

ographic and MR data for localization of subdural electrodes. J Comput Assist Tomogr 16:764—773, 1992.

Levin DN, Pelizzari CA, Chen GTY, et al: Retrospective geometric correlation of MR, CT, and PET images. Radiology 169:817-823, 1988.

23.

8.

Mundinger F, Birg W: The imaging-compatible Riechert-Mundinger system, in Lunsford LD (ed): Modern Stereotactic Neurosurgery. Boston: Martinus Nijhoff, 1988, pp 13-25.

24.

9.

Brown RA: A computerized tomography-computer graphics approach to stereotaxic localization. J Neurosurg 50:715-720, 1979. Apuzzo MLJ, Fredericks CA: The Brown-Roberts-Wells system, in Lunsford LD (ed): Modern Stereotactic Neurosurgery. Boston: Martinus Nijhoff, 1988, pp 63-77.

Pelizzari CA, Chen GTY, Spelbring DR, et al: Accurate three-dimen¬ sional registration of CT, PET, and/or MR images of the brain. J Comput Assist Tomogr 13:20-26, 1989. Tan KK, Grzeszczuk R, Levin DN, et al: A frameless stereotactic ap¬ proach to neurosurgical planning based on retrospective patientimage registration: Technical note. J Neurosurg 79:296-303, 1993. Jiang H, Robb RA, Holton KS: A new approach to 3-D registration of multimodality medical images by surface matching, in Proceedings of the Second Conference on Visualization in Biomedical Computing. Chapel Hill, NC, 1992, pp 196-213. Mangin JF, Frouin V, Bloch I, et al: Fast Nonsupervised 3D Registra¬ tion of PET and MR Images of the Brain. Paris: Telecom Paris, 1993. Hemler PF, Sumanaweera TS, van den Elsen P, et al: A versatile sys¬ tem for multimodality image fusion. J Image Guid Surg 1:35-45, 1995.

7.

10.

11.

12.

13. 14.

Grzeszczuk R, Tan KK, Levin DN, et al: Retrospective fusion of radi¬

Friets EM, Strohbehn JW, Hatch JF, Roberts DW: A frameless stereo¬ tactic operating microscope for neurosurgery. IEEE Trans Biomed Eng 36:608-617, 1989. Roberts DW, Strohbehn JW, Hatch JF: A frameless stereotaxic inte¬ gration of computerized tomographic imaging and the operating mi¬ croscope. J Neurosurg 65:545-549, 1986. Galloway RL Jr, Maciunas RJ, Edwards CA: Interactive imageguided neurosurgery. IEEE Trans Biomed Eng 39:1226-1231, 1992. Maciunas RJ, Fitzpatrick JM, Galloway RL, Allen GS: Beyond stereotaxy: Extreme levels of application accuracy are provided by implantable fiducial markers for interactive image-guided neuro¬

25.

26. 27.

28. 29.

Simon DA, Hebert M, Kanada T: Techniques for fast and accurate intrasurgical registration. J Image Guid Surg 1:17-29, 1995. Cuchet E, Knoplioch J, Dormont D, Marsault C: Registration in neu¬ rosurgery and neuroradiotherapy applications. J Image Guid Surg 1:198-207, 1995.

■

-»

CHAPTER

3

HISTORICAL DEVELOPMENT OF STEREOTACTIC FRAMES

Eric M. Gabriel and Blaine S. Nashold, Jr. Tools used by the surgeon must be adapted to the task, and, where the brain is concerned, they cannot be too refined. Lars Leksell

General Principles

Historically, the basal plane passed through the external audi¬ tory meatus and the lower borders of the orbits, which is similar to the Frankfort plane used by anthropologists in their measure¬ ments of the skull. The practical use of stereotaxis in the mon¬ key required the elevation of this plane by 10 mm in order to encompass the base of the brain. The third plane also transects the external auditory meati orthogonal to the midsagittal and basal planes. The Cartesian coordinate system has withstood the test of time, as technologically advanced stereotactic frames still employ this technique in their designs.

Localization and functional analysis of intracerebral structures has captured the intellect of neuroscientists since the advent of neurology. Perhaps the earliest conceptual attempt to link ex¬ ternal landmarks to intracranial processes involved the work of Franz Joseph Gall (1758-1828). He espoused the doctrine of cranioscopy, or phrenology, which linked irregularities of the skull to a person’s mental characteristics.87 Although his work was unfounded scientifically and not popularly accepted, it did portray an effort to relate brain function to a reference point.

Another system of stereotaxis, related to the Cartesian coor¬ dinate system albeit less frequently used, is based upon a polar, or spherical, coordinate system (Fig. 3-15). As opposed to three distances, target points are defined by a distance and two angles (R, 0, and o>) from a zero reference point.66 The threedimensional distance from the zero point to the target point is defined as R, while 0 and u> are the two angles of incidence in the horizontal and vertical planes, respectively.66 This system was used by the older burr-hole systems and now serves the modern arc-phantom systems, often in conjunction with Cartesian coordinates. As this system requires knowledge of spherical geometry and trigonometric tables, most surgeons perform the needed calculations with the aid of computers.

The task of cerebral localization had been limited for many years to careful anatomic and physiological studies in animals and clinicopathological correlates in humans with neurological diseases. With the origin of neurosurgery in the latter nine¬ teenth century came new opportunities to study the brain and its inherent structures. However, deep structures and lesions beneath the cortex still posed a problem in terms of accessibil¬ ity. From this need for better techniques to identify subcortical brain structures without harming the overlying cortex arose the field of stereotactic neurosurgery. Stereotaxis, from the Greek meaning “three-dimensional, or¬ derly arrangement,” is based upon the principle that any point in the brain can be referenced to a specific coordinate system using precise measurements. The Cartesian coordinate concept is based on the principles developed by the great French philoso¬ pher and mathematician Rene Descartes in the seventeenth cen¬ tury28 and forms the basis of most modern frames. Descartes supported the contention that any point in space can be defined by its relationship to three planes; traditionally, x, y, and z, which intersect at right angles to each other (Fig. 3-M). These three planes, the abscissa, ordina, and applicata, meet at one point, defined as the origin or zero point.1 Any point in space can thus be defined by its distances from the three reference planes. Utilizing the Cartesian coordinate system in animal stereotaxis, a midsagittal plane is used as one reference while a basal plane perpendicular to the first defines the second plane.38

Types of Stereotactic Frames Utilization of the coordinate systems mentioned above enabled neuroscientists to construct various stereotactic apparatuses in an effort to access deep intracranial sites. As the field of stereo¬ tactic and functional neurosurgery evolved, many improve¬ ments in design have been incorporated to capitalize on the dis¬ advantages of prior frames. Although the quest for the perfect stereotactic frame is a noble one, it has yet to be achieved. Thus, most frames have different advantages and disadvan¬ tages, making them suitable for different applications. Stereotactic frames can be categorized into one of four sys¬ tems: (1) the translational or rectilinear system; (2) the arc

29

30

Part 1/Stereotactic Principles

A, Illustration of cartesian coordinate system, which consists of three axes, x, y, and z, that intersect at x = 0, y = 0, and z = 0. Coordinates for the target point (P) are determined from the distance that point lies from each of the three axes. For purpose of stereotaxis, it is best to conceive of the axes as three intersecting planes and project perpendicular from each of the three planes to the target point. Thus, the x-y plane will correspond to a horizontal or axial projection, the x-z plane will correspond to a coronal projection, and the y-z plane will define the sagittal projection. B, Illustration of the polar coordinate system. Point lies in space with reference to target point (0). A straight line is drawn from the zero point to the target point. This line has a distance (R). The line also has a slope or an inclination from the horizontal plane (0) and an angle from the verticle plane (*■_ N \ V

• \ \ \ | > 1 \ \

^

~ ^

\ \ i i * s Figure 7-3. Radiologic images acquired in stereotactic conditions. All the steps of the stereotactic procedure yield x-rays, showing the ventricles, vessels, and position of the probes (during biopsies or during implantation of cannulas). On each x-ray. certain features are always visible: pins, tidueials, even the skull bone. These can be used to match x-rays and to draw on a common diagram all the relevant data of every modality. A. Position of the deep brain EEG electrodes, B. Drawing of arterial vessels, superficial (continuous lines), and deep (dotted lines). C. Superposition of vessels and sulci from MRI. D. Planning of temporal resection.

Chapter 7/The Talairach System

83

1 2 3

j

4 5

6

£

/

Af

LFS

A

CS

7 8

PC SS

9 10 \

AC-PC

[AC

g^STS

11 12

abcd

e

fghi

Figure 7-4. Proportional grid system: the borders or the rectangle are tangent to the inner table of the skull, parallel and perpendicular to the intercommissural AC-PC line. Various structures, such as sulci, may be located using the grid parcellation. AC,PC: anterior and posterior commissures; SS: sylvian sulcus; STS: superior temporal sulcus; LFS: lower frontal sulcus; RS: rolandic sulcus; CS: calcarine sulcus; MF: motor fibers; PT: pyramidal tract; upper diagram: lateral; lower diagram: anteroposterior.

ordinates for accurate probe placements. X-ray images in stereotactic conditions provide spatial localization of points within the cerebral space, but this localization is inaccurate be¬ cause of two phenomena:

1.

2.

Magnification. Magnification depends on the respective distances to the film, of the point of the cerebral space (d) and of the x-ray tube (D). The magnification coefficient that enlarges every measured distance between two points in the space is: G = D/(D-d). Our setup, in which tubes are 3.5 m away from the center of the frame, achieves a low magnification ratio of 1.05. Correction of parallax errors. Parallax depends on the dis¬ tance of a given point in the cerebral space to the axis of the x-ray beam, which is the zero point. Every point that has, with respect to this central x-ray, coordinates x, y, will actually have coordinates X, Y on the film. These are X = G*x and Y = G* y

This must be taken into account in calculating the setup para¬ meters of the frame. Precise data regarding the central x-ray beam, perpendicular to the frame faces, can be determined on the double-grid image where the central beam passes through similar holes on both grids (Fig. 7-5). The simplest situation corresponds to a central beam placed on the area of interest and centered on the target. When this central beam is centered at distance from the target, its actual position is used for exact correction of the parallax distortion for any point in the brain.30

Detection of vascular injury along a DOUBLE OBLIQUE BIOPSY TRACK With any penetrating trajectory into the brain there is the risk of encountering a vascular structure; this risk is greatest in the case of biopsies.31 The Talairach grid system is mainly set up for orthogonal, frontal, or lateral approaches. Biopsy tracks performed through the grids are aligned along the x-ray axes

Part 1/Stereotactic Principles

84

A

B Figure 7-5. A. lateral x-ray of a grid with an array of 27 X 31 holes. B. interference pattern of the two grids. One may recognize the central beam (cross). The next interference corresponds to a shift of one hole spacing (3 mm).

and provide the safest procedures, since it is possible to check on the corresponding x-ray images that the projected track, which appears as a point, does not correspond to any projection of a vessel. In the case of double-oblique approaches, the prob¬ lem of detecting vascular collision is not as easy to solve, despite the fact that CT-guided stereotactic biopsies without angiographic control are popular.726-28’32-33 Effective solutions must be found, and some have already been designed and used. The intrinsic features of the Talairach system has led Szikla et al.1016 to develop a routine procedure proven to be effective and easy to perform without any computation, but which can be easily computerized and automated. Provided that the two xray beams are orthogonal, a given point in the brain appears on x-rays as two pairs of coordinates (x, z) on the frontal view and (y, z) on the lateral view, z being the same in both pairs (Fig. 76). Therefore, projections of the intersection of a putative track with a vessel must have the same z value (as measured on x-ray films from the base plate of the frame or from any other refer¬ ence plane) on both lateral and frontal planes (Fig. 7-7). Obviously, the reciprocal is not true, and it may happen that lat¬ eral and frontal intersections having a same z value do not correspond to the same vessel: In these cases of false collision, the decision between true and false collision is made by the surgeon’s expertise. This method of collision detection, which can be computerized on digitized angiograms, is much easier and faster to achieve but less elegant than true collision detec¬ tion without false-positive points provided by real 3-D recon¬ struction of the vascular network. Another approach is derived from the "floating line” con¬ cept.3'’ A specially built stereocomparator features two movable lines on transparent grids, applied onto two stereoscopic an¬ giograms and representing the projections on these tilted an¬ giograms of a theoretical line in brain space. Observation of this line through the stereocomparator allows the surgeon to check for eventual collision of the line with vessels and eventu¬ ally to change it. The Talairach system provides another approach that has been used profitably in routine practice16-36 to recognize the indepth position of the vessels using small-angle double¬ incidence angiograms (SADIA) taken under a 5° tilt angle, which corresponds to the natural binocular vision angle. One

may use a stereocomparator or, with some training, it is possi¬ ble to squint and obtain a 3-D perception of the vascular net¬ work. One may also superimpose the two angiograms and try to make the vessels correspond. Coincidence of the two images of the vessels is possible only for those that are in the same plane perpendicular to the x-ray axis (Fig. 7-8). Slightly sliding the films one over the other will change this “coincidence plane” and display another array of vessels situated within it. This technique is easily used in daily routine to evaluate the depth of vessels projecting on a proposed trajectory. Obviously, the approach described above can be formally demonstrated and could be used as a possible basis for 3-D re¬ construction.30 Consider lateral views taken as SADIAs. Every

Figure 7-6. X-ray setup. Any point of the brain with xi. yi, zi coordinates will have Xi. Zi radiologic coordinates w ith a magnification coefficient G(xi) that depends on the geometry of the system.

Chapter 7/The Talairach System

85

Figure 7-7. Vascular collision between a vessel and a track must have the same Z altitudes on frontal and lateral x-rays. In this case B and E correspond to a probable vascular collision.

point P of the brain is assigned a triplet of coordinates (x, y, and z) in brain space, a pair of coordinates (Y, Z) on the regular lat¬ eral view film, and (Y, Z') on the lateral view film of the 5° tilted head. Therefore, x corresponds to the “depth” of a point along an axis Ox perpendicular to the film plane. When the two films are superimposed with a given shift 8 with respect to an arbitrary reference (T + 8 = Y'), two sets of points belonging to the two films are placed in coincidence. One may easily demonstrate30 that there is a relationship between 8 and x, which is dependent on y (Fig. 7-6). When superimposition of the films is achieved, some structures, such as vessels, can be matched on both films when there is a shift equal to 8. Therefore: x= -11.9 8 - 0.04E The depth x can therefore be calculated for all points of the film that are situated at the coordinate Y and coincident to their ho¬ mologous projection on the tilted film when the shift is equal to 8. A paradigm can be derived from this procedure. A complete set of coordinates is therefore generated and, when displayed, provides a 3-D reconstruction of the vascular network. Connection of a stereotactic frame to a COMPUTERIZED IMAGING SYSTEM The Talairach frame does not have localizers designed for MRI or CT examinations in stereotactic conditions. Moreover, its present metallic composition makes it incompatible with MRI, and the pins verniers are too clumsy to fit easily within the MRI gantry. Several solutions have been proposed to overcome this problem.

Computed Tomography For CT data obtained in stereotactic conditions using other MRI-compatible frames, specific adapters can be designed. Sedan has adapted the Leksell frame system in which the pa¬ tient is initially set up and CT examination is performed using the localizers and software developed for this system. While still on the Leksell frame, the patient is then transferred to the Talairach frame, using a specifically designed adapter. We have adapted the Fischer-Leibinger frame and simply transfer vernier values from one frame to the other.

Figure 7-8. Superposition of two x-ray angiograms taken with a 5° tilt angle of the x-ray beam. Coincidence of vessels can be obtained only for limited segments situated in the same plane. On this figure, only the pericallosal artery (midline plane) is matched, while more superficial branches of the sylvian artery are, shifted.

When CT examination has been done under regular circum¬ stances, several methods help in reporting the shape of the le¬ sion in terms of the stereotactic diagram, making possible the use of this information for stereotactic procedures.30,37

Magnetic Resonance Imaging It has been stated that MRI cannot provide a precise spatial lo¬ calization because of its nonlinearity.38,39 This is actually wrong: precision is a matter of tuning the system correctly. The easiest way is to enlarge the images at the scale of the stereo¬ tactic pictures and to match them to similarly visible features and anatomic structures. Sedan et al.29 designed a televisionbased system that can pick up MRI parasagittal views and re¬ display them, using a variable gain along the X and Y axes. The recent MRI systems can actually display hard copies at any de¬ sired magnification. Provided that MRI gradients are properly checked and adjusted if needed, MRI images are used by su¬ perimposition of a calibration grid positioned identically on each picture. This provides a composite picture featuring all relevant data, such as the inner contour of the skull, the coronal suture, depression of the torcular, the ventricular system and essentially the third ventricle, the aqueduct of Sylvius and the fourth ventricle, the rostrum and splenium of the corpus callo¬ sum, and sometimes the siphon of the carotid artery. All these structures are visible on the stereotactic ventriculogram and an¬ giograms, providing a stereotactic diagram that can therefore be matched to the MRI diagram. There is no doubt that in the near future such procedures will be computerized.

Digital Radiology Digital subtraction angiography (DSA) and ventriculography are replacing conventional x-ray films. These digital radiologic images are easily processed and matched with other image

86

Part 1/Stereotactic Principles

modalities. Target coordinates are then precisely and quickly obtained and may be used to drive a computerized or robotized system.

16.

17.

CONCLUSION The main characteristic of the Talairach system is that it ren¬ ders compatible all procedures (diagnostic and therapeutic) performed on the frame during the same or during subsequent sessions, which may be separated from each other by weeks or even months. It is also designed to provide minimally distorted numerical spatial data and to allow corrections of these distor¬ tions. The Talairach system has been the basis of a rational ap¬ proach, taking advantage of the orthogonality of x-ray inci¬ dence to define precisely the position of the targets and vascular structures within the brain with respect to the coordi¬ nates of the frame system. These features have been used to de¬ velop methods of computation accessible to surgical teams with little or no computational means but also applicable to automated software. The stereotactic Talairach frame is suited for connection with spatially guided and computer-assisted ro¬ bots, as it provides a basic spatial reference that is easy to inte¬ grate into a routine for driving a robot toward a spatially de¬ fined target.

18.

19. 20.

Benabid AL, Lavallee S, Hoffmann D. et al: Computer driven robot for stereotactic neurosurgery, in Kelly P. Kail A (eds): Computers in Stereotactic Neurosurgery. Cambridge, MA: Blackwell, 1992, pp 330-342.

22.

Goerss SJ, Kelly PJ, Kail BA, Alker GJ: A computed tomographic stereotactic adaptation system. Neurosurgery 10:375-379, 1982. Kail BA, Kelly PJ, Goerss SJ, Earnest F IV: Cross-registration of points and lesion volumes from MR and CT. Proceedings of the Seventh Annual Meeting of Frontiers of Engineering and Computing in Health Care. 1985:935-942. Kelly PJ. Kail BA. Goerss SJ: Transposition of volumetric informa¬

23.

24.

tion derived from computed tomography scanning into stereotactic space. Surg Neurol 21:465^171, 1984. 25.

Lavallee S: Gestes medico-chirurgicaux assistes par ordinateur. These sciences mathdmatiques. Grenoble, France: Universite Joseph Fourier. 1989.

26.

Sedan R, Duparet R: Stereometre adaptable au cadre stereotaxique de J Talairach. Neurochirurgie 14: 577-582, 1968. Scerrati M. Fiorentino A, Fiorentino M, Pola P: Stereotaxic device for polar approaches in orthogonal systems (technical note). J Neurosurg 61:1146-1147, 1984.

27.

2. 3.

4. 5.

6. 7. 8.

9.

10. 11.

12.

13. 14. 15.

Horsley VA, Clarke RH: On the intrinsic fibers of the cerebellum, its nuclei and its effect tracts. Brain 28: 12-29, 1905. Spiegel EA, Wycis HT, Marks M, Lee A: Stereotactic apparatus for operations on the human brain. Science 57:164-167, 1947. Picard C, Olivier A, Bertrand G: The first human stereotaxic appara¬ tus: The contribution of Aubrey Mussen to the field of stereotaxis. J Neurosurg 59:673-676, 1983. Gildenberg PL: Whatever happened to stereotactic surgery? Neuro¬ surgery 20:983-987, 1987. Olivier A: Extratemporal resections, in Engel J (ed): Surgical Treatment of the Epilepsies, 2d ed. New York: Raven Press, 1993, pp 489-500. Talairach J, David M, Tournoux P: L’exploration chirurgicale stereotaxique du lohe temporal. Paris, Manon et Cie, 1958:123. Crandall PH: Cortical resections, in Engel J (ed): Surgical Treatment of the Epilepsies. New York: Raven Press, 1987, pp 377-404. Talairach J, Ajuriaguerra JD. David M: A propos des coagulations therapeutiques sous-corticales: Etude topographique du systcme ventriculaire en fonction des noyaux gris centraux. Presse Medicate 58: 697-701, 1950. Talairach J, Tournoux P: Co-planar stereotaxic atlas of the human brain: 3-dimensional proportional system: An approach to cerebral imaging. Stuttgart: Thieme Medical Publishers, 1988. Szikla G, Bouvier G, Hori T, Petrov V: Angiography of the Human Brain Cortex. New York: Springer-Verlag, 1977. Talairach J, Ruggiero G, Aboulker J, David M: A new method of treatment ot inoperable brain tumors by stereotaxic implantation of radioactive gold: A preliminary report. Br J Radiol 28:62-74, 1955. Talairach J, Ajuriaguerra J de, David M: Etudes stereotaxiques des structures encephuliques profondes chez I'Homme Technique, interet physiologique et therapcutiquc. Presse Med 28:605-609, 1952. Talairach J, David M, Tournoux P, et al: Atlas d'anatomie stereolaxique des noyaux gris centraux. Paris: Masson. 1957. Talairach J, Szikla G, Tournoux P. et al: Atlas d'anatomie stereotaxique du tilencephale. Paris: Masson. 1967. Benabid AL. Chirossel JP, Mercier C. et al: Removable, adjustable and reusable implants for stereotactic interstitial radiosurgery of brain tumors. Appl Neurophysiol 50:278-280, 1987.

Olivier A: Double-headed stereotaxic carrier apparatus for insertion of depth electrodes. J Neurosurg 65:258-259. 1986. Peters TM, Clark JA. Olivier A, et al: Integrated stereotaxic imaging with CT, MR imaging, and digital subtraction angiography. Radiology 161:821-826, 1986.

21.

References 1.

Szikla G, Peragut JC: Irradiation interstitielle des gliomes, in Constans JP, Schlienger M (eds): Radiotherapie des tumeurs du systeme nerveux central. Neurochirurgie (Suppl) 21:187-228. 1975. Bancaud J, Talairach J. Bonis A, et al: La Stereo-Jlectro-encephalographie dans Vepilepsie. Paris: Masson, 1965. Bouvier G, Saint Hilaire JM. Giard N, et al: Depth electrode implanta¬ tion at Notre-Dame Hospital. Montreal, in Engel J Jr (ed): Surgical Treatment of the Epilepsies. New York: Raven Press, 1987, pp 589-594.

28.

29.

30.

31.

32. 33.

34.

35.

36.

37.

38.

39.

Colombo F, Angrilli F, Zanardo A, et al: A universal method to em¬ ploy CT scanner spatial information in stereotactic surgery. Appl Neurophysiol 45:352-354, 1982. Steinmetz H, Fiirst G, Freund HJ: Cerebral cortical localization: Application and validation of the proportional grid system in MR imaging. J Comput Assist Tomogr 13:10-19, 1989. Benabid AL, Lavallee S, Hoffmann D, et al. Computer support for the Talairach system, in Kelly P, Kali A (eds): Computers in Stereotactic Neurosurgery. Cambridge, MA: Blackwell. 1992, pp 230-245. Munari C. Betti OO: The stereotactic biopsy of brain lesions: A criti¬ cal review, in Broggi G, Gerosa MA (eds): Cerebral Gliomas. New York: Elsevier. 1989. pp 179-206. Brown RA: A computerized tomography-computer graphics ap¬ proach to stereotactic localization../ Neurosurg 50:715-720, 1979. Mundinger F, Birg W. Klar M: Computer-assisted stereotactic brain operations by means including computerized axial tomography. Appl Neurophysiol 41: 169-182, 1978. Perry JH, Rosenbaum AE, Junsford LD, et al: Computed tomogra¬ phy-guided stereotactic surgery: Conception and development of a new stereotactic methodology. Neurosurgery 7:376-381. 1980. Cloutier L. Nguyen DN. Ghosh S. et al: Simulator allowing spatial viewing of cerebral probes by using a floating line concept. Symposium on Optical and Electro-Optical Applied Science and Engineering, Cannes. France. 1985. Szikla G, Bouvier G. Hori T: Localization of brain sulci and convolu¬ tions by arteriography: A stereotactic anatomo-radiological study. Brain Res 95:497-502, 1975. Nguyen JP, Van Effentere R, Fohanno D, et al: Methode pratique de re pd rage spatial des petites neofornuuions intracraniennes it partir des donnees de la tomodensitomdtrie. Neurochirurgie 26:333—339, 1980. Schad L. Lott S. Schmitt F. et al: Correction of spatial distortion in MR imaging: A prerequisite for accurate stereotaxy. J Comput Assist Tomogr 11:499-505, 1987. Wyper DJ, Turner JW, Patterson J, et al: Accuracy of stereotactic lo¬ calisation using MRI and CT. J Neurol Neurosurg Psychiatry 49:1445-1448. 1986.

CHAPTER

8

THE LAITINEN APPARATUS

Manvan I. Hariz and Lauri V. Laitinen

The Laitinen stereotactic system consists of the Stereoadapter and Stereoguide with auxiliaries for various radiological and surgical uses.

ear arm. Cogwheel cases join the lateral triangle components to the nasion support arms, which have millimeter scales. By winding the cogwheel screws, the nasion support is pressed against the bridge of the nose. The earplugs lie at the posterior ear arms and are pressed against the external auditory meati by means of a threaded lever in front of the nasion support. The connector plate at the vertex joins the lateral triangle compo¬ nents together and serves to press the triangle components against the scalp. A frontal pin mounted between the vertex connector plate and the nasion support serves as the laterality reference structure (Fig. 8-1).

The Stereoadapter is mainly used for stereotactic imaging with computed tomography (CT), magnetic resonance imaging (MRI), and stereotactic angiography. Together with the biopsy kit, the Stereoadapter is used for localization, biopsy, or stereo¬ tactic resection of brain lesions. It has also been used with the linear accelerator for fractionated stereotactic irradiation of brain tumors and arteriovenous malformations. The Stereoguide is used together with the Stereoadapter in functional neurosurgery such as pallidotomy, thalamotomy, and deep brain stimulation for movement disorders and pain as well as anterior capsulotomy and hypothalamotomy for psychiatric disorders.

When the Stereoadapter has been mounted on the head, its position is recorded by the symmetrical millimeter scales on both sides of the nasion support arms and on the connector plate of the Stereoadapter. The Cartesian reference structures of the Stereoadapter are the sagittal midplane passing through the frontal pin for the lat¬ erality x coordinate, the frontal plane between the anterior bor¬ ders of the right and the left posterior ear arms for the antero¬ posterior (AP) y coordinate, and the transverse plane between a pair of transverse bars for the dorsoventral z coordinate. With the Stereoadapter mounted to the head, the dorsalmost trans¬ verse bar level corresponds to the average height level of the cingulum, the second dorsalmost bars to the average height level of the intercommissural line, and the third bar pair to the average level of the amygdala.

NONINVASIVE MULTIPURPOSE STEREOADAPTER The Stereoadapter was developed in 1982-1983.' The original aim was to design a noninvasive, imaging-compatible, relocat¬ able instrument for biopsy of brain tumors. It soon became evi¬ dent that the Stereoadapter was accurate enough for functional neurosurgery, and since 1987 it has been used in all functional neurosurgery without ventriculography or plain radiology. The key for the high localizing accuracy is that the three reference points of the skull—i.e., the external auditory meatus and the bridge of the nose—give a good relocating stability. The sec¬ ond reason for the high accuracy is that the imaging fiducials lie immediately on the scalp and not at a far distance from it, as is the case with other stereotactic frames.

For CT, MRI, or angiography study as well as for stereotac¬ tic irradiation, the Stereoadapter is mounted to the head and then immobilized to a plastic plate with a multijoint mecha¬ nism (Fig. 8-1). For MRI studies, thin tubes containing 2 mmol copper sulfate or olive oil are attached to the reference struc¬ tures of the Stereoadapter. These fiducials give an artifact-free sharp image. For single photon emission computed tomogra¬ phy (SPECT) or positron emission tomography (PET) studies, the tubes mentioned above can be filled with an appropriate so¬ lution of isotope, thus providing visible reference marks on the respective pictures. For angiography, either a conventional or digital angiography, the ordinary earplugs of the Stereoadapter are replaced by similar earplugs containing a 1-cm lead pin, and, a 1-cm lead pin is placed on the forehead of the patient. These lead pins provide the magnification factor on the AP view. On the side view, the magnification is given by the al¬ ready known distance of 25 mm between two sets of the trans¬ verse bars.5

The Stereoadapter is mounted to the patient’s head by means of a nasion support, two earplugs, and a strapping band at the occiput. Neither general nor local anesthesia is needed. Repeated mountings of the Stereoadapter have shown a high degree of reproducibility and tolerability.2-4 The Stereoadapter is made of an aluminum alloy and rein¬ forced plastic. It consists of two lateral triangular components with four transverse bars each, a connector plate, a nasion sup¬ port component, and frontal laterality indicator pins (Fig. 8-1). The transverse bars are 2 mm thick in a dorsoventral direction and lie 25 mm apart from each other. They connect the anterior and posterior ear arms and are perpendicular to the posterior

87

88

Part 1/Stereotaxic Principles

Figure 8-1. The Stereoadapter mounted on the head. Left: The patient’s head is lying on a plastic cushion, and the Stereoadapter is immobilized by a multijoint mechanism prior to the imaging study. The star indicates the posterior ear arm of the right triangular component. TB = transverse bar. Right: Frontal view. CP = connector plate, holding the lateral triangular components pressed to the scalp.

For stereotactic irradiation, plastic plates are attached to the triangular components of the Stereopadapter (Fig. 8-2). These plates have lines indicating the position of the transverse bars and posterior ear arms, respectively, and serve to align the pa¬ tient's head according to the lateral laser beams of the linear accelerator. Instead of the ordinary frontal pin, a ruler with slid¬ ing millimeter scales and a cone are used (Fig. 8-2). This de¬ vice serves to align the brain target in a lateral direction accord¬ ing to the frontal laser beam. The laser beam must coincide with the tip of the cone. Thus, the cone allows for a visual veri¬ fication of the proper alignement of the target when the couch is rotated for multiplanar irradiation.

TUMOR BIOPSY KIT The biopsy kit consists of a phantom base, probe carrier, twist drill, diathermy probe, and biopsy cannula. The phantom base is mounted between the right and left transverse bars of the Stereoadapter at a desired height level (Fig. 8-3). It has two slide components with millimeter scales for the .v and the _y co¬ ordinates, respectively. The slide component for the y coordi¬ nate has a millimeter-scaled vertical rod for the z coordinate. The probe carrier has two steel rods, two hinge clamps, and two concentric probe-guiding cannulas. The probe carrier is rigidly attached to the connector plate of the Stereoadapter for either an anterior (frontal) or posterior (parietooccipital) ap¬ proach (Fig. 8-3). The ordinary rod of the probe carrier can be replaced by a long curved one should a lateral or posterior

Figure 8-2. The Stereoadapter mounted to the head prior to stereotactic irradiation. Plastic plates to indicate the brain target's y and z coordinates are attached to the lateral triangular components. The laser cross lines are aligned with the reference markings of the AP and height coordinates on the plate. The cone on the forehead is attached to a laterality ruler. Both can slide according to the laterality of the target. The couch is moved until the frontal laser line hits the tip of the cone.

Chapter 8/The Laitinen Apparatus

89

Figure 8-3. The biopsy procedure. Left: The biopsy kit mounted to the Stereoadapter. The phantom base is mounted at the level of the second dorsalmost transverse bars and shows the x, y, and z positions of the brain target. The probe carrier is mounted to the connector plate of the Stereoadapter for a parietal approach. The biopsy needle points to the phantom target and the hinge clamps are tightened. Right: The Stereoadapter mounted to a dummy. The probe carrier is attached and the guiding cannula is directed toward the intracranial target.

fossa approach be needed. The Sedan biopsy probe consists of an outer cannula 250 mm long and 2 mm thick, with a 5-mm side opening at its distal end. An inner cannula with a sharp¬ ened end functions as a guillotine when it is advanced through the outer cannula during aspiration of a brain tumor specimen. After setting the phantom base according to the CT/MRI coor¬ dinates of the target, the tip of the biopsy cannula is directed against the phantom target, after which the hinge clamps are tightened (Fig. 8-3).

Stereoguide, mounted on the patient, may be attached rigidly to a floor stand for surgery. Then, if intraoperative radiology is needed, the central beams of suitably adjusted lateral and AP x-ray tubes will pass through the y, z, and x origins of the frame, respectively.7

STEREOTACTIC RADIOLOGICAL AND SURGICAL APPLICATIONS

STEREOGUIDE

Nonfunctional Stereotaxis

The Laitinen Stereoguide is a stereotactic frame that functions according to the arc-radius principle.6 It consists of an oval base ring fixed to the head with four steel pins (Fig. 8-4). Cylindrical components with millimeter scales are mounted on the lateral sides of the base ring. Cogwheel mechanisms permit the cylinder components to slide in such a way that their com¬ mon axis coincides with the y and z positions of the intracranial target. A vernier scale ensures an accuracy of ±0.25 mm. A semicircular arc carrying the electrode, endoscope, or other probe is mounted to the cylindrical components. It can slide in a lateral direction to bring the probe tip to the lateral x position of the target (Fig. 8-4). Thus the target lies at the center of the spherical system of the Stereoguide and can be reached from any suitable direction. If needed, the base ring of the

The stereotactic management of a brain tumor, abscess, cyst, deep brain hematoma, etc., begins by mounting the Stereoadapter to the head and performing a stereotactic CT (or MRI) study.8-10 The scanning is performed throughout the tu¬ mor area with 2- or 3-mm-thick contiguous slices parallel to the transverse bars of the Stereoadapter (Fig. 8-5). The Stereoadapter is then detached from the head. The calculation of target coordinates may be done manually or using the soft¬ ware of the CT or MRI machine. The y coordinate of the target is its distance from the interaural plane, the x coordinate is the distance from the medial border of the right posterior ear arm, and the z is the distance from the CT scan containing the target point and to that showing the nearest pair of transverse bars8 (Fig. 8-5).

90

Part 1/Stereotaxic Principles

Surgery may take place at any suitable time after the CT / MRI study. The phantom base and probe carrier are set accord¬ ing to the CT/MRI target coordinates, after which the phantom base is detached (Fig. 8-3). The Stereoadapter with the probe carrier locked to it is remounted to the head. The inner probeguiding cannula is replaced by a similar sterile one. Using local anesthesia, the skull is trephined with a 2.15-mm-thick twist drill introduced through the guiding cannula. Diathermy coagu¬ lation is applied to the dura and cortex. The biopsy needle is then introduced to the target. Tumor specimens are obtained from various depths along the track of the needle. The proce¬ dure usually takes 25 to 35 min.8 The same instrumentation and technique can be used for the stereotactic placement of a drainage catheter in cases of cyst or abscess. Similarly, for a deep-seated tumor scheduled for stereotactic craniotomy and resection, a guiding catheter can be placed stereotactically at the edge of the tumor, after which the Stereoadapter is detached. The catheter is cut along the surface of the skin, a small centered flap is created, and a craniotomy is done. The catheter is then followed toward the tumor using small spatulas and routine microsurgical techniques. For resection of small superficial brain tumors, the location of the tumor in relation to the Stereoadapter can be drawn on the scalp using the same technique. The Stereoadapter is then removed and a small centered craniotomy is done.9

Fractionated stereotactic irradiation When a brain lesion is scheduled for stereotactic irradiation, the stereotactic CT scanning ought to include not only the area of the brain pathology but also the whole calvarium. With an arteriovenous malformation (AVM), stereotactic an¬ giography with the Stereoadapter is done. The target coordi¬ nates are indicated on special side plates attached to the tri¬ angular components of the Stereoadapter. The lateral x coordinate is measured on the CT scan in relation to the midsagittal plane of the Stereoadapter (Fig. 8-5). The Stereoadapter is remounted to the head with the patient ly¬ ing on the couch of the linear accelerator (Fig. 8-2). The couch is moved so that the two laser cross lines from each side and the vertical laser beam from the ceiling indicate that the isocenter of the accelerator coincides with the Stereoadapter markings of the brain target—that is, the markings on the side plates and the frontal cone (Fig. 8-2). The Stereoadapter is then locked to the couch with a multi¬ joint mechanism similar to that used for CT and MRI. During irradiation, the patient is monitored using a video camera. Each irradiation session, comprising five or six multiplanar fixed beams with variable collimation, lasts for about 30 min. The procedure may be repeated according to the schedule of fractionation.51112

Figure 8-4. The Stereoadapter and Stereoguide mounted to a patient during a functional stereotactic procedure. A. The base ring of the Stereoguide is fixed to the head with screws. A steel pin introduced through the cylindrical component points at the y and z origins of the Stereoadapter {arrow) during setting of the surgical y and z coordinates. B. The probe carrier arc is attached to the cylindrical components. The electrode points to the frontal pin of the Stereoadapter (arrow) during setting of the surgical x coordinate (see text for details).

Chapter 8/The Laitinen Apparatus

h

T0M

2N

uMEh F8 1 3

91

however, not as crucial as positioning into the CT gantry as far as the right-left alignment is concerned. The sagittal survey im¬ age of the triangular components should be obtained first. On this image, the tubes filled with copper sulfate or olive oil, indi¬ cating the references for the AP and height coordinates, are vi¬ sualized (Fig. 8-6). The axial MRI scanning should also be done parallel to the transverse bars, and coronal scanning should be parallel to the posterior ear arms. In our experience, a stereotactic MRI study with axial thin slices takes about 15 min. Determination of the ventricular LANDMARKS AND TARGET COORDINATES

Figure 8-5. A 2-mm-thick stereotactic CT scan at the level of the second dorsal most transverse bars of the Stereoadapter. The dotted line xb indicates the laterality x of the biopsy target, measured from the right transverse bar (see text). The AP coordinate of the target is indicated by y. The target’s laterality measured from the sagittal midplane of the Stereoadapter is indicated by x.

Functional Stereotaxis The

CT

and

MRI

studies

After mounting the Stereoadapter, the head, resting on a plastic cushion, is aligned so that the connector plate of the Stereoadapter is parallel to the transverse laser beam of the gantry, after which the Stereoadapter is locked to a plastic plate on the CT table and a lateral Scoutview of the head is obtained. The cursor line is brought to the level of and parallel to the dorsalmost transverse bars of the Stereoadapter, so that the scan¬ ning plane is parallel to the transverse bars and perpendicular to the posterior ear arms of the Stereoadapter. The visualization of the transverse bars is checked on the first CT slice to assure parallel alignment. Beginning from the level of the dorsalmost transverse bars, 1.5- or 2-mm thick slices are scanned in 2-mm steps until the second transverse bars and the proximal part of the aqueduct are visualized, following which the Stereoadapter is detached. The CT study lasts for 10 to 15 min. Basically, MRI and CT scanning with the Stereoadapter are very similar. The positioning of the patient into the coil is.

Enlarged film copies of the CT/MRI scans are obtained from the area between the foramina of Monro (FM) and the proximal aqueduct, including the second pair of transverse bars. On the CT scan, the anterior commissure (AC) is localized according to the method of Laitinen and coworkers1 on a slice lying 4 mm ventral to the ventralmost margin of the foramina of Monro. If the scanning plane is parallel to the intercommissural line (ICL)—i.e., the transverse bars of the Stereoadapter are parallel to the ICL—the posterior commissure (PC) is seen on the same slice. If the scanning plane is not parallel to the ICL, adjacent CT/MRI slices of the area are studied in order to visualize the beginning of the aqueduct; the last slice before the appearance of the aqueduct is chosen to represent the level of the PC. This film copy is superimposed on that where the AC had been marked, and the position of the PC is transferred to the latter. Thus, the level of the ICL is determined in relation to the scan¬ ning level.3 The mean angulation between the transverse bars and intercommissural line is 0.75 degrees with a range of ± 7 degrees.7 The anatomic position of the brain target—be it the ventro¬ lateral thalamus, the posteroventral pallidum, or the anterior in¬ ternal capsule, etc.—can now be plotted on the appropriate CT/MRI slice in relation to the AC and PC. Then, the coordi¬ nates of the target point are measured in relation to the refer¬ ence structures of the Stereoadapter (Fig. 8-6). The y coordi¬ nate of the target is its distance from the interaural plane of the Stereo-adapter. The x coordinate is measured in relation to the sagittal midplane of the Stereoadapter, formed by projecting the frontal laterality indicator pin perpendicularly onto the in¬ teraural line. The z coordinate is the distance between the target level and the level of the second pair of transverse bars. In rou¬ tine procedures, calculation of the functional brain target coor¬ dinates on either CT or MRI scans lasts for 5 to 10 min. Surgery The surgery may be performed at convenience after the CT/MRI study. The Stereoadapter is remounted on the head. The base ring of Laitinen’s Stereoguide is mounted around the Stereoadapter fairly parallel to its transverse bars. By means of two adjustable lateral support components, the base ring is so positioned that it lies as symmetrically as possible in relation to the Stereoadapter. Under local anesthesia, the base ring is rigidly fixed to the skull by means of four percutaneous pins. The patient is placed on the surgical table. The cylinder compo¬ nents of the Stereoguide are mounted on the left and the right sides of the base ring. Plastic cylinder blocks with axial steel

92

Part 1/Stereotaxic Principles

pins are introduced through the cylinders, which are moved into such a position that the steel pins point to the y and z ori¬ gins of the Stereoadapter—i.e., to the intersection of the second transverse bar and the anterior margin of the posterior ear arm. In this way, the y and z origins of the Stereoadapter are trans¬ ferred to the cylinder components, and recorded on the corre¬ sponding millimeter scales of the Stereoguide (Fig. 8-4). The CT coordinates y and z of the surgical target are then added to the y and z readings of the Stereoadapter’s origin, after which the cylinder components of the Stereoguide are positioned ac¬ cording to the sum. Thus the steel pins of the cylinder blocks point to the brain target, the y and the z coordinates of which are read on the millimeter-scales of the Stereoguide. The semi¬ circular arc of the Stereoguide is mounted to the cylinder com¬ ponents. The electrode carrier on the arc is moved into a 90° position. The surgical probe is directed toward the frontal pin (Fig. 8-4). The position of the pin is recorded on the lateral mil¬ limeter scale of the cylinder components. Then the CT x value of the target is added to the recorded position of the frontal pin; the sum is the final stereotactic x coordinate. The arc is moved into this position. The Stereoadapter is then detached, and the surgery may proceed as usual.3 Remote postoperative imaging studies The noninvasive Stereoadapter permits a stereotactic imaging study to be performed months after surgery for control of the fi¬ nal size and site of the stereotactic lesion.13 This unique feature is of outmost importance, since a remote postoperative imaging study may show the final shape of the lesion after the complete resolution of postoperative edema (Fig. 8-7). The stereotactic

imaging study is performed in a manner similar to the preoper¬ ative study. In this way the lesion can be accurately assessed in relation to the preoperative target point and in relation to the reference structures of the third ventricle (Fig. 8-7). Since the Stereoadapter’s position on the head will be the same postoperatively as it was pre- and intraoperatively, an exact radiological correlation between pre- and postoperative scanning can be made.13 In cases where a permanent electrode for chronic elec¬ trical stimulation had been implanted in the brain, a plain x-ray performed in a stereotactic manner with the Stereoadapter re¬ mounted to the head provides a stereotactic control of the exact position and coordinates of the electrode tip at any time after the surgery.

CONCLUSIONS The Laitinen system is based on stereotactic imaging using the noninvasive Stereoadapter. The Stereoadapter is not individual¬ ized and fits most heads.2 The reference structures of the Stereoadapter lie extremely close to the head and therefore to the target, which is a unique feature of this system. Calculation of target coordinates can be done easily and quickly by using the inherent software of the CT/MRI machine or manually with a ruler, an ink pen, and a minicalculator. The noninvasive design permits flexible and rational plan¬ ning of different diagnostic and therapeutic stereotactic proce¬ dures. The technique obviates the need for surgery inside the CT machine. Patients can be operated on or irradiated when suitable for them, the surgeon, the radiotherapists, and the in¬ volved staffs.

Figure 8-6. CT and MRI scans of one patient performed on consecutive days. Both scans are 2 mm thick at a dorsoventral level 4 mm ventral to that of the anterior commissure-posterior commissure line and at the level of the second dorsalmost transverse bars of the Stereoadapter. The left posteroventral pallidal target is indicated by an encircled dot.

Chapter 8/The Laitinen Apparatus

93

Figure 8-7. Preoperative and remote postoperative stereotactic CT scans of one patient. On the left scan, which is 2 mm thick, the preoperative pallidal target is indicated by a dot (arrow). The right scan, performed 4 months after surgery, represents the superposition of two contiguous, 2-mm-thick CT slices of the same area. The pallidal radiofrequency lesion is thus enhanced.

For brain biopsy, there is no need for an additional frame, since the Stereoadapter as such also functions as a probe car¬ rier. This simplifies the procedure and markedly reduces the duration and costs of surgery. For stereotactic open resection of small brain tumors, the Stereoadapter does not interfere with the craniotomy, since it is removed from the head once the po¬ sition of the tumor has been indicated on the scalp or by a catheter. The reproducibility of results from the noninvasive Stereoadapter permits an accurate repositioning of the brain target into the isocenter of the linear accelerator for fractiona¬ tion of stereotactic irradiation. Furthermore, the use of the Stereoadapter for target localization can be combined with a neurosurgical navigation system by providing relocatable Cartesian references.14 A great advantage to the patient in functional stereotaxy is the avoidance of ventriculography.15’16 The accuracy of the method permits a functional stereotactic procedure to be car¬ ried on with minimal side effects and short hospital stays.16’17 The noninvasive Stereoadapter makes possible a remote post¬ operative stereotactic CT study for checking the site and the size of the final radiofrequency lesions and also for assessing the accuracy of the whole stereotactic procedure.2,3’13 It is important to keep in mind that the noninvasive fixation of the Stereoadapter to the head requires good cooperation of the patient unless sedation is used.2 The pressure exerted by the earplugs on the external auditory meatus and by the nasion sup¬ port on the bridge of the nose, although generally well toler¬ ated, may be uncomfortable to some patients. Besides, the non-

invasivity calls for great care on the part of the surgeon in mounting the frame, positioning the patient, and closely super¬ vising the scanning or irradiation procedure. Through 10 years of intensive use on more than one thou¬ sand patients for all stereotactic imaging, surgical, and radiotherapeutic procedures, it is felt that the Laitinen system has been versatile, reliable, easy to use, time-saving, and inexpen¬ sive. The lack of sophistication and simplicity of the system have been experienced as an advantage rather than an inconve¬ nience. However, as in any system, the surgeon should be well acquainted with it and learn to profit from its advantages while avoiding its pitfalls.

References 1.

Laitinen LV, Liliequist B, Fagerlund M, Eriksson AT: An adapter for computed tomography-guided stereotaxis. Surg Neurol 23:559-566, 1985.

2.

Hariz MI: A Non-Invasive Adaptation System for Computed Tomography—Guided Stereotactic Neurosurgery. Thesis. Umea University Medical Dissertations, New series no 269, ISSN 0346-6612. Umea, Sweden: Umea University Printing Office, 1990. Hariz MI: Clinical study on the accuracy of the Laitinen’s non-invasive CT-guidance system in functional stereotaxis. Stereotact Fund Neurosurg 56: 109-128, 1991.

3.

4. 5.

Hariz MI, Eriksson AT: Reproducibility of repeated mountings of a non¬ invasive CT/MRI stereoadapter. Appl Neurophysiol 49:336-347, 1986. Bergenheim AT, Hariz MI, Henriksson R, Lofroth P-O: Fractionated stereo¬ tactic irradiation of brain tumors and arteriovenous malformations using the linear accelerator and a non-invasive frame, in Lunsford LD (ed): Stereotactic Radiosurgery Update. New York: Elsevier, 1992, pp 73-75.

94

6. 7.

8.

9. 10.

11.

Part 1/Stereotaxic Principles

Laitinen LV: The Laitinen System, in Lunsford LD (ed): Modern Stereotactic Neurosurgery. Boston: Martinus Nijhoff, 1988, pp 99-116. Hariz Ml, Bergenheim AT: A comparative study on ventriculographic and computed tomography-guided determinations of brain targets in functional stereotaxis. J Neurosurg 73:565-571, 1990. Hariz MI, Bergenheim AT, DeSalles AAF, et al: Percutaneous stereo¬ tactic brain tumor biopsy and cyst aspiration using a non-invasive frame. Br J Neurosurg 4:397-406, 1990.

12.

Hariz MI, Henriksson R, Lofroth P-O, et al: A non- invasive method for fractionated stereotactic irradiation of brain tumors with linear ac¬ celerator. Radiother Oncol 17:57-72, 1990.

13.

14.

Hariz MI: Correlation between clinical outcome and size and site of the lesion in CT-guided thalamotomy and pallidotomy. Stereotact Fund Neurosurg 54/55:172-185, 1990. Takizawa T: Neurosurgical navigation using a noninvasive Stereo¬ adapter. Surg Neurol 40:299-305, 1993.

Hariz MI, Fodstad H: Stereotactic localization of small subcortical brain tumors for open surgery. Surg Neurol 25:345-350, 1987. Nguyen J-P, Decq P, Brugieres P, et al: A technique for stereotactic aspiration of deep intracerebral hema-tomas under computed tomo¬ graphic control using a new device. Neurosurgery 31:330-335, 1992.

15.

Hariz MI. Bergenheim AT: Clinical evaluation of CT-guided versus ventriculography-guided thalamotomy for movement disorders. Acta Neurochir Suppl 58:53-55, 1993.

16.

Laitinen LV, Bergenheim AT, Hariz MI: Leksell's posteroventral pal¬ lidotomy in the treatment of Parkinson’s disease. J Neurosurg 76:53-61, 1992.

Delannes M. Daly NJ. Bonnet J, et al: Fractionated radiotherapy of small inoperable lesions of the brain using a non-invasive stereotactic frame. Int J Radiat Oncol Biol Phys 21:749-755, 1991.

17.

Hariz MI, Bergenheim AT. Fodstad H: Air-ventriculography provokes an anterior displacement of the third ventricle during functional stereotactic surgery. Acta Neurochir 123:147-152. 1993.

CHAPTER

9

THE TODD-WELLS APPARATUS

Trent H. Wells, Jr., and Edwin M. Todd

In 1947, Trent Wells, an ex-World War II fighter pilot, was founding an engineering company in a garage in South Gate, California, and Edwin Todd, an ex-army sergeant and veteran of the North African and Italian campaigns, was majoring in English at Temple University. In the same year, Spiegel and Wycis sparked the neurosurgery community with the introduc¬ tion of human stereotaxy.1 For different reasons and in contrasting styles, these future collaborators marked the event and pursued a continuing inter¬ est. By a curious coincidence, without actually meeting, both became involved with the work of Jack French and Horace Magoun at the time they were elaborating the reticular forma¬ tion. Wells worked on developing an animal stereotactic instru¬ ment in California, while Todd, an inquisitive intern and resi¬ dent, was making a nuisance of himself but grudgingly being allowed by French to clean up electrode infections in animals and perform other menial tasks in the laboratory. Finally, to rid himself of the meddlesome kibitzer, French picked up the tele¬ phone and made a call that persuaded W. James Gardner to ac¬ cept Todd in the residency program at the Cleveland Clinic. While Wells steadily broadened his innovative stereotactic technology at Long Beach V.A. Hospital and UCLA, Todd be¬ came absorbed in the management of disorders of motion, us¬ ing the Cooper instrument, the Gillingham-Guiot apparatus (briefly), and then a series of very simple burr-hole protractor devices which, in skilled hands, achieved superior results com¬ pared with many of the more decorative contrivances relying on atlas coordinates.2 Unfortunately it was an acquired skill at a time when mortality and morbidity were high, and later (that is, by the late 1950s) these procedures were considered too deadly for resident participation. It was an era when the technology of microelectrodes, radiofrequency, radiological adaptation, and stereotactic precision instrumentation was making rapid progress, and harpooning techniques, however refined, were becoming obsolete. Empirical success with crude methodolo¬ gies that could no longer be taught was actually impeding the progress of stereotaxy.

THE PRINCIPLES What was specified by the surgeon was simple enough in con¬ cept—an instrument system capable of delivering a probe with pinpoint accuracy to anywhere in the head or neck from any di¬ rection. This would require arc systems movable in the pa¬ tient’s vertical axis, biplane x-ray equipment, and a head holder that could move the head in the anteroposterior (AP) and lateral directions relative to the arc systems so that a target could be brought to the epicenter of the arc systems. The portable model instrument developed by these investigators filled these specifi¬ cations and also provided head rotation about the patient’s lon¬ gitudinal axis. Later, a specification change was made to allow the arc systems to be located in the operating room, so that xray sources could also be fixed in the room, while the head holder provided true three-axis movement relative to the arcs. The transverse arc system had been developed previously for the Rand-Wells hypophysectomy guide and was incorpo¬ rated as one of the arc systems in the Todd-Wells instrument. With a cross-and-ring reticule (from fighter aircraft gunsights) on each side of the instrument, the central x-ray beam could easily be aligned with the axis of the arc. To give the vertical arc the same capability, a pair of Lucite reticules was provided with the same cross-and-ring sights, located exactly the same distance from the midline of the instrument on the axis of rota¬ tion of the vertical arc. As both arc systems were of the “arc-centered” type, the tar¬ get to be approached had only to be positioned on the axis of the arc, on the midline, and a probe could be directed to it from any direction in the available hemisphere, always the same dis¬ tance from a reference surface. This concept was developed in an instrument featuring a fixed and constant focal point. Two x-ray tubes are arranged at right angles, forming AP and lateral extensions of the unit, with beams aligned to converge at the focal point of the instrument (Fig. 9-1). In the ideal situation, the instrument and orthogonal tubes are permanent installations, but collimation devices facil¬ itate rapid alignment in any operating theater. Inset A in

It was at this time, in the early 1960s, that the fortuitous meeting of a prospective stereotactic surgeon and a highly mo¬ tivated stereotactic apparatus inventor occurred; the former knew what he wanted, but not how to get it and the latter had the experience and engineering ingenuity to turn seminal ideas into reality.

Fig. 9-1 demonstrates the multidirectional movement capabil¬ ity of the head holder, which firmly transfixes the anatomic part in which the target lies. When the target is precisely identified with x-rays, it is moved with microscopic exactness to super¬ impose upon the focal point. A free choice of access options is

95

96

Part 1/Stereotactic Principles

PREFIXED X RAY SOURCE

ANATOMICAL TARGET FOCAL POINT

PREFIXED X RAY SOURCE

X RAY FILMS

Figure 9-1. Diagrammatic representation of concept underlying the procedures described in the text.

provided along infinite radii from the target, which is now cen¬ tered within a spherical area. The modus operandi from this stage depends upon the particular problem and the purposes of the operator. The Todd-Wells instrument was the first modular human stereotactic device because it had two interchangeable arcs having a common arc center, permitting approaches to all parts of the head or neck from any direction.3

THE INSTRUMENT A portable instrument was, by dint of necessity, the prototype model, owing to the exigencies of an itinerant practice that in¬ cluded a university hospital, the City of Hope, and several pri¬ vate hospitals. This presented the problem of differing operat¬ ing room configurations that did not permit the ideal fixed alignment of tubes. Accordingly, image enlargement factor scales were devised to accommodate the differences.4 The problem of measurability of magnification in films used in stereotaxis was overcome with the Todd-Wells instrument, because in the lateral view, the target was always placed on the midline of the instrument, the film was always the same dis¬ tance from the midline, and—if the distance from the x-ray source to the midline was known—a correction factor scale could be made for making measurements on the developed film. For the AP view, the target was always placed at the same

height from the base plate as the arc center, and, as the film was placed on the base plate, it was always the same distance from the target, which was, however, not necessarily identical to the lateral target-to-film distance. Then, if the distance from the arc center to the AP x-ray source was known, a correction factor scale could be made and used for making direct measurements on the AP film. Following a program of clinical utilization intended to in¬ clude as many different applications as possible, although pre¬ dominantly the standard approach for parkinsonism, the appa¬ ratus was formally introduced at the International Neurological Surgery Meeting in Copenhagen in 1965. In Fig. 9-2, a blue ribbon committee of internationally known neurosurgeons (Walker of the United States, Busch of Denmark, and Northridge of Great Britain) is seen inspecting the Todd-Wells portable apparatus. Clinical success led to fi¬ nancial support from institutions where stereotaxy was prac¬ ticed. When it became possible to install permanently placed orthogonal x-ray tubes at optimal distances from the focal point of the instrument, it was time to consider a pedestal-based ap¬ paratus that could be permanently fastened to the floor or, where this was impractical, to obtain fixation by using a vac¬ uum system (Fig. 9-3). In these fixed systems, only one correction factor scale had to be provided for the lateral x-ray tube and one for the AP tube. Although these installations were considered permanent, it was considered good practice to verify collimation prior to each use, especially in earthquake-prone areas.

Chapter 9/The Todd-Wells Apparatus

97

Figure 9-2. Todd-Wells exhibit in Copenhagen, 1965.

APPLICATIONS Versatility was an essential quality of the instrument. This notwithstanding, by far the greatest application was in the man¬ agement of movement disorders, where attention focused on the thalamus. Nevertheless, it was a period—the 1960’s—of prodigious growth and development in stereotaxy, and a robust spirit of inquiry produced new ideas that rapidly shaped the clinical experience. Figure 9-4 illustrates the three principal adaptations of the Todd-Wells apparatus to these exciting chal¬ lenges. The encephalotomy position allowed access to all supratentorial areas for whatever purpose, and deeper probes could easily access the upper brainstem, as in the case of peri¬ aqueductal studies for pain problems. Our personal experience ranged from thalamotomy to amygdalotomy and cingulotomy, and much of our time was oc¬ cupied with emergency measures for the removal of foreign bodies. It was much less traumatic to remove a bullet or indriven bone fragament stereotactically than by other means. Ingenious applications by adventurous neurosurgeons else¬ where included the placement of multiple depth electrodes,5 electrothrombosis ot intracranial aneurysms,6 and metallic thrombosis of intracranial aneurysms,7 matters described in es¬ oteric detail in the literature of the time (see Ref. 8). The hypophysectomy position owed much to the work of Talairach,'* Rand,10 Zervas," and others unknown to the au¬ thors. We used this approach with radiofrequency lesion mak¬ ing for diabetic retinopothy, acromegaly, and metastatic cancer of the breast and prostate; as well as for biopsy of lesions in the areas of the sphenoid sinus and clivus and occasionally for evacuation of parasphenoidal mucoceles.12

Figure 9-3. The Todd-Wells stereotaxy instrument, naked and adorable.

Following a path worn by the experiences of Mullan,13 Rosomoff,14 and Lin15 in percutaneous cordotomy, Crue and coworkers16 extended alternatives with a posterior entry, as shown in Fig. 9-3, which dealt more favorably with the devious propensity of the cord to bob, shift, and twist away from the

98

Part I/Stereotactic Principles

ENCEPHALOTOMY

Figure 9-4. Illustrates the versatility of the instrument through a broad spectrum of applications.

impaling needle electrode. In a limited series, posterior percu¬ taneous cordotomy led to a rather tentative and limited series of percutaneous trigeminal tractotomies, but obvious hazards of the technique limited enthusiam and discouraged adequate pur¬ suit of this practice.17 We were indebted to many stereotactic surgeons from wide¬ spread areas of the world for a true picture of the enormous versatility of the instrument in the wild 1960s. Once comfort¬ able with the unit, the surgeon could use it to solve problems never dreamed of by its inventors. McFadden18 found it effec¬ tive for the reduction of cervical fracture dislocations and for employment in other techniques for the extraction of foreign bodies in the hands, elbows, and feet;19 Mason20 and, in unre¬ lated instances, others integrated the Todd-Wells unit into portable assemblies of stereotactic, x-ray, and lesion-making systems. Horizons were broad and the spectrum of activities was vast; therefore we vigorously applied our energies to the problems of our age with some measure of success.

EPILOGUE But time, a patient predator, Will always have its way, And like the noble dinosaur, The Todd-Wells had its day.

References 1. 2. 3. 4.

Spiegel EA, Wyeis HT, Marks M. l.ee AJ: Stereotaxic apparatus for operations on the human brain. Science 106:349, 1947. Todd EM. Shelden CH, Pudenz RH, Crue BE: Surgical management of diskinesia. Am J Sttrg 102: 265, 1961. Todd EM: Manual of Stereotaxic Procedures. South Gate. CA: Mechanical Developments Co., 1967 (privately published). Todd EM, Crue BE: An image enlargement scale for stereotaxic surgery. Am J Roentgenol Radiat Titer Nucl Med 105:270, 1969.

Chapter 9/The Todd-Wells Apparatus

99

5.

Crandall PH: Current UCLA stereotaxic techniques for implanta¬ tion of multiple electrode arrays and the results in stereotaxic accuracy. (Publication pending as of 1972; illustrated in Ref. 8, pp 23-25.)

13.

Mullan S, Harper PV, Hekmatpanah J, et al: Percutaneous interrup¬ tion of spinal pain-tracts by means of a strontium-90 needle. J Neurosurg 20:931, 1963.

14.

6.

Mullan S, Raimondi AJ, Dobben G, et al: Electrically induced throm¬ bosis in intracranial aneurysms. J Neurosurg 22:539, 1965.

Rosomoff HL, Carroll F, Sheptak P: Percutaneous radiofrequency cervical cordotomy: Technique. J Neurosurg 23:639, 1965.

15.

7.

Alksne JF: Stereotaxic thrombosis of intracranial aneurysms. N Engl JMed 284:171, 1971.

16.

8.

Todd EM: Stereotaxy—Procedural Aspects. South Gate, CA: Trentwells, 1972.

17.

9.

Talairach J, Szikla G, Tournoux PB, Bancaud J: La chirurgie stereotaxique hypophysaire. Confin Neurol 22:204, 1962.

Lin PM, Gildenberg PL, Polakoff PP: An anterior approach to percu¬ taneous lower cervical cordotomy. /Neurosurg 25:553, 1966. Crue BL, Todd EM, Carrigal EJA: Posterior approach for high cervical percutaneous radiofrequency cordotomy. Confin Neurol 30:41, 1968. Crue BL, Todd EM, Carrigal EJA, Kilham O: Percutaneous trigemi¬ nal tractotomy (case report) utilizing stereotaxic radiofrequency le¬ sion. Bull LA Neurol Soc 32:86, 1967.

10.

Rand RW: Stereotactic transsphenoidal cryohyphosectomy. Bull LA Neurol Soc 29:40, 1964.

18.

McFadden JT: Stereotaxic realignment of the dislocated cervical spine. Surg Gynecol Obstet 133:262, 1971.

11.

Zervas NT: Technique of radiofrequency hypophysectomy. Confin Neurol 26:157, 1965.

19.

McFadden JT: Stereotaxic pinpointing of foreign bodies in the limbs. (Illustrated in Ref. 8, pp. 37-39).

12.

Todd EM: Sphenoidotomy for mucocele, in Stereotaxy—Procedural Aspects. South Gate, CA: Trentwells, 1972, pp 45-46.

20.

Mason MS: Personal communication. (Illustrated in Ref. 8, pp 57-58.)

CHAPTER

1 0

THE HITCHCOCK APPARATUS

Colin Shiejf

Edward Hitchcock was innovative. On the basis of a great per¬ sonal knowledge of neuroanatomy and physiology and with an awareness of the developing field of functional neurosurgery, he conceived of the idea of percutaneous high spinal stereotac¬ tic commissural myelotomy in the 1960s. This procedure re¬ quired a stable, reliable, and versatile stereotactic frame that would permit access below the plane of the frame itself.12 In essence, he invented a target-centered arc system with a flat base ring employing simple cartesian coordinates. Over the next three decades he refined and developed the system that bears his name, enabling it to be used for a wide variety of in¬ tracranial procedures.3

capable of all that is expected of a stereotactic apparatus. Current usage includes functional procedures and biopsy both above and below the tentorium and in the upper cervical spine, implantation of electrodes and dopaminergic tissue for Parkinson’s disease, the removal of foreign bodies, multistage real-time clipping of “inoperable” cerebral arteriovenous mal¬ formations, as a platform for open craniotomy performed on image-directed stereotactic coordinates, and in the planning and therapy stages of external-beam stereotactic radiosurgery with a linear accelerator. In conventional radiography, target coordinates are obtained by direct reading from the radiopaque ruler; in stereotactic CT or MRI scanning, the coordinates are read directly from the video display unit without further calculation.

Ideally, any stereotactic instrument should be extremely accurate and practical in any position yet simple to use to minimize operator error. In the days when stereotaxy was lim¬ ited to functional procedures using contrast ventriculography, many systems required expensive additional equipment for fixed-beam radiography or image intensification. In contrast, the Hitchcock frame required only a simple standard portable x-ray machine. After minimal modification it remains equally suited to computed tomography (CT) and magnetic resonance imaging (MRI) scans and cerebral angiography and is still

THE APPARATUS: COMPONENTS AND USE The use of this system is probably best described, where rele¬ vant, in relation to its component parts (Fig. 10-1), although it

Figure 10-1. Photograph of the complete frame assembly showing (A) the square with millimeter markings, fixation pins, and extension pieces at each comer, (B) left side, the block holder with cylinder, arc, and electrode carrier, (Q front, a self-retaining retractor base, and, (D) posterior/right, cassette holder.

101

102

Part 1/Stereotactic Principles

is not the intention of this chapter to explain all the details. The major parts are as follows: 1. 2. 3. 4.

Square L-grid Grid and/or block holder Arc assembly, consisting of a cylinder, arc, and electrode

5. 6. 7. 8.

carrier Alignment plates Cassette holder Carrying case Stereotactic CT scan interface device (SCID)

The Square The characteristic and major component of the system is the square frame. The 15-mm2 cross-sectional plane hollow square (measuring 26 by 26 cm) was originally constructed from a sin¬ gle plate of anodized aluminum alloy without joints. It is now manufactured as a discontinuous square with one detachable relocating side attached rigidly via carbon fiber/nylon bushes and screws, permitting MRI compatibility. The outer surface of each side of the square is engraved at 1-, 5-, and 10-mm inter¬ vals from the midpoint of the side; this is the center of its hori¬ zontal plane. Either the top or the bottom edge of the square can be used for the vertical zero reference plane. Hitchcock preferred to use the bottom edge as zero, while this author uses the top edge as the reference plane in CT scan work and supra¬ tentorial functional procedures. Each corner and the center of one side (usually chosen as anterior) hold fixation pins of inter¬ changeable steel (for teleradiography) or CT-compatible alu¬ minum. Extension pieces of similar material can be attached to the inner aspect of the corners. The fixation pins are screwed through the scalp to the outer table of the skull, using interlock¬ ing but removable bolts, each of which carries a 2-mm scale; the depth of each bolt can be noted to allow subsequent repeat fixation. After skull fixation, the patient’s head and the square can lie on the operating table without external fixation, but it is more convenient, especially if the sitting position is used, to se¬ cure the square to the table with a standard fixation device such as the Mayfield clamp. This simple skull fixation facilitates “open” stereotactic procedures, including supratentorial craniotomy and posterior fossa exposures. Potential exposure can be increase^ with¬ out compromising stability by removing the detachable side, while laser beam systems can be attached directly to the arc and self-retaining retractors and instrument racks can be an¬ chored to points on the square or, in more recent developments, to the arc.

sectional L-shaped bar machined from a single aluminum plate without joints. Horizontal and vertical radiopaque engravings are at 1-, 5-, and 10-mm intervals from each respective zero point together with a radiopaque line along each of the two lon¬ gitudinal axes. The grid is usually fixed on the right or left side at zero (midpoint of the side of the frame) for an anteroposte¬ rior (AP) picture of the third ventricle, assuming that the third ventricle lies in the lateral plane. If a lateral radiograph reveals that it does not, the grid is replaced at the distance anterior or posterior to zero that corresponds, and another picture is taken. In practice, this is rarely necessary; even for targets that are very anterior or posterior, such as the pituitary fossa and the fourth ventricle, it usually is possible to estimate a good posi¬ tion for the L-grid fairly accurately. Accurate measurements are obtained directly from the image of the grid markings (see be¬ low) on the developed x-ray film. A line projected at right an¬ gles from the AP target to the horizontal ruler gives the lateral offset of the image (Zs). The grid is then fixed at this laterality and at the zero setting on the vertical arm of the grid. Lines projected at right angles to the horizontal and vertical rulers on the grid provide the AP (Xs) and superoinferior (Ys) coordi¬ nates (Fig. 10-2). When conventional radiography is used, simplicity is achieved by means of teleradiography, which reduces magnifi¬ cation (0.96 magnification factor at 3 m and 0.98 at 4 m). A ra¬ diopaque ruler (the grid) adjusted to the target plane makes ex¬ act centration unnecessary. The principle here is that with parallel rays, parallax affects all objects in the same plane as the target equally. Thus, the apparatus need not be set exactly at 90 degrees in relation to the x-ray source, since any obliquity or magnification in the target plane is mirrored exactly in the ruler. With the elimination of time-consuming centration and magnification correction, target coordinates are obtained di¬ rectly by projection of lines onto the radiopaque ruler. Shorterdistance radiography also can be used, in which case the mag¬ nification factor is determined from the radiopaque ruler, but in practice, teleradiography at 3 m has proved satisfactory. If the target is localized by a proportional system, such as two-thirds

In practice, the frame has been left attached to the skull for up to 5 days without problems, permitting staged biopsy, ther¬ apy planning, and radiosurgery. Placed routinely, it does not impede access to the face, obscure vision, or endanger the air¬ way. Despite its incongruity, patients do not have any problems in their normal daily activities when wearing it.

The L-Grid The use of an L-grid is essential in undertaking classical func¬ tional stereotaxy using ventriculography. This is a 2-cm2 cross¬

Figure 10-2. Lateral radiograph (thalamotomy) showing target construction from an operative ventriculogram using vertical and horizontal radiopaque markings on the L-grid.

Chapter 10/The Hitchcock Apparatus

along the anterior commissure-posterior commissure (AC-PC) line, or is directly visualized (foreign body), no correction is necessary.

Grid and/or Block Holder The grid and/or block holder fixes to any side of the square and is used to hold the vertical limb of the L-grid or the cylinder block of the arc assembly at the chosen horizontal or vertical plane. It can be mounted to carry the cylinder block projecting upward or downward according to the approach or trajectory required.

Arc Assembly The arc is attached to the rectilinear system so that the target point is at the center of the spherical system and can be ap¬ proached by any route. The cylinder block is secured to any side of the square by the grid and/or block holder. It is engraved at vertical 1-, 5-, and 10-mm intervals and at 5-degree intervals around the cylin¬ der mounting hole and is secured by the grid and/or block holder at the desired horizontal and vertical coordinates. The arc cylinder fits into the block and can be rotated 360 degrees. It is engraved along its length at 1-, 5-, and 10-mm intervals with numerals indicating the distance of the target from the square’s central zero. The quadrant arc is engraved in degrees and can be fixed to the cylinder at the selected horizontal and

Figure 10-3. Lateral radiograph showing electrode position at the target.

103

AP coordinate. Its eccentric cross section prevents incorrect at¬ tachment of the slide assembly. As the cylinder revolves, the quadrant describes a hemisphere at whose center is the target point. The slide assembly moves along the quadrant so that an instrument can be introduced through it along any trajectory. “Dead areas” are limited to the thickness of the square and can be avoided by fixing the square well above or below the pre¬ sumed target, a practice that also is necessary to obtain reliable CT scan coordinates. The assembly has a graduated electrode holder with a 0.1 -mm vernier scale advanced by a wheel-driven rack and pinion designed to accept a variety of commercial electrodes. Very fine electrodes are stabilized by cannulas and stops held in an extension arm. A transparent sighting rod with fiducial markings fits inside the cylinder. The length of an in¬ strument is checked by advancing it via the electrode carrier until its tip appears at the central point of the sighting rod; this may be further verified by a lateral radiograph (Fig. 10-3).

Alignment Plates The alignment plates are rectangular and are made of alu¬ minum alloy with a thin oblique fiducial. They fasten to the side of the square at selected heights and also are used to main¬ tain the square at a predetermined height for skull fixation when the SCID (see below) has been used. CT alignment is checked by squaring the pillars as they appear in sectional scans (Fig. 10-4). For large targets such as tumors, fixation to the CT is unnecessary after the head and square have been placed securely on the couch, using alignment beam centration. Coordinates are then obtained from the images by simple cal¬ culation. For more precise measurement, the square is fixed to the CT couch by a rigid attachment. The laser beam of the scanner is zeroed to the chosen vertical plane (upper/lower edge of the square), and the couch is adjusted until the horizon-

Figure 10-4. CT scan showing a superimposed grid confirming the coincidence of CT and stereotactic frame centers. Diagonals are drawn between the vertical limbs of the alignment plates.

104

Part 1/Stereotactic Principles

tal and vertical laser lights coincide with the midline zero point along each edge. The CT scan center and the stereotactic frame center then coincide; any offset can be identified and measured on the produced image, as all measurements relating to the stereotactic square are derived from the CT computer, even from reformatted images. Personal choice permits the transcription of coordinates in a number of ways. A hard copy of the diagnostic scan with super¬ imposed measurements provides a permanent record, while transparent templates with grid markings can be produced eas¬ ily for any degree of magnification if this is preferred. To avoid confusion in transcribing CT-generated coordi¬ nates to the stereotactic procedure, I insist that trainees refer to actual cartesian coordinates by distance and direction from their declared reference plane (e.g., “48 mm right, 15 mm ante¬ rior, 6 mm above”) (Fig. 10-5).

Cassette Holder The cassette holder is required only with teleradiography. It can be attached to any side of the square and is adjustable to vari¬ ous heights. It is arranged so that for lateral radiography the horizontal and vertical portions of the L-grid appear on the film.

Carrying Case All components are secured in an aluminum alloy case with ad¬ justable vents for gas or autoclave sterilization. Gas steriliza¬ tion is recommended, but these instruments have been steril¬ ized by autoclaving many times without damage. After sterilization, the vents are closed and the instrument is ready for use. Our current practice is to keep the square sterile and packed separately for application in the x-ray or scan depart¬ ment unless the SCID (see below) is used before the definitive procedure.

Figure 10-5. CT scan showing target coordinates obtained directly 48 mm right (from common center), 15 mm anterior (from common center), and 6 mm above the top of the frame (slice height).

with adjustment for height. The device permits outpatient and repeat scanning, eliminating the need to use the square or pin fixation. Adapters for MR1 and angiographic localization are now available and perform in a similar fashion to those for other systems.

POSTSCRIPT SCID SCID was developed primarily because of the impossibility of scanning patients on first-generation scanners with the stereo¬ tactic device in place. The initial version was basically an in¬ complete angled base closely applied to the patient’s head with nasion and earplugs; the original alignment plates were mounted on this structure and were passed into the scan aper¬ ture. At that time target coordinates were derived (often by this author) using elementary computer-driven statistical packages from individual images on the visual display unit (VDU); this could take as long as 1 h, during which time the machine was not available for routine use. Later machines are capable of ac¬ cepting the full-size frame and provide coordinates, trajecto¬ ries, and measurements directly by using graphics. The stereotactic CT scan interface device can be temporar¬ ily fixed to the head by nasion rests and meatal plugs, although skull fixation is also possible. The meatal and nasion measure¬ ments are noted, and the device is fixed to the CT couch. After the scanner alignment beams have been zeroed to the SCID, XYZ coordinates can be transcribed to the stereotactic square

Approximately 15 years ago. Hitchcock wrote of the frame that bears his name, “the design and construction make this one of the most accurate, adaptable and simplest of modern stereotac¬ tic instruments.” That it remains in daily use in Europe, Africa, Central and South America, and Asia bears witness to the truth of his words. He was professor of neurosurgery at the University of Birmingham when he died suddenly in his hospital in December 1993. He is missed by all who knew him as a friend, a teacher, or a doctor.

References 1. 2. 3.

Hitchcock E: An apparatus for stereotactic spinal surgery, Lancet 1:705-706, 1969. Hitchcock E: Stereotaxic spinal surgery: A preliminary report. J Neurosurg 31:386-392, 1969. Hitchcock E: The Hitchcock system, in Lunsford LD (ed): Modern Stereotactic Neurosurgery. Boston: Martinus Nijhoff. 1988, pp 47-61.

CHAPTER

11

THE PATIL APPARATUS

Arun Angelo Patil

Although computed tomography (CT) and magnetic resonance imaging (MRI) are two-dimensional, scanner computers pro¬ vide three-dimensional information with a direct readout of all three coordinates. In addition, these scanners can reformat im¬ ages in the coronal, sagittal, and other planes so that a trajec¬ tory can be visualized in different planes. The Patil'-3 stereotac¬ tic system enables surgeons to obtain stereotactic coordinates directly from a scanner computer without the need for addi¬ tional computers.

DESCRIPTION AND METHOD The Patil system is a center-of-arc system (Fig. 11-1) that con¬ sists of a base plate, a head holder, two side stanchions with pivot blocks, a yoke, an arc, and a probe holder. The radius of the arc is 21 cm. The calibrations for the coordinates are on ei¬ ther side of the base plate (Z coordinate), on the side stanchions (y coordinate), and on the horizontal part of the yoke (X coor¬ dinate). The top surface of the base plate is zero for the Y coor¬ dinate, and the midline marker on the base plate is zero for the X coordinate. The base plate is mounted parallel and perfectly horizontal to the scanner table, using a table interface. The head holder is fixed to the base plate, and the patient’s head is fixed in the head holder. The standard (Watt’s) head holder in this system has four pin holders (Fig. 11-2). An op¬ tional C-shaped head holder is also available (Fig. 11-1). The head pins are attached to the head in a plane that is not in the plane of the target. The approximate plane of the target can be determined by reviewing preoperative scans. A side stanchion with a localizer in the pivot block is then attached to one of the sides of the base plate at the zero (Z-zero) position (Fig. 11-3). The scanner table is then moved to align the vertical laser light of the scanner with the center marker on the localizer. This po¬ sition is then set as the zero table position for scanning. Contrast is injected, and a scout image is obtained. On the scout view (Fig. 11-4), the center marker on the localizer is vis¬ ible. The marker should be on the same vertical line as the zero scan position, and this indicates that the scanner zero for Z is the same as that for the stereotactic frame. If there is an error, the amount of error is noted and necessary corrections are made. Vertical CT images are obtained in the area of the target. On one of these images, the target is chosen. The scan position (Fig. 11-5A) for the target is the stereotactic Z coordinate for

105

Figure 11-1. The frame is mounted on the CT table. The head is fixed in a C-shaped head holder with the patient supine. Arrow = midline marker; B = base plate; H = head holder; S = side stanchion; P = pivot; Y = yoke; A = arc; PR = probe holder.

the target, since the Z coordinate for the scanner is the same as that for the stereotactic frame. A vertical line (Y coordinate) is drawn from the target to the top surface of the base plate, using the cursor. A horizontal line (X coordinate) is drawn from the vertical line to the midline marker. The scanner automatically

106

Part 1/Stereotactic Principles

Figure 11-2. Patient in prone position. The probe is in a posterior fossa tumor. Arrow points to the Watt’s head holder.

Figure 11-3. The side stanchion is moved to the zero position on the base plate (arrow). The localizer (L) is in the pivot block (PB). Arrowhead points to the center marker.

reads out both of these distances. Then the trajectory is drawn, and the scanner reads out the angle of the trajectory. This angle is the coronal angle of the trajectory. An off-axis reconstruction is performed in the plane of the trajectory; the trajectory is drawn on the reconstructed image (Fig. 11-5#). The computer displays the angle, which is the sagittal angle of the trajectory. If indicated, images perpendicular to the trajectory are refor¬

form the procedure in the operating room, the frame is discon¬ nected from the scanner interface and the patient is taken to the operating room while in the frame. On the operating table, the base plate serves as a support stand for the system. The procedure can then be performed through a small drill hole, burr hole, craniectomy, or craniotomy. The drill hole is made through the probe holder with a Steinmann pin with the shaft diameter of the pin equal to that of a 12-gauge needle. The length of the Steinmann pin during drilling is equal to the length from the proximal end of the probe holder to the surface of the bone plus 5 to 8 mm. When the procedure is performed on the CT table, intraoperative scans are obtained to confirm accurate probe placement (Fig. 11-5E).

matted (Fig. 11-50The Z coordinate is adjusted by moving the side stanchions. The Y coordinate is adjusted by moving the pivot blocks to the required height. A localizer is placed in the pivot block, and a scan is obtained in the plane of the target. Accurate Y and Z co¬ ordinate adjustments4 are confirmed (Fig. 11-5D) by the pres¬ ence of the center marker of the localizer on the same horizon¬ tal line and image as the target. The yoke is then attached to the pivot block at an angle equal to the sagittal angle of the trajectory. The X coordinate is adjusted by moving the arc on the yoke. The probe holder is placed on the arc at an angle equal to the coronal angle of the trajectory. If the surgeon wants to approach the target through a preexisting hole in the skull, necessary changes are made in the angles of the yoke on the pivot and the probe holder on the arc. After the coordinates are measured, the procedure can be performed on the CT table or in the operating room. To per¬

ACCURACY The system had an accuracy of 0.5 mm for the X and Y coordi¬ nates and 0.7 mm for the Z coordinate with a 1.5-mm scan thickness in a phantom study. Intraoperative scans were ob¬ tained in over 350 procedures. In 10 cases the probe tip was oil the target by 1 mm. and in all other cases it was on the target point. The inaccuracies in the 10 off-target cases were due to a

Chapter 11/The Patil Apparatus

107

Figure 11-4. Scout view shows that the center marker of the localizer {arrow) is on the same vertical line as the zero point {arrowhead).

bend in the probe or technical errors. In all these cases, the errors were corrected and accurate probe placement was achieved.

eral position is used. For a transnasal or transoral approach, the supine position is used. When the patient is positioned prone (Fig. 11-2), bolsters are placed under the chest.

POSITIONS

STEREOTAXIS WITH MRI

The procedure can be performed in the prone, supine, or lateral position. The supine position is used for most supratentorial le¬ sions. For occipital and posterior fossa lesions, the prone or lat-

An oil capsule in the base of the Watt’s head holder is the refer¬ ence marker and marks the stereotactic zero point (Fig. 11-6A). Long head pin holders and stabilizing plates are attached to the

Figure 11-5. A. A tumor in the pineal area. The scan position (Z coordinate) is displayed in the left upper corner {arrow). Line 1 = Y coordinate line; line 2 = X coor¬ dinate line; line 3 = trajectory. At the bottom of the picture, distance 1 = Y coordinate; distance 2 = X coordinate; angle (56 degrees) in front of distance 3 = coronal angle of the trajectory. B. Off-axis reconstruction in the plane of the trajectory. The line represents the trajectory. The angle (51 degrees) displayed at the bottom of the picture is the sagittal angle of the trajectory. C. Reformatted images perpendicular to the trajectory. D. The center marker in the localizer block (arrow) is on the same horizontal line and image as the target (arrowhead). E. Intraopera¬ tive scan shows the needle tip on the target (arrow). A

Part 1/Stereotactic Principles

108

B

D

C Figure 11-5. (continued)

head holder. The base of the head holder and the patient's head with the head pins attached are inserted into the head coil (Fig. 11-6fi). The capsule is visible on the sagittal MRI image (Fig. 11-6Q, and the scanner coordinates for this point are ob¬ tained by placing a cursor on it. The cursor is then placed on

E

Chapter 11/The Patil Apparatus

sagittal image to obtain the scanner coordinates. The scanner coordinates for the target minus those for the zero point equal the stereotactic coordinates for the target. The plus sign and mi¬ nus sign of the coordinates are taken into account during sub¬ traction. Note that R is +X, L is -X, A is + Y, P is - Y, S is +Z, and I is —Z. After scans are obtained, the head holder is at¬ tached to the base plate with the center of the oil capsule at the stereotactic zero point. When this technique is used and a cap¬ sule with the appropriate isotope is placed at the stereotactic zero point, coordinates on positron emission tomography im¬ ages can be obtained.

APPLICATION The system is used for (1) biopsy,5’6 (2) craniotomy,7"9 (3) thala¬ motomy,10 (4) linear accelerator radiation,11 (5) seizure surgery,12 including the placement of depth electrodes, and radiofrequency lesioning of the amygdala-hippocampal complex and corpus cal¬ losum, (6) brachytherapy,5 and (7) aspiration of cysts, abscesses, and hematomas. During brachytherapy, the shape of the cursor on CT or MRI is configured to the area of radiation that would be delivered by the radionuclide and placed over the target. The coordinates for the center of this area are obtained (Fig. 11-6D).

109

After the needle is placed at the target, scans are obtained to confirm accuracy before deposition of the radionuclide. During craniotomy, the scanner computer is used to reformat images perpendicular to the trajectory (Fig. 11-50 and a special adap¬ tor is used to place the microscope along the trajectory7"9 (Fig. 11-7).

DISCUSSION Because this is a center-of-arc system, infinite trajectories are possible. The coordinates are obtained directly from the scan¬ ner computer, eliminating the need to purchase another com¬ puter. There is no transfer of information from one computer to another, eliminating the risk of error during the transfer of in¬ formation. The apparatus can be used in the CT room or operat¬ ing room. It is compact and is made of material that is CT-compatible, allowing the surgeon to perform the procedures on the CT table and obtain intraoperative scans. When the procedure is performed on the CT table, it becomes a one-step procedure, reducing the total procedure time. In addition, since intraopera¬ tive scans can be obtained, accuracy of probe placement can be confirmed, and if inaccuracy is detected, it can be corrected. Furthermore, the procedure is safe because intraoperative im-

Figure 11-6. A. The Watt’s head holder with longer pin holder (P), the stabilizing plates (S), and the base (B) with an oil capsule (arrow). B. The pin holders and part (containing the oil capsule) of the base are in the MRI coil. C. Sagittal MRI shows the oil capsule (circled by the cursor and pointed to by an arrow), which is the stereotactic center. The X (R = 2.0 mm), Y (P = 114.9 mm), and Z (I = 43.9 mm) scanner coordinates for this point are displayed at the bottom of the picture. D. Axial MRI with the cursor in the center of the tumor. The scanner displays the X (L = 7.3 mm), y (P = R.3 mm), and Z (S = 16.5 mm) scanner coordinates for the target. The configured cursor marks the zone of radiation that will be delivered when radionuclide is placed at the target.

110

Part 1/Stereotactic Principles

C

I) Figure 11-6. (continued)

Chapter 11/The Patil Apparatus

111

The same frame can be used for all stereotactic procedures, in¬ cluding craniotomy and linear accelerator focal radiation. The configuration of the frame makes it easy to gain access to the target during craniotomy and posterior fossa procedures. In conclusion, this system is suitable for all stereotactic proce¬ dures, easy to use, and accurate.

References 1.

Patil AA: Computed tomography (CT) plane of the target approach in CT stereotaxis. Neurosurgery 15:410—415, 1984.

2.

Patil AA: The Patil stereotactic system, in Lunsford LD (ed): Modem Stereotactic Surgery. Boston: Nijhoff, 1988, pp 117-125. Patil AA, Kumar PP, Leibrock LG, et al: The value of intraoperative

3.

scans during computed tomography (CT) guided stereotactic proce¬ dures. Neuroradiology 34:451^(56, 1992. 4.

5. 6.

7. 8.

9.

10.

Figure 11-7. The microscope is attached to the frame by a special adapter (A) to place it along the trajectory. After the microscope is fixed in this position, the arc is moved out of the field.

ages can detect complications. A phantom is not needed be¬ cause the surgeon can actually visualize the probe on the target.

Patil AA: Intraoperative calibration of the Patil stereotactic system during computed tomography (CT) guided stereotactic procedures—a technical note. Stereotact Fund Neurosurg 56:179-183, 1991. Patil AA, Kumar P, Leibrock L, Arabi B: Stereotactic approach to skull base lesions. Skull Base Surg 1:235-239, 1991. Patil AA: Transoral stereotactic biopsy of the second cervical verte¬ bral body: A case report with technical note. Neurosurgery 25: 999-1002, 1989. Patil AA: Stereotactic excision of deep brain lesions using probe guided brain retractor. Acta Neurochir (Wien) 87:150-152, 1987. Patil AA: Free-standing stereotactic microsurgical retractor technique in “key hole” intracranial procedures. Acta Neurochir (Wien) 108: 148-153, 1991. Patil AA, Yamanashi W: Stereotactic microsurgical resection of in¬ tracranial tumors using the electromagnetic field focusing system. Stereotact Fund Neurosurg 59:128-134, 1992. Patil AA, Gelber B: Accuracy of thalamotomy target determination using axial images only. Stereotact Fund Neurosurg 56:104-108, 1991.

11.

Patil AA: Adaption of linear accelerators to stereotactic systems, in Lunsford LD (ed): Modern Stereotactic Surgery. Boston: Nijhoff, 1988, pp 471-480.

12.

Patil AA, McConnell JR, Torkelson RD: Stereotactic localization and excision of seizure focus using xenon enhanced computed tomogra¬ phy (XE-CT). AJNR 16:644-646, 1995.

CHAPTER

12

THE GOUDA APPARATUS

Kasim I. Gouda and Stephen R. Freidberg

In 1973, before computed tomography (CT), Kasim Gouda at¬ tended a course on stereotactic neurosurgery in Edinburgh. Stereotaxis was then used mainly for functional neurosurgery. The characteristics of many demonstrated frames were pre¬ sented.1'4 All required atlases and ventriculography. Some used calculations to correct for the errors of x-ray magnification.3,4 Others required placing the x-ray tube 6 tn from the frame to reduce magnification.1 Capabilities for parasagittal or posterior electrode insertions were limited.2 Surgery was usually done in two stages to allow the surgeon to refer to atlases and do calculations.

planes—are printed on the CT screen. The coordinates are then transferred directly to the frame. The biopsy can be performed through a convenient burr hole. The rectangular frame is made of aluminum with a Lexan (General Electric Co.) block in each corner. The block supports a heavy Lexan screw containing a small, removable stainless steel pin. The frame is designed so that the height of the pos¬ terior blocks is 1.5 cm shorter than the height of the anterior blocks so as to minimize the artifacts produced by the pins in a single slice.

The prototype Gouda frame was reported in 1980s (Fig. 12-1). This frame was designed for use with the then standard ventriculogram techniques. In 1981 the original frame was adapted to interface with CT scanning.6 Subsequently the frame was redesigned specifically for use with CT scanning while the basic concept was maintained.7,8 (Fig. 12-2). The Gouda frame is based on the principle of a movable arc with a target that is the center of a sphere with an infinite num¬ ber of radii. Computed tomography localizes the target. The coordinates—which are in reference to the zero x, y, and z

The frame is best attached with the patient awake and sit¬ ting in a chair. The patient is then moved to the CT suite. The base plate is attached to the CT table with an adjustable clamp. The clamp (Fig. 12-3) is manufactured for the specific table model. The clamp with the base plate attached must be adjusted for the table prior to the operation in order to square the CT alignment with the base plate. When the clamp’s bolts are tightened, it will not be necessary to readjust the clamp unless the CT table is altered. In an institution with more than one CT scanner, a separate clamp should be obtained for each table.

Figure 12-1. The original Gouda frame assembled for functional surgery.

Figure 12-2. The redesigned Gouda frame assembled for biopsy.

113

114

Part 1/Stereotactic Principles

Figure 12-3. The base frame with the CT adapter. The Lexan blocks contain the lead shot for establishing the zero z plane.

Figure 12-4. The system test. The probe touches the 2-mm metal target.

One of four removable 3X2X1 Lexan blocks, each with a 1 -mm lead shot embedded in cross hair markings at the upper end, is inserted in the center of each arm of the plate. It is the plane of the lead shots that establishes the zero CT reference plane for the z axis and assures proper perpendicular alignment of the CT grid in the x and y axes.

cross hairs are aligned with the red laser aiming light of the CT. This approximates the zero plane in the z axis but is not accu¬ rate enough. When the initial scout image has been seen, the plane of the lead shot artifact is marked by a cursor, and a new CT run is made with the cursor at zero. After the initial scan, the alignment markers are removed to minimize artifact. The CT study is completed in 1.5- to 5-mm slices, depending upon the size of the lesion. At the CT slice that most clearly demon¬ strates the lesion, the jc, y, and z coordinates of the target or of multiple targets are chosen.

All of the operations, biopsy and functional, have been per¬ formed with the patient under local anesthesia with an anesthe¬ siologist available. Only rarely has mild sedation been given. Patient discomfort is minimal, and the operation has been toler¬ ated even by neurologically impaired patients. We have chosen to perform all operations in the operating room, where asepsis, light, suction, and access to emergency equipment is optimal. Prior to using the system on a patient, it was tested on a model. The top of the calvarium was removed from a skull (Fig. 12-4). A target was produced by gluing a 2-mm lead ball to a plastic stick. This was moved to different locations within the cranial vault, including deep thalamic, subfrontal. and very lateral parietooccipital areas. In each case the probe touched the lesion, demonstrating the accuracy of our system to within 2 mm, which is the smallest slice thickness of the scan. The most lateral lesions on the model and in our patients are techni¬ cally the most difficult to approach and require the most care¬ fully planned burr holes.

BIOPSY TECHNIQUE The base reference plate is fastened to the patient's head under local anesthesia. Initially, the lateral scout film is taken after the

The patient is then taken to the operating room, where the frame is clamped to the operating table with a clamp that adapts to the Mayfield head rest. The frame is attached to the base plate. The four small holes punched through the drapes have not produced a problem for sterility. The biopsy needle is placed on the arc and is adjusted to zero locus with the phan¬ tom rod (Fig. 12-5), which is then removed. Before the sup¬ porting bars for the arc are attached to the frame, the chosen coordinates are set. After the bars are attached to the frame, the arc is attached. At this point all of the adjustments and coordi¬ nates are set (Fig. 12-6). A burr hole is then made at an appro¬ priate site, the biopsy needle is inserted to the appropriate depth, and the biopsy taken. As a rule, we have sampled at the chosen target plus 5.0 mm proximal and distal. The target is chosen toward the center of the lesion. We use either the Todd-Wells biopsy needle, which has a sharpened rim after the blunt trochar is removed, or the Nashold biopsy needle, which is side-cutting (Radionics Inc., Burlington. MA). A frozen section examination is performed on the tissue to con¬ firm that diagnostic tissue has been obtained. A second target is

Chapter 12/The Gouda Apparatus

115

Figure 12-5. The arc with the attached needle zeroed with the phantom bar.

chosen when the tissue obtained is insufficient for diagnosis. The final diagnosis must await permanent sections. A CT scan can be obtained postoperatively if it is clinically necessary, but this is not part of our standard procedure.

TECHNIQUE FOR FUNCTIONAL NEUROSURGERY

posterior commissure (PC), and the AC-PC line. The current technique for functional surgery differs from that of biopsy in the manner in which the arc is supported and guided to the tar¬ get. The supporting arms for the arc for the functional opera¬ tion allow for adjustment for a calculated but unseen target. As imaging techniques improve, the target may be directly chosen and the technique will proceed in the same manner as for biopsy.

The Gouda frame has been redesigned to permit calculation of the target in the ventrolateral nucleus of the thalamus using established landmarks:9-11 the anterior commissure (AC), the

The initial placement of the frame is done in the same man¬ ner as for biopsy. Zero planes in the x, y, and z axes are estab¬ lished. Axial scans are then taken through the region of the third ventricle in consecutive 1.5-mm slices. At least 20 slices are required to obtain adequate reconstruction. Midsagittal re¬ construction of the region of the third ventricle is made at a width of 2 pixels. The AC and PC are identified on the recon¬ structed image (Figs. 12-7A and B), with the image magnified to a factor of 3.

Figure 12-6. The x, y, and z coordinates are set on the calibrated bars.

The x, y, and z coordinates of the AC and PC are then deter¬ mined and printed with the use of the cursor and software of the CT scanner. The x coordinate should be midline. If the pa¬ tient is placed in the frame off the midline, the x coordinate can be compensated by adjustment (Fig. 12-8) on the vertical AC or PC bar or both. At this point the patient is taken from the CT suite to the op¬ erating room, the frame is clamped to the operating table with the Mayfield head-rest adapter, and the patient is prepped and draped. The paired vertical bars with the bridge attached (Fig. 12-9) are fitted to the side arms of the frame and adjusted to correspond to the coordinates of the AC and PC. The bridges, right and left, are equidistant from the middle of the third ven¬ tricle. The AC-PC distance on the bridges is the same as that of the patient. The small horizontal bars are set on the bridges at appropriate positions corresponding to the AC-PC line. The choice of the surgical target for resting and intention tremor has been low in the nucleus ventralis lateralis—that is, the posterior portion of Hassler’s nucleus ventralis oralis.10’11 The location of the electrode tip varies with the intercommissural distance as determined by atlas data.12 The initial target point is located two-thirds of the distance posterior from AC to PC. Lateral displacement from the midline is set on the small horizontal bars. At this step the adjustment is made for dis-

Neuroablative surgery is now performed far less frequently than in the 1960s, when the medical treatment of Parkinson’s disease became effective. Tasker and coworkers9 have pointed out that thalamotomy remains a useful operation for the relief of tremor.

116

Part 1/Stereotactic Principles

IS

RUN 051 18 PAT ID 1O52503 PAT NM 38 SCAN DATE 24-SEP-:84

100:1

PLANE TYPE X CEN Y CEN Z CEN ANGLE 1 ANGLES THICK

I1 SAG - 12 3 00 17 8 80 O 0 1 80

MAGN

CM CM MM DG OG MM PX

■

2 00

A

82

HINDU O': 1 : : FAT ID PAT NM SLAM

1O52503

DATE

14 - : E P

PLhNE TYPE ::

C En

v

cEh

12 04

Z CEN

14 7

ANGLE 1

-

?0 0

hNGLE2 THICt

Figure 12-7. Midsagittal reconstruction. A. Cursor placed on AC. B. Cursor placed on PC.

B

placement of the target from the midlinc, usually 13 to 14 mm lateral, and is dependent on the width of the third ventricle. The small vertical adjustments, which hang from the horizontal bars, adjust the height above or below the AC-PC line and en¬ sure that displacement is perpendicular to the AC-PC line. The distance from the arc to the target is set on the phantom, as for biopsy. The arc is then set in the small vertical displace¬ ments. The site for the burr hole is chosen and marked. The electrode is directed to the target. To avoid penetration of the lateral ventricle and minimize the possibility of damage to the internal capsule, an anterior-to-posterior and lateral-to-medial

trajectory is chosen. A monopolar stimulus is administered through the same electrode and is gradually increased to 2 V at 25 pulses per second. Usually, with the tip of the electrode in the nucleus ventralis lateralis, a consistent observation has been that of de¬ layed activity in the contralateral extremities with a varying pattern of irregular dysrhythmic and at times dystonic muscular contractions. The appearance of rhythmic contractions with no latency, suggesting close proximity to the posterior internal capsule, would require at least a reevaluation of the target area and a change in the position of the electrode.

Chapter 12/The Gouda Apparatus

117

Figure 12-9. Two vertical bars are set for the y and z coordinates of AC and PC on the side arms of the frame. The horizontal bar simulates the AC-PC line, a = the distance of the target posterior from AC to PC. Figure 12-8. The letter b is used to adjust for the x coordinate of AC or PC; a is used for adjustment of the target position lateral to the midline; and c is used to adjust the target position above or below the AC-PC line.

The lesion is produced with whatever technique is chosen by the surgeon. We use a radiofrequency probe (Radionics Inc., Burlington, MA) to produce a thermal lesion.13 The lesion pro¬ duced around the 0.5 X 1.1 cm tip of the electrode is re¬ stricted by time and temperature controls. The temperature is maintained between 70 and 75°C for 2 min.12 The lesion can be enlarged by moving the electrode. It will usually be expanded upward into nucleus ventralis lateralis rather than into the subthalamic structures. Thermal coagulation is discontin¬ ued when a satisfactory result has been achieved. The patient is monitored throughout the procedure for any evidence of hemiparesis.

MAGNETIC RESONANCE IMAGING COMPATIBILITY For MRI compatibility, we replaced the rectangular frame with a circular aluminum frame (Fig. 12-10). The three marker blocks with an imbedded oil drop as an artifact are made of Lexan. The frame can fit easily in the head coil of the Siemens Magnetom Impact. The MRI table is moved to the scanning po¬ sition after the locator light is aligned to the frame markers. An axial scan is performed with a field of view of 250 mm and

Figure 12-10. MRI-compatible circular frame with adapter enabling it to rest in the head coil of the Siemens Magnetom Impact scanner.

118

Part 1/Stereotactic Principles

slice thickness of 2 mm. The SP (slice position) that corre¬ sponds to the z axis in the axial scan should read as 0. The grid of the MRI must superimpose the three markers of the frame. The x coordinate represented by the sagittal and the y coordi¬ nate represented by the coronal coordinate should each read 0. The biopsy target is marked by the cursor. The target may be viewed in either the axial, coronal, or sagittal planes. The coor¬ dinates of the target are read off of the MRI image, as noted in Table 12-1. The target coordinates are transferred to the frame. In the operating room, two rods are connected to the circular frame to convert it to the rectangular frame and the procedure is com¬ pleted as described above. For functional neurosurgery, the grid is first superimposed on the frame markers in the axial plane. Sagittal scans are per¬ formed in the region of the third ventricle. Two or three midline cuts will be sufficient. The AC and PC coordinates are then chosen in the slice that show them best. These coordinates are then applied to the bars for functional neurosurgery and the process proceeds as described above.

CONCLUSION

the scanner. Additional computers, atlases, and software modi¬ fication are not necessary.

References 1. 2. 3. 4.

5. 6.

7.

8.

The Gouda frame has proved easily adaptable for both biopsy and functional surgery. It is a useful, accurate, inexpensive, and relatively simple frame to use. It uses the computer intrinsic to

9.

10. 11.

TABLE 12-1.

Target Coordinates

12.

Frame coordinates

X

y

z

Coronal Sagital Axial

Sag SP Sag

SP Cor Cor

Tra Tra SP

13. 14.

Bennett AMH: A stereotaxic apparatus for use in cerebral surgery. Br J Radiol 33:33, 1973. Guiot G: Le traitement des syndromes parkinsoniens par la destruc¬ tion du pallidum interne. Neurochirurgia 1:94-98, 1958. Leksell L: A stereotaxic apparatus for intracerebral surgery. Acta Chir Scand 99:229-233, 1949. Riechert T, Mundinger F: Beschreibung und Anwedung eines Zielgerates fur stereotaktische Hirnoperationen (II. Modell). Acta Neurochir (suppl 3):308-337. 1955. Gouda KI, Gibson RM: New frame for stereotactic surgery: Technical note, J Neumsurg 53:256-259, 1980. Gouda KI, Freidberg SR, Larsen CR, et al: Modification of the Gouda frame to allow stereotactic biopsy of the brain using the GE 8800 computer tomographic scanner.Neurosurgery 13:176-181. 1983. Gouda KI, Freidberg SR, Baker RA, et al: Gouda frame redesigned specifically for computed tomographic compatibility. Appl Neurophysio! 49:192-200. 1986. Gouda KI, Freidberg SR, Fager CA, et al: Stereotactic computed tomographic-guided functional neurosurgery using the redesigned Gouda frame. Appl Neurophysiol 49:201-212, 1986. Tasker RR, Siqueira J, Hawrylyshyn P, Organ LW: What happened to VIM thalamotomy for Parkinson’s disease. Appl Neurophysiol 46:68-83, 1983. Fager CA: Evaluation of thalamic and subthalamic surgical lesions in the alleviation of Parkinson’s disease. J Neurosurg 28:145-149, 1968. Fager CA: Surgical treatment of involuntary movement disorders. Lahey Clin Found Bull 22:79-83, 1973. Schaltenbrand G, Bailey P: Introduction to Stereotaxis with an Atlas of the Human Brain. Stuttgart: Thieme. 1959. Cosman ER, Nashold BS, Bedenbaugh P: Stereotactic radiofrequency lesion making. Appl Neurophysiol 46:160-166, 1983. Van Buren JM: Incremental coagulation in stereotactic surgery. J Neurosurg 24(suppl):458-481, 1966.

CHAPTER

13

THE PELORUS APPARATUS

William D. Tobler

The Pelorus (Ohio Medical Instrument Company, Inc., Cincinnati, OH) stereotactic system is a phantom-based system used to perform an array of procedures (i.e., biopsy, hematoma aspiration, stereotaxy-guided craniotomy, functional stereotac¬ tic surgery, radiation implants) with simplicity and precision (see Chap. 62).1-6 It provides an unobstructed approach to areas such as regions of the temporal lobe and posterior fossa that are difficult to access using most frame-based stereotactic systems. The Pelorus is named after an ancient navigational instrument, resembling a mariner’s compass without magnetic needles, that uses two sight vanes to measure bearings. The Pelorus system was first introduced in 1985 by Carol at the Meeting of the World Society for Stereotactic and Functional Neurosurgery in Toronto.7 Its design was simple and derived from the burr-hole-mounted ball-and-socket stereotactic device introduced by Austin and colleagues in 1956.8 Technical refine¬ ments have resulted in a stereotactic device that is recognized and used increasingly throughout the world. It was easily com¬ patible with magnetic resonance imaging (MRI) and did not require any major design changes to accommodate MRI re¬ quirements. The Pelorus stereotactic system was recently inte¬ grated with the Mayfield Arc Centered Computer Imaged Stereotactic System (ACCISS; Ohio Medical Instrument Company, Inc., Cincinnati, OH) computerized workstation for obtaining stereotactic biopsies through twist-drill holes. This chapter describes the principles of the Pelorus system and methods of application in various cases. The author’s own experience and opinions are presented.

double transfer plate is attached to a 4 cm skull ring fixed to the patient prior to the imaging procedure. The apparatus is fixed to an adapter attached to the CT or MRI table so that no patient movement occurs during the scanning procedure. An axial im¬ age is made through the external reference point and the stereo¬ tactic target. The x, y, and z coordinates of the reference point and target are obtained at the CT or MRI workstation. These coordinates are transferred to the phantom base (Fig. 13-1), where the three-dimensional relationship between the reference point and the target is reconstructed. A biopsy ball and socket is placed in the double transfer plate in a fixed relationship to the reference point on the phantom, where the surgeon determines the trajectory and depth to the target in order to simulate the procedure on the phantom. The fixed biopsy ball and socket, maintaining the same relationship to the reference point and target, is transferred from the phantom back to the patient for the actual procedure.

Point Localization in a Cartesian Coordinate System In a Cartesian coordinate system, the unique position of a point in space is described by the x, y, and z coordinates. Current imaging modalities can assign Cartesian coordinates to stereo¬ tactic points. Axial slices through the reference point and the stereotactic target are chosen and obtained via standard scan¬ ning techniques. At the computer console, the cursor is placed appropriately over the reference point and stereotactic target to obtain two sets of x, y, and z coordinates. In the Pelorus stereo¬ tactic system, the relationship between the reference point and the target point is described as Ax, Ay, and Az. These are com¬ puted by subtracting the absolute values of x, y, and z for the reference point from the values of the target point.

DESCRIPTION OF THE PELORUS STEREOTACTIC SYSTEM Overview of the Design and Function of the Pelorus System

SURGICAL TECHNIQUE

The Pelorus stereotactic system uses the Cartesian coordinate system that is inherent in the software programming of com¬ puted tomography (CT) and MRI scanning units to determine the coordinates of the reference point and stereotactic target point. A defined reference or fiducial point is fixed externally to the patient before the stereotactic imaging procedure. The ref¬ erence point is a 3-mm silver pellet for CT or a vitamin E sphere for MRI. It is embedded in a plastic reference ball and socket and attached to an aluminum double transfer plate. The

Application of the Skull Mount Ring The Pelorus stereotactic system does not use the standard base ring or frame common to other stereotactic devices that encir¬ cle or “frame” the skull base and on which other stereotactic components are mounted. Rather, it uses a 4-cm-diameter skull mount ring (aluminum for CT or Lexan for MRI) with multiple

119

120

Part 1/Stereotactic Principles

Figure 13-2. The biopsy ball and socket and single transfer plate affixed to a skull.

Figure 13-1. The Pelorus phantom and target rod. The reference point is a 3-mm silver sphere contained in the reference ball and socket (A), which is attached to the phantom. The double transfer plate (B) holds both the reference ball and socket and the biopsy ball and socket, where the trajectory and depth to the target are mechanically determined by the surgeon. This phantom relationship of reference point and target is a precise reproduction of the relationship of reference point and target on the patient. The phantom base (C) is scaled in the x, y, and z axes. The stereotactic target (D) is localized by determining the Ax, Ay, and As, which represent the respective distances along the x, y, and z axes from the reference point to the target on the CT or MRI. The target pointer (E), scaled in 2-mnt increments, represents the z axis.

openings through which self-tapping screws are placed in the skull. First the ring is placed over a small area of shaved, prepped scalp, which is infiltrated with local anesthetic. The skin is punctured with a pointed scalpel blade and the skull is perforated with a disposable twist drill and 3.2-mm (external diameter) drill bit. Self-tapping screws in 15- or 18-mm lengths are then placed through openings in the ring to engage the inner table of the skull. The ring can be secured with as few as two screws for a simple biopsy or up to four screws for a more complicated stereotactic procedure. The ring is applied to the convexity of the skull to permit access to the intracranial cavity; it cannot be applied over any area where there is muscle, specifically over the temporalis muscle laterally or the paracervical musculature in the poste¬ rior fossa region. The intracranial cavity is accessed by one of two approaches: a direct approach through the skull ring with a biopsy ball-and-socket device attached to the ring (Fig. 13-2) or a remote approach with an arc adapter attached to the skull ring, which converts the Pelorus stereotactic system to a centerof-arc stereotactic system (Fig. 13-3). The neurosurgeon determines the strategic location of the skull ring with respect to the stereotactic target. I he ring can be

affixed to the patient at the time of imaging or, for convenience, the night before surgery. The patient is able to sleep unencum¬ bered because of the small size of the ring. There is a brief learning curve for ensuring secure and stable application of the ring to the skull; it can be more difficult if the patient has a thick scalp. Once this is mastered, the ring can be applied in 10 min or less. The disposable ring and all the components for attachment to the patient are supplied in a convenient, prepack¬ aged kit.

Figure 13-3. The arc adapter system converts the Pelorus to a center-of-arc system for multiple or remote entry to the stereotactic target. The arc adapter system attached to the skull shows the arc carrier with calibrated post (A), mounting bracket (8), 120° arc with a 19-cm radius (C), and adjustable biopsy ring (/)). Once targeted, the arc can rotate unimpeded about the target point for an infinite variety of trajectories.

Chapter 13/The Pelorus Apparatus

121

erence ball and socket into a fixed position in the double trans¬ fer plate with a Bondhus ball driver. The purpose of the table adapter is to fix the patient’s cranium in three-dimensional stereotactic space for completion of the imaging study. The imaging modality can be performed quickly (i.e., 2 to 3 min) and patient discomfort is minimal. Coordinates are rou¬ tinely and most accurately obtained at the CT console; how¬ ever, direct measurements can be made if a superimposed grid is printed on the images. For MRI stereotaxis, the Lexan skull mount is secured to the convexity of the skull and the reference ball and socket is at¬ tached to the MRI table adapter in the same fashion. Coordinate determination, targeting, and trajectory generation are accomplished as for MRI stereotaxis. The spatial con¬ straints of MRI do not pose any problems for the Pelorus stereotactic system, since there is no hardware mounted later¬ ally on the patient during the scanning procedure.

Figure 13-4. The double transfer plate is placed over the skull mount ring (A) in the right frontal area, where it is secured with two lock nuts. The reference point is inside the reference ball and socket (B) and its position is fixed.

Fixation Procedure for Stereotactic Imaging After the ring is securely attached to the patient, the imaging procedure can be carried out. A small table adapter mounts into the bracket at the head of the CT table. The reference ball and socket, containing the silver pellet for CT or the vitamin E sphere for MRI, is then placed into one opening of the double transfer plate; this aluminum plate has two circular openings: one holds the biopsy ball and socket and the other holds the ref¬ erence ball and socket. The double transfer plate fits over the skull mount ring and is secured with two locking nuts (Fig. 13-4). The plate is eventually transferred to the phantom, where it is critical in the stereotactic simulation. The reference ball and socket is attached to the mounting post of the CT table adapter and tightened with a locking screw. All connections are hand-tightened and the fixation screws secure the rotatable ref¬

Figure 13-5. The relationship of the skull fixed to the CT table adapter (A) is reproduced in the phantom (right). The double transfer plate (B) and the reference ball and socket are fixed and transferred from the patient to the phantom. The target is located in the phantom and a trajectory to the target is mechanically determined on the phantom. The fixed biopsy ball and socket is then returned to the patient for the stereotactic procedure. Two double transfer plates are shown for illustration only.

Localization of the Target in the Phantom Once the imaging is completed, the reference ball and socket and double transfer plate assembly is disconnected from the table mount. The double transfer plate, containing the fixed ref¬ erence ball and socket, is removed from the patient as a unit. All fixation screws are checked to make certain they are secure, so that the reference ball and socket cannot rotate. The fixed position of the reference ball and socket preserves the relationship of the patient and the stereotactic device. It is then taken to the phantom base and attached to the central bar at the top of the phantom base. The position of the fixed refer¬ ence ball and socket and double transfer plate on the phantom base is an exact duplication of the three-dimensional position of the patient on the imaging table (Fig. 13-5). The Ax, Ay, and Az values are calculated and transferred to the phantom base. The phantom base has x and y grids that correspond to the axial plane of the CT or MRI scan. A target localizing post is mov¬ able in the x and y axis and is scored at 2-mm increments to establish a target point along the z axis. The Az, Ay, and Az val¬ ues are set in the phantom base along the corresponding x, y, and z axes and the position of the target is established in the three-dimensional space of the phantom. This is a duplication

122

Part 1/Stereotactic Principles

of the intracranial target and its spatial relationship to the dou¬ ble transfer plate and reference point as it was attached to the patient. The absolute values of the x, y, and z coordinates of the reference point in the reference ball and socket as it is attached to the phantom become 0, 0, and 0; therefore, it is the reference point or zero point of the phantom. The relationship of the target to the reference point is also called the offset; it is a direct measurement in millimeters along the x, v, and z axes from the reference point to the target point. Some manufacturers have built into their imaging software the capacity to set the x, y, and z intersection or zero point of the scanner’s coordinate system directly on the Pelorus reference point in the axial slice of the scan; in this case, the absolute tar¬ get values in the coordinate system of the scanner correspond with the absolute values in the phantom base. No calculations are required, and these values are simply transferred to the phantom for the targeting simulation.

Simulation of a Biopsy on the Phantom Once the Ax, Ay, and Az values have been determined and the location of the target pointer established in the phantom, a sim¬ ulation of the stereotactic procedure can be performed. A rotat¬ able biopsy ball and socket is placed in the second opening of the double transfer plate. A series of collars can be chosen with diameters to accommodate various sizes of catheters and can¬ nulas and placed in the central opening of the biopsy ball and socket. Typically a 3.2-mm (outer diameter) cannula with an adjustable depth stop is placed through the center of the ball and socket and rotated so that the tip of the cannula touches the tip of the target. The three fixation screws are tightened to fix the biopsy ball and socket and cannula in position. With this simple simulation, a direct trajectory and depth to the target are determined on the phantom. The biopsy ball and socket is re¬ moved from the double transfer plate and placed on a single fixation ring or single transfer plate, which attaches to the skull mount ring on the patient.

Performance of a Simple Biopsy The fixed biopsy ball and socket, single transfer plate, variable sized collars, and biopsy forceps or cannula are autoclaved or soaked before the surgical procedure. Routine prepping and draping of the stereotactic ring and encircled scalp is done. The scalp inside the ring is infiltrated with local anesthetic. The au¬ thor prefers to make a twist-drill hole using a disposable hand drill with a 3.2-mm drill bit passed through the adjustable 3.2mm collar that has been placed in the biopsy ball and socket. If preferred, a routine burr hole can be made in the center of the ring, allowing direct visualization of the cerebral cortex. Once the cranial opening is made, the dura is punctured with an 18gauge spinal needle and the biopsy cannula or forceps is ad¬ vanced to the depth determined on the phantom to reach the stereotactic target (Fig. 13-6).

Arc Adapter System: Description and Function The arc adapter system can be used to increase the range of ac¬ cessibility to a stereotactic target (Fig. 13-3). The system com¬ prises four components: (1) the arc carrier, which is a cali-

Figure 13-6. The biopsy needle is passed to the target. The biopsy ball and socket is mounted to the skull ring (hidden) and single transfer plate. Only the area of the skull ring needs to be prepped and the sterility of the entire field maintained. brated post that secures with a locking screw to a stainless steel arc ball and socket; (2) the arc mounting bracket, which at¬ taches to the stereotactic arc; (3) the arc, with a fixed radius of 19 cm from the calibrated point; and (4) the biopsy ring, which adjusts to allow the passage of parallel catheters. All of these components can be moved along the arc. The arc swivels about the calibrated post, allowing for an infinite number of centerof-arc approaches to reach the target. The arc is centered to the target on the Pelorus stereotactic phantom by passing a cannula through the stainless steel arc ball and socket. The trajectory is established by placing the cannula on the preselected target and fixing it in place, the same as the targeting procedure for the biopsy ball and socket described above. A locking screw secures the calibrated post to the arc ball and socket. The calibrated post then represents a radius of the arc theoretically pointing at the target. The arc has a diameter of 19 cm and the calibrated post has a vertical length of 19 cm. The arc mounting bracket is lowered from the top of the calibrated post to intersect the target. This dis¬ tance is measured from the depth stop of the targeting cannula at the top of the arc ball and socket to the target during the initial targeting procedure. Any trajectory along the 19-cm sphere will hit the target. The fixed arc ball and socket and its components are removed from the phantom and sterilized be¬ fore placement in the draped, surgically prepped operating field. Once the targeted arc adapter system is secured to the skull mount ring on the patient, the surgeon can swivel and rotate the arc adapter and choose the entry point based on the anatomic considerations with respect to the location and tra¬ jectory to the target.

APPLICATIONS OF THE PELORUS SYSTEM FOR CLINICAL NEUROSURGERY The Pelorus stereotactic system has a unique appeal because the target can be accessed directly through the ring (Fig. 13-2).

Chapter 13/The Pelorus Apparatus

123

It can also be used as a center-of-arc system for more complex stereotactic procedures (Fig. 13-3).

Through-the-Ring Biopsy Most stereotactic procedures are simple biopsies in the supra¬ tentorial compartment, which can be accessed directly through the ring. The stereotactic ring can be mounted directly over the frontal, parietal, or occipital lobes. Only the area involved with the ring placement needs to be shaved, prepped, and draped in the sterile field. There is minimal hardware for this procedure and simple biopsies and hematoma or cyst aspira¬ tions can be carried out in the CT suite. Once one has gained experience with the Pelorus stereotactic system, a through-thering biopsy or aspiration procedure can be completed in ap¬ proximately 1 h.

Center-of-Arc Stereotaxy-Guided Craniotomy There are two methods for a stereotactic-guided craniotomy. The direct method is performed through the ring and biopsy ball-and-socket by passing a ventricular-type catheter directly to the target. The ring is removed before the craniotomy, leav¬ ing the catheter in place for localization. The recommended method is with the center-of-arc system. With this method, the craniotomy flap is made directly over the lesion with the bone flap being as small as 2.5 to 3 cm in diameter, depending on the size of the lesion. The stereotactic ring is generally placed adja¬ cent to the craniotomy site. A major advantage of the Pelorus center-of-arc system is that a stereotaxy-guided craniotomy can be performed rou¬ tinely with no disruption in the draping process (Fig. 13-7). There is no cumbersome frame around the base of the skull to interfere with the draping procedure and raise concerns about sterility in the operative field. In addition, there is no risk of a cumbersome base ring interfering with anesthetic management. Using this method, a stereotaxy-guided craniotomy can be per¬ formed with the patient awake, under local anesthesia, and without placing the patient in a three-point stabilization device. Because there is no frame, base ring, or stabilization post, there is no interference with access or trajectory to any region of the posterior fossa or lateral approach to the mid and/or temporal region. The unimpeded access of the Pelorus stereotactic arc also allows targeting in areas of the upper cervical spine. It can also be used for implantation of radioactive seeds for the treat¬ ment of patients who have head and neck cancer.

CLINICAL EXPERIENCE WITH THE PELORUS STEREOTACTIC SYSTEM Accuracy and Verification of the Pelorus System The Pelorus stereotactic system was introduced at the University of Cincinnati Medical Center (UCMC) and Mayfield Neurological Institute in 1988; it was first used by the author in 1989. The most appealing features of the system were the compactness of the skull mount ring compared with the stereotactic frame and the elimination of the computer pro-

Figure 13-7. The arc adapter system is positioned for a posterior fossa biopsy. Note the right ear (A). The skull mount ring and single transfer plate (8) are placed in right occipital area. This demonstrates some of the advantages of the center-of-arc approach: easy and unobstructed access to the posterior fossa, and the operative site is routinely draped, as the cranial attachment is included in the sterile field.

gram, which was time-consuming, difficult to understand, and not always reliable. The Pelorus stereotactic system relies on scanning devices to measure precisely the distances along the z axis; framebased stereotactic systems depend on scanning devices to measure distances along the x and y axes. The familiar Nshaped fiducial system used with other stereotactic devices to ascertain the distance along the z axis is not necessary with the Pelorus system because the measurements along the z axis are reliable. The Pelorus stereotactic system was initially criticized for its mechanical instability and inaccuracy compared with other systems.3 Refinements and modifications have yielded an accurate stereotactic system that is as versatile as or more ver¬ satile than any other instrument for the performance of stereo¬ tactic procedures. One must critically recognize that stereotac¬ tic accuracy is proportional to slice thickness, and ongoing verification of the scanning device is required regardless of the system used. It is incumbent upon any neurosurgeon to be knowledgeable about the principles, function, and applications of the system and all of its components. Successful targeting procedures with phantom skulls will always confirm one’s understanding of the stereotactic device, the accuracy and function of its compo¬ nents, and the precision of the imaging device. The Pelorus stereotactic system has been the primary stereotactic device used by some faculty at the University of Cincinnati Medical Center (UCMC) for 7 years. Independent

124

Part 1/Stereotactic Principles

verifications of accuracy obtained by scanning and targeting phantom skulls and dependable performance in over four hun¬ dred procedures at our institution have confirmed the reliability and performance of this stereotactic system.

cases where a diagnosis was not obtained, but the quality of the specimen was inadequate for diagnosis.

Stereotactic Aspiration of Intracerebral Hematomas

Stereotactic Biopsy Stereotactic biopsy can be accomplished efficiently using the direct approach through the skull mount ring. This can be per¬ formed in the CT suite or the operating room under local anesthesia with minimal disruption to the patient. More com¬ plicated procedures require placement of the arc for the indirect approach using the center-of-arc system. Figure 13-7 shows the arc adapter system in place for a stereotactic biopsy in the posterior fossa. The skull mount ring, which is positioned in the occipital area, provides direct and unimpeded access to the posterior fossa. The center-of-arc sys¬ tem permits the surgeon to choose the entry point at the operat¬ ing table, thereby avoiding vascular structures such as the transverse sinus. The preoperative CT scan (Fig. 13-8A) shows the cystic nodular lesion in the right cerebellar hemisphere, with the enhancing cyst on the deep side, adjacent to the dorsolateral brain stem. The postbiopsy scan demonstrates air bubbles tracking to the target (Fig. 13-85), adjacent to the dor¬ solateral brain stem, with precise localization of the lesion as planned in the preoperative scan. A positive biopsy for metasta¬ tic adenocarcinoma was obtained. Table 13-1 discloses the author’s experience with the Pelorus stereotactic device for biopsy or hematoma aspiration in 96 patients. Complications, including hemorrhage and fail¬ ure to obtain diagnostic material, are consistent with results reported elsewhere and confirm the precision of the stereotactic device (Table 13-2).9 There were no targeting errors in the three

The aspiration of intracerebral hematomas by stereotactic methods has been a controversial topic. There are few reports in the literature.11 Since 1990. the author has performed stereo¬ tactic aspiration on 18 patients.5 Indications have been for hematomas in critical areas and in elderly or debilitated pa¬ tients unable to undergo a craniotomy. Additionally, the author believes there is an indication to aspirate, or internally decom¬ press, a small focal hematoma that is producing an incomplete neurological deficit. For many cases, this has resulted in rapid recovery or improvement of the focal deficit, which had failed to improve with observation. Figure 13-9A shows an MRI of a 76-year-old woman with a large, deep parietal hematoma and a dense hemiparesis that failed to improve in a few days. Open surgery was contraindicated due to a chronic coagulopathy. Angiography disclosed slow filling of the right hemisphere, likely due to the pressure effects of the hematoma. The patient underwent stereotactic aspiration with a single trajectory 13 days after hemorrhage; 30 mL of liquified hematoma was removed. Figure 13-96 shows the residual clot with a catheter in place. Rapid improvement of the dense hemi¬ paresis began the day after surgery, with almost complete recov¬ ery. The stereotactic placement of one or two cannulas and aspira¬ tion with a syringe 24 to 48 h or longer after the initial hemorrhage can result in significant or nearly complete evacua¬ tion of the hematoma. In 18 cases there have been no episodes of rebleeding, worsening of deficit, or death. Further experience in refining selected indications for this procedure is warranted.

Figure 13-8. Computed tomography scans of a patient who underwent stereotactic biopsy and aspiration. A. Preoperative targeting CT scan shows a cystic nodular enhancing posterior fossa metastasis. The nodule is marked with number 1 (arrow); the cyst is labeled b. B. Noncontrast CT scan obtained after biopsy discloses a tract of air bubbles leading to the target. The cyst was aspirated after the biopsy was taken. Figure 13-7 shows the surgical approach to the lesion.

Chapter 13/The Pelorus Apparatus

125

TABLE 13-1. Pathology Obtained following Stereotactic Biopsy or Aspiration No. of Patients, n = 96a

Pathology Primary CNS Metastatic Lymphoma Abscess Cerebritis Gliosis Necrosis Infarction No diagnosis Hematoma (aspiration)

46 11 6 5 2 2 1 1 3 19

“Patients treated between January 1989 and August 1995.

TABLE 13-2. or Aspiration

Complications following Stereotactic Biopsy

Complication Bleed with neurological deterioration Bleed requiring surgery Infection No diagnosis Death Total Morbidity Total Mortality

No. of Patients, n = 96a

Percent of Patients

3 1 1 3 0

3.2 1 10 3.21 0

5 0

5.2 0

“Patients treated between January 1989 and August 1995.

Stereotactic Craniotomy for Tumors B The Pelorus stereotactic device has been used for hundreds of stereotaxy-assisted craniotomy procedures at UCMC. Indications have been varied and pathology ranges from primary tumors, localization of arteriovenous malformations, peripheral aneurysms, metastasis, and brachytherapy im¬ plants.4,5 An important use of stereotactic craniotomy is for lo¬ calization of keyhole craniotomy flaps for small metastatic lesions (Fig. 13-10). With refinement of technique, a 2- to 4-cm craniotomy using a linear incision can easily be placed over the lesion. The time savings, cosmetic appeal to the patient, and economy of surgical effort are clearly significant. Experience with resection of metastatic lesions in eloquent cortex using these techniques has been reported elsewhere.5

Figure 13-9. Magnetic resonance imaging scans of a patient who underwent stereotactic aspiration of an intracerebral hematoma. Preoperative MRI scan (A) discloses a moderately large right parietal hematoma with mild midline mass effect in a patient with a coagulopathy and dense hemiparesis. The patient underwent aspiration and decompression of the hematoma; 30 mL of liquified hematoma was evacuated with a single trajectory. Postoperative MRI scan (B) shows the small residual hematoma and ventricular catheter.

Targeting is completed with MRI localization. Forty-five pa¬ tients have been treated with no complications with respect to targeting, hematomas, cerebral hemorrhage, or infection.

Functional Stereotaxis Functional stereotactic procedures for the implantation of depth electrodes for epilepsy monitoring have been performed at UCMC since 1989.7 The Pelorus arc adapter is used for these procedures. Multiple electrodes are placed bilaterally to reach mesial temporal lobe targets. For this procedure, the skull mount ring is placed in the midline frontal area, allowing ac¬ cess to both temporal lobe targets during the same procedure.

Multiple Trajectories for Brachytherapy The author has satisfactorily used the Pelorus stereotactic de¬ vice for implantation of catheters for the administration of brachytherapy in 18 cases, with the implantation of as few as 4 and as many as 12 catheters. It has not been necessary to repo-

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Part 1/Stereotactic Principles

geting procedure by a colleague, resident, or neurosurgical nurse clinician thoroughly trained in the application of the stereotactic device.

SUMMARY The Pelorus stereotactic system is particularly appealing be¬ cause it is a simple stereotactic device for obtaining biopsies in the supratentorial compartment. The system can be converted to a center-of-arc system to perform the most complex procedures. The Pelorus stereotactic system uses a logical approach to target generation which can be easily and thoroughly understood. It has few mechanical parts and hardware; therefore, it is less ex¬ pensive than many other frame-based stereotactic systems. It has been 10 years since the Pelorus stereotactic system was introduced. Technical refinements have yielded a device that is reliable, accurate, and simple. Its compactness has improved stereotactic accessibility to difficult regions of the posterior fossa and temporal area because of the lack of an ob¬ structive frame and side posts. It is easily suited for MRI-based stereotactic surgery. Clinical experience has proven its reliabil¬ ity and accuracy. The pressure to control expenses for medical equipment has enhanced the appeal of this affordable system, even though there is a current shift toward costly computerbased, interactive, frameless stereotactic systems.

References 1. 2. 3.

4.

B 5.

Figure 13-10. Localization of stereotactic keyhole craniotomy. A. Computed tomography scan showing a 2.5-ctn subcortical metastatic lesion in the left frontal area. The lesion was removed by a stereotaxy-guided keyhole craniotomy using the Pelorus arc adapter system. B. Postoperative CT scout view demonstrates a 3cnt keyhole craniotomy flap stereotactically placed precisely over the lesion.

6.

7. 8. 9.

sition any catheters because of stereotactic error; one case was aborted because of intracerebral hemorrhage. It is this author’s strict recommendation that no stereo¬ tactic procedure be performed without confirmation of the tar¬

10.

Carol M, Smith D, Love L, et al: Experience with the Pelorus stereo¬ tactic system. Appl Neurophysiol 50: 133-135, 1987. Engelhard H: A simplified method for CT-guided stereotactic brain biopsy. KM A 78:24-27. 1992. Engelhard H, Nazar G. Grieser G: Evaluation of the Pelorus stereo¬ tactic surgical system for CT-guided stereotactic brain biopsy. South Med J 86:760-766, 1993. Ghobashy A. Tobler W: Intraosseous calvarial meningioma of the skull presenting as a solitary osteolytic skull lesion: Case report and review of the literature. Acta Neurochir (Wien) 129:105-108, 1994. Tobler W, Stanley M: Stereotactic resection of brain metastases in eloquent brain. Stereotact Fund Neurosurg 63:38-44, 1994. Yeh HS, Taha JM. Tobler WD: Implantation of intracerebral depth electrodes for monitoring seizures using the Pelorus stereotactic sys¬ tem guided by magnetic resonance imaging. J Neurosurg 78: 138-141, 1993. Carol M: A true “advanced imaging assisted" skull-mounted stereo¬ tactic system. Appl Neurophysiol 48: 69-72, 1985. Austin GM, Lee ASJ, Grant FC: A new type of locally applied stereo¬ taxic instrument. JAMA 161:147-148. 1956. Apuzzo MJL, Chundrasoma PT, Cohen D. et al: Computed imaging stereotaxy: Experience and perspective related to 500 procedures ap¬ plied to brain masses. Neurosurgery 20:930-937. 1987. Kaufman H: Stereotactic aspiration with fibrinolytic and mechanical assistance, in Kaufman H (cd): Intracerebral Hematomas. New York: Raven Press, 1992, pp 181-185.

CHAPTER

1 4

THE NARABAYASHI APPARATUS

Hirotaro Narabayashi

START OF STEREOTACTIC SURGERY IN TOKYO1

ing in order to reduce its weight (Fig. 14-15). The insertion electrode was controlled three-dimensionally by a manipulator. The reference structure for measurement on the pneumoven¬ triculogram picture for targeting the globus pallidus and the thalamic nuclei was the anterior edge of the massa intermedia, as there was no brain atlas available. With the kind encourage¬ ment of Dr. Amako, Director of the Geriatric Hospital and Institute in Tokyo, I measured and mapped the coordinates in six cadaver brains. The measurement was not published. As in other centers abroad, the first target of stereotactic lesioning was the dorsomedial nucleus of the thalamus, for the purpose of replacing the imprecise procedure of prefrontal leukotomy. However, this dorsomedial thalamotomy was discontinued af¬ ter several cases because no marked change was effected by the procedure.

World War II ended in August 1945 with the unconditional sur¬ render of Japan. The entire country was totally paralyzed at the end of the war and for several years afterwards. Big cities were in ashes. The damage in cultural and scientific fields was also severe, and scientists were almost completely isolated from the progress in the western world. Having graduated from the University of Tokyo Faculty of Medicine in 1946,1 was interested in the mystery of the human brain, especially in the dynamic mechanistic aspect of the extrapyramidal structures, since during my undergraduate years I had been inspired by A. Jacob’s Die extrapyramdale Erkrankungen and several papers by such German neuro¬ pathologists as C. and V. Vogt, H. Spatz, and O. Foerster. Dr. Uchimura, Professor of Neuropsychiatry and an eminent neuropathologist in his own right, was one of my teachers, and he also had an interest in extrapyramidal diseases. One day in 1948, Dr. Uchimura and I were sitting together with Dr. Ogawa, Professor of Neuroanatomy at the Brain Research Institute of the University, who showed us a copy of a HorsleyClarke instrument and discussed the possibility of establishing a stereotactic approach to the human brain with the aim of treating involuntary movement. We were not informed that similar trials were going on in Philadelphia and also in Europe, because there was no chance to see any recent foreign literature.

This first instrument, employed with the patient in the sit¬ ting position, was often found to be inconvenient, as it could not be fixed to the scalp easily. Therefore a second model, de¬ signed for use in the supine position, was developed 2 years later. My collaborators and I were interested mainly in the in¬ voluntary movement disorders due to extrapyramidal pathol¬ ogy. The hypothesis suggested by German neuropathologists, that the striatal pathology might release the activity of the lower-lying centers, such as the pallidum, from the control of the striatum, led us to start pallidal surgery in patients with choreoathetosis. The first pallidotomy was conducted on a 19year-old boy with severe athetosis in June 1951, which was about a year earlier than the first surgery on parkinsonism. During the surgery for choreoathetosis, a reduction of muscular hypertonus was often observed, which suggested the possible application of the procedure to alleviate parkinsonian symp¬ toms, especially rigidity. The first pallidotomy on a case of parkinsonism was carried out on June 4, 1952.‘M5 The patient was 27 years old and pre¬ sented with symptoms of juvenile or early-onset parkinsonism. Blocking of the pallidum by injection of a small amount of oilwax mixed with procaine and a radiopaque material produced immediate and complete abolition of the rigidity and tremor on the contralateral side of the body, which we found to be an un¬ forgettable and impressive observation. The preceding re¬ versible blocking of the caudate nucleus and putamen with an aqueous solution of procaine had produced no change.

It took about 2 years for us to complete the manufacture of the first instrument, which was accomplished with the coopera¬ tion of Mr. Ikeda, who was running a small factory affiliated with the Shimazu Precision Manufacturing Co. Ltd., in Kyoto. Report of this first instrument was made in April 1950 at the 40th Meeting of the Japanese Society for Psychiatry and Neurology in Kyoto; a summary of it can be found in the Proceedings.2 The first publication on the instrument in Japanese was that by Uchimura and Narabayashi.3 Figure 14-1 is a copy of the photo of the instrument; however, the reproduc¬ tion is not clear because of the poor quality of the paper used in Japanese journals at that time. The first instrument (Fig. 14-1 A) was used with the patient in the sitting position, the instrument being hung from the ceil¬

127

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Part 1/Stereotactic Principles

PSYCH 1 ATRIA ET NEUROLOGIA JAPONICA Vol.52 1951 P.34 A

B Figure 14-1. A. First model of a stereotactic instrument for use in the sitting position. B. Instrument in use.

THE LATEST MODEL OF THE NARABAYASHI APPARATUS The latest model is not an instrument in the sense of classic stereotaxy, in which the angle and depth of electrode insertion to the target is determined before trephination in a phantom frame according to precalculated measurements. In the author’s model, manipulation of the electrode, i.e.. its angles and depth, is planned on the operating table after the trephine opening and pneumo- or radiopaque ventriculography. We are still of the opinion that reading the delicate image of the third ventricle in detail is of basic importance, as the image seen by CT or MRI is sometimes not satisfactorily clear as to its details. Measurement and calculation of the coordinates of target struc¬ tures, mostly the subdivisions of the pallidum or thalamus, are made with reference to the Bailey-Schaltenbrand brain atlas. The instrument is composed of two main parts, i.e.. the skull-fixation frame and the needle holder mounted on the frame (Fig. 14-2/1 and B). The skull of the supine patient is fixed in place with four pins under local anesthesia, two frontal and two occipital. The midline of the skull and of the two hemispheres should be placed in exact coincidence with the focus of the midsagittal xray beam. The x-ray tube for anteroposterior radiation is fixed in a cavity in the ceiling about 2 m above the center of the patient's skull. A lateral x-ray tube is placed at about 2.5 m from the midsagittal plane of the patient's skull, and the focus of the radia¬

tion is fixed at a point 3 cm above the external auditory meatus and about 1 cm in front of it. We feel that it is essential to have a specialized stereotactic operating room in which all radiolog¬ ical measurements can be oriented in relation to the center of the patient’s skull. The manipulation part of the instrument is designed to allow electrode measurement in both millimeter and micron steps. After first deciding the angle and depth of electrode insertion on the film, the operator places the electrode on the cortical surface or 1 or 2 cm deep below the cortex, with a roughly esti¬ mated direction toward the target, which is again x-rayed. If there is a small misdirection, the angle of the electrode may be delicately corrected, which is a simple procedure taking only a few minutes. After confirming that the angle is correctly adjusted to the proper direction, the operator slowly advances the electrode into the cerebral tissue to the target. This proce¬ dure might be considered similar to “the pneumotaxic guide" of Bertrand.7 Next, it is important to detect any individual variation of the target structure in each patient, especially when there is a long-standing atrophic disease process. For this purpose, neu¬ rophysiological devices become essential. First, electrical stimulation is done to see changes in somatic symptoms, such as rigidity, tremor, and other motor and sensory phenomena. Second, analysis of cortical evoked potentials for depth stimu¬ lation, especially of the thalamus, is useful for detecting inva¬ sion of the capsular fibers.* Third, a most delicate and reliable micro- or semimicroelectrode technique is used to record neu¬ ronal activities of individual deep structures during the course

Chapter 14/The Narabayashi Apparatus

129

Figure 14-2. A. Latest model of instrument. B. Electrode manipulation part.

of needle insertion. This technique was introduced by AlbeFessard and others in 19639 and has been used in the author’s operating room continuously since 1972. This axial technique confirms the correctness of insertion into both the pallidum and the thalamus and is now widely used by many neurosurgi¬ cal centers. The details of the technique may be found in other papers. The last important confirmation is to ensure that the final electrode position is precisely the prescribed one, which confir¬ mation should be done with repeated radiological studies by xray or computed tomography before the coagulation lesion is produced, but in MRI-stereotaxis this is usually not done. A possibility of a slight bending of the electrode needle during the long course of insertion cannot be ignored; also MRI mea¬ surement can reportedly be inaccurate by a small percentage 10-12 j_)r Maeda, a colleague of mine, indicated that, in pa¬ tients with a widely dilated third ventricle—e.g., more than 12 mm in width—Vim neurons responding to arm movement were dislocated about 3 mm laterally, which shift would suffice to allow recurrence of tremor after thalamotomy.'3 In the history of stereotactic surgery, the efforts to look for more precision in locating the target structures and to produce the minimum necessary size of lesion14 have been uninterrupt¬ edly pursued. Only achievement of these goals will allow us to unravel the underlying mechanism of each clinical symptom in the strict sense of basic neuroscience.

2.

3.

4.

5.

6. 7.

8. 9.

10.

11.

12.

13.

References 1. Narabayashi H: Beginning and development of stereotaxic surgery in Tokyo. Confin Neurol 37:364-373, 1975.

14.

Uchimura Y. Narabayashi H, Shiotsuki M: Two new instruments in neurosurgery: (1) Stereoencephalotomy, (2) Polygraph (only sum¬ mary, in Japanese). Psychiatr Neurol Jpn 52:86. 1950. Uchimura Y, Narabayashi H: Stereotaxic instrument for operation on the basal ganglia (in Japanese). Psychiatr Neurol Jpn 52:265-270, 1951. Narabayashi H, Okuma T: Procaine oil blocking of the globus pallidus for the treatment of rigidity and tremor of parkinsonism: Preliminary report. Proc Jpn Acad 29:134-137, 1953. Narabayashi H: Procaine oil blocking of the globus pallidus for the treatment of rigidity and tremor of parkinsonism (in Japanese). Psychiatr Neurol Jpn 56: 471-495, 1954. Narabayashi H, Okuma T, Shikiba S: Procaine oil blocking of the globus pallidus. Arch Neurol Psychiatry 75:36^18, 1956. Bertrand CM: A pneumotaxic technique for producing localized cere¬ bral lesions and its use in the treatment of Parkinson’s disease. J Neurosurg 15:951-964, 1958. Yoshida M, Yanagisawa N, Shimazu H, et al: Physiological identifica¬ tion of the thalamic nucleus. Arch Neurol 11:435-443, 1964. Albe-Fessard D, Arfel G, Guiot G: Activites dlectriques caracteristiques de quelques structures cerebrales chez 1’homme. Ann Chir 17:1185-1214, 1963. Kondziolka D, Dempsey PK. Lunsford LD, et al: A comparison be¬ tween magnetic resonance imaging and computed tomography for stereotactic coordinate determination. Neurosurgety 30:402-407, 1992. Lunsford LD: Magnetic resonance imaging stereotactic thalamotomy: Report of a case with comparison to computed tomography. Neurosurgery 23:363-367. 1988. Peters TM, Pike GB, Oliver A: Image distortion considerations for stereotactic image analysis. Stereotact Fund Neurosurg 54/55: 499-500, 1990. Maeda T: Lateral coordinates of nucleus ventralis intermedius target for tremor alleviation. Stereotact Fund Neurosurg 52:191-199, 1989. Hirai T, Miyazaki M, Nakajima H, et al: The correlation between tremor characteristics and the predicted volume of effective lesions in stereotaxic nucleus ventralis intermedius thalamotomy. Brain 106: 1001-1018, 1983.

'

CHAPTER

15

THE SUGITA APPARATUS

Kenichiro Sugita and Naomi Mutsuga Most neurosurgeons involved in functional neurosurgery agree that no other aspect of neurosurgery has so fascinated the me¬ chanically minded surgeon as has stereotactic surgery. Basically there are four groups of stereotactic apparatus: (1) the polar coordinate instrument1-4 (burr-hole type5-9); (2) the paral¬ lel x-ray beam instrument (Talairach apparatus10); (3) phantom target instruments (Riechert-Mundinger system);11 and (4) Sugita apparatus type I12 and triplane stereotactic instru¬ ment.13-15 Nowadays the most common stereotactic apparatus is the triplane stereotactic instrument, and it is easily applied to computed tomography-based stereotactic procedures and also to stereotactic radiosurgery. The Sugita apparatus was initially developed as a phantom target instrument (Sugita apparatus type II)14 and was then modified to a triplane stereotactic system.

ular to both cannot be overemphasized. In contrast to the Riechert-Mundinger system, the Sugita head frame was made into a square shape. There is a pinhole in the midpoint of each parallel side of the Sugita frame for aligning the central x-ray beam perpendicular to the head frame. Four cones stick out on both sides of the frame, and two cones are placed 100 mm apart. Four cones on each side of the frame are essential to find the magnification ratio at the midsagittal plane and the center of the frame (Fig. 15-1).12 The disadvantage of the type I apparatus was that a same size phantom frame was essential. Each target required a sepa¬ rate burr hole, and more complicated electrode supports were necessary. The triplane stereotactic system has been employed in the Sugita type II apparatus because of simplicity in manipu¬ lation and decrease in the number of components.

SUGITA APPARATUS TYPE I TO TYPE II

SUGITA APPARATUS TYPE II

The Sugita apparatus, developed in 1965, was basically in the group of phantom target systems, like the Riechert-Mundinger system. Since all localization is based upon relations of the tar¬ get to the midsagittal plane, the importance of aligning this par¬ allel to the x-ray cassette and the central x-ray beam perpendic¬

This system is, in essence, developed so that the target point is always located in the center of the imaginary sphere, and when any electrode equal in length to the radius of this sphere pene¬ trates perpendicular to a plane tangent to the sphere, the tip of

Figure 15-1.

Sugita apparatus type I. A. Original patient frame. B. Phantom frame.

131

132

Part 1/Stereotactic Principles

the electrode will by necessity strike the target point; that is, it is an arc-centered apparatus. The basic head frame of the type II apparatus is a square shape and is composed of an outer frame and an inner frame. The outer frame has 16 cones like the type I apparatus for measuring the magnification ratio and determining the center of the system. Preparation for stereotac¬ tic surgery is the same as for the type I. The patient’s head is fixed in the inner frame with four pins. The inner frame can be rotated around the vertical axis a total of 5° in either direction so that the midsagittal plane of the fixed head can be aligned to the vertical central x-ray beam (Fig. 15-2). The electrode car¬ rier system is a square shape with smooth corners, and it moves in the saggital plane only. For transverse movement, the elec¬ trode holder system moves on the horizontal plane of the elec¬ trode carrier system. The entire electrode carrier system is moved with 3° of free¬ dom to place the center of the imaginary sphere at the desired intracranial target point, as with the Leksell13 and Van Buren instruments.15 There are two rings (5 cm in diameter) on either end of the carrier system. For axial (Y axes) and anteroposterior (X axes) movement of the carrier system, graduated members are attached on either side of the outer head frame and a cruci¬ form slider system moves on the graduated member. For axial movement (Y axes), another slider system with the same ring diameter as the electrode carrier system moves on the gradu¬ ated horizontal bar of the cruciform slider system. For trans¬ verse movement (Z axes) the cursor on the graduated horizon¬ tal plane of the electrode carrier system is used. A long rectangular plate is attached to the cursor and an arc (a part of imaginary sphere, 26 cm in diameter) is grooved on the plate where the electrode holder system moves in the groove, so that the electrode passes through the center of the burr hole. When the square electrode carrier system is attached to the head frame, the X and Y coordinates are adjusted to zero on ei¬ ther member on the lateral side of the frame and the rings of the electrode carrier system and those of the horizontal sliding bar are duplicated and attached by a ring screw in which a clear plas¬

tic plate is fixed (Fig. 15-3A). Two cruciform radiopaque lines are drawn, and the zero point is located on the line connecting the two crossed points in each ring screw. This ring permits x-ray verification of the relationship of the electrode and the target area

Figure 15-2. Sugita apparatus type II. The patient’s head is fixed in the inner frame and the fixed head can be rotated around the vertical axis a total of 5° in either direction.

B

Figure 15-3. Sugita apparatus type II. A. Basic head frame and attached members of X and Y axes and the rotation rings and ring screws. The cursor for Z axes moves on the transverse plane of the electrode carrier system. The electrode holder system moves in the groove on the rectangular plate fixed on the cursor. B. Collimation stand.

Chapter ] 5/The Sugita Apparatus

133

Figure 15-4.

The center (zero point) of the system (C) and the X and Y coordinates of the target point (7). The magnification ratio of the x-ray film is calculated and the zero point (C) is the point where lines A1B4 and A4B1 cross.

(Fig. 15-4). The electrode carrier system rotates around the rings by unscrewing it (Fig. 15-3A). For measuring the coordinate of the target point on the film, the magnification rules (each magni¬ fication rate; 105 percent up to 135 percent, increased in 0.5 per¬ cent increments) are made. The magnification rate of each film is easily calculated by measuring the distance between the two cones on each side of the head frame (Fig. 15-5). In phantom tar¬ get instruments (Sugita type I), collimation of the system and of the electrode bending are done in each procedure. However, tri¬ plane stereotactic instruments (Sugita type II) have no collima¬ tion system when the patient’s head is fixed in the head frame. A stand for the square electrode carrier system is made for collima¬ tion of the system and of electrode bending. There are two of the same rings as the electrode carrier system on either side of the

Figure 15-5.

Lateral view of x-ray film when the electrode is placed in the target point.

stand, and a target indicating cone lies in the center of the bar (Fig. 15-35). For collimation of the x-ray beam after mounting, a leveling device is made, which is adapted not only to the antero¬ posterior x-ray beam but also the lateral x-ray beam.

NEUROPHYSIOLOGICAL LOCALIZATION Radiological information concerning structural localization within the human thalamus must be supplemented by neuro¬ physiological methods. In our early functional stereotactic pro¬ cedures, the targets were localized from a ventriculogram, and

134

Part 1/Stereotactic Principles

evoked activities in the electroencephalogram (EEG) following stimulation in the thalamus were recorded.16'18 The threshold study of mydriasis following stimulation of the target area was a more accurate method to identify the bottom of the ventrolat¬ eral nucleus of the thalamus (Fig. 15-6). Although those stimu¬ lation methods are beneficial to the localization in the trajec¬ tory, they do not provide any neurophysiological information outside the trajectory. A stimulation study reproduces tremor, but it is just a physiological confirmation method at the target area.

THE MICROMANIPULATOR SYSTEM The depth microelectrode studies are the most reliable method to determine the physiological target point and to correct the anatomic target point if a group of neurons respond to a certain stimulation. Ohye described that there are some rhythmic burst neurons in some restricted areas in and around the ventralis intermedius (Vim) nucleus and that the tactile neurons are dis¬ tributed in the ventralis caudalis (Vc) nucleus and the kines¬ thetic neurons in the Vim nucleus.19 Our micromanipulator is driven by a pulse motor in lO-pim steps and is able to carry up to nine microelectrodes simultaneously. The distance between two electrodes is 3 mm center to center, but usually two elec¬ trodes are used (Fig. 15-7). The distance from the target point to the tip of the electrode is shown by the digital display in the control unit of the microdrive. It is manipulated at three speeds: fast (1 mm/s) continuous movement, medium (0.1 mm/s), and slow (10 p,m/s), and also 10-p.m steps by each manual control. The control unit stops at a preset distance from the target point. The slow continuous movement of the electrode is the opti¬ mum speed for finding either firing kinesthetic or tactile neu¬ rons (Fig. 15-8). In order to record a group of those firing neurons, a bipolar, concentric, fine-tipped electrode (semi¬ microelectrode) is optimal. The semimicroelectrode is fabri¬ cated from electrically insulated steel wire in an insulated steel tube (outer diameter 0.5 mm), polished on a rotating grindstone at its tip to about 10 to 20 pm. The impedance of the electrode is 40 kfl to 60 kfl, and the conditions for recording by the elec¬ trodes are stable in the operating room. In order to measure the

Figure 15-7. Microdrive unit with two semimicroelectrodes. While the microdrive unit moves in the groove of the rectangular plate, the tip of semimicroelectrode is placed at the tip of the cone on the collimation stand.

impedance of the electrode at any time, an impedance meter fed by an exciting voltage frequency is made. It is very helpful to check the condition of the tip of one electrode by the change of impedance without removing it whenever recording condi¬ tion might become worse. The semimicroelectrode is so thin that it is carried inside a stainless pipette 2 mm in diameter. The tip of the electrode, 10 to 15 mm in length, is extruded. For a recording system, we have employed a stable amplifier, made for electromyography (Medelec MS-6), which is beneficial for reducing background noise, even in the unshielded operating room. The audiomonitor of Medelec MS-6 is very helpful for evaluating the change in background noises before neuronal firing is detected on the oscilloscope (Fig. 15-9).

LESION PRODUCTION AND ELECTRODES

Figure 15-6. Schematic illustrations of neurophysiological responses by stimulation studies at various depths of the trajectory (abscissa) in the ventrolateral nucleus of the thalamus.

The most common and safe lesion production method is ra¬ diofrequency heating. A radiofrequency coagulator was devel¬ oped in our laboratory for stereotactic lesion production. It consists of three components: a high-frequency generator with an output power controller, a thermometer, and a timer (Fig. 15-10). The radio-frequency generator generates sine waves of 300 ±5 kHz, and its output power is set up to 20 W when con¬ nected to a suitable load. A thermistor is mounted in the elec¬ trode tip and is graduated from 0° to 100°C. The output is fed to the controller of the generator so that the temperature at the electrode tip is maintained within the preset range. When the temperature at the electrode tip reaches the preset degree, the

Chapter 15/The Sugita Apparatus

135

L-Thal. Electrode b.

B L-Vim. Electrode a. R-Thumb abduction

L-Vc. Electrode b. R-Thumb touch

j.JsOuV 100MS

Figure 15-8. A.

Rhythmic burst discharges by the anterior semimicroelectrode (electrode a) 2.0 mm behind the target point. B. Responses of kinesthetic neurons in the ventralis intermedius nucleus (Vim) of the thalamus by the anterior semimicroelectrode (electrode a) and responses of tactile neurons in the ventralis caudalis nucleus (Vc) by the posterior semimicroelectrode (electrode b) at 1.6 mm behind the target point.

timer starts. After the desired coagulation time, the output of the coagulator is switched off by a signal from the timer. The size of the coagulation lesion can be controlled by the coagula¬ tion temperature and time. If there is overheating or extraordi¬ nary electric current in the electrode, the radiofrequency cur¬ rent to the electrode is immediately disconnected and a flashing red warning lamp is activated simultaneously (Fig. 15-11).

Coagulation Electrode 1.

2.

3.

4.

Figure 15-9.

This block diagram illustrates all our depth microelectrode studies and our stimulation and coagulation systems.

Standard electrode (Fig. 15-12E and F). The electrode con¬ sists of a stainless steel tube (300 mm in length, 2.0 mm in diameter) and a round gold tip (4.0 mm, 2.0 mm in length) with a built-in thermistor. The entire electrode surface is insulated except at its gold tip. A quarter-exposed electrode (Fig. 15-12D). This electrode is similar in configuration and size to the standard type with only a quarter of the tip uninsulated. String electrode (Fig. 15-125).This type of electrode is de¬ signed to coagulate a lesion next to the target, and if it is rotated around the target, a coagulation lesion will be made in any direction around the target. The thermistor is not built in the branch of the electrode, so manual control of coagulation is required. However, application of this elec¬ trode has decreased since the development of semimicro¬ electrode recording. Coagulation lesion of egg white by a standard electrode at each temperature (Fig. 15-13): (1) 30 s at 50°C; (2) 22 s at 65°C; (3) 30 s at 65°C; (4) 60 s at 65°C; (5) 30 s at 95°C.

The stimulation electrode (Fig. 15-12C) is a concentric bipolar electrode, the length and diameter of which are same as those of the coagulation electrode. The axial electrode pro¬ trudes to 1.0 to 3.0 mm.

Part 1/Stereotactic Principles

136

it*

■

• I ■ &a

11 i ft* TOHAI NIKA CO..LT™

Figure 15-10. Radiofrequency coagulator.

k)

a

b

c

d

e

f

l!!i!!lilillll!!iiil!l!lil!!!llll!!lllllli!lllll!!!l!l!lllllllliill

Figure 15-11. Block diagram of the radiofrequency coagulator.

Figure 15-13. Coagulation lesion of egg white by a standard electrode at each temperature: (1) 30 s at 5()°C; (2) 22 s at 65°C; (3) 30 s at 65°C; (4) 60 s at 65°C; (5) 30 s at 95°C.

Figure 15-12. Various types of electrode tips. A. Cannula of each electrode. B. String electrode. C. Bipolar stimulation electrode. D. A quarter-exposed electrode. E and F. Coagulation electrode, 2-mm and 4-mm tips.

Chapter 15/The Sugita Apparatus

COMPUTED TOMOGRAPHY-BASED STEREOTACTIC APPARATUS The type II apparatus is easily modified to a CT-based stereotac¬ tic apparatus by replacing only the fixing pins and the electrode carrier system with carbon fiber material. For calculating stereo¬ tactic coordinates, the localizer devices made of carbon fiber rods are used; these are attached to each pair of cones on the head frame (Fig. 15-14). The head frame is attached to the CT table by carbon fiber attachment units. This unit can be used for stereotactic procedures in the posterior fossa and the brain stem. The advantage of this stereotactic apparatus is that the le¬ sion can be observed by CT even while a hematoma is being aspirated or a biopsy taken.

References 1.

2. 3. 4. 5. 6. 7. 8. 9. 10.

11.

12.

13. 14. 15. 16.

17.

Figure 15-14.

A CT-based stereotaxic apparatus. The head-fixing pins and electrode carrier system are replaced by carbon fiber material. The four localizer devices are attached to each pair of cones.

137

18. 19.

Bailey P, Stein SU, Seymour U: A stereotactic instrument for use on the human brain, in Studies in Medicine III. Springfield, IL: Thomas, 1951, pp 40-49. Narabayashi H, Okuma T: Procain oil blocking of pallidum in case of athetose double. Psychiatr Neurol Jpn 54:672-677, 1952. Spiegel EA, Wycis HT, Marks M, Lee A: Stereotaxic apparatus for operations on the human brain. Science 106:349-350, 1947. Wada T: A modified stereotaxic apparatus for brain surgery of deep portions. Tohoku J Exp Med 58: 299-303, 1953. Austin GM, Lee AS: A plastic ball and socket type of stereotactic di¬ rector. J Neurosurg 15:264—268, 1958. Cooper IS: Chemopallidectomy: An investigative technique in geri¬ atric Parkinsonism. Science 121: 217-218, 1955. Gillingham FJ, Watson WS, Donaldson AA, Naughton JAL: The sur¬ gical treatment of Parkinsonism. BrMerf 72:1395-1402, 1960. Sano K: A simple stereotaxic apparatus. Neurol Med Chir 1:253-256, 1959. Walker AE: Stereotactic instrumentation. J Neurosurg 24:468, 1966. Talairach J, Hecaen H, David M, et al: Recherches sur la coagulation therapeutique des structures sous-corticales chez l’homme. Rev Neurol 81:4-24, 1949. Riechert T, Wolff M: Uber ein neues Zielgerat zur intrakraniellen elektronische Ableitung und Ausschaltung. Arch Psychiatr Nervenkr 186:225-230, 1951. Sugita K, Murata K: A stereotaxic apparatus for brain surgery and high frequency coagulator with automatic thermocontrol. Nagoya J Med Sci 28:126-141, 1966. Leksell L: A stereotaxic apparatus for intracerebral surgery. Acta Chir Scand 99:229-233, 1949. Sugita K, Hirota T: Stereotaxic surgery. Noshinkeigeka 4:219-228, 1976. Van Buren JM: A stereotaxic instrument for man. Electoencephalogr Clin Neurophysiol 19:398—403, 1965. Sugita K, Doi T: The effects of electrical stimulation on the motor and sensory system during stereotaxic operations. Conf Neurol 29; 224-229, 1967. Sugita K, Takaoka Y, Mutsuga N, et al: Correlation between anatomi¬ cally calculated target point and physiologically determined point in stereotaxic surgery. Conf Neurol 34:83-93, 1972. Sugita K, Mutsuga N, Takaoka Y, Doi T: Results of stereotaxic thala¬ motomy for pain. Conf Neurol 34: 265-274, 1972. Ohye C: Depth microelectrode studies, in Schaltenbrand G, Walker AE (eds): Stereotaxy of the Human Brain. 2d ed. New York: Thieme, 1982, pp 372-389.

CHAPTER

16

THE GUIOT-GILLINGHAM APPARATUS

John Gillingham

Early in 1953, after Reichert in Freiberg and Leksell in Stockholm had developed stereotactic prototypes based on the work of Spiegel and Wycis in 1947,1 received a telegram from Gerard Guiot in Paris that read, “I have something interesting to show you—come over.” Guiot had visited Edinburgh to see our work on ruptured intracranial aneurysms, and we had de¬ veloped a good rapport. I quickly responded, and we spent 4 days operating on patients with parkinsonism, using the open craniotomy approach to the globus pallidus under local anes¬ thesia that was devised in 1948 by Fenelon and Thiebaut.1 The results were immediately impressive, and when I returned to Edinburgh, two patients were treated in this way, again with good results and with surprisingly long-lasting benefits in terms of relief from tremor and rigidity and an improvement in the quality of life. These two patients, among others with palli¬ dal lesions made stereotactically, were reported in 1960. Their animation was also restored and a review of motion pictures made at that time confirms that bradykinesia was also conspic¬ uously improved. This result lends support to recent claims by Laitinen in Sweden of the effectiveness of the ventral pallidal lesions interrupting the ansa lenticularis.2 These two operations also made a valuable contribution to the operative management of ruptured intracranial aneurysms. They showed the effect and danger of prolonged retraction of the frontal lobe and the ischemic effect of stretching the striate branches of the anterior circle of Willis on the hypothalamus and basal brain structures.3 However, the open operation under local anesthesia was ex¬ acting both for the patient and for the surgeon. While I was in Paris, Guiot and I discussed this problem, the encouraging re¬ sults, and the advantages of stereotactic surgery. In retrospect, it is interesting to realize that intracranial stereotaxis gave birth to minimal interventional surgery, which has been widely em¬ braced in other specialties besides surgical neurology. Guiot already had an outline plan and a mock-up of his own frame. He wanted to avoid clamping the patient’s head and re¬ stricting the patient’s movements during an operation. A com¬ fortable patient would make subjective and objective neurolog¬ ical examination easier and more informative, particularly in regard to consciousness level and speech. He was against rely¬ ing too much on calculation for target siting. He planned to pass an electrode 17 mm lateral and parallel to the midline (marked by the septum pellucidum and the center of the third ventricle), with the tip being maneuvered indirectly to its tar¬ get, doing screening with an image amplifier. Contrast media inserted into the third ventricle would outline the midline, the

anterior and posterior commissures, and the intercommissural line. We discussed these ideas in some detail, modifying them here and there. However, rather than pass the electrode from the usual coronal burr hole to the pallidum, the prime target site at that time, I preferred a posterior entry. This would eliminate the possibility of transgressing the many and important striate arteries en route from an anterior approach. Therefore, despite the longer route, we decided to reach the pallidum from an oc¬ cipitoparietal entry. The midline was outlined for each patient by placing ra¬ diopaque markers at coronal and occipital sites against the cen¬ ter line of the third ventricle and the septum pellucidum. In Edinburgh, we added further markers in the frontal region for increased accuracy (Figs. 16-1 and 16-2). We also emphasized the fact that radiological studies and the operative procedure were always done in the horizontal position, which eliminated “sagging” of the brain in older patients or when atrophy was evident during the use of the half-sitting position. This factor had led to major errors in target siting.4,5 After a lesion approximately 5 mm in diameter was made using fractionated heat with endothermy, a stainless steel ball with a diameter of 1 mm would be left at the anterior part of the lesion for subsequent charting on stereotactic atlases. As the weeks passed, the ball was seen to fall posteriorly and interi¬ orly through the necrotic sphere, providing an approximate size of the lesion. As things turned out, we were fortunate in choosing the pos¬ terior route for two reasons. After Hassler5a indicated that the ventralis oralis posterior (V.o.p) [ventro lateral nucleus (VL)] of the thalamus was an improved target for the elimination of tremor, we had only to drop the trajectory of our electrode 2 to 3 mm at the burr hole and move it 2 mm more medially (Fig. 16-3). Thus, the electrode would pass through the V.o.p. and on to the target in the pallidum. Only one pass would be required. We remained convinced that a lesion in the pallidum was es¬ sential for the complete relief of rigidity. Indeed, it was inter¬ esting to observe and measure further loss of rigidity as the electrode slowly crossed the internal capsule; this loss became complete as the lesion was made in the pallidum.6 This was the basis for our preference for a double lesion which strategically interrupted the connections of the thalamus and pallidum, crossing the internal capsule (Fig. 16-3). However, it was evident that the results from our lesions were not consistent despite intraoperative neurological assessment un¬ der local anesthesia. We were aware of the work of Brierley and

139

140

Part 1/Stereotactic Principles

Figure 16-1. Myodil (iophendylate, Pantopaque) in the third ventricle to outline the midline (note the patient's horizontal position and the fact that the small amount of dye is removed afterward from the lumbar theca).

STUD

Figure 16-2. The frame in position, showing the tip of the electrode lined up on the anterior commissure. The patient's head is manipulated under the image intensifier until the radiopaque stud lies within the ring on the opposite side of the head, corresponding to the electrode tip.

Chapter 16/The Guiot-Gillingham Apparatus

141

Figure 16-3.

Lowering of the trajectory to allow one pass of the electrode to traverse both the thalamic and the pallidal targets.

Beck,7 who had shown the fallacy of relating the anatomic struc¬ tures of the basal ganglia to the anterior and posterior commis¬ sures. As much as 1 cm of error could occur in the relationship of the posterior commissure to the thalamic nuclei.8,9 It was fortunate that in 1961 I had been introduced to depth microelectrode recording by Whitteridge, a neurophysiologist in Edinburgh, as a means of accurately defining the borders of gray and white matter. He had used this technique in exploring the external geniculate ganglia of the cat as part of his original work on the visual system. This seemed to be a possible solu¬ tion to the problem of inaccuracy in target siting and immedi¬ ately led to our application of the technique to humans. Guiot and associates10 were developing a similar method. The definition of the borders of gray and white matter was precise, but what was surprising was the clear and exact outlin¬ ing of all the nuclei of the thalamus, the reticular nucleus, the capsule, the pallidum and of course the V.o.p., each with its own frequency and amplitude (Fig. 16-4). Thus, localization of targets could be done accurately with a margin of error less than 1 mm. Our own studies of the anatomic variation of the nuclei of the basal ganglia from one patient to another (and even from one hemisphere to the other) and also of the commissures con¬ firmed the work of Brierley and Beck7 (Fig. 16-5). The posterior route we were using was rich in information when explored with depth microelectrode recording, but unfor¬ tunately, the coronal track gave relatively poor information. As one would expect, evolution of our apparatus was necessary as new opportunities for therapy arose, such as temporal lobe epilepsy and the obsessive neuroses. A phantom was employed

to allow an oblique track to reach more medial targets, and an extension downward of the posterior limb of the frame was made to permit exploration of the cerebellum and the upper cervical spinal cord for dystonias and intractable pain. The 1977 version of the apparatus was developed, based on the old model by I. M. L. Donaldson and myself, to add further precision and allow single-cell recording, using a small sterlizable motor to drive the electrode slowly to the target (Fig. 16-6). Electrodes had been modified over the years, and nee¬ dles had been developed for microbiopsy and biochemical as¬ say from target sites before lesion making. Techniques for the precise measurement of tremor and rigidity before, during, and after an operation were developed similarly.11 Our interest in stereotactic techniques following these early beginnings in 1953 encompassed the dyskinesias, including parkinsonism, epilepsy, the obsessive neuroses, and the effectiveness of the evacuation of deep hematomas and tu¬ mor biopsy. The effectiveness of these procedures and the rea¬ sons for their success or failure have been published.12,13 There is no doubt that the work of a closely knit, disci¬ plined, and comprehensive team using this type of minimal in¬ terventional surgery, particularly with modern computer tech¬ nology, can greatly increase the quality of life for many patients. Above all, the opportunities for unraveling the basic mechanisms of chronic neurological disease are considerable. These opportunities are well illustrated in the unfolding of the story of the surgical management of parkinsonism. An objec¬ tive ten-year study of our patients treated between 1965 and 1967 was carried out in 1978 by Kelly.13 The findings were summarized as follows:

142

Part I/Stereotactic Principles

Figure 16-4. Electrode track (lateral 16 mm). Records f and h show regular bursts of action potentials in response to rhythmic tap stimulation of the face

Figure 16-5. Superimposed recordings from several patients showing the anatomic variation of the nuclei of the basal ganglia from one patient to another. Laterality 15.0 mm (includes 14.3 mm to 15.5 mm from the midline).

Chapter 16/The Guiot-Gillingham Apparatus

143

Figure 16-6. The 1977 frame with a small electric motor that drives the electrode slowly through the subcortical areas, recording as it goes.

Sixty patients with Parkinson’s disease underwent stereo¬ tactic surgery in Edinburgh between 1965 and 1967 and were examined by the full team (neurological, rehabilita¬ tion, and psychological) every 2 years for a total follow-up period of 10 years. Although stereotactic surgery had been extremely effective in treating tremor and rigidity, the other manifestations of the disease were noted progressively to affect more patients at each follow-up examination. L-dopa therapy was instituted in 36 patients in 1968. The effect on bradykinesia was remarkable but the long-term benefits on the other manifestations of Parkinson’s disease was negligible. Furthermore, in most cases L-dopa became progressively ineffective for bradykinesia in 3 to 5 years. Ldopa-induced tremor and involuntary movements were less frequently noted in limbs contralateral to the side of a previ¬ ous srereotactic procedure. It was concluded in patients pre¬ senting with tremor and rigidity as the major problems in their parkinsonian syndrome, the most effective form of pal¬ liative therapy is stereotactic surgery, and that L-dopa should be reserved for bradykinesia. Since the time of that study, the side effects of prolonged L-dopa therapy have become an increasing problem and con¬ siderable interest is being shown in returning to surgical man¬ agement and to the possibility of prolonged relief of bradykine¬ sia with the lesion in the ventral pallidum. The benefits of dopamine cell transplantation to the striatum have yet to be es¬

tablished, although recent work on implantation within the putamen has raised new interest. Perhaps we have been unduly preoccupied by the signifi¬ cance of dopaminergic transmission in the whole parkinsonian syndrome and have lost sight of the importance of transmitter systems that determine aspects of the disease other than brady¬ kinesia, namely tremor and rigidity—the adrenergic and cho¬ linergic systems and their interdependence. The different surgi¬ cal targets providing the optimum relief would seem to point in this direction for future research.

References 1.

Fenelon F, Thiebaut F: Resultats du traitment neurochirurgical du syndrome parkinsonien par intervention direct sur les voies extrapyrimidales immediatement sous-striopallidales (anse lenticulaire). Rev Neurol (Paris) 83:437-^440, 1950. 2. Gillingham FJ, Watson WS, Donaldson AA, Naughton JA: Surgical treatment of parkinsonism. Br Med J 2:1395-1402. 1960. 3. Gillingham FJ: The management of ruptured intracranial aneurysms. Ann R Coll Surg Engl 23:89-117, 1958. 4. Smith MC: Location of stereotactic lesions confirmed at necropsy. Br Med J \:900-906, 1962. 5. Hanieh A, Maloney AFJ: Localisation of stereotactic lesions in the treatment of parkinsonism: A clinico-pathological comparison. J Neurosurg 31:393-399, 1969. 5a. Hassler R: 1. The pathological and patho-physiological basis of tremor of parkinsonism. IV. The influence of stimulations and coagu-

144

6.

7.

8. 9.

Part 1/Stereotactic Principles

lations in the human thalamus on the tremor at rest and its physiopathological mechanism. Proceedings Second International Congress Neuropathology. London 1:29(4)637, 1955. Gillingham FJ. Tsukamoto Y, Walsh. EG: Treatment of rigidity, in Siegfried J (ed): Parkinson's Disease. Bern-Stuttgart-Vienna: H. Huber, 1987, vol 1, pp 94-114. Brierley JB, Beck E: The significance in human stereotactic brain surgery of individual variation in the diencephalon and globus pallidus. J Neurol Neurosurg Psychiatry 22:287-298, 1959. Gillingham FJ: Small localised lesions of the internal capsule in the treatment of the dyskinesias. Conf Neurol 22:385-392. 1962. Gillingham FJ: Accidents in stereotaxy: Side effects or bonus? Acta Neurochir Wien, 21:5-12, 1974.

10.

11. 12.

13.

Guiot G, Hardy J, Albe-Fessard D, et al: Precise definition of the subcortical structures and identification of thalamic nuclei in man by stereotactic electrophysiology. Neurochurgia (Stuttg) 5:1-18. 1962. Gaze RM, Gillingham FJ. Kalyanaraman S. et al: Microelectrode recordings from the human thalamus. Brain 87:691-704. 1964. Gillingham FJ, Watson WS, Chung S, Yates C: Central brain lesions for the control of intractable epilepsy. Adv. Epilept. X: Epilepsy International Symposium, Wada JA, Penry JA (eds): New York: Raven Press. 1980, pp 251-255. Kelly P, Gillingham FJ: Long-term results of stereotactic surgery and L-Dopa therapy in patients with Parkinson's disease: A ten-year follow-up. J Neurosurg 53:332-337, 1980.

CHAPTER

17

THE UTEC STEREOTACTIC APPARATUS

Rudi Verbeeck, Bart Nuttin, Jan Gybels, Dirk Vandermeulen, Paul Suetens, and Guy Marchal

In the late 1950s, a stereotactic apparatus was developed at the Technical Experimental Center of the University of Leuven, Belgium. The system was called UTEC, after the Dutch name of the center: Universitair Technisch Experimented Centrum. Although this technology is now outperformed by modern

tional stereotactic intervention on the basis of the principles described above.2 A general view of the system is shown in Fig. 17-1. The patient is seated in a chair. A comfortable position is important; the height of the chair can be adjusted for this pur¬

stereotactic equipment, it had distinct benefits that made it a valuable tool that is still used for some indications.

pose. The sitting position was required for the puncture of the frontal horn of the lateral ventricles and the injection of con¬ trast fluid into the ventricular system. In the supine position, the contrast fluid would drain through the third and fourth ven¬ tricles to the spinal canal. The stereotactic frame itself was swung down over the patient’s head and locked in a horizontal position, aligned with the x-ray equipment. The frame supports the patient, not the other way around. The patient has to be po¬ sitioned carefully and fixed in the frame because the accuracy of the target coordinates depends on the positioning of the patient.

HISTORICAL NOTE In 1959, Dereymaeker, a neurosurgeon, and De Dobbeleer, an engineer, published a paper titled “Contribution au progres de la stereotaxie cerebrale: Un nouvel encephalotome humain.”1 In the introduction, they cited 24 different instruments that had been constructed by others since 1947 and concluded, “Leur multiplicite traduit deja leurs imperfections” (“Their sheer number tells us of their imperfections”). Approximately five units of the UTEC system were sold worldwide. After having seen at the beginning of his professional life the instruments designed by the leaders in the field of stereotaxis at that time, Gybels, the senior author of this chapter, adopted the UTEC system in 1964. At the end of his professional life in 1994, he was still using, with a few minor modifications, the same in¬ strument for patients with movement disorders and for most patients in whom a deep brain electrode was implanted for the treatment of persistent pain.

TECHNICAL DESCRIPTION OF THE SYSTEM When the UTEC system was developed, stereotactic tech¬ niques were applied mainly in the treatment of functional dis¬ orders. During those interventions, selective cerebral pathways or nuclei were stimulated or destroyed. With the imaging modalities of that period, direct position measurements of the target nuclei were not possible. The nearest internal brain struc¬ tures that could be visualized on an x-ray picture were the ven¬ tricles. Two characteristic points on these ventriculograms, the anterior commissure (AC) and the posterior commissure (PC), together with the midsagittal plane, served as reference struc¬ tures. The position of the target nucleus relative to these refer¬ ence structures was inferred from a stereotactic atlas. The UTEC stereotactic equipment is custom-designed for func¬

Figure 17-1. 145

General view of the UTEC stereotactic system.

146

Part 1/Stereotactic Principles

Screw for tightening posterior fixation pin

Posterior fixation pin

Anterior fixation pin Screw for fine-tuning patient position (rotation around vertical axis)

Screw for fine-tuning patient position (rotation

Screw for tightening

around horizontal axis)

anterior fixation pins

Figure 17-2. The UTEC stereotactic frame with the fixation pins.

The position of the projection of the target nucleus on the midsagittal plane relative to the AC and PC reference points is known from the stereotactic atlas. This position can be trans¬ ferred to the stereotactic frame by identifying and measuring the target on a lateral ventriculogram. If the midsagittal plane of the patient does not correspond to the sagittal symmetry plane of the stereotactic frame (but both planes meet at an an¬ gle a, for example), the error at the target point is equal to the laterality of the target times tg(a), which can amount to about 1 mm. The head of the patient is first fixed by using the two ante¬ rior fixation pins. The 15-mm stainless steel pins are detachable because they have to be sterilized. The fixation arms rotate around their vertical support axis as the surgeon tightens the central anterior screw of the frame (Fig. 17-2). As the arms turn, sharp pins at the ends of the fixation arms approach each other. A local anesthetic is applied before this treatment. The pins penetrate the skin and the scalp of the patient, and so no skin incision or drilling is necessary. The penetration points of the screws are chosen at about two finger widths above the ex¬ ternal canthus of the eyes. This type of motion of the anterior fixation pins ensures that the midpoint between the pins is al¬ ways the same and is in the sagittal symmetry plane of the frame. If the patient is positioned symmetrically, the midsagit¬ tal plane of the patient will coincide with the sagittal symmetry plane of the frame. The positioning of the patient is verified by taking a frontal x-ray and measuring the distance from two comparable points (left and right) to the midsagittal plane. Two additional screws on the anterior side of the frame allow the surgeon to adjust the patient's position slightly by rotating the anterior fixation pins around a vertical or horizontal (anteroposterior) axis. After that, the posterior pins fix the patient in the frame after the application of a local anesthetic (Fig. 17-3). As shown in Fig. 17-2, the only possible direction of motion for these pins is inward-outward. In a profile view, the line through the anterior and posterior pins should be parallel to the Frankfort plane, which is represented by a line through the inferior orbital rims and the external auditory meati.

The anteroposterior and vertical coordinates of the target point are calculated from a lateral ventriculogram. The x-ray film is mounted in a special holder on the frame (Fig. 17-3). The x-ray source is aligned with the stereotactic frame and can easily be positioned correctly for an exact lateral or frontal acquisition. The distance from source to film is small, however (on the order of 2 m), so that the assumption of orthogonal pro¬ jections, as in teleradiographic techniques, is not valid. In a perspective projection geometry, as in our situation, structures close to the source are imaged with a different magnification than are structures farther away. This distortion obviously has to be taken into account in calculating the target coordinates.

Figure 17-3. Configuration for the acquisition of a lateral ventriculogram. A graduated arc is placed in the midsagittal plane. The scales project on the x-ray. The radiographic film is attached to the stereotactic frame.

Chapter 17/The UTEC Stereotactic Apparatus

When the UTEC system was developed, the avoidance of tele¬ radiographic techniques, which required an adapted operating theater and image intensifiers, was an important design deci¬ sion that cut the cost of the system considerably. A sagittal arc is placed on the frame (Fig. 17-3). Two metric scales of lead amalgam are embedded in the arc and are pro¬ jected onto the lateral ventriculogram (Fig. 17-4). If we take care to place the arc in the midsagittal plane,* the magnification at the position of the AC and PC reference structures can be in¬ ferred directly from the metric scale on the film. The exact value of the AC-PC distance can be verified by measurement. The orthogonal projection of the target position on the midsagittal plane can be marked on the film according to the coor¬ dinates given by the atlas or known from experience. Two arbitrary lines are drawn that intersect at the position of the target point. These lines intersect the scales on the film at four points (Fig. 17-4). From those four values, both the an¬ teroposterior and vertical coordinates of the target point can be calculated by solving a linear set of two equations with two un¬ knowns. Using a modern programmable calculator, the target coordinates can be obtained in a few seconds. The designers of the UTEC stereotactic system wanted to avoid all possible sources of human error and did not want to take the attention of the surgeon away from the patient. Thus, instead of using a slide rule for the calculations, they developed a dedicated ana¬ logue computer. In this computer, the two lines on the x-ray are represented electrically by two potentiometers (variable resistors; the resis¬ tance value represents the position along the line). The voltage that is applied to these resistors depends on the output of four other potentiometers that represent the intersection points on the scales. These four potentiometers are labeled with digits and can be set accurately to the intersection values. We can find the cross-sectional point of the two lines by simultaneously

147

* The lateral position of the arc can be read off scales on the stereotactic frame, with the midsagittal plane being defined by the value zero.

tuning the former two potentiometers to a point of equal volt¬ age. These potentiometers are also labeled with digits. The co¬ ordinate of the intersection point is given by the value to which these resistors are tuned. To tune the potentiometers quickly and accurately, their output is alternately applied to an oscillo¬ scope with an appropriate time base. The oscilloscope shows two lines that coincide when the potentiometers are tuned to the same voltage. Calculation of the target coordinates using this method takes about 40 s and is accurate to 0.05 mm. The potentiometers are arranged in a configuration on the switch¬ board of the analogue computer that prevents mistakes. A target-centered stereotactic arc then replaces the sagittal arc. The stereotactic arc is placed in a coronal plane at the an¬ teroposterior coordinate of the target point (Fig. 17-5). The height of the stereotactic arc is adjusted to the vertical position of the target point. The vertical legs of the arc contain a metric scale in lead amalgam that projects onto the frontal ventriculo¬ gram. The arc therefore should be positioned in a strict vertical plane; otherwise, the scale will be distorted on the x-ray. Since the stereotactic arc is placed in the same plane as the target point, the magnification of the x-ray at that position can be read directly off the scales. As the height of the arc has been set to the vertical target coordinate, the vertical position of the target can be indicated on the frontal ventriculogram by draw¬ ing a horizontal line through a fixed value on the scales (500) (Fig. 17-6). A line perpendicular to this line, halfway between the left and right intersection points with the third ventricle, in¬ dicates the midsagittal plane (if this does not correspond to the midsagittal plane of the patient, the patient was positioned in¬ correctly). The laterality of the target point,which is known from the atlas, is measured off the scales on the film, and the position of the target is marked. Using the same intersecting line construction as on the lateral ventriculogram, one can de¬ termine the vertical and lateral target coordinates. The resulting value that is obtained for the vertical coordinate should equal 500. The lateral position of the stereotactic arc is adjusted to the lateral coordinate value of the target point.

Figure 17-4. Two arbitrary lines are drawn through the target point on a lateral ventriculogram. The anteroposterior and vertical target coordinates can be calculated from the intersection points of these lines with two vertical scales.

Figure 17-5. The stereotactic arc is positioned in a coronal plane at the anteroposterior level of the target point.

148

Part 1/Stereotactic Principles

Figure 17-6. A construction similar to that shown in Fig. 17-4 is drawn on the frontal ventriculogram to determine the laterality of the target point.

The stereotactic arc is target-centered and has 2 degrees of freedom. It can rotate about a left-right axis (through the target point). The probe guide moves on a sector of a circle that has its rotation point on the target (Fig. 17-7), allowing the surgeon to approach the target from any suitable position on the cra¬ nium. When the burr hole, which usually is made during a preparatory intervention a few days earlier, can be seen through the probe guide, the position of the stereotactic arc is fixed, and the actual surgical intervention can start. When flexible electrodes are inserted into the brain, they may bend by their own weight and deviate from the trajectory to the target point. To avoid these deviations, the whole UTEC system can rotate to bring the electrode path into a vertical

Figure 17-7. The UTEC stereotactic arc is target-centered. The sector of the circle that holds the probe guide has its rotational center on the left-right rotation axis of the stereotactic arc. These degrees of freedom of the arc allow the surgeon to approach the target from any admissible direction.

plane (Fig. 17-8). The length of the electrode has to be the same as the radius of the sphere that is described by the rotation of the stereotactic arc. If electrostimulation at the target site suggests that the po¬ sition of the target should be changed, the surgeon can rely on the millimeter scales on the frame. There is no need for another x-ray localization of the new target point. However, additional x-ray images may be acquired with the electrode in place as a final check. Overlaying these images onto the original ventricu¬ lograms should show the electrode tip at the indicated target position.

SUMMARY The UTEC stereotactic system has certain specific characteris¬ tics and distinct benefits: •

The patient is rigidly fixed in the stereotactic frame without the need for drilling into the bone or repeat fixation. The rigid fixation makes the system well suited for the treatment of parkinsonian patients.

*Thi\ is not a prerequisite with the UTFC system.

Figure 17-8. The whole UTEC system can be rotated from a horizontal plane to a vertical plane.

Chapter 17/The UTEC Stereotactic Apparatus

•

Nevertheless, the system is comfortable for the patient, who is supported by the frame. Without a loss of comfort, the UTEC system allows all the necessary freedom to the sur¬ geon to position the patient correctly into the frame and tilt the whole system to bring the electrode into a vertical plane for implantation. Normally, a procedure can be completed in 1 h.

•

The system initially was relatively cheap because the use of teleradiographic techniques and image intensifiers was avoided. There was no need for a specially designed operat¬ ing theater. The effect of the distortions in the resulting perspective projection geometry of the x-ray images was minimized by placing the measurement scales at the depth of the structures that were measured (the midsagittal plane or the coronal plane through the target position).

•

•

•

The determination of the target coordinates avoids absolute measurements on the film. Any nonparallelism of the ra¬ diopaque scales of the sagittal arc or the stereotactic arc with the film plane does not introduce an error in the target coordinates.’ It is recommended that one position the x-ray source on a line perpendicular to the film plane and passing through the target point. Failure to do so, however, does not produce an error in the target point coordinates. A special-purpose analogue computer was developed to calculate the target coordinates from the film measurements quickly and accurately. The UTEC system was the first to use a computer for the calculation of the target coordinates. The overall accuracy of the system is on the order of 0.5 mm.

• The intersection point of the line construction on the film is still the pro¬ jection of the intersection point of the reconstruction of those lines in space even if the film plane and the plane of the arc are not strictly parallel.

149

•

For scientific purposes, it is interesting to be able to calcu¬ late the settings of the stereotactic arc for a two-point trajec¬ tory or to know the three-dimensional position of the elec¬ trode tip if the depth of the electrode is known without resorting to the acquisition of two orthogonal x-rays. With the advent of digital computers, these calculations became straightforward, allowing the surgeon to keep track of the electrode position on brain maps and make scattergrams of the physiological data.3-5

•

Forty years after its development, the UTEC stereotactic system is still being used at our hospital for applications in which direct target visualization, even with modern radiological techniques, is not possible. For electrode im¬ plantation, it outperforms a magnetic resonance imaging (MRI)-based intervention in terms of operating time.

References 1.

2. 3.

4. 5.

Dereymaeker A, De Dobbeleer G: Contribution au progres de la stereotaxie cerebrale: Un nouvel encephalotome humain. Acta Neurol Psychiatr Belg 5:652-666, 1959. De Dobbeleer G: Stereotaxie-apparatuur. Technisch-Wetenschappelijk Tijdschr 31:1962. Gybels J, Kempen D, Peluso F, Vanbael M: Computer techniques for tracking penetrating electrodes, plotting two-target trajectories and performing two-stage stereotactic surgery in humans. Confin Neurol 36:302-309, 1974. Peluso F, Gybels J: Calculation of position of electrode point during penetration in human brain. Confin Neurol 32:213-218, 1970. Peluso F, Gybels J: Computer calculation of two target trajectory dur¬ ing stereotactic surgery. Med Biol Eng 8:91-94, 1970.

.» 1

CHAPTER

18

THE COMPASS SYSTEM

Stephan J. Goerss

The development of the COMPASS stereotactic system (Stereotactic Medical Systems, Inc., Rochester, MN) revolves around the concept of generating a volumetric database of all anatomic and pathological structures in their correct spatial ori¬ entation. The concept immobilizes a patient’s head in a threedimensional (3D) array of cubic millimeters, with each being cube-defined by whatever tissue is occupying it. Surgical tar¬ gets are defined as volumes, maintaining their location, size, and orientation. Creation and utilization of this array requires integration of radiological images, computers, software pro¬ grams, and stereotactic instrumentation. The three phases of stereotactic procedures are (1) the ac¬ quisition of data, (2) treatment planning, and (3) surgery. The association between these phases is managed through the surgi¬ cal computer system and the stereotactic software. In describ¬ ing the COMPASS stereotactic system, it is best to start with a description of the computer system, followed by a description of the software and instrumentation as they are used on a pa¬ tient going through a stereotactic procedure. The COMPASS system has gone through several revisions of instrumentation, software, and computer systems to (1) im¬ prove the types of data incorporated into the volumetric data¬ base for more comprehensive planning, (2) ease the inter¬ action between the surgeon and the planning program, and (3) facilitate implementation of the surgical plan. New tech¬ nologies are continually being incorporated to expand the information being stored in the data array and improve the in¬ terface between the database and the surgical procedure. It continues to change and bring in new technologies, such as the Regulus measuring unit, to expand what the COMPASS sys¬ tem is capable of performing.

into a TPC or remain as a desktop workstation. Both systems provide the same basic functions, with the Admiral having ad¬ ditional features to perform surgical planning.

The Host Computer System Either the Admiral or Commander system can function as the host. Peripheral equipment needed for maintaining the system, inputting diagnostic data, and supporting surgical procedures is installed into the base of the TPC. This equipment includes a CD-ROM player (Sun Microsystems, Inc., Mountain View, CA) for loading system software. A variety of tape drives are required to match the tape drives on the various diagnostic scanners. A 1/2-in tape drive (Hewlett Packard, Inc., Palo Alto, CA) is used for loading computed tomography (CT) and digi¬ tal subtraction angiography (DSA) images and a 4-mm DAT drive (Hewlett Packard, Inc., Palo Alto, CA) for loading mag¬ netic resonance (MR) images. The 4-mm DAT drive (Sun Microsystems, Inc., Mountain View, CA) also serves to archive

THE COMPASS COMPUTER AND DISPLAY SYSTEM A SPARCstation 10 (Sun Microsystems, Inc., Mountainview, CA) is the host platform. COMPASS has two display systems, the Admiral and Commander, to interact with the surgical data¬ base and generate surgical plans. The Admiral is a threemonitor system housed in a treatment planning console (TPC) (Fig. 18-1). Each monitor displays a single 780 X 780 image providing displays of different image combinations for multi¬ modality correlation. The Commander has a single monitor dis¬ playing two 512 X 512 images. It also may be incorporated

Figure 18-1. The Admiral TPC has three monitors for multimodality visualization and correlation. All the computer equipment necessary to support stereotactic surgery is in the base of the TPC. 151

152

Part 1/Stereotactic Principles

PHYSICIAN OFFICE

SCANNING SUITE

Figure 18-2. A complete COMPASS installation incorporates an Admiral TPC in a room adjacent to the primary stereotactic operating room. Monitors suspended from the operating room ceiling allow visualization of the computer display. The stereotactic positioner mounts to a standard operating table and is situated at the isocenter of a fixed tube teleradiographic system. In the comer of the operating room is the COMPASS remote control rack that contains the necessary equipment to interface the motorized stereotactic positioner with the computer system. Utilizing the network, the data are available to physicians in their offices or additional operating rooms. Key. — = institutional network; — = surgery network;-= radiology network.

patient data. A printer provides permanent records of surgical targets and trajectories. Although smaller disks can accommo¬ date the system, we have chosen a 1.2 Gbyte disk drive, which can handle 15 to 20 patients, depending on the number of im¬

surgical support. The information displayed on the left and middle monitors can also be viewed on the two ceilingmounted monitors in the operating room. The mouse control to access the program may be switched from the TPC to the

ages acquired per patient. Figure 18-2 illustrates both the physical layout of the stereo¬ tactic equipment and incorporation of institutional networking for accessing and sharing information. Radiological data are sent via the network Admiral TPC in the room adjacent to the stereotactic suite, which serves as the primary site for treatment planning. Commander workstations can access the data and store surgical plans anywhere they have access to the network. Surgical plans may be created in the physician's office. A Commander TPC can be rolled into any operating room with network access for providing intraoperative support. The Admiral TPC. in the room adjacent to the operating room, is the primary computer for treatment planning and

operating room.

STEREOTACTIC DATA ACQUISITION The fundamental requirement of stereotaxy is to isolate the head within the stereotactic system so the diagnostic images may be applied to surgery. The COMPASS head holder func¬ tions to immobilize the head in the 3D array, the lace of the base ring is the common reference plane to which all localiza¬ tion devices are attached and forms the base of the 3D array. Each device incorporates reference marks, or fiducials. into each image for placing the images into stereotactic space. The

Chapter 18/The COMPASS System

process of data acquisition begins with the application of the COMPASS head holder.

The

COMPASS

Head Holder

The design of the head holder allows it to be applied, removed, and reapplied in the original position,1 which reduces the pres¬ sure of acquiring the radiological database, planning the surgi¬ cal procedure, and performing it in the same day. Better time management is possible for treatment planning and surgery, as data acquisition and surgery may occur on separate days. Data may also be reused at later dates for follow-up procedures. The head holder is made up of several components, starting with the aluminum base ring. The anterior section of the base ring is removable (mouthpiece), providing access to the pa¬ tient for intubation. The mouthpiece is held in place with two thumb screws and may be removed at any time after the head holder has been applied. The base ring has two attachment sites for each anterior vertical support and three for each pos¬ terior support, providing options for support placements to better accommodate different patients. Each position is marked with the letters A to J. The face of the base ring has tick marks engraved every 5 degrees, which indicate the rota¬ tion of the patient’s head (patient orientation) intraoperatively. A rotation of zero represents the supine position, while 90, 180, and 270 represent right decubitus, prone, and left decubi¬ tus, respectively. Four vertical supports function to offset the base ring from the surgical field. They lock into aluminum bases which, in turn, attach to the base ring with two stainless steel screws at the sites that best accommodate the patient. Each vertical support has a tapered hole at the top for the collet-and-nut assembly. The plastic sleeves insert through the collet and maintain the space between the scalp and collet. There are four lengths of sleeves for different-size heads. Tightening of the collet nut draws the collet into the vertical support, forcing the collet’s jaws together and securing the sleeve into place. A carbon fiber pin provides the actual anchor to the skull. The tip has a reduced diameter of 2.78 mm, for a length of 4 mm (Fig. 18-3). These insert through the center of a sleeve

CARBON FIBER PIN LOCKING CAP PLASTIC SLEEVE VERTICAL SUPPORT

153

and are taped into the twist-drill holes in the skull until the flange rests against the surface. The sleeve’s locking cap tight¬ ens the jaws on the sleeve to lock the carbon pin in place. Micrometer attachments mount to each vertical support for measuring the length of carbon fiber pin extending beyond the vertical support. This measurement provides the capability to reapply the head holder. Reapplicability requires recreating the conditions of the first application. The head holder is reassem¬ bled and the carbon fiber pins are inserted into the original holes. The micrometers adjust the length of carbon fiber pin ex¬ tending beyond each vertical support to match the original length. In doing so, the orientation of the head holder is ad¬ justed to match the original application.

Applying the

COMPASS

Head Holder

During the application, a set of ear and nose supports is at¬ tached to the assembled head holder to help to stabilize it dur¬ ing the application procedure. The patient’s head is suspended over the end of a gurney on a pedestal, giving access all around the head. The scalp is prepped with a Betadine solution at the four pin sites. After the head holder is placed over the head, the ear bars are placed in the external auditory canals and ad¬ justed to center the head holder left and right. The pad of the nose support is lowered onto the forehead to adjust the antero¬ posterior (AP) position. It also provides a front/back tilt adjust¬ ment to hold the head holder at the right angulation. Once in position, each sleeve is advanced to the scalp and locked into place with the collet. A drill guide/tissue punch in¬ serts through the center of the sleeve and bores through the scalp to the skull. A calibrated drill bit makes the 4-mm-deep hole required to seat the carbon fiber pin. The drill and guide are withdrawn and replaced with a carbon fiber fixation pin. It is tapped into the hole until its flange seats against the skull. The locking cap of the sleeve is tightened, and this process is repeated for the other three sites. The four micrometer attachments are attached to the vertical supports to measure the length that each pin extends from the vertical support. These lengths are recorded with the corre¬ sponding vertical support positions for reference in reapplica¬ tion of the head holder. For reapplication, the head holder is again centered over the patient and the pin sites prepped and injected with local anes¬ thetic. A Steinmann pin is inserted through a collet and used to locate the hole. A fixation pin is tapped into each hole until the flange rests against the skull. A plastic sleeve is passed over each pin and through the collet. The four micrometers are at¬ tached to the vertical supports and reset to their original values to replicate the length of the pin extending beyond the vertical support. Both the collets and the locking caps are fully tight¬ ened, locking the head holder in place.

COLLET & NUT Data Acquisition and Image Registration

Figure 18-3. The carbon fiber fixation pin anchors the head holder to the patient’s skull. The flange of the pin seats against the surface, providing the basis for the replaceable head holder.

Following application of the head holder, the patient undergoes a combination of CT, MRI, and/or DSA to provide the neces¬ sary data for surgical planning. Other sources, such as positron emission tomography (PET), have also been used experimen¬ tally as databases.2

154

Part 1/Stereotactic Principles

Each modality has a specific localization device, compatible with the scanner, to incorporate reference marks into the images for stereotactic registration. Computed tomography was the first data source to be incorporated into the system.’ Presently, we use a GE 9800 CT scanner (General Electric, Inc.. Milwaukee, WI) outfitted with an adaptation plate to secure the COMPASS head holder during the scan. This eliminates motion during the study and ensures parallel, contiguous images. The CT localization device has three sets of three carbon fiber rods (Fig. 18-4A). Each set is configured like the letter “N,” with two parallel rods and a center oblique rod. The rods create three sets of reference marks (fiducials) labeled A to I, starting with the fiducial on the lower left of the image and pro¬ ceeding clockwise (Fig. 18-45). The intersection of lines AG and Cl defines the x,y origin of the image. The distance be¬ tween the center and outside fiducials (BC, EF, HI) determines the leg of the triangle formed by the outer and middle carbon fiber rods. The height, in z, above the base ring is a trigonomet¬ ric calculation. Three sets of fiducials provides three z values in the image to determine if the image plane is angled to the stereotaxic axes.3 At the completion of the study, the images are delivered to the surgical computer via the network. The MRI localization frame is attached to the head holder device (Fig. 18-5A) and functions on the same principle as the CT localization device.4 Five acrylic plates form a box that sur¬ rounds the patient anteriorly, posteriorly, bilaterally and superi¬ orly. Channels in acrylic plates filled with a 0.2% CuS04 solu¬ tion create the reference marks on the images (Fig. 18-55), as the carbon fiber rods did with CT. Each channel is a square, with a diagonal channel connecting two corners. Having five

plates provides fiducials on transverse, coronal, and sagittal planes. The head holder and MRI localization device are in¬ serted into a GE Signa 1.5T MRI scanner (General Electric, Milwaukee, WI). The planes and sequences acquired are deter¬ mined by the parameters that display the region of interest best. At the completion of the examination, each series is sent to the surgical computer system via the network. Lateral and AP DSA images, being projection images, re¬ quire a different technique to incorporate them into the data¬ base. The head holder is secured onto an adaptation plate for the GE 3000 or 5000 DSA unit. Angiographic fiducials (Fig. 18-6A), comprising four plates with nine radiopaque pellets in an “X” configuration, are attached to the head holder. The physical location of each pellet is known in stereotactic coordi¬ nates. The fiducials from the plate proximal and distal to the x-ray tube (Fig. 18-65) are displayed on each scout image as large and small fiducials. The size and spacing differences are caused by magnification resulting from diverging x-ray beams. Immobilization is imperative since, as the fiducials are sub¬ tracted from the vascular images, perfect alignment between the scout and subsequent images is needed to apply the fidu¬ cials. Each vessel studied requires four series for treatment planning. The first series is an orthogonal lateral projection, where the center fiducials superimpose. Without moving any x-ray equipment, the head holder is rotated 6 degrees and a sec¬ ond series is acquired. The third and fourth series are repeti¬ tions of the first two in the AP plane. This sequence is repeated for each vessel to be studied. For each series, the scout and fullest arterial and venous phases are stored on magnetic tape. The tape is carried to the surgical system to be studied.

Figure 18-4. A. The “N" bar CT localization system is attached to the face of the COMPASS stereotactic head holder. B. The calrbon fiber rod creates nine (A-I) reference marks on every axial CT image. These reference marks determine the height of the image above the base ring and the stereotactic xv origin.

Chapter 18/The COMPASS System

155

Figure 18-5. A. The multiplanar MRI localization system attaches to the base ring to generate reference marks on every transverse, coronal, and sagittal image. B. Demonstrates a coronal image with the fiducials.

Figure 18-6. A. The angiographic fiducial suspends nine markers anteriorly, posteriorly, and bilaterally. B. The projection images show a superimposition of the plates. The larger set of markers is generated by the reference plate proximal to the x-ray tube. During digitization, the positions of the large and small sets of markers are registered in the order indicated in the upper right corner.

156

Part 1/Stereotactic Principles

Once on the surgical computer system, the (iducials for each study need to be registered and stored as part of the patient’s database. Registration of MRI and CT fiducials follows the same algorithm. The fiducials (A to I) are manually registered on the first image of each series. An autodetection routine com¬ pletes the fiducial registration on the remaining images. Registration of DSA fiducials requires manual selection of all 18 fiducials on every scout image. Knowing the physical co¬ ordinate for each of these allows determination of magnifica¬ tion factors needed for locating surgical targets.

SURGICAL PLANNING AND SIMULATION The treatment-planning programs, admiral.e and compass.e, run on the Admiral and Commander respectively. Both pro¬ grams are tools for registering fiducials, planning and simulat¬ ing surgical procedures, and providing intraoperative support. They graphically emulate the COMPASS stereotactic posi¬ tioner to create and simulate surgical plans. Interaction with either program is accomplished by placing a mouse-driven cur¬ sor over menu selections and depressing the “select key” of the mouse. The structures of the two are very similar, so discussion will focus on the admiral.e program. The menu tree has branches representing the different phases of the planning and surgical process. A menu selection either spawns another menu or executes a function. The combi¬ nation of menu selections sets the parameters for the executed function. Pressing the “select” and “exit” keys, one climbs up or down the menu tree, accessing different sections of the program. Point-in-space procedures such as biopsies, third ventricu¬ lostomies, and thalamotomies require selecting a target and de¬ termining a desired path to it. In addition to these volumetric procedures, such as tumor resection,32P instillation, and amyg¬ dala hippocampectomies require mapping the entire boundary of the target to determine the location, size, and orientation of the target.

Selecting a Target Targets are selected primarily from CT or MRI, although tar¬ gets may be selected from DSA images. Both CT and MRI are used to target intracranial lesions or anatomic structures, while DSA images are useful for targeting AVMs, aneurysms, or avascular entry points. Defining the target on CT or MR requires that the desired image be displayed on the middle monitor. A cross-hair cursor is positioned on the point in the image to be selected as the target (Fig. 18-7). The target coordinates are calculated from the point selected and from the fiducials in the image.1 -5 The ro¬ tation of the head holder, or patient orientation, is entered based on the direction from which the target is to be ap¬ proached. Most commonly, the orientation is either supine (0 degrees), right decubitus (90 degrees), prone (180 degrees), or left decubitus (270 degrees). Intermediate patient rotations are sometimes used to improve the surgical approach. Completing the target record requires entering a unique de¬ scription of the target.

Figure 18-7. Selecting a target on CT requires placing the cursor on a point within the lesion that is to become the “active” target. The process is the same as that in the selection of MRI targets.

Defining a DSA target requires visualization of the target on both AP and lateral projections (Fig. 18-8). Viewing the lateral arterial and venous projection, the surgeon places the cursor on the target. Once selected, the AP projection is displayed, and annotated with a line representing the path of the x-ray beam that passed through the point selected on the lateral image. The line is angled as would be the divergent x-ray beam. The cursor is placed on the intersection of the beam path and the target. The combination of points determines the stereotactic coordi¬ nate of the target. Like CT and MRI images, target and patient orientation description are required. Target points are classified as active targets or entry points. Active targets are the points to be positioned at the focus of the arc-quadrant. Entry points are proximal points used to calculate a trajectory that will pass through the entry point on the way to the active target. Common entry points include points selected on the cortical surface, specific anatomic structures, and the tu¬ mor’s perimeter. Trajectories are defined by the arc and collar angles of the arc-quadrant. Determination of these values may be made by several methods, based on the available data and the type of procedure being performed. In the manual method, one simply inputs the arc and collar values manually. This method is used mainly after the patient has been positioned in the stereotactic positioners. The arcquadrant always directs the instruments to the focus where the target point has been positioned. The surgeon manually manip¬ ulates the arc and collar adjustments of the arc-quadrant to en¬ ter at the desired place. The arc and collar values are input into the computer to allow a review of this trajectory. A second technique is the “two point" method, where the trajectory is calculated using an entry point and the active tar¬ get. Entry points are often CT or MRI target points selected on the cortical surface where the surgeon wants to enter. Avascular entry points may also be selected from DSA data. This tech-

Chapter 18/The COMPASS System

A

157

B Figure 18-8. Angiographic targets are used to access AVMs, aneurysms, and avascular entry points. Target selection requires selecting a point on the lateral projection (A). The AP projection (5) is displayed with a line representing the path of the x-ray beam that passed through the point selected on the lateral image. Using the combined points, a target point is calculated that has compensated for magnification caused by the diverging x-ray beams.3

nique is also used for third ventriculostomies and depth elec¬ trode placements where the trajectory is required to pass through one anatomic structure on the way to another. In the case of a third ventriculostomy, an endoscope is passed through the foramen of Monro to the dorsum sellae.6J Depth recording electrodes are directed through the hippocampus to the amyg¬ dala for monitoring seizure activity.8 Trajectories may also be determined by angiographic im¬ ages to determine an avascular trajectory. This technique is valid only with patient orientations of 0, 90, 180, or 270 de¬ grees because they are projection images. This is a tool to aid in visualization of the trajectory and is correct only when the tra¬ jectory is orthogonal to the projection plane. The target is dis¬ played on the view affected by the collar angle. This is lateral for orientations of 0 and 180; otherwise, the AP projection would be used. The angle formed between the cursor location and the target determines the collar setting (Fig. 18-9). The cur¬ sor is moved to take an avascular path to the target. The process is repeated on the opposite projection to set the arc angle. After a trajectory is calculated, it is reviewed on CT and/or MRI to monitor what anatomy is being passed through, at what depth along the trajectory the lesion or anatomical structure is encountered, and at what depth the target volume is exited. The information is used to determine starting and stopping depths for serial biopsies, where to place contacts of an electrode, or the depths to position radioactive isotopes. Different graphic representations are used to display a tra¬ jectory, depending on whether the path is parallel or oblique to

the image plane. Most trajectories are oblique to the image planes, so the trajectory path intersects the image at a single point (Fig. 18-10). This point, annotated by a cross-hair mark, is displayed as the slices are viewed sequentially. The distance between the point of intersection and the surgical target is cal¬ culated and displayed on the image. A review of the anatomy being affected and the depth to the target volume is performed. The trajectory may be adjusted with any of the above methods until a satisfactory trajectory is selected. Trajectories parallel to the plane of the image occur on transverse MRI or axial CT images when the collar angle is 0 degrees, on sagittal MR images with an arc angle of 0 de¬ grees, and on coronal MRI images with a collar of 90 degrees. With these settings, the surgical path remains on one image, so a line is drawn to represent the path of an instrument. One can review the anatomy affected by the path. Starting and stopping points are selected on the line to determine the depths for serial biopsies. The line is cross-hatched to represent the location of biopsy samples acquired with a 5- or 10-mm Sudan biopsy trochar (Fig. 18-11).

Volumetric Targets Volumetric targets indicate the entire boundary of the target in stereotactic space. This concept is primarily used for tumor resection4-9'10 but may also be used for resecting anatomical struc¬ tures."12 Constructing a target volume begins by selecting an

158

Part 1 /Stereotactic Principles

Figure 18-9. A target selected from CT or MR is displayed on AP (A) and lateral (B) angiograms. Moving the cursor demonstrates the trajectory through the vascular tree, allowing the user to adjust the surgical approach.

Figure 18-10. The “+" determines where the surgical instrument is penetrating this image. Paging through the CT study, a review of the trajectory is made, with particular attention paid to the anatomy affected by the trajectory. In the upper right corner, the distance between the point of intersection and the "active" target is displayed to determine the depth at which the intracranial lesion is encountered.

Figure 18-11. Trajectories that are parallel to the image plane are represented by a line traversing the image. For serial biopsies, the starting and ending points are selected on the trajectory path. The hash marks represent the location of each biopsy site.

Chapter 18/The COMPASS System

active target (see “Selecting a Target” above). Next, the in¬ tracranial lesion or anatomic structure is segmented from ap¬ propriate CT and MRI images. Segmenting a volume requires entering a description of what is being traced. Descriptions include whether the image is from a contrast-enhanced CT, a pregadolinium T2 axial MRI, or a postgadolinium Tt sagittal MRI. Next, the images demon¬ strating the limits of the structure are selected. These, plus all intermediate images, are placed into image memory. Each im¬ age is sequentially displayed on the middle monitor. Tracing target boundaries requires the user to place a cursor at the edge and deposit a series of points around the periphery (Fig. 18-12A). As each image is completed, it is redisplayed on the left monitor with the traced contour and the following im¬ age is displayed on the middle monitor. The following image is displayed on the right monitor. Contours traced from different image planes and by different modalities may be included in the volume data base. With tracing and target selection complete, the computer places each contour in stereotactic space and interpolates inter¬ mediate slices at millimeter increments. The volume target’s location, size, and orientation in stereotactic coordinates are

159

now defined and can be used to resect the volume quantita¬ tively. Selecting a safe trajectory to a volumetric target is ac¬ complished using the same techniques described earlier. This becomes the surgical view line to the volume. Cross sections of 1-mm-thick slices are constructed in planes orthogonal to the surgical view line (Fig. 18-125). Each slice is labeled as a dis¬ tance from the zero plane that incorporates the active target. Coupled with viewing the cross sections, the user selects which size stereotactic retractor or trephine is appropriate to re¬ move the lesion. The retractor or trephine is displayed as a scaled circle on the cross-section display. The display provides the relationship between the cylindrical retractor directed by the stereotactic positioner and the tumor boundary. A translation feature is available for altering the location with respect to the retractor or trephine. It is used to center the trephine over the volume or to access regions of the volume that extend beyond the limits of the retractor. Once activated, the cursor becomes a scaled circle the size of the trephine or re¬ tractor. It is moved with the mouse to position the circle in the desired location. At completion, a translation factor is applied to the active target to alter the position of the head so as to syn¬ chronize the surgical field to the computer display.

Figure 18-12. A. Creation of a target volume requires tracing the boundary of every image demonstrating the lesion. Upon completion, the tracings are stacked together and an interpolation routine generates the volume. B. The volume is cut in planes orthogonal to the surgical approach to guide the surgeon during the resection. The circle about the lesion represents the stereotactic retractor, which provides the physical reference for locating the boundary of the lesion in the surgical field. This image can also be projected in the surgical microscope and superimposed upon the surgical field to aid in defining the boundaries.

160

Part 1/Stereotactic Principles

IMPLEMENTING THE SURGICAL PLAN In the operating room, the COMPASS stereotactic positioner is mounted to the side rails of the operating table. It may also be placed on a floor stand as illustrated in Fig. 18-13 for a more rigid mount or for performing procedures with an inverted head holder. This also illustrates the head holder attached to the y axis of the 3D slide and the 160-mm arc-quadrant fixed to the extension arms of the stereotactic positioner. The COMPASS system is classified as an arc-centered device, since the arcquadrant directs all surgical instruments to its center or focus. The arc-quadrant remains in a stationary position and the head holder is moved relative to the arc-quadrant along the three axes by the stereotactic positioner to bring the active target to the focus. Setting the coordinates of the active target on the stereotac¬ tic positioner may be accomplished manually, by remote motor control, or automatically by the computer. Manual positioning

Figure 18-13. The COMPASS stereotactic positioner mounts onto a standard operating table or on a vacuum-based floor stand, as shown. Each axis of the three slides is equipped with a stepper motor and linear encoders, which are interfaced to the surgical computer. The head holder mounts to the 3D slide, which alters the position of the patient’s head with respect to the stationary arcquadrant. The arc-quadrant directs surgical instruments, such as the Sudan trochar to the focus of the system, where the "active” target is positioned. The rotation of the arc and position of the instrument carrier on the arc allow the target to he approached from any direction. Setting the values of these positions is determined by the surgical software package.

requires setting the mechanical scales of each axis to the coor¬ dinate values of the active target. Turning the hand crank of each axis drives the positioner to a new location. The readings of the mechanical scales reflect the coordinates of the point at the focus. The positioner may also be set to the coordinates of the ac¬ tive target by using stepper motors and linear encoders. The motors mount to each axis with a 70:1 gear reduction, mechan¬ ically limiting the maximum velocity. The motors may be acti¬ vated by remote switches or automatically through the software package. The digital display provides visual feedback of each axis position. The linear encoders (Acu-Rite, Inc.. Jamestown, NY) generate a digital readout of positioner settings, which may be read visually or input into the surgical computer. The values displayed are identical to the mechanical scales. A remote control rack (Fig. 18-14) contains a GE Faunc (General Electric Faunc Automation, Inc., Charlottesville, VA) motor control system with the indexers and drivers to activate the motors. It is connected to the stereotactic positioner by two cables. The operator interface terminal (OIT) at the top of the

Figure 18-14. The RCR contains all the equipment needed to activate the motorized positioner, either remotely or through an automatic process. The screen at the top is the user interface for the system. It also generates a digital display of the coordinate located at the focus of the stereotactic positioner.

Chapter 18/The COMPASS System

rack is the site for direct user interface to remote control of the motors. This screen also displays the digital readout generated by the encoders. A Commander workstation may also be installed in the rack to allow local control of the software if the operating room is not readily available to the host computer. With the OIT, each motor may be individually activated with a positive/negative toggle switch. As the motor drives the axis, the digital display reflects the coordinate at the focus. The switch remains on until the desired value is read on the display. This process is repeated for the other two axes. The automated mode allows the user to direct the motors with software control. Interfaced, via RS-232, the computer reads the starting position from the digital display and deter¬ mines the distance to the new position. The distance is trans¬ lated to the number of steps for each motor to complete the movement. Depression of a foot switch is required to initiate the translation. Once this is started, the velocity at which each axis will move is determined as a proportion of the maximum velocity, which is established by the ratio of the distance to move and largest distance between the three axes. The motors immediately stop if the foot switch is released. Each time the motor stops, the digital display is reread and compared to the final values. If there are discrepancies, the system will repeat the process. The patient is transferred to the operating table, and the base ring of the head holder is locked into the cradle on the y axis of the slide. The patient and head holder are rotated to match the patient orientation of the surgical plan. The surgical target is now in the focus of the system. The 160-mm arc-quadrant is attached by the extension arms to the positioner. The two degrees of freedom, arc and collar angles, are set to direct surgical instruments to the focus along the desired trajectory. Since this is an arc-centered system, every setting of the two angles will project a path to the focus. The two carriers, the microdrive instrument carrier and the re¬ tractor mount, respectively, direct small-diameter instruments and retractors to the focus. A fixed-tube teleradiography and image-intensifier system is used to confirm the location of the surgical target and record the location of surgical instruments or devices intraoperatively. Lateral x-ray reticules mount to the sides of the arc quadrant and mark the location of the focus on the lateral teleradiograph. Likewise, an AP reticule spans between the extension arms of the positioner to mark the focus for AP radiographs. Both AP and lateral x-ray tubes are equipped with laser collimators which emit an 0.5-mW HeNe laser coaxial to demonstrate the central x-ray beam. The lateral laser is directed to the center of the reticule. A mirror on the reticule reflects the beam. The tilt of the tube is adjusted until the beam reflects to its source and points to the center of the reticule. Aligning the AP tube re¬ quires that the positioner be level and the laser beam hit the center of the reticule. Two image intensifiers mounted perpendicular to each other on a portable cart receive the x-ray beams for each projection. The video signal is sent to the S1V video digitizer in the host computer, generating digital images of the teleradiographs. Single-point procedures include serial biopsies, third ventriculosomies, shunt placements, depth electrode placement, and placement of Ommaya reservoirs; they follow the same general process in accessing the target. The microdriver carrier is placed on the arc and the proper arc and collar angles are set.

161

A stab wound is made in the scalp and the guide tube is ad¬ vanced to the skull. The guide tube directs a 4-mm twist drill to make a hole in the skull. A coagulation probe (Radionics, Inc.) is inserted through the guide tube to open the dura with a monopolar cautery. A modified Sudan trochar is used to obtain biopsy speci¬ mens. It mounts to the carrier of the microdrive, so its scale determines the depth of the trochar cutting window. The trochar is advanced to the site of the first biopsy and a speci¬ men is acquired. An x-ray set is acquired to mark the biopsy site. The trochar is advanced the length of the cutting window (5 or 10 mm) for the second biopsy site. This process is re¬ peated until a sample is acquired for every site preselected by the surgical plan. Placement of catheters and electrodes requires measuring the length of the instrument needed to reach from the proximal end of the guide tube. This calculation is made by measuring the length of the guide tube extending beyond the instrument carrier and adding it to 135 mm (the radius of the instrument carrier to the focus). A mark or a depth stop is placed on the in¬ strument and it is inserted through the guide tube until the mark reaches the proximal end. Third ventriculostomies, performed for treatment of ob¬ structive hydrocephalus, require a target point between the basilar artery and the dorsum sellae.6'7 The trajectory is a path that projects through the right foramen of Monro to the target. A Storz pediatric endoscope with an outer sheath is directed by a guide tube through a burr hole to the lateral ventricle. Under direct vision, the endoscope and sheath are advanced through the foramen of Monro to the floor of the third ventricle. The en¬ doscope is withdrawn from the outer sheath and replaced with a leukotome to penetrate the floor. The endoscope is reinserted to observe the location of the basilar artery and determine if ex¬ pansion of the leukotome is prudent. The leukotome is rein¬ serted and the cutting loop expanded anteriorly. Withdrawal of both the outer sheath and the expanded leukotome slices a hole in the floor. Instillation of 32P for treatment of recurrent cysts is a combi¬ nation of a point-in-space procedure and a volumetric proce¬ dure. The surgical procedure requires a point within the cyst to be accessed to insert a long 28-gauge needle, through which a specific volume of 32P colloid is injected, based on the activity of the colloid and size of the cyst. The surgical panning soft¬ ware is used to determine the volume of the cyst. Pure volumetric procedures are typically used for resecting an intracranial lesion. A trephine is accurately centered directly over superficial lesions to reduce the size of the craniotomy needed for the resection. Since the trephine is stereotactically placed, the relationship between the edge of the trephine and the cross sections displayed on the intraoperative monitor is used as a guide for the orientation of the lesion in the surgical field. The system was designed for and excels at resecting deepseated intracranial lesions. The surgical plan orients the lesion volume at the focus and determines a safe trajectory. A trephine craniotomy is stereotactically placed and the dura opened. A cortical incision is made to introduce the stereotactic retrac¬ tor,10 the size of which has been determined during treatment planning. A Sharplan 1100 C02 laser (Sharplan, Tel Aviv, Israel) is used to make a linear incision through the cortex. A dilator inserted through the retractor tube spreads the inci¬ sion, allowing the advancement of the tube. This process is re-

162

Part 1/Stereotactic Principles

peated to advance the tube toward the lesion. Graduations on the outside of the retractor determine the depth of the surgical field. The computer display determines the depth at which the boundary of the lesion will first be encountered. As the retrac¬ tor approaches this depth, the surgeon uses the cross-section display to delineate between normal and tumor tissue. As the dissection progresses, the retractor is advanced and the depth of the cross-sectional display is updated to guide the resection. Lesions larger than the retractor tube can be removed by moving the patient’s head to bring different portions of the le¬ sion under the retractor. This process requires the surgeon to enter the TRANSLATE function and determine which portion of the lesion is to be accessed, as described earlier. Calculations are made to determine new coordinates for the stereotactic po¬ sitioner. The translation may be made by any of the methods for moving the positioner; however, the motorized methods are the safest and most convenient, as they do not disturb the ster¬ ile drapes. Prior to making the translation, the articulations of the arc-quadrant are released, allowing the retractor to move with the patient during the translation. The motors are activated to bring the new coordinate to the focus. When this is com¬ pleted, the surgeon tightens the articulations, which applies the retraction necessary to access the new section of the lesion. Several translations may be required to access every section of the lesion.

CONCLUSION The COMPASS stereotactic system has provided a good foundation for incorporating computer technology into neuro¬ surgery. The instrumentation is a good platform, allowing the treatment-planning software to emulate the surgical pro¬ cedure. The system can perform a wide variety of surgical procedures. It was built with a modular design and is capable of incorporating new procedures and techniques easily. Work on incorporating new technologies into the system continues. The use of articulated arm digitizers, optical digitizers, and magnetic field digitizers is being evaluated to relate stereotactic space to the images in so-called frameless stereo¬

tactic systems, which are intended to reduce the amount of mechanical intervention to the surgery while maintaining quantitative control. The COMPASS system is a good foundation for develop¬ ing and evaluating these systems, since software for frameless systems has evolved from the COMPASS treatment planning software.

References L

Goerss SJ, Kelly PJ, Kail BA: An automated stereotactic system. Appl Neurophysiol 50:100-106, 1987.

2.

Maciunas RJ, Kessler RM, Maurer C, et al: Positron emission tomog¬ raphy imaging-directed stereotactic neurosurgery. Strereotact Fund Neurosurg 58: 134-140, 1992.

3.

Goerss SJ, Kelly PJ, Kali BA, Alder GJ: A computed tomographic stereotactic adaption system. Neurosurgery 10:375-379, 1982.

4.

Kelly PJ, Kail BA, Goerss SJ: Computer-interactive stereotactic re¬ section of deep-seated and centrally located intraaxial brain lesions. Appl Neurophys 50: 107-113, 1987.

5.

Kelly PJ: Tumor Stereotaxis. Philadelphia: Saunders, 1991

pp

88-121. 6. 7.

Jack CR, Kelly PJ: Stereotactic third ventriculostomy: Assessment of patency with MR imaging. Am J Neuroradiol 10:515-522, 1989. Kelly PJ, Kail BA, Goerss SJ, Kispert DB: Computer tomographybased stereotactic third ventriculostomy: Technical note. Neuro¬ surgery 18:791-794, 1986.

8.

Camacho A, Kelly PJ: Volumetric stereotactic resection of superficial and deep-seated intra-axial brain lesions. Ada Neurochir Suppl 54:83-88, 1992.

9.

Kelly PJ: Computed tomography and histological limits in glial neo¬ plasms: Tumor types and selection for volumetric resection. Surg Neurol 39:458-465, 1993.

10.

Kelly PJ, Goerss SJ, Kail BA: The stereotactic retractor in computerassisted stereotactic microsurgery: Technical note. J Neurosurg 69 301-306, 1988.

11.

Cassino GD, Jack CR, Parisi JE, et al: Operative strategy in patients with MRI-identified dual pathology and temporal lobe epilepsy. Epilepsy Res 14:175-182, 1993.

12.

Kelly PJ, Sharbrough FW. Kali BA, Goerss SJ: Magnetic resonance imaging-based computer-assisted stereotactic resection of the hip¬ pocampus and amygdala in patients with temporal lobe epilepsy. Mayo Clin Proc 62:103-108, 1987.

CHAPTER

19

REAPPLICATION OF HEAD FRAMES

David G. T. Thomas and Neil D. Kitchen

BACKGROUND

example is the Compass stereotactic system (Stereotactic Medical Systems, Rochester, MN), in which reapplication in the same stereotactic space is achieved by having the surgeon relo¬ cate the holes previously drilled into the outer table of the skull to accommodate the carbon fiber pins and measure accurately their replacement with puipose-built micrometers. This method is acceptable in experienced hands but remains invasive, requir¬ ing local or general anesthesia for relocation. What hardware needs to be reapplied for stereotactic repro¬ duction? The answer to this question is clearly the fiducial-patient interface. With the Compass method, the base ring, which accom¬ modates the fiducials and the operating frame, is reapplied. With the Gill-Thomas-Cosman (GTC; Radionics, Burlington, MA) re¬ peat stereotactic localizer, the Cosman-Roberts-Wells (CRW) base ring itself is replaced by the device. Thus, fiducials and an operating arc are fitted to it in turn. With other methods, such as Laitinen’s stereoadapter and the stereotactic CT scan interface de¬ vice (SCID) of the Hitchcock system, the relocatable device acts as an intermediate adapter between fiducials and the traditional frame but does not generally provide support during surgery.

Conceptually, the reapplication of a stereotactic head frame has been important in the development of stereotaxy, because it al¬ lows flexible yet accurate reproducibility of an identical stereo¬ tactic space between stereotactic image acquisitions and surgery or between repeated treatment sessions in fractionated stereotac¬ tic radiosurgery; this is done without the necessity for applica¬ tion of the head frame throughout the period. In other words, the reapplication concept allows the frame to be taken on and off at will without losing the ability to reproduce the same stereotactic space. Thus, reapplication of the frame is aimed at reproducing accurately the previously defined stereotactic space. Though the reapplication of head frames has arisen from a desire to modify and modernize traditional frame-based stereo¬ taxy, it is no coincidence that frameless methodologies are also being developed; both developments are driven by the increasing sophistication of neuroradiologic imaging modalities, everincreasing computer power available to the surgeon, and the trend toward less invasive or “minimally invasive” neurosurgery.1 Traditional frame-based stereotaxy offers a high degree of point target localization, but in general this accuracy is not easily repro¬ ducible in an individual patient on different occasions. Skull fixa¬ tion using screws or pins is invasive to a certain extent and certainly is uncomfortable for the patient. Recent ffameless methodologies offer the potential for comprehensive image guidance that is not possible with point-based stereotaxy and may increase the scope of stereotactic localization to include more general neurosurgical practice. Such techniques are exciting but have not achieved wide¬ spread use. There remain a number of clinical issues to address, in¬ cluding accuracy, image acquisition parameters, and instrument carriage and stability. Meanwhile, the limited numbers of truly noninvasive relocatable head frames/stereoadapters has increased, probably representing the fact that it is easier to change to a more suitable head fixation than to change to a completely different set of frameless fiducials for registration (i.e., changing the image-patient registration methodology is far more complex than changing the reregistration of the same frame-based stereotactic space). Repositioning a stereotactic frame to precisely the same posi¬ tion on the patient’s head, and therefore in the identical position with respect to the brain, is not a trivial matter but has been achieved in a clinically useful way by a number of workers. With traditional invasive head frames, the two phases of stereotaxy (image acquisition and surgery) must be closely related to one another in time, generally with one following directly after the other. To overcome this inflexibility, the repositioning of some of these frames has been attempted and is clinically workable. An

THE GILL-THOMAS-COSMAN REPEAT STEREOTACTIC LOCALIZER The GTC repeat stereotactic localizer is one of the two most ad¬ vanced examples of the reapplication of head frames (the other is Laitinen’s stereoadapter). From its earliest prototype2 (Fig. 19-1), the GTC’s development has been aimed at use in combi¬ nation with the existing Brown-Roberts-Wells (BRW)/CRW stereotactic system, first as a noninvasive method of carrying the base ring and later as a replacement for the base ring itself. Its success lies in the accurate repeat but noninvasive fixation, which has been achieved while maintaining continuity with the proven clinical efficacy of the BRW/CRW frame-based operat¬ ing system (Radionics, Burlington, MA) and all its comprehen¬ sive accessories. This feature represents a clear advantage over the numerous frameless systems under development, in which stable instrument carriage, an essential feature of stereotactic surgery, and instruments specifically designed for use with a par¬ ticular stereotactic frame are not present.

REAPPLICATION METHOD With the GTC, fixation to the skull is achieved indirectly by us¬ ing the unique dental impression of the patient’s upper teeth, as

163

164

Part 1/Stereotactic Principles

Figure 19-1. The original GTC prototype. In this version, the frame was manufactured from an epoxy-based composite material containing finely woven cotton fabric. The conventional BRW base ring was attached to the frame. In later versions, the GTC itself becomes the base ring. (Courtesy of S. Gill.)

fixation to these teeth equates with fixation to the skull. Hence, the method of tooth fixation is critical, but in practice it is rela¬ tively simple to perform using standard dental cement [the au¬ thors currently use Light don-U hard or medium in the UK (Panadent UK, London)] in a specially designed dental tray. Once a dental impression has been made, the cement is hard¬ ened under ultraviolet light for 5 min (Fig. 19-2). The dental impression in the tray is then attached to the GTC, which acts as the conventional BRW/CRW base ring and is compatible for all BRW- and CRW-based systems. In addition, soft dental putty is used to form an occipital rest to provide comfort and stability to the patient but does not contribute to the relocatability. Finally, the GTC is secured to the patient with elasticated straps that pass over the vertex from the occipital rest and from the sides of the frame (Fig. 19-3/4 and B). Clinically, repeat fix¬ ation accuracy can be tested simply by noting the frame’s posi¬ tion with respect to certain external landmarks, such as the ex¬ ternal auditory meati, or by performing plain radiographs of the head in two planes after each fixation. A helmet has been de¬ signed so that distance measurements to multiple sites on the head can be made quickly and easily in clinical use, thus achieving a comprehensive and objective indication of relocatability (Fig. 19-4). Validation studies on both phantoms and patients have consistently indicated that the repeat fixation ac¬ curacy is generally in the range of 0.5 to I mm.3 Once fitted, the patient is able to wear the GTC during image acquisition, which may involve separate sittings for computed tomography (CT), positron emission tomography (PET), and angiography and again during surgery. This is especially useful if different hospitals, different sites, and different days are being used.

CLINICAL APPLICATIONS The authors have used the GTC in a variety of clinical settings, including stereotactic biopsy,1 interstitial brachytherapy,4 and stereotactic fractionated external-beam radiotherapy.56

Figure 19-2. Dental tray, inferior view. The dental tray comes in three sizes: small, medium, and large. Once the correct size has been fitted to the patient, dental cement is placed in the tray and an impression is taken of the upper teeth. An optional modification (shown here) is an additional impression of the patient’s premolar teeth in the lower jaw. Some patients find a full bite on the tray more comfortable. The authors have found this extra fixation particularly useful when using the GTC for fractionated stereotactic radiotherapy, in which the patient may have to wear the GTC bolted to the radiotherapy couch for up to an hour.

Surgically, the GTC can replace the CRW base ring in any situation in which BRW/CRW-based stereotaxis is to be per¬ formed, for example, stereotactic biopsy.3 The advantage of do¬ ing this in standard cases is that stereotactic image acquisition and planning can be performed before surgery, so that valuable theater time is not wasted while the patient undergoes stereo¬ tactic CT scanning; this is particularly valuable when the oper¬ ations are to be performed under general anesthesia. However, the authors have found the GTC to be of most use in situations in which the surgical planning is complex and prolonged, often involving multiple image acquisitions of, for example, CT and PET, and dose planning in which radiotherapeutic implants are to be performed. The GTC allows this planning to be separated from the surgery; the planning thus may be performed at the surgeon’s convenience over several days before surgery. Furthermore, the GTC may be used in follow-up studies on the same patients, maintaining the same stereotactic space that was used in the preoperative investigations and surgery. The value of reapplication of the GTC can be illustrated by its application to the insertion of catheters for brachytherapy,4 the infusion of monoclonal antibodies in the treatment of ma¬ lignant brain tumors.7 and the insertion of multiple-depth electrodes in the investigation of medically intractable epilepsy.11 Thus, in the authors’ treatment protocol for iodine

Chapter 19/Reapplication of Head Frames

165

Figure 19-4. Relocatability check helmet. On each reapplication of the GTC, a ruled pointer is passed through the lettered holes and the measurements to the scalp are noted.

Figure 19-5. Stereotactic image acquisition. Planning CT during a brachytherapy workup. The occipital rest of the GTC is seen posteriorly on the scan. The standard BRW/CRW fiducials are also clearly visible.

B Figure 19-3. GTC repeat stereotactic localizer, anteroposterior (A) and lateral (B) views. The unique dental impression of the upper teeth is responsible for the accurate repeat fixation. The occipital head rest mold (B) and the head straps offer stability and support. Patient comfort and measurement from the top of the frame to the ears on both sides provide quick but useful checks regarding accurate relocation. In B the posterior wing nuts are seen for attachment of the GTC to the Mayfield head rest adapter during surgery.

125 brachytherapy for recurrent malignant gliomas, preopera¬ tive stereotactic fluoro-deoxyglucose positron emission to¬ mography (FDG)-PET and CT (Fig. 19-5) are performed. Dosimetry is determined after three-dimensional reconstruc¬ tion of the CT images and takes several hours, so that surgery is performed 1 or 2 days later. After initial placement of the catheters, perioperative stereotactic anteroposterior (AP) and lateral plain radiographs are taken using the SGOV localizer (Fig. 19-6) to confirm the position of the catheters before af-

166

Part 1/Stereotactic Principles

Figure 19-6. Perioperative confirmation of correct placement of Gutin catheters for iodine 125 brachytherapy. The operating arc has been removed, and the SGOV angiographic localizer has been fitted to the GTC. Lateral and AP plain x-rays are performed under stereotactic conditions.

terloading with radioiodine (in this way, the dosimetry may be adjusted according to the actual catheter position achieved). Six weeks after treatment, a further PET scan is performed, using the GTC for reference and the treatment re¬ sponse gauged using image registration. When one is using radiolabeled monoclonal antibody infusions for the treatment of recurrent brain tumors, surgery is followed by several sin¬ gle photon emission computed tomography (SPECT) studies over the next week, all performed under stereotactic condi¬ tions with the GTC. In implanting depth electrodes for the further investigation of drug-resistant epilepsy, the most criti¬ cal feature the neurophysiologist is required to know is ex¬ actly where the electrodes are at the time of postoperative recording. Their initial placement within 5 mm of the in¬ tended target is limited by their flexible nature. Fortunately, their exact position is not critical; it is important to know their exact position when one is interpreting the electroencephalographic (EEG) findings. Therefore, postoperative plain radi¬ ographs under stereotactic conditions using the GTC and the SGOV angiographic localizer (Fig. 19-7) make it possible to determine the exact postoperative electrode position and then translate the corrected position to the planning neuroradio¬ logic imaging modalities of magnetic resonance imaging (MRI) and CT. In two other research studies, the GTC has proved invaluable. The first compared the CT and PET ap¬ pearances of primary brain tumors and correlated those ap¬ pearances with the histopathologic features of serial stereo¬ tactic biopsies.9 The second assessed accuracy in frame-based and frameless stereotaxy, which is a complex issue. The GTC has been applied to frameless methods as a noninvasive con¬ trol against which these newer methods can be compared. Despite these surgical uses the authors anticipate that the prime use of the GTC will be the field of stereotactic radiother¬ apy,56 where treatment planning and fractionation can be per¬ formed simply but accurately while maintaining patient com¬ fort (Fig. 19-8). The feature of head and couch fixation makes the GTC ideal for this use. With stereotactic external-beam ra¬ diotherapy, it is possible to irradiate small lesions in the cra-

Figure 19-7. Postoperative stereotactic AP plain radiograph confirming the position of the depth electrodes for EEG recording. At a convenient time during the recording period (which may last several days), the patient is refitted with the GTC and stereotactic plain radiographs are taken, using the SGOV angiographic localizer. In this AP view, the multicontact platinum electrodes are seen, as are the eight lettered lead shot fiducials of the SGOV localizer. The head straps and the occipital rest of the GTC are just visible.

Figure 19-8. GTC in radiosurgical use. The GTC is ideal for fractionated stereotactic radiotherapy, as it provides both secure and accurate head-to-frame fixation and frame-to-couch fixation. The fitting of the GTC is simpler, quicker, and more comfortable for the patient than is the case with conventional radiotherapy head molds. The GTC has the significant advantage that it is more accurately replaced on the patient’s head for each radiation dose. As a result, the clinical use of the GTC is spreading to more general neuro-oncology radiotherapy regimens.

Chapter 19/Reapplication of Head Frames

nium with high accuracy. The accurate delivery of radiation re¬ quires a precise and firm mode of fixation, and this is tradition¬ ally achieved by using a neurosurgical stereotactic frame. The current technique of “radiosurgery” involves the delivery of a single large dose of irradiation. Gamma Knife units cannot yet perform repeat localization, and complicated treatment regi¬ mens with multiple isocenters have to be performed within a short period of time, usually a single sitting. However, for cer¬ tain indications, such as the treatment of certain brain tumors, fractionated treatment may be more suitable, and this requires a relocatable fixation device. The GTC therefore serves two im¬ portant functions: proven accurate frame-to-head fixation that is also suitable frame to linear accelerator (LINAC) table fixa¬ tion. Furthermore, fixation of the frame takes 20 min and re¬ quires less than $15 of disposable materials. The traditional cellulose acetate mask is expensive and requires prolonged and skilled fitting. Though other methods of repeat head fixation for stereotactic external-beam radiotherapy have been described,10 the GTC appears to offer considerable advantages and has been proved clinically effective by several groups.

167

similar light-cast helmet. Kingsley and associates14 evaluated the reproducibility of light-cast helmets and found it to be within 3 mm. However, they also found that the mask was highly individ¬ ual, took time to be made, and required that a hole be cut in it to make a burr hole at operation. The GTC differs from most other stereoadapters in that it actually replaces the CRW base ring and does not require an in¬ termediate frame for the surgical procedure; the surgical arc is applied directly to the GTC. This implies that the fixation is rigid enough to withstand the forces of surgery, such as eccen¬ tric head positioning and skull drilling. The ideal device for image-directed surgery has not been pro¬ duced despite the explosion of commercial devices employing novel methods for frameless registration. A relocatable head

The practical problems with the GTC are minor. However, poor, particularly partial, dentition may necessitate a formal fit¬ ting by a dental technician, though in our experience this is rarely necessary and even edentulous patients can provide enough landmarks for a unique and stable gum impression. Fitting the GTC to a cooperative conscious patient is easier than is the case when the patient is anesthetized. Thus, if general anesthesia is employed, an armored endotracheal tube should al¬ ways be used. We have not used the GTC for functional proce¬ dures because of the difficulty for the patient of speaking with the frame fitted; clearly, patients’ responses to trial stimulations and during lesioning are critical in these procedures.

OTHER RELOCATABLE HEAD FRAMES The Laitinen “stereoadapter”1112 is described in detail in Chap. 8. The authors believe it to be an excellent device, and it has the ad¬ vantage of being suitable for use in functional neurosurgery. The SCID of the Hitchcock stereotactic system is noninvasive and al¬ lows accurate repeat fixation, using the external auditory meati and the bridge of the nose for reference points. More recently, Waltregny13 has popularized his ingeneous WRIR system (Waltregny Repositioning System for Imaging and Stereotactic Radiosurgery; Fig. 19-9A and B). This system reverts to the head mask principle, using a mask made from a moldable synthetic cast (made and assembled within 1 h) that is fitted to the head and gives good fixation as a result of the multitude of supporting points. In addition, there is a metallic localizer frame or adapter that is attached to the mask by four solid screws plus an interme¬ diate supporting frame made of a light composite material that fits to the four reference screws. Finally, for each imaging appa¬ ratus there is a custom-built adapter with a specially dedicated set of fiducials. Other noninvasive frames have been used in the past, but only a minority have been developed and used to any extent clinically. Bergstom and Greitz’s adapter1415 consists of a plastic mask that is made individually for each patient and is fixed to the Leksell stereotactic frame. Meyerson and associates, for instance, have described the use of this mask in a CT-directed bilateral capsulotomy.16 Later they added dental fixation to a

Figure 19-9. WRIR system. The head mask is made of a moldable synthetic cast, which is then split coronally to allow reapplication when required (A). B. The head mask is secured to the stereotactic frame with four metal reference screws. (Courtesy of A. Waltregny.)

168

Part 1/Stereotactic Principles

frame has a more modest aim but is more immediately clinically applicable and is simpler in concept. It is therefore not surprising that there is considerable interest in this area on the part of prac¬ ticing stereotactic surgeons who wish to add to their armamen¬ tarium without departing from proven stereotactic principles. Thus, a perfect relocatable head frame would have the fol¬

References 1. 2. 3.

lowing features; 1. 2.

Entirely noninvasive Compatible with all traditional stereotactic frames

3. 4.

Well tolerated by the patient Accuracy comparable to that of traditional invasive frames

5.

Easily adaptable for routine clinical use

The GTC, for example, is completely noninvasive but is compatible only with the CRW system and is relatively easy to fit but requires a cooperative patient. Patients with very large heads or partial or poor dentition can be problematic. In comparison, the Laitinen stereoadapter has the potential for use with other proprietary head frames with an adapter (see Chap. 8) and can be used directly for simple stereotactic surgery such as a tumor biopsy but is generally used with the

4.

The fixation of a stereotactic frame to a patient through the use of invasive skull pins implies rigidity and immobility that are intended to, and usually do, eliminate movement between im¬ age acquisition and surgery or during the surgical procedure. Any relocatable head frame not only must be more advanta¬ geous in terms of flexibility and comfort but also must be com¬ parable to traditional frames in terms of the crucial issues of ac¬ curacy and immobility. There is a welcome trend toward minimally invasive neuro¬ surgery.' The GTC represents a significant advance in mini¬ mally invasive stereotaxy, as it combines the advantages of tra¬ ditional frame-based systems (instrument carriage and proven accuracy) with the flexibility of the numerous frameless methodologies under development.

308:126-128, 1994. Warrington AP, Laing RW, Brada M: Quality assurance in fraction¬ ated stereotactic radiotherapy. Radiother Oncol 30:239-246, 1994. Sofat A. Kratimenos G, Thomas DGT: Early experience with the GillThomas locator for computed tomography-directed biopsy of in¬ tracranial lesions. Neurosurgery 31:972-974, 1992. Sofat A, Hughes S, Briggs J, et al: Stereotactic brachytherapy for ma¬ lignant glioma using a relocatable frame. Br J Neurosurg 6:543-548,

5.

1992. Gill SS, Thomas DGT, Warrington AP, Brada M: Relocatable frame for stereotactic external beam radiotherapy. Int J Radial Oncol Biol

6.

Phys 20:599-603, 1991. Graham JD, Warrington AP, Gill SS, Brada M: A non-invasive relo¬ catable frame for fractionated radiotherapy and multiple imaging.

7.

8.

9.

usual Laitinen surgical stereoguide arc.

SUMMARY

Thomas DGT, Kitchen ND; Minimally invasive neurosurgery. BMJ

10.

11.

12. 13. 14. 15. 16.

Radiother Oncol 21:60-62. 1991. Thomas R, Brada M, Carnochan P, et al: Diffusion characteristics of intralesional administered I131 monoclonal antibody in patients with high grade gliomas. J Neurooncol 15S:28, 1993. Kratimenos GP, Thomas DGT, Shorvon SD, Fish DR: Stereotactic in¬ sertion of intracerebral electrodes in the investigation of epilepsy. Br J Neurosurg 7:45-52, 1993. Thomas DGT, Gill SS, Wilson CB, et al: Use of a relocatable stereo¬ tactic frame to integrate positron emission tomography and computed tomography images: Application in human malignant brain tumours. Stereotact Fund Neurosurg 54,55:388-392, 1990. Scwade JG, Houdek PV, Landy HJ. et al: Small-field stereotactic ex¬ ternal beam radiation therapy of intracranial lesions: Fractionated treatment of with a fixed halo immobilisation device. Radiology 176: 563-565, 1990. Hariz MI, Eriksson AT: Reproducibility of repeated mountings of a noninvasive CT/MRI stereoadapter. Appl Neurophysiol 49:336-347, 1986. Laitinen LV: Noninvasive multipurpose stereoadapter. Neurol Res 9:137-141, 1987. Waltregny A: A noninvasive repositioning system for imaging locali¬ sation and radiosurgery. Stereotact Fund Neurosurg 63:291, 1994. Kingsley DPE, Bergstrom M, Berggren BM; A critical evaluation of two methods of head fixation. Neuroradiology 19:7-12, 1980. Bergstrom M, Greitz T: Stereotactic computed tomography. AJR 127:167-170, 1976. Meyerson BA, Bergstrom M, Gretz T: Target localisation in stereo¬ tactic capsulotomy with the aid of computed tomography, in Hitchcock ER, Ballantine HT, Meyerson BA (eds): Modem Concepts in Psychiatric Surgery. Amsterdam: Elsevier, 1979, pp 217-224.

CHAPTER 20

THE GILDENBERG-LAITINEN ADAPTER DEVICE (GLAD): A NONINVASIVE REAPPLICATION SYSTEM FOR STEREOTACTIC HEAD RINGS

Philip L. Gildenberg

The GLAD (Gildenberg-Laitinen Adapter Device) system makes it possible to use the Laitinen Stereoadapter, an estab¬ lished noninvasive fiducial system, to define stereotactic local¬ ization for use with a Brown-Roberts-Wells/Cosman-RobertsWells (BRW/CRW), Leksell, or Fischer stereotactic apparatus. Imaging can be done at any convenient outpatient time, and at the time of treatment, the Stereoadapter coordinates can be transferred directly to compatible systems.

until now the Stereoadapter could not be used with any other system. Few neurosurgeons, especially in the United States, have the Laitinen Stereoguide stereotactic apparatus, but many have another stereotactic system.5,6 GLAD makes it possible to separate the scanning session from the operating day by using the Stereoadapter with the BRW/CRW, Leksell, or Fischer systems which are the most commonly used systems throughout the world.5,6 The GLAD system provides the advantages of the noninvasive Stereo¬ adapter for use with most other stereotactic apparatuses as well. The Laitinen Stereoadapter consists of a bracket that is se¬ cured to the head noninvasively, being aligned by earplugs and a saddle that is seated in the depression of the nasion (Fig. 20-1). The side pieces consist of a radiopaque plastic lattice with a vertical piece that aligns with the earplugs, a diagonal

As it is currently practiced, stereotactic surgery often begins in the radiology department rather than the operating room. Before the patient is transported to the operating room for surgery or to the radiation oncology department for radiation therapy, the stereotactic head ring and the fiducial localizer sys¬ tem must be applied and the scanning and calculation or com¬ puterized planning must be performed. With complicated pro¬ cedures, several imaging studies, such as angiography, computed tomography (CT), and/or magnetic resonance imag¬ ing (MRI), may be required. The data may have to be entered into a graphics workstation where reconstruction of the anat¬ omy and targets is performed and pretreatment and/or presurgical planning is done. It is not unusual for treatment to begin late in the day, sometimes forcing the patient to wait many hours with the head ring in place, possibly under anesthesia. The more elaborate and sophisticated the planning is, the more time is required before the procedure can begin. The goal of the GLAD system is to allow the imaging and planning sessions to be separated from the treatment so that imaging can be accom¬ plished on an outpatient basis before the treatment day while assuring the reliability and accuracy of the stereotactic fiducials obtained and recorded during scanning. The Laitinen Stereoadapter has been in use for many years.1 It can be applied reproducibly and accurately2 and has been used in many centers. It incorporates into the x-ray or imaging studies a finite fiducial system3 and has been approved by the U.S. Federal Drug Administration (FDA) for use in the United States. The system originally was designed to be used with the Laitinen Stereoguide,4 an arc-centered apparatus that can be aligned with the cartesian coordinates registered to the Stereoadapter, with which the stereotactic procedure can be performed as it is with any other system. Although the Stereoadapter works elegantly with the Laitinen Stereoguide,

Figure 20-1. The Laitinen Stereoadapter is aligned by earplugs and a saddle that is seated on the nasion, with a fiducial system on each side and a fiducial rod (anterior laterality detector) that combine to define a cartesian stereotactic coordinate system.

169

170

Part 1/Stereotactic Principles

Figure 20-2. The GLAD devices have an alignment system on each side, which consists of a trapezoidal plate that aligns with a similar configuration of the side pieces of the Stereoadapter: the GLAD-S (A) and the GLAD-X (B).

piece angulating anteriorly to that, and three horizontal pieces at 25-mm intervals that, along with the vertical and diagonal planes, form trapezoidal figures on each side. The horizontal plate at the top holds the side pieces so that they can be ad¬ justed to be seated firmly against the sides of the head. The sup¬ port arms holding the nasion saddle are adjusted to hold it firmly in place, with a millimeter scale on each arm to assure that the Stereoadapter can be replaced accurately each time. The Stereoadapter is applied for the imaging study and then ap¬ plied again to align the patient’s head during treatment with the target defined by that study.

Second, it allows noninvasive alignment of the patient’s head with the BRW/CRW, Leksell, or Fischer head rings secured to the linear accelerator (LINAC) couch or floor mount to align the patient’s head during fractionated stereotactic radiotherapy. Both the GLAD-S and the GLAD-X have an alignment sys¬ tem on each side (Fig. 20-4). A system of trapezoidal plates at¬ tached to brackets at the side of the GLAD ring has the same trapezoidal configuration as the lateral fiducial grids of the Laitinen Stereoadapter (Fig. 20-1). Neither of the GLAD plates

Hariz and Eriksson7 studied the reproducibility of reapplica¬ tion of the Stereoadapter and found it to be within 0.2 mm in all three planes. In a study comparing the coordinates obtained with ventriculography and those obtained by using the Stereoadapter with CT scanning, the maximum error in any plane was 2.75 mm, which is within the error produced by CT slice thickness.3 There are two different GLAD devices (Ohio Medical Corporation, Cincinnati). The GLAD-S (surgery) (Fig. 20-2A) allows alignment with the Stereoadapter and several of the most frequently used stereotactic systems, including the BRW/CRW system, the Leksell system, and the Fischer sys¬ tem, so that the head ring for any of those devices can be se¬ cured to the patient’s head just before surgery with the particu¬ lar system’s coordinates coinciding with the Stereoadapter coordinates. The GLAD-X (x-ray) (Fig. 20-2B) has two separate func¬ tions. First, it allows the imaging studies to superimpose the Laitinen coordinates on the BRW/CRW, Leksell, or Fischer co¬ ordinates (with both fiducial systems appearing on the films) so that surgical or planning systems that depend on the fiducial systems of the particular apparatus can be used (Fig. 20-3).

Figure 20-3. Both the Stereoadapter and the GLAD system have stereotactic fiducial systems defining cartesian coordinates that are superimposed when the systems are aligned.

Chapter 20/The Gildenberg/Laitinen Adapter Device (GLAD)

171

posterior (AP) coordinate is measured from a line connecting the vertical arm on each side. The midsagittal plane, from which the lateral coordinate is measured, is defined from a line connecting the midpoint of that line with the frontal laterality indicator. The horizontal plane from which the vertical coordi¬ nate is measured is at right angles to those two planes and passes along the second horizontal piece of the lateral triangu¬ lar component (Fig. 20-3).

Figure 20-4. The GLAD-S is attached to the CRW head ring, which is then aligned with the Stereoadapter.

comes in physical contact with the Laitinen Stereoadapter, ensur¬ ing that the Stereoadapter position is not distorted in any way. The alignment procedure involves several steps. 1. 2.

The Laitinen Stereoadapter is secured to the patient’s head. The trapezoidal plates of the GLAD are advanced symmet¬ rically to lie adjacent to the Stereoadapter fiducials that have a similar shape.

3.

The patient’s head (and thus the Stereoadapter) is aligned by raising the patient’s head on an occipital rest or advanc¬ ing the occipital rest to contact the back of the patient’s head.

4.

Pins (GLAD-S) or noninvasive probes (GLAD-X) are ex¬ tended through the opening at the side of the Stereoadapter to hold the patient’s head in the midline. The neck is flexed or extended slightly to align the top of the trapezoidal plates with the Stereoadapter fiducials. A forehead pin (GLAD-S) or a noninvasive probe (GLADX) is used to secure the final alignment of the two systems. Again, both GLAD devices touch the head and not the Stereoadapter so that it is not stressed during the procedure; this assures that Stereoadapter alignment is maintained.

5. 6.

The GLAD system has several different functions, and the procedure is somewhat different for each one. If the targeting is two-dimensional, that is, a point or several points in space, the Stereoadapter coordinates can be used directly. It is applied to the patient’s head for the CT or MRI scan, usually at a time separate from the planned stereotactic surgery or radiosurgery, and adjusted to fit snugly. The settings for the lateral adjust¬ ments and the nasion saddle support arms are recorded just be¬ fore the imaging study. The intersection of each imaging slice with the side pieces and a removable plastic rod forming the frontal laterality indicator provide an identifiable fiducial sys¬ tem on the images displayed on scanner console or on the films, which define a cartesian coordinate system. The antero¬

The surgical planning can be done at the time of scanning or afterward, and the patient need not be present. On the day of the procedure, the patient is taken directly to the operating room, where the Stereoadapter is reapplied with the same na¬ sion settings used at the scanning session. The BRW/CRW, Leksell, or Fischer apparatus is then aligned with the Stereoguide by means of the GLAD-S, (Fig. 20-4) and the surgery is performed in the usual manner. The GLAD-S consists of a ring that is attached to the BRW/CRW, Leksell, or Fischer head ring so that it can be se¬ cured to the patient in the usual invasive fashion in alignment with the Stereoadapter coordinate system. The ring has the same diameter as the BRW/CRW head ring and allows either the Leksell ring or the Fischer ring to be seated within it, using separate adapters for each type. The GLAD-S and the conven¬ tional head holder are finked together in a manner that automat¬ ically registers the coordinate systems to each other before ap¬ plication to the patient, allowing the interchange of the two sets of coordinates (Figs. 20-3 and 20-4). The GLAD-X is primarily for use with the BRW/CRW sur¬ gical system or XKnife stereotactic radiosurgery, both of which require the BRW/CRW fiducials. If the patient’s head will be aligned noninvasively for CT imaging or fractionated radio¬ surgery, the GLAD-X is used. It requires patient cooperation throughout the procedure and indicates to the patient the proper head position rather than forcing the head to remain in align¬ ment. It is an alignment system, not a positioning system or head holder. The GLAD-X consists of a ring with the same dimensions as the BRW/CRW head ring, with the same three sockets and cams used to secure the BRW/CRW CT fiducial assembly and the XKnife localizer system. On the bottom surface of the ring there are threaded holes to attach it to the XKnife CT table at¬ tachment or the LINAC couch mount or floor stand bracket (Fig. 20-5). When the GLAD-X is used, it takes the place of the BRW/CRW head ring.

GLAD-S FOR STEREOTACTIC SURGICAL PROCEDURES The GLAD-S is used if alignment of the invasive stereotactic head ring is desired to secure the patient’s head for surgery, such as a biopsy or a stereotactic directed craniotomy, where two-dimensional coordinates indicating points in space are used. The preoperative scan can be done with the Stereoadapter alone, with care being taken to align the slices with the lateral horizontal bars so that the coordinates can be read directly from the Stereoadapter fiducials. The GLAD-S consists of a ring that is attached to the surgical head holder of the BRW/CRW, Leksell, or Fischer stereotactic apparatus before it is applied to the patient’s head (Fig. 20-4). The trapezoidal alignment sys¬ tem on each side of the ring is aligned with the Stereoadapter,

172

Part 1/Stereotactic Principles

ring is attached to the GLAD-X, and so both the BRW/CRW and the Stereoadapter fiducial systems appear in the scan. The patient’s neck is flexed or extended slightly to align the trape¬ zoidal plates with the Stereoadapter fiducials. The forehead probe is advanced to finalize the head position, the frontal lat¬ erality indicator is placed in the midline on the forehead, and the CT scan is done. Thus, the required BRW/CRW fiducial system is available from the scan for the planning software. When the patient returns on another day for treatment, the Stereoadapter is reapplied to realign the patient’s head for frac¬ tionated stereotactic radiotherapy (GLAD-X) (Fig. 20-5) or three-dimensional volumetric stereotactically directed surgery (GLAD-S).

GLAD-X FOR FRACTIONATED STEREOTACTIC RADIOSURGERY Figure 20-5. The GLAD-X is mounted on the CT table or the couch mount, just as the CRW head ring would be. Here, the patient lies down into the GLAD-X. the isocenters are aligned in the ordinary fashion, and the head is aligned with the GLAD-X, bringing the target into the isocenter of the LINAC.

which registers the coordinate system of the stereotactic head ring to the coordinate system of the Stereoadapter. The GLADS is secured to the patient’s head by pins that puncture the scalp to sit securely on the skull to minimize movement while the in¬ vasive pins of the BRW/CRW, Leksell, or Fischer stereotactic head ring are inserted. The GLAD-S and the Stereoadapter are then removed, leaving the usual head holder attached to the pa¬ tient’s head in alignment with the stereotactic coordinates ob¬ tained with the Stereoadapter during the imaging session.

GLAD-X FOR IMAGING STUDIES The GLAD-X can be used to obtain a CT scan that incorporates the BRW/CRW fiducials, and so the noninvasive imaging study can be used just as if it had been obtained with the BRW/CRW head ring secured to the patient’s head with invasive pins in the usual fashion, since those fiducials form the basis for alignment of the computer graphics object reconstruction in BRW/CRWbased software applications such as the XKnife, StereoPlan, and Exoscope. The GLAD-X ring is secured to the CT table, and the front of the ring is opened, allowing the patient to lie down directly into the ring without having to lie down first and then squirm up into the ring. After the Laitinen Stereoadapter is secured to the patient’s head, the patient lies down into the GLAD-X ring so that the head is supported by the occipital rest, which is then adjusted to raise the patient's head into the correct AP position (Fig. 20-5). The side trapezoidal plates are advanced to just about touch the Stereoadapter fiducials, and the occipital rest is adjusted more critically. The side probes are advanced symmet¬ rically into the crotch between the vertical and the top horizon¬ tal fiducial bars of the Stereoadapter to align the patient’s head in the midline and establish the center of AP rotation for final alignment. The ring then is closed. The BRW/CRW fiducial

If the plan calls for fractionated stereotactic radiotherapy, the same GLAD-X is used both in the CT scanner for planning and in the LINAC for treatment. The images are obtained as de¬ scribed above, the data are entered into the XKnife worksta¬ tion, and dosimetry is performed. The patient may later go to the radiotherapy department for the predetermined number of fractionated daily treatments. The same protocol is followed each time the patient comes for a treatment session. The XKnife couch mount or floor stand is attached as it is in any radiosurgical procedure. The usual quality assurance protocol is done. The GLAD-X ring is then secured to the couch mount or floor stand, just as the BRW/CRW head ring would be secured (Fig. 20-5). The front of the GLAD-X ring is opened. The Laitinen Stereoadapter is secured to the patient’s head. The patient lies down into the GLAD-X (the same procedure followed when it is used for CT scanning), and the ring is closed. The laser alignment localizer is attached to the GLAD-X. The isocenter is localized by using the LINAC alignment lasers in the usual fashion. The localizer rod is removed, which may necessitate temporarily opening the front of the GLAD-X ring. The front of the GLAD-X ring is re¬ closed, and the Stereoadapter, and thus the head, is aligned with the GLAD-X in the manner described above. Just before each arc of radiation is administered, it is verified that the Stereoadapter, and thus the patient’s head, is properly aligned with the trapezoidal plates of the GLAD-X.

DISCUSSION Even though the use of the GLAD system facilitates stereotac¬ tic surgery, the accuracy of the GLAD system or any other alignment system is not as good as that of a fixation system in which the head frame is mechanically secured throughout the imaging and treatment sessions. It has been established that the Stereoadapter can be mounted repeatedly with an accuracy of better than 1 mm, with an overall accuracy better than 2 mm, using the Laitinen Stereoguide.8 Since the GLAD system relies on similar alignment with the Stereoadapter, it is reasonable to assume similar accuracy. The GLAD system is not advocated for functional neuro¬ surgery or single-dose stereotactic radiosurgery, where preci¬ sion is paramount, or even to introduce a probe into a small le-

Chapter 20/The Gildenberg/Laitinen Adapter Device (GLAD)

sion or one dangerously near a critical structure. However, most lesions approached in surgery for biopsy or resection do not require that level of accuracy, and the use of stereotactic techniques of any kind is a marked improvement over conven¬ tional craniotomy. The accuracy of this sytem should be as good as or better than that of most frameless systems that are currently under investigation for guidance at craniotomy. The improved convenience and cost-effectiveness make this an ideal system for most surgical or stereotactic radiotherapy applications. The ability to perform the imaging studies and surgical or treatment planning before admission allows the pro¬ cedure to begin at the usual morning surgical time, saving 1 to 3 h for each procedure. Not only does this contribute signifi¬ cantly to convenience, it decreases the operating room and staff time, lowering the cost of stereotactic surgery and making it even more cost-effective. Application of the Stereoadapter can be done by the neuro¬ surgical resident, a radiologist, or a carefully trained scanner technician, and so it may not be necessary for the surgeon to be in attendance for the CT study if another trained responsible in¬ dividual manages the imaging study. Where software is avail¬ able to merge MRI and CT scans, both imaging studies may be done without the presence of the surgeon, who may then do the treatment planning at any convenient time. Scheduling the imaging study as an outpatient session relieves the staff of the burden of coordinating the imaging and operating room sched¬ ules, which is extremely difficult in many institutions. The GLAD-X is used both for imaging and to fractionate XKnife stereotactic radiotherapy. Although other systems make fractionated stereotactic radiotherapy possible, the GLAD-X

173

system does not require the manufacture of a dental mold for each patient, does not require the patient to keep his or her mouth closed during the treatment (which may be a problem in patients with nasal stuffiness or obstruction), and consequently may be more acceptable to some patients or neurosurgeons. The GLAD system allows the surgeon to separate the time of imaging from the treatment time for many stereotactic appli¬ cations, using a device that is convenient and cost-effective.

References 1.

2.

3.

4. 5.

Laitinen LV, Liliequist B, Fagerlund M, Eriksson AT: An adapter for computed tomography-guided stereotaxis. Surg Neurol 23:559-566, 1985. Hariz MI: Clinical study on the accuracy of the Laitinen CT-guidance system in functional stereotactic neurosurgery. Stereotact Fund Neurosurg 56:109-128, 1991. Hariz MI, Bergenheim AT: A comparative study on ventriculographic and computerized tomography-guided determinations of brain targets in functional stereotaxis. JNeurosurg 73:565-571, 1990. Laitinen L: A new stereoencephalotome. Zentralbl Neurochir 32: 67-73, 1971. Gildenberg PL, Franklin PO: Survey of CT-guided stereotactic surgery. Appl Neurophysiol 48:477^180, 1985.

6.

Gildenberg PL: Survey of stereotactic and functional neurosurgery in

7.

the United States and Canada. Appl Neurophysiol 38:31-37, 1975. Hariz MI, Eriksson AT: Reproducibility of repeated mountings of a noninvasive CT/MRI stereoadapter. Appl Neurophysiol 49:336-347, 1986.

8.

Hariz MI: A Non-Invasive Adaptation System for Computed Tomography-Guided Stereotactic Neurosurgery. Thesis, University of Umea, Umea, Sweden, 1990.

. '

Section

2

Frameless Systems

CHAPTER

21

FRAMELESS STEREOTACTIC SYSTEMS

Robert L. Galloway, Jr.

THREE-DIMENSIONAL LOCALIZATION

the frame as well as structures within the brain could be seen in the images. But the pneumoencephalography/ventriculography tech¬ nique was not without its difficulties. Since both types of im¬ ages are shadowgrams or projection images, they compress information about a three-dimensional object onto a twodimensional image plane. If a point could be uniquely deter¬ mined in both anteroposterior (AP) and lateral films, a probe could be guided to that point by a series of frame adjustments. The ability to define exactly the point of surgical interest in both films was in no way guaranteed. In the absence of exactly definable points, the surgeon’s experience and knowledge of general anatomy could help approximate the site of surgical in¬ terest. If the target were visually or electrically distinguishable from the rest of the anatomy, the site’s location could be refined from the rough position determined by the frame. The concep¬ tual breakthrough was that the ventriculogram provided surgeons with patient-specific information to modify their three-dimensional understanding of general neuroanatomy. Surgical frames were designed to guide an instrument to a specific point in frame space, that point being the center of their rotational axes. In order to deliver the instrument to any point in the brain, the desired point in head space had to be moved to the rotational center of the frame space. This was ac¬ complished by either displacing the frame relative to the head2 or the head relative to the frame.3 By creating devices that al¬ ways guided their instruments to their rotational center, the mechanical stability was maximized and, since the center of ro¬ tation is easily visualized, the surgeons could visually check for gross errors in the frame adjustments. The technique of requir¬ ing the site of surgical interest to be placed at the frame’s center of rotation meant that stereotaxy was inherently a point-bypoint process. A target point and trajectory were chosen and the frame was adjusted to guide the instrument to that location. For procedures such as ablation of specific seizure foci, this was not a major concern. If there are multiple sites of surgical inter¬ est, however, each must be dealt with individually. The point must be identified on images in frame space and the framepatient relationship adjusted to place the new point at the rota¬ tional center of the frame. The mathematics of the frame are such that, in moving from one point to another, even if the sec¬ ond point is adjacent to the first, the frame adjustments are not intuitive. A simple spatial displacement of the target point in head space, even retaining the same entry point, may involve

It seems almost axiomatic to begin any discussion of stereotaxy with a bow to Horsley and Clarke. In this case however, it is not merely for scholarly completeness but to acknowledge that the Horsley and Clarke system originated two ideas fundamen¬ tal to surgical guidance.1 The first process was that of image space and physical space mapping. In their case the image space consisted of anatomic drawings and sectioned samples, but it inaugurated the concept that direct surgical visualization was no longer necessary for accurate placement and guidance of medical devices. Once the spatial locations have been determined, the second original concept, that of an extracra¬ nial device for implementing the positions and motions re¬ quired by some map or atlas, was developed. In order for this process to work, the image space and the physical space must be in some way registered; that is, the transformational relationship between the two threedimensional spaces must be determined. Techniques for regis¬ tration are discussed in Chap. 40. In the case of the Horsley and Clarke frame, the registration was accomplished by mounting the frame on the basis of anatomic landmarks, such as external auditory canals and the inferior orbital rims.1 Since the frame was identically mounted on each subject based on these land¬ marks, previously obtained maps (i.e., frame adjustment “A” guides you to anatomic location “B”), could be used to place electrodes, make lesions, and take tissue samples. There is an implied relationship here: that intracranial structures of the brain have a stationary relationship to extracranial anatomic landmarks across the subject population. The fundamental problem in moving to use on humans was that the map between external anatomic landmarks and intracerebral locations proved not to be stationary across a collection of human sub¬ jects. Thus, generalized atlases and tissue sections alone were inadequate for accurate guidance. With general charts proving to be unacceptable for use in hu¬ mans, stereotaxy had to await an improved method of determin¬ ing the desired location within the brain. The development of pneumoencephalograms and, later, iodine-based contrast agents for ventriculography started the process of patient-specific lo¬ calization. Now structures within the individual’s brain could be visualized and landmarks and distances determined for each subject. By constructing the frame out of radiopaque materials,

177

178

Part 1/Stereotactic Principles

major changes in each of the frame’s rotational axes. Some sur¬ geons recognized this problem and have created procedural modifications to attempt to deal with sites of surgical interest as volumes, not points.4

image-guided neurosurgery” by others,12 the process had three major components: 1.

TOMOGRAPHIC CHANGES There were two factors keeping stereotaxy a point-by-point process: (1) the need to identify the target point in two images to unambiguously determine its three-dimensional position and (2) the frame mechanics that prevented intuitive motion of either target point or entry point. With the advent of computed tomography (CT), the surgeon had a three-dimensional repre¬ sentation of the patient’s head. Inherent in the CT image sets was spatial information required to locate not just a single point but all positions and structures within the brain on a pixel-by¬ pixel basis. The structure of the CT scans made each pixel self¬ referent; all the information needed to determine the relative three-dimensional location of one pixel to another was in the image set. It was this democracy of points, that with identifica¬ tion came location, that was first realized by Brown.5 While other frame systems were adapted to the use of CT,6-8 the frame arising from Brown’s work was the first to require tomographic information. Although Brown’s work eliminated one process that con¬ strained stereotaxy into a point-by-point mode, it did not break the paradigm of the frame. Even though the BRW frame did not require that the target point be moved to its rotational center, all rotational axes of the frame had to be adjusted in order to select a new target or entry point. Again, small changes in target or entry points might involve large motions of any particular rota¬ tional axis. In using tomographic images to determine entry and target points and, from that information, the frame settings, there was enormous data reduction. A multimegabyte set of CT slices had been reduced to five or six frame-adjustment values. The pri¬ mary reason for this reduction was that the only computers available at the time to the surgeons capable of manipulating these large data sets were those belonging to the CT scanner. Since the images could not be transported to the operating room, the data from the images had to be. This necessitated reducing the data to values that could be copied into the pa¬ tient’s chart.

CONCEPT REVERSAL In stereotaxy, the frame is the thing; surgical targets are local¬ ized from images in frame coordinates. The only real reason images are used at all is the lack of a stationary relationship be¬ tween extracranial landmarks and intracranial targets. Frame development from Horsley and Clarke had been evolution¬ ary—more appropriate, more accurate, and easier to use, but essentially the same concepts. In the mid to late 1980s, a num¬ ber of researchers began to develop systems that, while varying greatly in implementation, shared a common idea: track the surgical position in physical space and display the position in image space. This constitutes a reversal of classic stereotaxy, in which the physical location is determined from the images. Dubbed “frameless stereotaxy’’ by some9'11 or “interactive.

2.

3.

A three-dimensional spatial localizer. This device could be freely moved in the operating room and the location and trajectory of its tip dynamically tracked. Thus the device would return a position triplet for the space defined by its motion. A registration technique. As with previous stereotaxy, the relationship between the space defined by an extracranial device and locations seen in the image space must be determined. Instead of mapping image location into frame adjustments, => , local¬ izer position is mapped into image space, •

•

K

&

»f< *hwr f*»•«***#

228

Part 1/Stereotactic Principles

A B Figure 28-1-2. First horizontal brain sections by Ambroise Pare, 1575.

Fran5ois Bayle developed a method for hardening (fixation) of the brain by immersing it in oil over a low flame, it was not un¬ til later that formaldehyde and freezing of the brain were used before sectioning. These techniques greatly improved the abil¬ ity of anatomists to make thin precise brain sections. The father of craniocerebral topometry was Vicq D’Azyr (1748-1794), who developed improved methods of preserving the brain and published life-size colored engravings of the brain as well as measurements of individual brain structures. The use of topom¬ etry marked the beginning of detailed brain atlases.1 As attention turned toward the internal structures of the brain, people began to produce the first detailed drawings and maps. In the nineteenth century, it was recognized that brain function is related to specific localized regions and structures of the brain, and early surgeons began to devise instruments that could introduce probes into specific brain structures. The first probes were guided to intracerebral targets from reference points on the surface of the skull (Fig. 28-1-3). This method had serious inherent errors because of the skull’s variability, and it was only when Horsley and Clarke2 constructed the first stereo¬ tactic instrument for exploration of the cerebellum of the mon¬ key that it became possible to construct detailed brain atlases based on the cartesian coordinates system. The first stereotactic monkey cerebellar maps by Horsley appeared in 1908.2 Clarke

and Henderson published additional stereotactic maps of the cat and monkey brain in 1911 and 1920.3'4 With the introduction of the first human stereotactic instru¬ ment and brain atlas by Spiegel and Wycis, there began a new era of brain exploration that accelerated the construction and use of stereotactic instruments, allowing neurosurgeons to nav¬ igate three-dimensionally in the brain of humans and perform treatments for specific nervous diseases5 (Table 28-1-1). The exploration of the depths of the brain also required the develop¬ ment of new techniques for localization and lesion making. The use of a stereotactic instrument to introduce a probe to the de¬ sired target point in the brain was based on a coordinate system derived from these atlases and brain maps. If one uses the cartesian system of rectangular coordinates, a target point can be selected from the maps of the brain, and these numerical data can be translated to the stereotactic instrument to guide a probe to the predetermined target point. The intracranial refer¬ ence points for localizing an intracranial target were arrived at in three ways: (1) cranial reference points, (2) intracranial ref¬ erence points or planes, and (3) linear reference points. The use of cranial reference points is only of historical interest, as this technique is no longer employed. The reference points based on the outline of the ventricular system are still useful, but the most important advance, initially proposed by Spiegel and

Chapter 28/The History of Stereotactic Atlases of the Human Brain and Spinal Cord: Part I

229

duced by the various imaging techniques, such as the positive contract roentgenogram, computed tomography (CT), and magnetic resonance imaging (MRI). The advantage of MRI of the brain lies in the visualization of the patient’s brain in real time. A major unsolved problem in using MRI to obtain stereo¬ tactic coordinates is the variability caused by different thick¬ nesses of MRI brain slices. The development of a stereotactic brain atlas requires the analysis of the variability of the “normal” brain. This has been achieved by using a statistical analysis of carefully prepared slices of the brain. A variety of techniques for brain preparation were used, and a variety of brain atlases have been produced. In 1952, Spiegel and Wycis published the first stereotactic brain atlas for use in human operations.5 The photographs of the brain sections in this atlas were made from the brain of a 71-year-old woman who had died of an acute coronary occlu¬ sion (Fig. 28-1-4). The authors studied a series of 30 brains sec¬ tioned at 5-mm intervals and established a cerebral directional line for each median section; this line connected the center of PC with the posterior border of the pons and was called the posterior commissure-pons line. The line was tangential to the surface of the medulla oblongata. Spiegel and Wycis pointed out the inaccuracies of using the pineal gland as a reference point. Along with photographs of the gross brain slices, there were myelin-stained sections. They also carried out post¬ mortem studies of their therapeutic lesions to assess the accu¬ racy of the target data derived from the atlas.

Figure 28-1-3. Upper drawing: Map of the variability and average topography of cortical sulci and basal ganglia in dolichocephalic and bradycephalic heads from Altukhov (1891). Lower drawing: Brain topographic early guidance apparatus by the Russian neurologist G. I. Rossolimo (1907).

Wycis, was the establishment of the intracranial planes of refer¬ ence such as the foramen of Monro reference line to the calci¬ fied pineal as visualized on a ventriculogram.5 This reference plane was not reliable in all patients and was replaced by the anterior commissure-posterior commissure plane (AC-PC plane) suggested by Talairach and associates.6 This reference plane has become the standard reference line. The AC-PC ref¬ erence plane has the advantage of being independent of the size or shape of the skull, but it may be altered by intracranial dis¬ ease or injury. A major technical problem for the stereotactic neurosurgeon is the variability of each human brain and its deep structures. Another problem is the variability of the brain images pro¬

In 1957, Talairach and his French colleagues published a brain stereotactic atlas with special emphasis on the temporal lobe structures.6 A total of 90 brains were studied, with Weigert-stained sections prepared in 10 brains. A cadaver head with air in the ventricular system was mounted with a lateral grid system through which they introduced metal probes. A lat¬ eral roentgenogram was then taken, and the brain was removed and sectioned (Fig. 28-1-5). The tracts of the probes through the brain were used to establish the directional planes. The cerebral directional reference line was from the AC to the PC, a line still in use today. The Talairach atlas was used extensively in clini¬ cal studies of patients with epilepsy. In 1959, Delmas and Pertuiset1 published Cranio-Cephalic Topometry in Man in French and English. A series of 29 heads were studied, with frozen sections made in the frontal, horizon¬ tal, and sagittal planes. They measured the cephalic index and translated the form of the skull into numbers corresponding to three standards: norma verticalis, lateralis, and posterior. The skull-brain sections were made in relation to the median line of the cranium, nasion, bregma, lambda, and inion. Three cerebral planes were established: (1) a sagittal plane passing through the midline of the third and fourth ventricles, (2) a horizontal plane passing rostrally through the lower part of the AC and tangent to the highest point of the third ventricle, and (3) a frontal plane perpendicular to the horizontal plane and tangent to the anterior edge of the PC plane. The tracing of the bony planes on each of the cross sections from the zero planes outward made it possi¬ ble to match the cerebral planes. The first part of the atlas gives a detailed description of the neuroanatomy of each cerebral structure. The enlarged plates of the brain cross sections are presented in the next section, followed by the statistical meth¬ ods correlating the numerical data and the cephalic indices, making this atlas unique.1

230

Part 1/Stereotactic Principles

Schaltenbrand and Bailey published one of the most com¬ plete and detailed stereotactic atlases.7 They studied 111 brains supplied by the Pathological Institute of Wurzburg and the Pathological Institute of Lund. Several series of macroscopic sections were selected: frontal, horizontal, and sagittal, with a magnification of 2 X 1; some complementary sections at 1:1;

tions at 4X. Hassler and Wahren made studies of the deeper nu¬ clear structures, depicting them in frontal and parasagittal sec¬ tions with nissl and myelin stains. Akert, Bucy, Walker, Snider, and Hassler contributed detailed chapters on the physiology and pathophysiology of the deeper structures of the human brain. Forty years later, this atlas is still a valuable resource for

and, for more exact orientation, a series of myelin-stained sec¬

stereotactic neurosurgeons.

TABLE 28-1-1. Date

Stereotactic Atlases

Authors

Atlas Details

Brain Atlas 1952

Spiegel and Wycis5

Formalin-fixed brain, intracerebral reference plane center of pineal or posterior commissure, variability studies on 30 brains, 7 mild hydrocephalus, age 12-65 years, range of error, postlesion injection of pantopaque, several postmortum studies.

1957

Talairach et al6

Stereotactic brain atlas with emphasis on temporal lobe structures

1959

Delmas and Pertuiset’

First atlas to relate cranial cephalic indices and internal brain structures

1959

Schaltenbrand and Bailey7

Large series of brains studied using 5-mm-thick slices, with variability diagrams of photographs of thick slices, reference points anterior commissure-posterior commissure, reference planes intercommissural plane, midcommissural plane plus the midline. Atlas with excellent photographs with overlay sheets and detailed neuroanatomical and neurophysiological texts by prominent neuroscientists

1969

Andews and Watkins8

Formal in-fixed (38 brains); measured the position of the thalamic centromedian nucleus using 1-mm slices in the coronal plane. Reference plane: posteroinferior margin of foramen of Monro (FM), to the midpoint of ventricular surface of posterior commissure (PC), the FM-PC distance, plus the distance between the midpoint of the ventricular surfaces of the AC-PC line. Measurements of each structure for each millimeter brain slice. The mean medial, lateral, superior, and inferior boundaries of each structure were obtained with standard deviations

1972

Van Buren and Borke9

Atlas with a detailed study of the human thalamic nuclei and a simplification of the thalamic nomenclature. Two volumes, the first on thalamic anatomy and the second illustrating the stereotactic coordinates of the thalamus

1975

Emmers and Tasker10

Atlas of somesthetic responses in awake humans during stereotactic operations in patients with intractable pain, Parkinson’s disease, and other hyperkinetic disorders. Experience of the Tasker group in Toronto

1978

Afshar et al15

Stereotactic atlas of the human brain stem and cerebellar nuclei

Cerebral Blood Vessels Stereotaxy

Stereotactic atlas of cerebral blood vessels

Szikla

A unique stereotactic atlas combining the cerebral arteries and veins superimposed over the structures of the brain. Work done at St. Ann’s Hospital in Paris in Talairach’s neurosurgical unit

1977

Cerebellar Stereotaxy 1965 1969

Nadvomik et al18 Slaughter and Nashold

Stereotactic charts of the cerebellar nuclei

Specific Stereotaxy

These authors presented stereotactic information in specific journal articles

1975

Guiot and Teujillo"

1978

Zlatos and Cierney

1959

Hassler13

1985

Kail et al14

Stereotactic coordinates for the human cerebellar dentate nucleus

Unpublished manuscript on spinal cord.

Spinal Cord Stereotaxy 1968

Nadvornik et al27

Model maps for experimental spinal cord stereotaxis

1972

Nadvomik

New apparatus for spinal cord stereotaxis and its use in the microscopy of lumbar enlargement

1985

Nadvomik

Woroschiloff’s locating device for interventions on the spinal cord and its influence on spinal stereotaxis

1995

Zlatos28

Stereotactic atlas of the human spinal cord, elaborated by means of topometric method ot microscopic anatomy

Chapter 28/The History of Stereotactic Atlases of the Human Brain and Spinal Cord: Part I

In 1969, Andrew and Watkins published a stereotactic atlas.8 They studied 38 brains that were formalin-fixed in situ in the skull. Histological studies were made on two of the brains. They measured the position of the thalamic centromedian nu¬ cleus by using 1-mm slices in the coronal plane. The reference planes were delineated from the posteroinferior margin of the foramen of Monro (FM) to the midpoint of the PC (FM-PC dis¬ tance), and their measurements were related to the midpoint of the line joining the AC and PC (AC-PC distance). Measure¬ ments were made on the 1-mm slices to determine the mean medial, lateral, superior, and inferior boundaries of each struc¬ ture plus the standard deviation of each thalamic nucleus. This atlas is useful because of the presentation of the statistical data in graphic form combined with the stereotactic coordinates on simple line drawings of the thalamus. The two-volume atlas of the thalamic nuclei by Van Buren and Borke was published in 1972.9 Volume 1 includes studies of the nuclei and central connections of the human thalamus, while Volume 2 is devoted to the variability of the human dien¬ cephalon. Up to that time, the nomenclature of the thalamic nuclei was not standardized and often reflected the bias of individual neuroanatomists. Van Buren standardized the no¬ menclature of the thalamus. The atlas nomenclature used was determined by Van Buren on the basis of his studies of the par-

231

cellation of the thalamus, based on the histology of the neuronal components, which, he pointed out, were often modified by the fiber tracts that traverse the individual thalamic nuclei. Van Buren simplified the thalamic nomenclature. He pointed out that in previous neuroanatomical studies it was customary to exam¬ ine the thalamus only in the transverse plane, and he cautioned against these “plane bound” studies of the thalamus. The brains used to construct the atlas were fixed in 15% formalin and sec¬ tioned every 2 mm. Variation diagrams were made on the photo¬ graphic plates so that 1 cm on the marking grids equaled 1 cm on the plates. Selected prints were then analyzed by placing them in a special rectilinear projection apparatus designed by Van Buren. Volume 1 contains four chapters detailing the stud¬ ies on the thalamus, the medial and intralaminar nuclei, and the region of the pulvinar and lateral geniculate. A group of 54 hu¬ man postmortem studies were made to delineate thalamic de¬ generation after a variety of cerebral lesions. Volume 2 presents enlarged photographs of the normal thalamus in three planes, showing variability in the thalamus, diencephalon, and mid¬ brain. The simplification of the thalamic nomenclature and the presentation of the thalamic anatomy in a variety of planes make this a useful and practical stereotactic atlas. The Emmers and Tasker atlas is unique in that it includes clinical experience with stereotactic neurosurgery at the

70 60 50 40 30 20 10 0 MONOGRAPHS IN BIOLOGY AND MEDICINE -

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VOLUME /

Edite.1 by E. A. SPIEGEL

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STEREOENCEPHALOTOMY (Thalamotomy and Related Procedures)

Part 1

•

Methods and Stereotaxic Atlas of the Human Brain

E. A. SPIEGEL, M.I). Professor of Experimental and Applied Neurology, Head of the Department of Experimental Neurology, Temple University School of Medicine and Hospital, Philadelphia

H. T. WYCIS, M.D., F.A.C.S. Clinical Professor of Neurosurgery, Temple Uni¬ versity School of Medicine and Hospital, Phila¬ delphia

gl

GRt'N'E & STRATTON

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NEW YORK

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1954

70 bO 50 40 50 20 10 0 A

B Figure 28-1-4. The first human stereotactic atlas by Spiegel and Wycis (1952).

232

Part 1/Stereotactic Principles

Toronto General Hospital in a group of patients with intractable pain, Parkinson’s disease, and a variety of hyperkinetic disor¬ ders.10 During stereotactic procedures done in awake patients, extensive electrical stimulation of the diencephalon was carried out, and each set of physiological observations was plotted on a series of five master brain maps. Emmers prepared the histo¬ logical sections for the atlas, and postmortem examinations of the brain were correlated with the site of the therapeutic le¬ sions. From the master maps, three-dimensional reconstruc¬ tions were made of the somesthetic thalamus. Interesting fea¬ tures of the atlas are Figs. 23 through 26, which depict the somesthetic thalamic nuclear groups in the form of a sensory homunculus. The atlas is unique, as it resulted from the experi¬ ence of the Toronto group of Tasker, using detailed clinical in¬ formation correlated with neuroanatomical and neurophysio¬ logical data obtained during stereotactic operations. Important and useful stereotactic data have also been pre¬ sented by neurosurgeons in individual journal articles, includ¬ ing Guiot, Afshar, Hassler. and Kail11-14 (Table 28-1-1). Stereotactic atlases have also been made of the human cere¬ bellum and spinal cord. However, stereotactic operations in these two regions of the central nervous system have been lim¬ ited. The impetus for the Afshar atlas of the human brain stem and cerebellar nuclei was the author’s interest in the treatment of spasticity in cerebral palsy by ablating the cerebellar dentate

B

nucleus.15 The effect of the cerebellum on muscle tone in ani¬ mals was well known to experimental physiologists. Other than the effects of trauma on the human cerebellum, there were few clinical observations until 1943, when Poole stimulated the ex¬ posed surface of the cerebellum of four patients undergoing posterior fossa surgery. He noted bilateral leg flexion and ipsilateral finger movements.16 In 1961, Toth, a Hungarian neuro¬ surgeon, noted reduction of parkinsonian tremor and rigidity after open surgical ablation of the cerebellar dentate nucleus.17 In 1965, Nadvomik and associates published stereotactic charts of the cerebellar nuclei.18 In 1965, Heimberger carried out the first stereotactic ablations of the human dentate nucleus for the treatment of hyperkinetic motor disorders.19 Two years later, Zervas and coworkers treated similar hyperkinetic disorders with dentate lesions and noted ipsilateral reduction of muscle tone; he also carried out electrical stimulation during the opera¬ tion but reported no effect.20 Nashold and Slaughter developed stereotactic coordinates for the cerebellar dentate nuclei and implanted chronic depth electrodes in the human dentate nu¬ cleus in a small group of patients with cerebral palsy. A variety of physiological effects were noted during electrical stimula¬ tion, including ocular and postural movements and increased flexor tone. Radiofrequency lesions of the dentate resulted in a profound reduction in muscle tone, but it was not longlasting.2122 Siegfried also reported similar effects after stereo-

C

Chapter 28/The History of Stereotactic Atlases of the Human Brain and Spinal Cord: Part I

tactic lesions in the dentate.23 The cerebellum is a region of the brain that is in need of reevaluation by today’s stereotactic neu¬ rosurgeons, and the Afshar atlas presents detailed stereotactic information about the human brain stem and cerebellar nuclei on which to base it.15 The brains used in the study were pre¬ pared by using positive-contrast ventriculography. The skull and brain in situ were mounted in the stereotactic frame to ob¬ tain an accurate correlation of the reference points and planes with the anatomic structures. Approximately 30 brains were used in the study. After formalin fixation, the brains were frozen, sectioned in 1-mm slices, and mounted for study. A modified Mulligan stain was used, and each brain section was then magnified, after which drawings were made using a cam¬ era lucida. The brain sections were then measured in relation to the reference planes based on the fourth ventricular floor and fastigium and the midsagittal plane. The resulting measure¬ ments were tabulated according to the position of each nucleus or tract in relation to the fastigium-fourth ventricular floor plane. The borders of a particular structure that could be clearly recognized were measured, and variability profiles and proba¬ bility tables were formulated. Standard deviations and errors of the mean were determined. Histograms of the frequency distri¬

Figure 28-1-6. The spinal cord atlas of Zlatos, showing the spinal cross section at the C1 level with the stereotactic coordinates below.

bution were constructed. This is a valuable atlas that will be useful in the future, when stereotactic neurosurgeons turn their attention to the cerebellum. Spinal stereotaxy has been in use for 50 years, but human application has been limited up to this time. In 1873, Dittmar, studying the vasoconstricture pathways in the spinal cords of animals, devised a guiding apparatus for a knife to selectively section small portions of the spinal cord.24 Over the years, labo¬ ratory experiments on the spinal cord have used a variety of ingenious guidance devices to make small lesions. The appli¬ cation of stereotactic principles to the human spinal cord lagged, although Taren and coauthors did publish gross mea¬ surements for spinal targets in cordotomy operations for pain.25 In 1965, the first true spinal stereotactic operation was carried out by Rand and associates, using a Rand-Wells Mark II guidance system.26 Nadvornik and coworkers in Bratislava used spinal stereotaxy that was based on their atlas of the spinal cord.27 The author of this chapter has recently designed a spinal stereotactic frame for use in the exposed human spinal cord. The most recent atlas of the spinal cord is by J. Zlatos of Comenius University, Faculty of Medicine, Bratislava, Slo¬ vakia28 (Fig. 28-1-6). Although the Zlatos manuscript has not

S EOMEN I

CI

Table of topometric values

Stan A B C D Dll Dill E Ell F G H J K L M N p

233

Structure name

Statistical coordinates Relative coordinates C oefficients X V RX RY_TX TV 18 10 -0.10 ■0*9 0.10 0.50 fasciculus gracilis 20 36 -0.12 0.36 1*1 -1.00 Fasciculus cuncatus 76 6* -0.44 -3*0 0.6* 3.42 Lateral corticospinal tract 63 90 •0.37 0.90 Posterior spinocerebellar tract 4.52 -3.15 76 92 -0.44 -3.S0 0.92 7.61 Posterior spinocerebellar tract *6 95 0.95 0.50 4.74 -4.30 Posterior spinocerebellar tract no 96 0.64 0.96 Anterior spinocerebellar tract 4 JO -5.50 91 116 0.91 0.67 •5.80 4.55 Anterior spinocerebellar tract 119 6* 0.69 -5.96 068 Lateral spinothalamic tract 3.42 150 0.87 5 0.25 -7.51 0.05 Anterior corticospinal tract 44 52 0.30 0.44 2.22 -2.61 Head of the Posterior horn 73 1.14 23 -3.65 -042 0.23 Cervix of die Posterior horn 101 0.59 15 -5.06 0.15 0.76 Intermediate rone 00 00 -0.00 0.00 0.00 0,00 Anterior hom - lateral pan 24 137 0*0 -6.S5 0.24 1.20 Anterior hom - medial part 74 2* 0.74 0.17 3.70 -1.42 Posterior lateral sulcus 100 -1.00 -*.60 LOO 5.00 fiction point (segment outline)

Segment length for orienteering

4 mm

234

Part 1/Stereotactic Principles

been generally available, it is a detailed study of the spinal cord structures, with measurements made at various levels of the spinal cord. The spinal cord structures were measured and analyzed by using a computer mathematical model for an analysis of each spinal segment studied.28 This type of spinal stereotactic atlas will be invaluable for stereotactic neurosur¬ geons who want to extend the boundaries of stereotaxy beyond the brain and will be an important next step in the history of stereotactic surgery. The use and development of new brain atlases in stereotac¬ tic neurosurgery continue to be an important feature of the sub¬ specialty. A recent important advance has been the direct oper¬ ating room accessibility of computer-generated brain maps. In the future, it is essential that stereotactic neurosurgeons, neuro¬ anatomists, neurophysiologists, neurologists, and computer sci¬ entists work together on the next generation of brain atlases and the improvement and enhanced safety of stereotactic operations.

11.

12.

13.

14.

15.

16.

17.

References 18. 1.

Delmas A, Pertuiset B: Cranio-Cephalic Topometry in Man. Springfield, IL: Charles C Thomas, 1959. 2. Horsley V, Clarke RH: The structure of the cerebellum examined by a new method. Brain 31:45-124. 1908. 3. Clarke RH, Henderson EE: Atlas of photographs of sections of the frozen cranium and brain of the cat: 1. Sagittal sections. J Psychol Neurol 18:391-409. Part II: Frontal sections. J Psychol Neurol 21:273-277, 1911. 4. Clarke RH, Henderson EE: Atlas of photographs of the cranium and brain of the rhesus monkey. Johns Hopkins Hosp Rep 163-172, 1920. 5. Spiegel EA, Wycis HT: Stereoencephalotomy: I. Methods and Stereotaxic Atlas of the Human Brain. New York: Grune & Stratton, 1952. 6. Talairach J, David M, Tournoux P, et al: Atlas d'Anatomic Stereotaxique. Paris: Masson, 1957. 7. Schaltenbrand G, Bailey P (eds): Introduction to Stereotaxis with an Atlas of the Human Brain. Stuttgart: Georg Thieme, 1959. 8. Andrews J, Watkins ES: A Stereotaxic Atlas of the Human Thalamus and Adjacent Structures. Baltimore: Williams & Wilkins, 1969. 9. Van Buren JM, Borke KC: The Nuclei and Cerebral Connections of the Human Thalamus: Variations and Connections of the Human Thalamus. New York: Springer, 1972. 10. Emmers R, Tasker RR: The Human Somesthetic Thalamus. New York: Raven Press, 1975.

19. 20. 21. 22.

23. 24.

25. 26. 27. 28.

Guiot G. Teujillo J: Radiology and electrophysiology in stereotactic thalamotomy. Third Symposium of Parkinson’s Disease. Edinburgh: Livingstone, 1969, pp 221-223. Afshar F: Three dimensional color-coded graphic display of anatom¬ ical data for the guidance of stereotactic surgery, in Tasker RR (ed): Stereotactic Surgery. Philadelphia: Hanley Belfus, 1987, pp 149-164. Hassler R: Gezielte Operationen gegen extrapyramidale Bewegungstorungen in Einfurhrung, in Schaltenbrand G, Bailey P (eds): Die Stereotaktischen Operationen mil einer Atlas des menschlichen Gehirn. Stuttgart: Thieme, 1959, vol I, pp 472-488. Kali BA, Kelly PJ, Goerss S: Geometric methodology and clinical ap¬ plications for anatomically labelled computer topographic sections. IX Meeting of the World Society for Stereotactic and Functional Neurosurgery, Toronto, 1985, p 89. Afshar F, Watkins ES, Yap JC: Stereotactic Atlas of the Human Brainstem and Cerebellar Nuclei: A Variability Study. New York: Raven Press, 1978. Poole JL: Effects of electrical stimulation of the human cerebellar cortex: A preliminary note. J Neuropathol Exp Neurol 2:203-204, 1943. Toth S: The effect of the removal of the nucleus dentatus on Parkinson’s syndrome. J Neurol Neurosurg Psychiatry 24:143-147, 1961. Nadvornik P, Petr R, Nemecek S, et al: Stereotactic charts of the cere¬ bellar nuclei. J Hirnforsch 8:67-91, 1965. Heimberger RF: Dentatectomy in the treatment of dyskinetic disor¬ ders. Confin Neurol 29:101-106, 1967. Zervas NT, Horner FA, Pichern KS: The treatment of dyskinesia by stereotactic dentatectomy. Confin Neurol 29:93-100, 1967. Nashold BS Jr, Slaughter DG: Effects of stimulating or destroying the deep cerebellar regions in man. J Neurosurg 31:172-186, 1969. Nashold BS Jr, Slaughter DG, Harrison J: A stereotactic approach and evaluation of the cerebellar nuclei of man. Confin Neurol 31:56, 1969. Siegfried J: Stereotaxic cerebellar surgery. Confin Neurol 33: 350-360, 1971. Dittmar C: Uber die Lage des sogenannten Gefafsszentrums in der Medulla oblongata. Ber Saechs Ges Wiss Leipzig [Math Phys] 25: 449—469, 1873. Taren JA, Davis R. Crosby EC: Target physiologic corroboration in stereotaxic cervical cordotomy. J Neurosurg 30:569-584, 1969. Rand RW, Bauer RO, Smart CR, et al: Experience with percutaneous stereotaxic cordotomy. Bull LA Neurol Soc 30:142-147, 1965. Nadvornik P, Nemecek S, Petr R, et al: Model maps for experimental spinal cord stereotaxis. Confin Neurol 30:273-279, 1968. Zlatos J: Unpublished Stereotactic Atlas of the Human Spinal Cord. Bratislava, Slovakia: Comenius University, Faculty of Medicine, Department of Histology and Embryology. 1995.

CHAPTER

28

THE HISTORY OF STEREOTACTIC ATLASES OF THE HUMAN BRAIN AND SPINAL CORD PART

II

ON MAKING STEREOTACTIC ATLASES

E. Sidney Watkins

In the 1950s, when I first started to develop stereotactic surgery in the Oxford Department of Neurosurgery at Joe Penneybacker’s request, the only atlas available was that of Spiegel and Wycis.1 The difficulty at that stage was that the basal gan¬ glia coordinates were based on the trilinear relationships to the pineal gland, itself a variable structure (and not always calci¬ fied for the convenience of the stereotaxist) or to the posterior commissure. Positive-pressure air ventriculography was neces¬ sary to visualize the landmarks of the third ventricle and iden¬ tify the posterior commissure. In any event, the coordinates had been obtained from the study of only a few brains. Almost contemporaneously, however, the next major ad¬ vance was the publication of atlases by Jean Talairach2 in Paris and Schaltenbrand and Bailey3 in Chicago. These atlases used the anterior commissure (AC) and poste¬ rior commissure (PC) as the principal reference points, and the line joining them (AC-PC line) as the reference plane. Structures could be related to these points or to the intercommissural plane erected at right angles to the AC-PC line at the midpoint. Again, only a limited number of brains were sec¬ tioned and measured to obtain the coordinates of the structures; in the Schaltenbrand and Bailey atlas, in fact, there were only seven. Unfortunately, the relationships from brain to brain were very variable, particularly the laterality of the internal capsule at the genu and posteriorly. To increase accuracy, Talairach and colleagues employed positive-contrast ventriculography, using iophendylate (Myodil) to outline the third ventricle, with dou¬ ble grid interposition in the teleradiology to reduce errors from parallax and magnification. These advances, together with the introduction of physiological stimulation and recording to ver¬ ify the target position before lesion production, massively im¬ proved the results in the treatment of tremor, parkinsonian rigidity, and dystonia. The popular targets in the 1960s moved from the globus pallidus and the ansa lenticularis to the lateral thalamus.

Interest in the stereotactic treatment of chronic pain by Valentine Logue,4 John Andrew,5 and myself6 was triggered in 1961 by the publication of Vernon Mark’s work on making le¬ sions in the medial posterior thalamus in the intralaminar and centrum medianum structures.7 Physiological verification of the accurate placement of the electrode tip in these structures was difficult, as there was no paresthetic response to stimula¬ tion or easily identifiable positive recording phenomena as in the somatosensory nuclei of the medial and lateral ventroposterior (VPM and VPL) and ventral intermediate (Vim) nuclei. Variability studies of the anatomy of a sufficient number of brains clearly became mandatory. In 1959, Brierley and Beck8 sectioned 40 cerebral hemi¬ spheres in 3- to 5-mm slices and made a convincing case for re¬ lating the structures to the anterior and posterior limits of the thalamus and the midthalamic point. The introduction of simul¬ taneous positive and air ventriculography using air in the cisterna ambiens to outline the pulvinar, so that the total thalamic length could be measured and the midthalamic point could be obtained, was tried, but not always successfully. John Andrew and myself5 sectioned 38 brains in 1-mm sec¬ tions to measure the position of the centrum medianum. Subsequently, a similar atlas prepared by Afshar, Watkins, and Yap9 measured the posterior fossa structures in the cerebellum and brain stem. Van Buren10 from the National Institutes of Health in Washington and subsequently Tasker and col¬ leagues11 in Toronto measured the variability of the thalamic outline and structures and the variability of physiological re¬ sponses to stimulation. These studies emphasized the need for positive functional verification before lesion production rather than reliance on purely radiographic coordinates. One of the major difficulties in measuring structures was the possibility of inaccuracy introduced by distortion of the anatomy, resulting from fixation and shrinkage. The early work took no special measures to avoid distortion during fixation,

235

236

Part 1/Stereotactic Principles

and shrinkage was assessed at about 10 percent. To reduce er¬ rors of distortion, Corsellis12 described a technique in which the brain and the skull, apart from the frontal and facial bone, were removed en bloc and fixed by suspension in formalin for 10 days reducing shrinkage to 2 to 5 percent. John Andrew and myself employed this technique for the basal ganglia atlas and measured the reference lines in vitro in the third ventricle for comparison with in vivo studies of the same lines in Myodil ventriculograms from patients. Afshar, Yap, and myself per¬ formed in vitro myelography of the fourth ventricle of the spec¬ imens for the posterior fossa structures to identify the reference planes and used the fastigium as the structure to which to relate these structures. The cosmetic implications of the Corsellis technique in the ca¬ davers caused some concern among funeral directors and under¬ takers, and so we devised a technique of using a plaster of Paris prothesis fixed on a 6-in. nail inserted into the cervical canal for stability, over which the scalp was replaced. This led to dif¬ ficulties with the grinding equipment when the cadavers were cremated instead of buried. To obviate this problem, we then sub¬ stituted a section of wooden broom handle to stabilize the head form; nevertheless, by the time we completed the posterior fossa atlas, we had precipitated a strike of undertakers, who refused to service cadavers of this nature from the London Hospital.

References

1.

Spiegel EA, Wycis HT: Stereoencephalotomy. New York: Grume &

2.

Stratton, 1952. Talairach J, David M, Tumoux P, et al: Atlas d’Anatomie Stereo-

3. 4.

taxique. Paris: Masson, 1957. Schaltenbrand G, Bailey P: Introduction to Stereotaxis with an Atlas of the Human Brain. Stuttgart: Thieme, 1959. Logue V, Watkins ES: The Treatment of Intractable Pain by Stereo¬

6.

taxic Thalamotomy. Report to M.R.C., U.K., 1962. Andrew J, Watkins ES: A Stereotaxic Atlas of the Human Thalamus and Adjacent Structures. Baltimore: Williams & Wilkins, 1969. Watkins ES: Stereotaxic Thalamotomy for Intractable Pain. Harvey

7.

Cushing Society 34th Meeting, St. Louis, 1966. Mark V II; 1st International Symposium on Stereoencephalotomy,

5.

8. 9.

10. 11.

12.

Philadelphia. 1961. Brierley JB, Beck E: J Neurol Neurosurg Psychiatry 22:287, 1959. Afshar F, Watkins ES, Yap JC: Stereotaxic Atlas of the Human Brain¬ stem and Cerebellar Nuclei (A Variability Study). New York: Raven Press, 1978. Van Buren JM, Barke RC: Variation and Connections of Human Thalamus. Heidelberg: Springer, 1972. Tasker RB, Organ LW, Hanrryshyn PA: The Thalamus and Mid-Brain of Man: A Physiological Atlas. Springfield, IL: Charles C Thomas, 1982. Corsellis JAN: J Neurol Neurosurg Psychiatry 21:279, 1958.

CHAPTER

29

STEREOTACTIC ATLASES IN PRINTED FORMATS

Robert J. Coffey

After over 100 years of advances in neuroimaging and electrophysiological technology, the continued use of printed stereo¬ tactic atlases to guide functional neurosurgical operations still represents the legacy of nineteenth-century neurological localizationalists and their phrenologist forebears. It is now known that even apparently simple neurological processes involve the interaction of integrated functional systems that often have com¬ ponents (nuclei, relays, and synapses) in different parts of the central nervous system and are connected by complex pathways (tracts, fiber bundles, and commissures). Although the concept of a discrete anatomic “center” for each specific function or behav¬ ior now seems oversimplified, the fact remains that a number of well-defined intracerebral targets have retained their therapeutic utility since the beginning of modem human stereotaxis nearly a half century ago. Unlike the pioneers of stereotactic surgery, who had to depend on the somewhat capricious appearance of nor¬ mally calcified midline landmarks (pineal gland or habenular commissure) to navigate the brain, and unlike their immediate successors, who had to depend on the positive or negative shad¬ ows cast by air- or contrast-filled ventricles on x-ray film, con¬ temporary neurosurgeons can work directly from computed to¬ mographic (CT) scans or magnetic resonance imaging (MRI) of the brain itself. Ironically, many important functional stereotactic targets are still indistinguishable from the surrounding structures on CT or MRI and thus remain invisible or at least well camou¬ flaged. For functional neurosurgeons, this dilemma can be solved only by referring to one of the published stereotactic at¬ lases or to a computerized version of an atlas. Computerized at¬ lases are the subject of Chap. 30. The prototypical stereotactic atlas is a ponderous, expensive folio-sized volume (or volumes) that contains an introductory text that is often neglected. The text usually is followed by highquality photographic plates of unstained whole brain sections or, more often, magnified and stained sections of the thalamus, basal ganglia, and upper brain stem. The sections are cut at regular in¬ tervals in two or more planes. Of necessity, more than one brain is required; over 100 brains were used to produce some atlases. Each section or photographic plate has a two-dimensional scale in the margins, on a clear overlay, or on an accompanying la¬ beled line drawing. The numerical coordinate of the section plane and the two-dimensional coordinates of the target structure within the plane determine the set of three-dimensional coordi¬ nates required to reach the target with a stereotactic instrument. Unfortunately for stereotactic surgeons, the dimensions of indi¬ vidual brains vary from each other and from the idealized or standard brains depicted in atlas sections. Thus arises another

ironic feature of functional stereotaxis: For all the effort and ex¬ pense required to produce a brain atlas, the best one can expect on the first pass of the stereotactic probe is to be in the vicinity of the desired target (within a few millimeters). In most instances, this is not good enough to justify the placement of a permanent therapeutic lesion or stimulating electrode. Therefore, the neuro¬ surgeon must undertake the sometimes tedious task of obtaining physiological corroboration of the probe’s position. This usually involves the use of intraoperative electrical stimulation, evoked potential recording, or other electroanatomic techniques on an awake, cooperative patient. The correlation of intraoperative electroanatomic phenomena with a stereotactic atlas, in fight of the surgeon’s knowledge and the published results of previous surgeons’ experiences, is the essence of functional stereotaxis. Based on intraoperative obser¬ vations during each probe trajectory, the surgeon must decide in which direction and by how many millimeters to adjust the target for each subsequent trajectory. In this manner, the stereotactic at¬ las and a compendium of prior electroanatomic observations (memorized by the surgeon) are complementary tools that guide the successful performance of the surgical procedure. With few exceptions, judging from their intraoperative responses, most pa¬ tients appear to have studied a stereotactic atlas as well.

A CHRONOLOGY OF SELECTED STEREOTACTIC ATLASES 1952: Stereoencephalotomy (Thalamotomyand Related Procedures), Part I: Methods and Stereotaxic Atlas of the Human Brain, E. A. Spiegel and H. T. Wycis In the spring of 1947, the collaboration of E. A. Spiegel, a clin¬ ical and research neurologist who had considerable experience in experimental animal stereotaxis, and H. T. Wycis, a neuro¬ surgeon who had worked in Spiegel’s laboratory at Temple University in Philadelphia, culminated in the first modern stereotactic operation performed on a human patient. More than 100 patients had been operated on by 1952. Spiegel and Wycis realized that functional stereotactic surgery “requires an exact preoperative calculation of the electrode position, and such a calculation depends on two conditions: (1) determina¬ tion of a reference point by means of an x-ray picture taken un-

237

238

Part 1/Stereotactic Principles

der definite standard conditions, and (2) an exact knowledge of the position of the area to be destroyed in relation to the refer¬ ence point. Thus ... a stereotaxic atlas of the human brain is presented.”1 This landmark publication of the first human stereotactic atlas emphasized important points that were to form the foundation for later work by Spiegel and Wycis and by all the investigators and atlas authors who followed. Brains destined for inclusion in an atlas had to be fixed in situ as soon as possible after death. Before opening the cranium, the authors applied a stereotactic frame to pass metal rods com¬ pletely through the skull and cerebrum at known distances from each other and at known stereotactic reference points in one or more planes. In this manner, shrinkage after fixation, freezing, or other processing could be quantified precisely and corrected by photographic enlargement or manipulation during the prepara¬ tion of the final atlas plates. Another major contribution of Spiegel and Wycis was to demonstrate the considerable variabil¬ ity in the contours and dimensions of the thalamus and other brain regions independently of variations in skull morphology. Even the cerebral midline was found to deviate unpredictably from the midline of the skull. While brain atlases based on exter¬ nal cranial landmarks were suitable for small and medium-sized laboratory mammals, that was not the case for human patients. Thus, Spiegel and Wycis began a systematic search for reliable, radiographically demonstrable reference points on which to base their stereotactic atlas planes and surgical procedures. Their ini¬ tial reference point—the center of pineal gland calcification on plain x-ray films—varied by 12 mm or more in the anteroposte¬ rior dimension and by up to 16 mm in location relative to the interaural plane. In some operations, they utilized the habenular calcification. In others, by means of lumbar pneumography, they visualized the posterior commissure (CP or PC), the foramen of Monro (FM), and rarely, the anterior commissure (AC). To construct their first atlas, Spiegel and Wycis employed a line connecting the center of the PC with the pontomedullary sulcus at the posterior border of the pons (PO), the CP-PO line (Fig. 29-1). They cut their 5-mm-thick frontal (coronal) un¬ stained sections and their 2- to 4-mm-thick myelin-stained frontal sections parallel to their so-called average cerebral di¬ rectional line (inclined 4 degrees behind the CP-PO line). Oblique unstained sections 5 mm thick were cut through the brain stem at an angle of 30 degrees anterior to the CP-PO line and centered at the PC. A series of myelin-stained oblique sec¬ tions 0.5 mm thick were cut parallel to the same plane. Unstained 5-mm-thick sagittal sections were cut parallel to the median plane. Unstained horizontal sections were cut perpen¬ dicular to both the median plane and the CP-PO line. The final two chapters of Sterencephalotomy (Part I) consist of anatomic and radiographic variability studies in 30 normal brains, plus postmortem examples of both accurately and incor¬ rectly placed lesions. In the variability studies, the authors cata¬ loged the range of coordinates at which the borders of various nuclei, tracts, and other selected structures could be found in relation to both the center of the pineal gland and the posterior commissure. The 15 anatomic structures studied in this manner included the head of the caudate nucleus; the putamen; the globus pallidus; the anterior, dorsomedial, and ventrolateral thalamic nuclei; the pulvinar. tuber cinereum, mamillary bod¬ ies, corpus Luysii (subthalamic nucleus), substantia nigra, red nucleus, and medial and lateral geniculate bodies; and the mes¬ encephalic spinothalamic tract. With the passage of time, inter¬ est in some of these targets would wane (dorsomedial nucleus

Cp

Figure 29-1. Landmarks for Spiegel and Wycis’s intracerebral coordinate system used in their first stereotactic atlas. Abbreviations: Ch = commissure habenularum; Cp = posterior commissure; Cp-Po = posterior commissure-pons line; cran. 1, cran. 2 = cranial direction lines; hi = horizontal line perpendicular to cran. 1; ho = horizontal line perpendicular to Cp-Po; — i +i = angles of inclination; Ob = medulla oblongata; Po = pons; Th = taenia habenulae. (From Spiegel and Wycis.1 Reproduced with permission.)

of the thalamus, for example) and other, more refined targets would emerge (the thalamic nucleus ventralis intermedius and the periaqueductal-periventricular gray matter, to cite a few). The postmortem studies, especially the off-target “misses,” demonstrated the significant shortcomings of the initial efforts at radiographic localization based on a single point such as the pineal gland, habenular calcification, or posterior commissurepontomedullary sulcus line (CP-PO line). By 1962, when Spiegel and Wycis published their second volume, Stereoencephalotomy (Part II), general acceptance of the anterior commissure-posterior commissure line (AC-PC line, intercommissural line, IC line) as the standard stereotactic reference system had overcome the limi¬ tations inherent in the earlier method. Nevertheless, Spiegel and Wycis’s Stereoencephalotomy (Part I) probably did more to stimu¬ late widespread interest and hence advancement in the field of stereotaxis than did any other single publication. Indeed, the early successes of Spiegel and Wycis were all the more remarkable given the nearly complete lack of previous experience in human stereotaxis between 1947 and 1952.

1957: Atlas d’Anatomie Stereotaxique: Re PER AGE RaDIOLOGIQUE INDIRECT DES Noyaux Gris Cextraux des Regions Mesencephalo-sous-optique et Hypothalamique de l'Homme,

J. Talairach, M. David, P. Tournoux, H. CORREDOR, ANI) T. KVASINA Although Talairach’s first stereotactic atlas in book format ap¬ peared in 1957 (a magnificently produced and bound folio-

Chapter 29/Stereotactic Atlases in Printed Formats

sized volume), his published scientific work on the subject dated back at least to 1949.2,3 Among the most important of Talairach’s contributions to stereotaxis were the introduction of the intercommissural line as the standard stereotactic reference system, the introduction and popularization of combined posi¬ tive-contrast and air ventriculography to demonstrate the AC and PC reliably, the invention of an accurately relocatable stereotactic instrument that utilized teleradiographic techniques and a “double-grid” localization system, and the integration of angiography and ventriculography to create the most advanced stereotactic system in the pre-CT era. These fundamental developments shaped Talairach’s first and subsequent stereotactic atlases and radiographic-anatomic research over more than four decades.4 One cannot overempha¬ size the importance of Talairach’s elegant demonstration that the deep structures of interest to stereotactic neurosurgeons bear a nearly constant relationship to the intercommissural line and its derivative planes [midsagittal plane, horizontal inter¬ commissural plane, and the two vertical planes orthogonal to the IC line passing through the AC (VCA) and PC (VCP), respectively]. Later investigators would abandon Talairach’s two vertical planes in favor of a single midcommissural plane. Still, because of variation in the length of the IC line between individuals (range, 23 to 28 mm from the center of AC to the center of PC; mean, 25.5 mm in Talairach’s work), one usually finds stereotactic coordinates listed as a distance anterior or posterior to PC (less often AC) as well as in relation to the midIC plane. Thus, Talairach’s system has exerted a lasting influ¬ ence even on workers who believe they have abandoned it for a

0

239

more modem one. Figures 29-2 and 29-3 show Talairach’s il¬ lustrations of how his intracerebral reference system (the IC line and the VCA and VCP planes) and hence the locations of deep cerebral structures could bear a firm anatomic relationship to each other yet vary considerably from the antiquated Horsley-Clarke reference system based on external landmarks. Even in a small sample of human ventriculograms, the axis of the IC line varied between 11.5 and 18.5 degrees from the infraorbitomeatal line (Frankfort line, Reid’s base line). Talairach used his double-grid stereotactic instrument to create perforations in craniocerebral specimens at known loca¬ tions and distances in the frontal and lateral planes. After this marking, accurate coordinate measurements and profiles were derived for deep cerebral nuclei, subnuclei, and tracts. The stereotactically marked brains were cut in either parasagittal or frontal sections along Talairach’s standard planes. He mapped the three-dimensional profiles of the thalamic nuclei and other structures on millimeter-ruled diagrams through each series of sections. By presenting each sectional profile drawing next to the appropriate unstained or myelin-stained photographic plate at the same magnification, Talairach set the standard for all fu¬ ture stereotactic atlases. In this sense, even the apparently novel utilization of transparent overlays by Schaltenbrand and coworkers5 could be considered derivative of Talairach. By de¬ veloping rules for proportionately subdividing the simple geo¬ metric forms outlined by the IC line and roof of the thalamus seen on lateral ventriculograms, Talairach invented a system to localize the ventral tier of thalamic nuclei in any patient. By drawing or scratching Talairach’s diagram directly on the lat¬ eral ventriculogram film, a neurosurgeon could instantly recre¬ ate a properly scaled atlas template from which stereotactic co¬ ordinates could be calculated. Those who do not read French may be intimidated by Talairach’s atlas. However, the illustra¬ tions, captions, and labels are so clear that most of the essential data require no translation.

1959: Introduction to Stereotaxis with an Atlas of the Human Brain (3 vols), EDITED BY G. SCHALTENBRAND and P. Bailey

Figure 29-2. Talairach’s illustration of the three early human stereotactic reference planes based on osseous cranial landmarks (as in animal stereotaxis). These were the infraortibomeatal plane (Reid’s base line or the Frankfort line), the intraaural plane (zero plane of Spiegel and Wycis), and the midline plane of the cranium. (From Talairach et al.3 Reproduced with permission.)

The Schaltenbrand and Bailey atlas probably was the world’s most widely used compendium of brain maps during the hey¬ day of stereotactic surgery for involuntary movement disorders in the pre-L-dopa era (early 1960s to mid-1970s).5 Two over¬ sized loose-leaf folio volumes contained the highest-quality myelin-stained and unstained photographic atlas plates avail¬ able at that time. The accompanying text, in both German and English, contained scholarly treatises on all aspects of neu¬ roanatomy, physiology, and stereotactic techniques by the edi¬ tors and 24 other contributors, including 14 from the United States, 9 from Germany, and 1 from Italy. Despite having one editor and a plurality of contributors from the United States, the Schaltenbrand and Bailey atlas is decidedly Teutonic in style and content. Schaltenbrand’s stereotactic suite in Wurzburg contained an elaborate bidirectional optical projec¬ tion system to superimpose atlas plates, anatomic outlines, ad¬ justable magnification scales, and the patient’s ventriculogram images on the same translucent screen. In the decades before computer graphics, the atlas sections and scales could be opti-

240

Part 1/Stereotactic Principles

Figure 29-3. Talairach s demonstration of the variability in the major intracerebral axis (the intercommissural line) from the osseous baseline. (From Talairach et al.3 Reproduced with permission.)

cally modeled to match an individual patient’s intercommis¬ sural distance and other anatomic features. Volume II, which contains the “meat” of the atlas, will never become obsolete. Although the first three series of maps in this volume (in each of three orthogonal planes) contain unstained sections that are of limited usefulness to stereotactic surgeons, the next three series of maps contain the most magnificently presented myelin-stained atlas plates of their day. The frontal series, cut orthogonal to both the midsagittal plane and the in¬ tercommissural line (and parallel to the midcommissural plane) (Fig. 29-4), begins with plate 36. The sections are presented four per page at 4X magnification, with a scaled and labeled transparent overlay attached to each plate. The 16 sections, each 1 to 4 mm thick and all cut from the same brain, span the region from 16.5 mm anterior to 16.5 mm posterior to the mid¬ commissural plane. The sagittal series, beginning with plate 42, is presented in exactly the same manner, except that only one or two sections appear on each page. The 18 sections are cut at 0.5- to 2.5-mm intervals, spanning the region between 2.0 and 27.5 mm lateral to the midline. Since the vast majority of functional stereotactic operations involve a transfrontal (precoronal) approach to the thalamus or upper midbrain through a parasagittal entry point. Schaltenbrand and Bailey s myelin-stained sagittal series has been a stereotactic bible for over 37 years. Among the 18 sec¬ tions in this series, there is something almost magical about plate 47 (brain LXXV1II), which depicts the 13.5-mm and 15.0-mm planes. In most individuals, the hand area (median nerve territory) of the thalamic somatosensory relay nucleus re¬ sides in one of these planes (usually at 13.5 mm) and corre¬ sponds to the laterality at which the therapeutic lesion most of¬ ten should be inflicted to relieve parkinsonian tremor or other involuntary movement disorders of the upper extremities (Fig. 29-5). Given the widespread use of the Schaltenbrand and Bailey atlas in both the printed format and as the basis for com¬

puterized software, the original owner of brain LXXVIII has made an immense contribution to functional stereotatic surgery. The myelin-stained horizontal series begins with plate 52 and. like the frontal series, is presented at four planes per page at 4X magnification. The 20 sections, all cut from a single brain, span the region from 16 mm above to 9.5 mm below the midcommissural point. Unfortunately, although the sections are all parallel to each other, they deivate from the axis of the IC line by about +7 degrees anteriorly, and so the +0.5-mm plane crosses the intercommissural plane within 0.5 mm of the midpoint of the IC line but crosses the anterior commissure ap¬ proximately 2.0 mm above its midpoint. Volume III contains 10-cresyl-violet-stained frontal sections and eight sagittal sections prepared in the same manner, each magnified 20X. Aside from occasional use by the odd neuro¬ physiologist or comparative anatomist, most copies of this vol¬ ume spend a lifetime undisturbed on a library shelf.

1962: Stereoencephalotomy, Part II: Clinical and Physiological Applications, E. A. Spiegel and H. T. Wycis Stereoncephalotomy (Part II), which was published 10 years after Part I, was primarily a textbook and only secondarily a revised and updated brain atlas.6 In fact, the series of myelinstained sections appeared 2 years earlier in Confinia Neurologica,78 In the interval between the two books, Spiegel and Wycis refined their stereotactic instrument (Stereoencephalotome Model V), improved and simplified their radiographiclocalization technique, and most importantly, embraced the Franco-German (Talairach and Schaltenbrand and Bailey) usage of the intercommissural line as a stereotactic reference. The 1960-1962 atlas portion of the volume reflected this step

Chapter 29/Stereotactic Atlases in Printed Formats

Figure 29-4. Schaltenbrand and Bailey’s three basic reference planes and their relation to the anterior and posterior commissures. The second edition of their atlas, as well as virtually every other stereotactic atlas and text published after 1959, employed the same reference system. This figure also shows the size of the central block of the brain (in millimeters) used to prepare the myelin-stained atlas plates. (From Schaltenbrand and Bailey.5 Reproduced with permission.)

Figure 29-5. Plate 47, brain LXXVIII, myelin-stained sagittal section 13.5 mm from the midline, with ruled and labeled overlay. This single atlas section probably has guided more stereotactic operations than have all the other brain maps in the world combined. (From Schaltenbrand and Bailey.5 Reproduced with permission.)

241

Part 1/Stereotactic Principles

242

in the evolution of their approach to neuroanatomy as applied to stereotaxis. Most of the book was devoted to stereotactic techniques and clinical results, including honest morbidity and mortality fig¬ ures for commonly performed stereotactic operations. Indications included psychosurgery, pain, involuntary move¬ ment disorders, epilepsy, and subcortical tumors. Perhaps the most valuable feature of the book was the presentation of post¬ mortem findings correlated with a patient’s radiographic, clini¬ cal, and surgical findings.

1972: Variations and Connections of the Human Thalamus, Volumes 1 and 2, J.

M.

Van Buren and R.

C.

Borke

Although Van Buren and Borke produced this fine text and at¬ las while working at the National Institutes of Health in Bethesda, Maryland, the folio-sized volumes were printed in Germany by Springer-Verlag.9 The work of Van Buren and Borke joined that of Schaltenbrand and Bailey (Georg Thieme, Stuttgart, 1959), Schaltenbrand and Wahren (Georg Thieme, Stuttgart, 1977), and Talairach and coworkers (Masson, Paris, 1957) to form the “big four” stereotactic atlases, all printed in Europe, three of them in Germany. Volume 1 includes a com¬ prehensive textbook and a cytoarchitectonic study of the thala¬ mus. Literally hundreds of high-quality photomicrographs of cresyl violet, myelin, and Golgi preparations are presented. In addition, extensive postmortem material from 54 patients shows both the original cerebral lesions and the site and extent of secondary thalamic degeneration. Volume 2, Variations of the Human Diencephalon, continues the stereotactic atlas in the three orthogonal planes relative to the intercommissural line: sagittal, horizontal, and transverse (“frontal” in the terminology of Schaltenbrand and Bailey). The atlas contains a catalogue of thalamic nuclei and their stereotac¬ tic coordinates relative to the IC line and the sagittal plane. Each series of cresyl-violet-stained plates is reproduced, one per page, at relatively high magnification (8 to 10X). The sagittal series consists of 10 slices at 10X magnification spanning the region between 2 and 25 mm lateral to the midline at 0.5- to 4-mm in¬ tervals. Outlines of nuclear groups and tracts are printed directly on the photographic plates, along with anatomic labels, coordi¬ nate index marks, and a magnification scale. Although the large¬ cell stained sections at first appear unusual to surgeons accus¬ tomed to working from myelin-stained atlas plates, the stereotactic coordinates derived from this atlas correspond closely to those obtained from other sources. The cresyl-violetstained horizontal series, presented at 8X magnification, consists of eight sections cut precisely parallel to the intercommissural plane. Sections approximately 3.5 mm thick span the region from 17 mm above to 8.1 mm below the IC line. The 10 trans¬ verse (frontal) sections are photographed at 10X magnification, the same as the sagittal series. The plates cover a span of 28.1 mm, from 23.4 mm anterior to PC to 4.7 mm posterior to PC. In the next chapters of the atlas, individual nuclear profiles from five or six brains, depending on the plane of section, are mapped on minified (0.7 X) grids in all three orthogonal planes at 5-mm intervals on one or two pages each. The final chapter presents similar data for the gross anatomic structural outlines

of 25 hemispheres normalized to superimpose either the AC or the PC. Simplified diagrams showing the region of densest overlap (median values) and extreme ranges also are presented. This feature allows a surgeon to visualize the potential varia¬ tions in the dimensions and locations of many structures conve¬ niently (Fig. 29-6). However, an important cautionary note re¬ garding this method of presenting variability data is in order. Focusing on the differences among individual brains in terms of the absolute values of stereotactic coordinates relative to the IC line neglects the tendency of such absolute discrepancies to correct themselves when recalculated as fractional proportions of the IC distance (and thalamic height). For example, a point 6 mm anterior to PC in a brain with a 24-mm IC distance could be mapped in exactly the same relative (proportional) position if it were located 6.5 mm anterior to PC in another brain with a 26-mm IC distance. Both points are exactly one-fourth of the intercommissural distance anterior to PC. Thus, if one bears in mind the lessons of Talairach and others, the Van Buren and Borke atlas can be a valuable, convenient, and useful tool.

1977: Atlas for Stereotaxy of the Human Brain, with an Accompanying Guide,

G.

Schaltenbrand and W. Wahren

This single-volume, oversized loose-leaf edition published in Germany nearly 20 years ago probably is the last of the great stereotactic atlases of the twentieth century.10 This “second, re¬ vised and enlarged” version of the Schaltenbrand and Bailey at¬ las represented, according to the authors, an effort to expand on the most clinically useful portions of the original work, debride the impractical or irrelevant material, and fit the finished product into a single volume. For all practical purposes, the authors were successful in their endeavor. They drastically reduced the num¬ ber of unstained macrosections to 34 and eliminated the entire set of quadruple-foldout 20 X Nissl-stained plates that occupied vol III of the first edition. Furthermore, the revision of the com¬ panion text that occupied vol I of the original atlas was delayed in publication until 1982, when it was released as an ordinary¬ sized book.11 Thus, interested readers and practicing stereotactic surgeons could purchase either volume separately, according to their needs. The contents of the 1977 atlas reflect some of the stereotactic procedures that were in vogue at that time. The myelin-stained transverse brain stem and cerebellar series in¬ cluded 21 planes from the pontomedullary junction to the medulla (a span of 46 mm). Like all the other myelin-stained mi¬ croseries in this volume, each photographic section was pre¬ sented at 4X magnification with a transparent overlay bearing anatomic legends and stereotactic coordinates. Surgeons inter¬ ested in dentatotomy (for movement disorders), pontine spinothalamic tractotomy, mesencephalic tractotomy, and medullary trigeminal tractotomy or nucleotomy would have found this series of plates more helpful than those in the earlier edition but still imperfect. Interest by the authors in ablative hy¬ pothalamic operations to control deviant sexual behavior led to the reproduction of the hypothalamic Nissl-stained sections from the first edition. The ten 8X magnified sections, plus two anatomic key sections, occupy only two pages of the atlas. Other additions to the 1977 atlas include 25 color diagrams (on six pages) that summarize the radiographic and electroanatomic ob-

Chapter 29/Stereotactic Atlases in Printed Formats

243

A

Figure 29-6.

A and B. Sagittal variability map from the Van Buren and Borke atlas normalized to AC and PC, respectively, in the 15-mm lateral plane. The solid outline represents the region of densest overlap of the given structure in 25 hemispheres. Broken outlines represent the extreme range of anatomic variability encountered among the same 25 hemispheres. (From Van Buren and Borke.9 Reproduced with permission.) B

servations during stereotactic surgery on more than 300 patients. While viewing six pages of such material is useful and informa¬ tive, neurosurgeons planning to perform functional stereotactic operations also should study one or more of the excellent 500plus-page texts on the subject. As was mentioned above, the Schaltenbrand and Wahren at¬ las contains only 34 macroseries photographs, all at 2X magni¬ fication and divided into three series as follows: 19 frontal planes from 57 mm anterior to 44 mm posterior to AC, five sagittal planes from the midline (0 plane) to 22 mm lateral to the midline, six horizontal planes from 18 mm above to 20 mm below the IC line from one brain, and four additional horizon¬ tal planes from 5 mm to 28 mm below the intercommissural line from another brain. The expanded interest in the horizontal

unstained macroseries and the myelin-stained microseries was stimulated by the advent of CT in the mid-1970s and by the au¬ thors’ foresignt in recognizing the important role axial imaging techniques would play in the future. Recognizing the unpre¬ dictable variability of intracerebral landmarks with respect to the infraorbitomeatal line, the authors cut all horizontal sec¬ tions parallel to the intercommissural plane in the 1977 atlas. In addition to the transverse myelin-stained brainstem series (21 planes) mentioned above, the three standard planes also were well represented, for a total of 78 myelin-stained atlas pho¬ tographs: 20 frontal planes from 16.5 mm anterior to 16.5 mm posterior to the midcommissural plane, 17 sagittal planes from 1.5 to 27.5 mm lateral to the midline, and 20 horizontal planes from 16 mm above to 9.5 mm below the IC line.

244

Part 1/Stereotactic Principles

Every neurosurgeon who performs functional stereotactic operations should own or have unlimited access to a stereotac¬ tic atlas. Although the older works are long out of print, Schaltenbrand and Wahren’s 1977 volume occasionally is available. Individuals fortunate enough to possess a copy of the first edition will find the older atlas suitable for most applica¬ tions.

1978: Stereotaxic Atlas of the Human Brainstem and Cerebellar Nuclei: A Variability Study,

F. Afshar, E. S.

Watkins, and

J. C. Yap

"This work began in 1971, a time when general interest was aroused to the possibility of treating the spasticity of cerebral palsy and other disturbances of muscle tone and posture by ablation of the dentate nucleus of the cerebellum. . . . The technique devised to measure the cerebellar nuclei was then extended to measure within the brainstem (1) the tracts in¬ volved in the treatment of pain and (2) the other important nu¬ clear structures and tracts.”12 This quote from the authors’ in¬ troduction aptly summarizes the purpose, content, and historical context of this atlas. While dentatotomy, stereotac¬ tic medullary trigeminal tractotomy, pontine or medullary spinothalamic tractotomy, and cerebellar stimulation are now performed rarely, the atlas of Afshar and associates remains a valuable anatomic reference for the performance of other, more recently introduced open surgical procedures. These in¬ clude ablation of the trigeminal nucleus caudalis for facial deaflerentation pain and ablation of the nucleus solitarius for visceral-branchial pain associated with malignancy. The atlas was based on a study of 30 brains, using positive-contrast ventriculography and stereotactic marking of the specimens in situ. The authors defined the three planes useful for stereo¬ tactic localization of structures near the rhombencephalon (Fig. 29-7). The ventricular floor plane defined the floor of the fourth ventricle, the fastigium-floor line (and plane) formed a right angle between the fastigium of the fourth ventricle and

the ventricular floor plane, and the plane through the fastigial point parallel to the ventricular floor plane defined the roof of the fourth ventricle. Most of the book consists of computer-generated variabil¬ ity profiles that demonstrate in graphic form the probability (from >90 percent to 0 percent) for finding every major lower brain stem nucleus and tract at a particular coordinate in any given plane of section. The atlas proper contains 54 myelinstained brain stem sections photographed at 5X magnification and presented one per page. All sections are cut parallel to the fastigium-floor line (FFL) and orthogonal to the ventricular floor plane. An outline diagram with stereotactic coordinates and anatomic labels accompanies each photographic plate (in the style of Talairach but presented more clearly). The 1-mmthick sections extend from 23 mm rostral to the FFL (corre¬ sponding to the level of the red nucleus) to 30 mm caudal to the FFL (corresponding to the spinal tract of the trigeminal nerve, caudal to the gracile and cuneate nuclei) (Fig. 29-8). Immediately after the brain stem variability study and atlas, the authors present a similar treatment of the four deep cere¬ bellar nuclei. The variability studies and statistical profiles are illustrated in parasagittal graphic illustrations as well as in the transverse planes parallel to the FFL. The 12 myelin-stained cerebellar atlas plates are presented in exactly the same man¬ ner and at the same magnification as the brain stem pho¬ tographs. They cover the range of transverse coordinates from 1 mm rostral to 10 mm caudal to the FFL. The anatomic detail presented in this atlas makes it one of the most valuable re¬ sources for brain stem stereotactic coordinates available in book format.

1982: The Thalamus and Midbrain of Man: A Physiological Atlas Using Electrical Stimulation,

R. R.

Tasker,

L. W. Organ, and P. A. Hawrylyshyn This 505-page 6- by 9-in. book by Tasker and colleagues does not contain a folio-sized photographic stereotactic atlas like the

Figure 29-7. The hemibrainstem, with reference points and planes defined by Afshar and associates. Abbreviations: F = fastigium of fourth ventricle; FB = line from fastigium to fourth ventricle floor; HBG = fourth ventricular floor plane, at right angles to the FB line; YFX = line passing through fastigial point and parallel to fourth ventricular floor plane. (From Afshar et al.12 Reproduced with permission.)

FASTIGIAL-FLOOR LINE

Chapter 29/Stereotactic Atlases in Printed Formats

245

I MEDIAN PLANE

Figure 29-8.

A. Reference planes for measuring structural borders rostral to the —15-mm level (15 mm caudal to FB in Figure 30-7). B. Reference planes for structures minus 15 mm or more caudal to the fastigial level are measured from the midline and the posterior medullary or cord surface. Abbreviations: a = anterior; 1 = lateral; m = medial; p = posterior. (From Afshar et al.'2 Reproduced with permission.) B

other works described in this chapter.13 Instead, Tasker’s physio¬ logical atlas provides the most lucid English-language analysis of electroanatomic observations (based on 9383 stimulation sites during 198 operations) relevant to stereotactic surgery on the thalamus and upper brain stem available to date. The 90-page at¬ las near the end of the volume depicts the results of stimulation mapping from the author’s clinical material in graphic form. The sites at which specific subjective experiences or observable phe¬ nomena were elicited are displayed on outline maps in the 2- to 20-mm sagittal planes based on the Schaltenbrand and Bailey at¬ las. Tasker’s simple yet elegant technique of anatomically and physiologically normalizing coordinates from different-sized brains made the pooling of data from many individual patients possible. To perform the actual surgical procedures, he con¬ structed sagittal brain maps for each patient, using a computer graphics program. The computer could expand or shrink the ap¬ propriate standard atlas diagrams to match the patient’s intercommissural distance as determined by stereotactic ventriculog¬

raphy. This was a refinement of Talairach’s system of proportion¬ ate coordinates and a simplification of Schaltenbrand’s system of optical modeling. Later, once data from many patients (in the form of observations during electrode trajectory “runs” in a given sagittal plane) were available, Tasker superimposed the re¬ sults on composite maps (Fig. 29-9). In addition, during surgery or between steps in a multistage procedure, he transposed the anatomic boundaries of thalamic nuclei on the individual pa¬ tient’s map according to the results of intraoperative stimulation. As a consequence, important generalizations and rules of thumb emerged, greatly enhancing the surgeon’s ability to make ratio¬ nal decisions about what to do next during functional stereotactic procedures. Most important. Tasker emphasized that physiologi¬ cally defined anatomy rather than blind obedience to atlas coor¬ dinates should determine the conduct of functional stereotactic operations. The other 80 percent of the book provides a detailed ac¬ count of the remarkably stereotypical experiences that pa-

246

Part 1/Stereotactic Principles

tients report and phenomena that neurosurgeons observe during stimulation mapping of the thalamus and midbrain. The reader learns how to identify responses arising from the stimulation of structures belonging to the dorsal columnlemniscus system, the spinothalamic pathway, the pyramidal and extrapyramidal systems, the auditory and vestibular sys¬ tems, the visual and occulomotor systems, and other miscel¬ laneous structures. The last section provides postmortem anatomic correlations of electrode trajectories, stimulation sites, and lesion sites with records of intraoperative physio¬ logical observations in six patients with involuntary move¬ ment disorders or intractable pain. One might compare the process of functional stereotaxis to the navigation of previ¬ ously charted but personally unfamiliar territory. In this sense, the brain atlases described earlier in this chapter are the maps, but the work of Tasker and colleagues is the Michelin Guide. Both are essential to complete the journey successfully.

1988: Co-Planar Stereotaxic Atlas of the Human Brain: 3-Dimensional Proportional System: An Approach to Cerebral Imaging, J. Talairach, and P. Tournoux

Figure 29-9. A. Pooled data from Tasker’s series, showing sites in the 13.5-mm sagittal plane at which electrical stimulation at any threshold arrested the tremor of parkinsonism, essential tremor, or cerebellar disease. B. Data from Tasker’s series, showing the sites of lesions in the 13.5-mm sagittal plane made to relieve tremor in Parkinson’s disease and essential tremor. (From Tasker el al.13 Reproduced with permission.)

This volume, the next to last of Talairach’s stereotactic atlases, departs from the usual focus of such works.4 In their preface, Talairach and Tournoux state, “In contrast to the majority of stereotaxic atlases that are primarily intended for the localization of the deep central nuclei, this Atlas emphasizes the interpreta¬ tion of the vast cortical and subcortical spaces.” The advances in high-resolution CT and MR imaging over the past 10 to 20 years and the accompanying resurgence of functional and anatomic stereotaxis (dealing with tumors and other structural lesions) make such a guide through the borderland between functional and structural neurosurgery timely and informative. As Mark Rayport observed in the translator’s foreword, the “images pro¬ duced by these instruments [MR1 and CT] have been utilized principally in the traditional manner of radiological interpreta¬ tion: verbal description, identification of lesions.” For Talairach and coworkers, the typically vague, imprecise, and frequently anatomically erroneous MRI report does not convey sufficient data for adequate neurosurgical planning and decision making. The potential pitfalls of traditional functional stereotactic opera¬ tions are well known to experienced practitioners. However, nowadays many neurosurgeons with no training or experience in functional stereotaxis routinely perform anatomic stereotactic procedures such as biopsy, tumor resection, brachytherapy, and radiosurgery. The planning and execution of such anatomic stereotactic procedures ideally should take into account possible immediate or delayed functional consequences. While some structures that surgeons might wish to avoid, such as the optic chiasm and the midbrain tectum, often are obvious on imaging studies, other important structures, including the subcortical course of the pyramidal tract, the optic radiations, Forel’s fields, and the hypothalamic nuclei, are invisible or at least not obvious even on excellent-quality MRI. Talairach's 1988 atlas provides neurosurgeons with a tool to help them navigate around and

Chapter 29/Stereotactic Atlases in Printed Formats

through such regions. In addition, by applying the lessons of this atlas to the interpretation of routine diagnostic studies, one can achieve a high degree of accuracy in anatomic localization and clinical correlation. The authors begin with an exposition of Talairach’s propor¬ tional grid system in three dimensions, based on the length, height, and width of the whole brain. The orthogonal reference planes are based on the midline, the intercommissural plane, and the two verticofrontal planes intersecting the anterior and posterior commissures. As the authors explain, direct distance coordinates (in millimeters) vary widely from one brain to an¬ other. This is especially true the farther the point of interest lies from the IC line. Thus, Talairach and Toumoux divided the en¬ tire volume of the brain into cuboidal and rectangular prism¬ shaped parcels called “orthogonal parellelograms.’’ Each hemi¬ sphere is 9 major parcels in length (A-I along the axis of the IC line), 4 parcels wide (a-d along the transverse plane orthogonal to the midline and IC plane), and 12 parcels high (1-12 in ver¬ tical planes parallel to those defined by the commissures). The

Figure 29-10. The brain is divided into orthogonal parallelograms, the dimensions of which vary with the principal axes of the brain. Each of these volumes is defined by its three dimensions (indicated by a capital letter, a lowercase letter, and a number, e.g., A-d-1) (shaded area). (From Talairach and Toumoux.4 Reproduced with permission.)

dimensions of each parcel are determined as follows: oneeighth of the distance between the IC line and the highest point of the parietal cortex and one-fourth of the distance between the IC line and the lowest point of the temporal cortex (parcels 1 through 12 in height); one-fourth of the distance from AC to the frontal pole, one-fourth of the distance from PC to the oc¬ cipital pole, and the whole distance (subdivided in thirds) be¬ tween AC and PC (nine parcels, A-I, in length); and one-fourth of the distance from the midline to the most lateral point of the parietotemporal cortex (4 parcels wide in each hemisphere). Even though this sounds complex when expressed verbally, things become more clear when one studies the authors’ excel¬ lent diagrams (Fig. 29-10 and 29-11). The authors are careful to point out the limitations of this atlas, noting that “the millimetric values are valid for the brain presented here [only].” While this atlas is not among those one would consult before perform¬ ing a procedure such as a thalamotomy for tremor, it is a valu¬ able adjunct in planning surgical approaches to the deep hemi¬ spheric structures using stereotactic techniques.

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248

Part 1/Stereotactic Principles

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References 1.

2.

7.

Baird RA, Spiegel EA, Wycis HT: Studies in stereoencephalotomy: IX. The variability in the extent and position of the amygdala. Confin Neurol 20:26-36, 1960.

8.

Benz RA, Wycis HT. Spiegel EA: Studies in stereoencephalotomy:

Spiegel EA, Wycis HT: Stereoencephalotomy, Thalamotomy and Related Procedures. Part I: Methods and Stereotaxic Atlas of the Human Brain. New York: Grune & Stratton, 1952.

XI. Variability studies of the nuclei ventralis lateralis thalami. Confin

Talairach J, Hecaen H, David M, et al: Recherches sur la coagulation

Neurol 20:366-374, 1960.

therapeutique de structures sous-corticales chez l’homme. Rev Neurol

9.

(Paris) 81:1-24, 1949.

3. 4.

6.

Van Buren JM, Borke RC: Variations and Connections of the Human Thalamus. Berlin, Heidelberg: Springer, 1972.

Talairach J, David M, Tournoux P, et al: Atlas d’Anatomie Stereotaxique. Paris: Masson, 1957.

10.

Talairach J, Tournoux P: Co-Planar Stereotaxic Atlas of the Human

11.

Schaltenbrand G, Walker AE: Stereotaxy of the Human Brain: Anatomi¬

Imaging. Stuttgart: Thieme, 1988.

12.

cal, Physiological and Clinical Applications. Stuttgart: Thieme, 1982. Afshar F, Watkins ES, Yap JC: Stereotaxic Atlas of the Human

Schaltenbrand G, Bailey P: Introduction to Stereotaxis with an Atlas of the Human Brain. Stuttgart: Thieme, 1959.

13.

Brainstem and Cerebellar Nuclei. New York: Raven Press, 1978. Tasker RR, Organ LW. Hawrylyshyn PA: The Thalamus and Mid¬

Schaltenbrand G, Wahren W: Atlas for Stereotaxy of the Human Brain. Stuttgart: Thieme, 1977.

Brain: 3-Dimensional Proportional System: An Approach to Cerebral

5.

Figure 29-11. Coronal (verticofrontal) section 20 mm behind AC, corresponding to plane E3. The original illustration is in color. The boldface numbers refer to Brodmann’s cortical areas. Abbreviations: GPrc = precentral gyrus; Ra = auditory radiation; Ro = optic radiation. Other anatomic abbreviations are standard. (From Talairach and Toumoux.4 Reproduced with permission.)

Spiegel EA, Wycis HT: Stereoencephalotomy. Part II: Clinical

brain of Man: A Physiological Atlas Using Electrical Stimulation.

and Physiological Applications. New York: Grune & Stratton, 1962.

Springfield, IL: Thomas, 1982.

CHAPTER 30

COMPUTERIZED STEREOTACTIC ATLASES

Masafumi Yoshida

Stereotactic functional neurosurgery consists of surgery per¬ formed with a three-dimensional (3-D) coordinate system, us¬ ing an anatomic atlas as a guide to reach the target structures. These are blind procedures in the sense that they are usually performed via a single burr hole without visualization of struc¬ tures along the trajectory of approach to a target. Basically, two 3-D coordinate systems are involved: (1) one that resides on the stereotactic instrument, a device by which any point in this 3-D coordinate system can be precisely reached, and (2) one that resides in the individual patient’s head, a 3-D coordinate system that shows the 3-D anatomic organization of the brain of the individual patient. Target structures in an individual pa¬ tient’s brain can be reached once their 3-D coordinates on the anatomic 3-D system are converted to those of the stereotactic device. Computed tomography (CT) or magnetic resonance imag¬ ing (MRI) images show the 3-D organization of an individual patient’s brain but in themselves cannot display a detailed 3-D organization of minutely parcellated fine anatomic structures. Instead, assuming that the 3-D geometric organization of the human brain is reasonably uniform, a standard anatomic atlas is used. This type of atlas is the product of a detailed histologi¬ cal analysis of an autopsy brain; that by Schaltenbrand and Bailey1 is one of the most popular. The 3-D coordinate system of a standard anatomic atlas usually is based on cerebral reference points, most commonly the anterior and posterior commissures (AC and PC), with the midcommissural point as the origin. Therefore, with the identi¬ fication of at least three reference structures or their equiva¬ lents, usually AC, PC, and the midsagittal plane, in the patient’s brain by means of a neuroimaging technique such as, ventricu¬ lography, CT, or MRI, the anatomic atlas with its detailed anatomic organization of fine parcellated structures can be fit¬ ted into the patient’s brain and any of these structures can be lo¬ cated in the patient’s brain. Thus, by identification of the 3-D coordinates on the stereo¬ tactic instrument of at least three key reference structures in the patient’s brain, 3-D conversion parameters between the 3-D co¬ ordinates in the anatomic atlas and the stereotactic device can be calculated. With the use of these parameters, the 3-D loca¬ tion of any point on one of the two 3-D coordinate systems can be interchangeably converted to those of the other. This means that any anatomic structure from the standard atlas can be lo¬ cated in terms of 3-D coordinates on the stereotactic instrument so that accurate stereotactic access to it can be achieved.

Conversely, using the same conversion parameters, any point located on the stereotactic device-based coordinate system, such as the tip of the advancing electrode, can be referred to the structures of the standard anatomic atlas. From the above, it is apparent that this is a technique of surgery based on a “hypothetical individual” anatomic atlas, and accurate access to the intended target depends on precise assessment of the individual’s anatomic deviation from the standard atlas, appropriate accuracy of the stereotactic instru¬ ment system, and elimination of other sources of surgeryrelated geometric errors. In stereotactic functional neurosurgery, even minute individ¬ ual deviations from a standard atlas are extremely critical. Unfortunately, this is an almost constant occurrence rather than an exception. Therefore, individual anatomic variation is deter¬ mined from both anatomic and functional data, and the standard atlas is modified to fit the individual patient accordingly. Anatomy-based correction usually is achieved with reference to anatomic data obtained by neuroimaging, for example, AC-PC distance and width of the third ventricle, width of the aqueduct, and dimension of the thalamus.2*10 Neurophysiological correc¬ tion is based on intraoperative neurophysiological studies in¬ cluding deep electroencephalography (EEG) recordings by semimicroelectrodes (field potential, general neuronal electrical activity, or neural noise), evoked potentials obtained from deep structures on stimulation of the contralateral median nerve, thal¬ amocortical evoked potentials, and clinical response elicited on stimulation of deep structures.9-18 The accuracy of a stereotactic instrument system is hard¬ ware-dependent. It also depends on the linearity and elasticity of the advancing electrodes and the compliance of brain sub¬ stance along the trajectory. Other sources of error include brain shift caused by cerebrospinal fluid (CSF) leak after the burr hole is made and situations in which an electrode follows a pre¬ vious trajectory when a second target is approached that is ex¬ tremely close to the first. These errors should always be moni¬ tored and corrected for by intraoperative radiological verification of the electrode position. In these circumstances, a computer atlas is convenient be¬ cause of its capability for modification to fit an individual patient’s anatomy and, with the use of computer graphics tech¬ niques, to produce a comprehensive 3-D display of all neces¬ sary intraoperative information, including trajectory location and neurophysiological data, together with a “hypothetical in¬ dividual” computer atlas (Fig. 30-1).2'4,5,8-10 This provides

249

250

Part 1/Stereotactic Principles

Figure 30-1. Three-dimensional display of the location of neurophysiologically identified anatomic structures and of a lesion-making electrode on frontal sections from the original Schaltenbrand and Bailey atlas. The location of anatomic structures is indicated by alphanumeric codes. C = caudate: W = white matter; T = thalamus; S = subthalamic field. The points of intersection between a trajectory and each plane of the anatomic atlas are indicated by alphanumeric codes in parentheses. The location of a lesion-making electrode is indicated by serially displayed octagonal circles. The point of intersection of a lesion-making electrode with a plane of the anatomic atlas is indicated by the absence of one of the serially placed octagonal circles.

instant precise visual integration of the entire operative proce¬ dure and increases the surgeon’s confidence in selecting the optimal target. Another aspect of a computer system associated with an electronic atlas is its ability to store a voluminous amount of intra- and perioperative data and create a huge database library. These data can be retrieved, processed with appropriate filtra¬ tion, and graphically displayed with an anatomic atlas for the understanding of the functional organization of the human thal¬ amus and adjacent structures.9,1013'14,18

shifted individually to match the actual measurements of a pa¬ tient’s third ventricle as determined by ventriculography. For navigational purposes, the probe tract could be shown in rela¬ tion to the corrected atlas in any of three planes, with the por¬ tion of the probe extending beyond the display plane appearing as a dotted line. The point at which a particular physiological phenomenon was encountered could be labeled and stored for future display and analysis.

HISTORICAL OVERVIEW

Since then, several 2-D computer atlases created by digiti¬ zation of standard anatomic atlases have been utilized.4'7,9,10,19 Before the era of CT and MR1 image-assisted stereotaxy, these 2-D computer atlas diagrams were stretched or com¬ pressed by simple linear and rigid transformation in accordance with the dimensions of the third ventricle—intercommissural distance and width of the third ventricle—as visualized by the intraoperative ventriculogram. With the use of this 2-D com¬ puter atlas system, an enormous volume of intraoperative physiological information was inputted to the computer and extensive neurophysiological mapping studies were performed.9,10,13,14

The first electronic atlas was reported by Bertrand and col¬ leagues.3 That system used the original Schaltenbrand and Bailey atlas—a two-dimensional (2-D) atlas—but was equipped with virtually all currently required functions. This computer program was capable of displaying any of the Schaltenbrand and Bailey atlas plates, including the legends, with any dimension of the atlas compressed, stretched, or

In the era of image-guided stereotaxy, with individual anatomic 3-D organization available as 3-D voxel data, the 3-D coordinates of an image-visualized point are easily converted to those on the stereotactic device-based 3-D coordinate system. By obtaining the 3-D coordinates of cerebral reference points visualized in CT or MRI images, such as AC and PC, on a stereotactic device-based 3-D system, one can calculate 3-D conversion parameters between atlas- and stereotactic

Thus, computer-assisted stereotactic functional neuro¬ surgery with computer data processing and graphic display of information with a 3-D anatomic atlas in an easily understand¬ able manner can turn a “blind procedure” into a vividly visual¬ ized, well-organized, and well-controlled precise procedure soundly based on detailed intraoperative neurophysiological studies.

Chapter 30/Computerized Stereotactic Atlases

device-based 3-D coordinate systems, avoiding the necessity for ventriculography.4-7,19 This technique is essentially the same as that using ventriculography but eliminates the time consumed for ventriculography and the complications of CSF leakage and brain shift associated with this procedure.19 With the combination of a 2-D anatomic atlas and 3-D im¬ age data, “2-D volume reconstruction” was conducted to create an “individual” atlas.5-7 To achieve this, 3-D thin-slice image data have to be reformatted after the allocation of cerebral reference points so that the planes of reformatted images are precisely aligned with sections of the standard atlas. Then the outlines of gross anatomic structures in the standard anatomic atlas, such as the thalamus and globus pallidus, are stretched, contracted, translated, or rotated to fit with their counterparts visualized in the image data; thus, subdivisions contained within the gross structures undergo the same reconstructive procedures and can also be located on image data. A 3-D atlas in the form of stacked-up 2-D atlas slices at short intervals was created by interpolation of a series of out¬ lines of structures from the Schaltenbrand and Bailey atlas. An example is the 0.5-mm step, 3-D atlas created by interpolation from the Schaltenbrand and Bailey atlas that is described be¬ low.20 Kazarnovskaya and coauthors21 went further to create a 3-D voxel anatomic atlas from a serial 2-D atlas similarly cre¬ ated by interpolation of sagittal sections of the Schaltenbrand and Bailey atlas. Neither was a true 3-D atlas, since interpola¬ tion was performed only in a single plane without taking into consideration the atlas plates in the two other planes. However, the 3-D voxel system of Kazarnovskaya and coauthors21 has the advantage of producing an atlas drawn at any given angle from the sagittal plane. Giorgi and colleagues3 reported a true 3-D voxel anatomic atlas reconstructed from sagittal sections of the Schaltenbrand and Wahren atlas by 3-D interpolation and further digital pro¬ cessing (3-D low-pass filtering) of the reconstructed volumes. This atlas has the capability of multiplanar reconstruction and display and, theoretically, of reconstructing an “individual” 3-D atlas by means of 3-D volume matching of the gross struc¬ tures of the standard atlas against thin-slice CT- or MRIvisualized counterparts.

251

intra- and perioperative data from any patient in any institution can be stored and from which cumulative data can be retrieved from data from an individual patient or a group of patients for intraoperative use at any institution.

Requirements for the Computer System For the best utilization of an electronic atlas, the computer sys¬ tem should be capable of the acquisition and storage of enor¬ mous amounts of varieties of long- and short-term pre- and postoperative data as well as intraoperative neurophysiological data. Almost all intraoperative data are inputted into the com¬ puter together with their 3-D coordinates. Those which are not directly correlated to 3-D coordinates, such as pre- and postop¬ erative clinical physical and functional data, will eventually be linked to the 3-D coordinates of therapeutic lesions or stimula¬ tion points as well as physiological data. Therefore, all data should be inputted into the computer so that they can be corre¬ lated to relevant 3-D coordinates. Various modes of capturing and processing peri- and intra¬ operative data should be available. Intraoperative x-rays are digitized two-dimensionally for calculation of the 3-D coordi¬ nates of anatomic reference points, sites where physiological data are obtained, and sites where therapeutic stimulation or coagulation is carried out. CT or MRI data are inputted into the computer as original digital data or by image capture to be used for 3-D coordinate calculation of cerebral reference points and customization of a standard atlas. Direct current (DC) electrical signals from intraoperative physiological studies are fed into the computer by analogue-to-digital (A-D) conversion to un¬ dergo various modes of analysis, such as fast Fourier transfor¬ mation (FFT)16,17 and averaging; they are ultimately stored as coded information. Intraoperative stimulation responses and pre- and postoperative clinical assessments are fed into the computer as coded information with the use of a keyboard or mouse.9'10

0.5-mm Slice Three-Dimensional Atlas Created by Interpolation from the

A COMPUTER SYSTEM WITH AN ELECTRONIC ATLAS FOR STEREOTACTIC FUNCTIONAL NEUROSURGERY Role of the Computer Atlas There are five objectives and applications of the computer atlas: (1) 3-D visualization of anatomic structures so that their 3-D organization can be well appreciated, (2) freedom to mod¬ ify the dimensions of the electronic atlas to fit an individual pa¬ tient’s anatomic organization as visualized by CT and/or MRI data, that is, customization of a standard atlas, (3) display of neurophysiological or clinical therapeutic data, collectively or individually, in relation to the anatomic atlas for optimal target localization, (4) display of an advancing electrode in relation to the anatomic atlas for navigation and monitoring of proper placement, and (5) creation of a universal anatomic atlas in the form of a 3-D voxel database system in which all pertinent

Schaltenbrand and Bailey Atlas The 3-D computer atlas described here is in 0.5-mm slices cre¬ ated by interpolation from the Schaltenbrand and Bailey atlas (Fig. 30-2A and B).20 With the use of this atlas, any threedimensionally located point can be displayed on an atlas within a perpendicular distance of 0.25 mm from that point. Interpolation is performed by subnuclei and labeled with the same nomenclature that appears on both of the adjacent two parallel atlas plates. This is only a simulated and not a truly 3-D atlas, since interpolation was performed only with the two par¬ allel adjacent atlas plates. That means that when a new coronal plate is to be created by interpolation, that interpolation is based only on the two adjacent coronal plates and no attention is paid to either the sagittal or the horizontal atlas plates that cover the 3-D area being interpolated. With this 0.5-mm interval anatomic atlas, a wide variety of forms of 3-D display are possible, but they are basically deter¬ mined by (1) the number of serially placed atlas plates (or visual thickness), (2) the 3-D rotation angle of the atlas, and (3) the rel-

252

Part 1/Stereotactic Principles

adjacent plates (Fig. 30-3A and B). In effect, this form of display creates the illusion of a brain sliced at a suitable thickness and visualized three-dimensionally.

Digitization of Intraoperative X-Ray Films with the Ventriculogram The purposes of digitization of the intraoperative x-ray with the ventriculogram are (1) calculation of coordinate conversion pa¬ rameters between the two different 3-D coordinate systems and (2) acquisition of basic morphological data for each patient taken from the intraoperative ventriculogram, which may be used later for filtering parameters. Usually the stereotactic instrument is equipped with fiducials to calculate accurately the stereotactic device-based 3-D coordinates of a point visualized on a set of anteroposterior (AP) and lateral intraoperative x-ray films. With 2-D digitiza¬ tion of pertinent points together with fiducial points visualized on a set of AP and lateral intraoperative x-ray films, the com¬ puter can execute all the necessary calculations to obtain the 3-D coordinates of these points on the stereotactic devicebased 3-D system. Thus, AC and PC, all pertinent points, including those that define the midsagittal plane, and tilt and rotation of the head revealed on a set of AP and lateral x-ray films during ventriculography are digitized. Then, with the radial divergence of the x-ray beam and parallax taken into con¬ sideration, these digitized points are converted to 3-D coordi¬ nates on the stereotactic frame-based 3-D coordinate system. Once this has been done, as was described above, 3-D conver¬ sion parameters between the standard anatomic atlas and the stereotactic device-based 3-D coordinate systems are calcu¬ lated. Unless frameless stereotaxy is being used, the patient’s head is securely fixed to the stereotactic frame. Therefore, using the same conversion parameters, any point localized on the framebased 3-D coordinate system can be converted to the 3-D coor¬ dinates of the AC-PC system or vice versa throughout the entire procedure.

Digitization of Intraoperative Films with an Electrode in Place

B Figure 30-2. An example of the serial display of a 0.5-mm step atlas in (A) sagittal and (B) frontal (coronal) planes with axis rotation for three-dimensional demonstration of anatomy. Display range: Sagittal = 10.0 to 13.5 mm lateral and 4.0 frontal-anterior to 1.5 posterior to middle of AC-PC line.

ative position (or spatial relationship) of each group of serially displayed atlas plates. The display method varies in accordance with the purposes of the display. For example, in plotting out 3-D functional data on an anatomic atlas in order to make a functional atlas, the method the author found most useful was to display a group of two to three atlas plates with 3-D rotation sufficiently separated from each other to avoid overlapping with

The purpose of digitization of electrode positions visualized by x-ray is (1) confirmation of proper electrode position and (2) calculation of 3-D coordinates along the trajectory correlated with the depth of the advancing electrode tip—the distance be¬ tween the tip of an electrode and the target point—which can be read as a calibrated number on the stereotactic device. Since the Schaltenbrand and Bailey atlas7 is based on the anterior and posterior commissures with the midcommissural point as the origin of the coordinate system, the 3-D positions of points related to peri- or intraoperative data are expressed in terms of the 3-D coordinates of the standard anatomic atlas. To obtain 3-D coordinates along the trajectory correlated to the depth of penetration of the advancing electrode tip, the po¬ sition of the electrode tip is digitized at at least two different positions with respect to depth readings. Once this information is obtained, the 3-D coordinates of any point along the trajec¬ tory can be calculated by linear interpolation or extrapolation as a factor of the depth reading of the advancing electrode. As a

Chapter 30/Computerized Stereotactic Atlases

B Figure 30-3. Examples of a functional atlas based on (A) sensory and (B) motor responses elicited by electrical stimulation of subcortical structures. The response modality is coded and plotted at each stimulation site. Display range is 11.0 to 13.5 mm lateral. Codes for response modalities are shown in the figure.

253

254

Part 1/Stereotactic Principles

result, given a trajectory identification (ID) number and the depth reading of a particular point of interest, intraoperative physiological data will be automatically inputted together with the 3-D coordinates of that point.

Sources of Intraoperative and Perioperative Information Electrophysiological data acquired during surgery include (1) spontaneous deep EEG recorded by semimicroelectrodes (field potentials), (2) sensory, motor, emotional, and autonomic re¬ sponses on stimulation of subcortical structures, (3) thalamic stimulated cortically evoked potentials, (4) contralateral me¬ dian nerve stimulated thalamic evoked potentials, and (5) recordings of thalamic burst discharges evoked by various types of peripheral sensory stimulation and by movements.9-18 These data are coded and subjected to keyboard (mouse) in¬ put. Those which are obtained as DC electrical signals and fed into the computer by A-D conversion to be processed in a suit¬ able format can be stored as raw (or original) data for possible reanalyses using different techniques. Among these functional data, field potentials seem to reflect primarily anatomic (cytoarchitectural) organization12 and with various digital process¬ ing methods may delineate the boundaries of parcellated sub¬ nuclei of the thalamus.1617 The rest of the data are oriented more toward the functional representation of neural pathways. For the input of functional data, the 3-D location of the datarelated point is fed into the computer in the form of a trajectory ID number and depth reading along with neurophysiological stimulation or recording parameters.

Intraoperative data include those visualized on the intra¬ operative ventriculogram and are obtained as 3-D data by dig¬ itization of the x-ray film, as described above. Structures or reference points seen on the intraoperative ventriculogram that are to be digitized include the outline of the third and lateral ventricles with AC-PC and the foramen of Monro, massa inter¬ media (if present), aqueduct of Sylvius, cranial vault, and other cranial landmarks, such as the external auditory meatus, infe¬ rior orbital margin, tuberculum sellae, posterior margin of the foramen magnum, basion, asterion, and bregma.

Data Processing and Display

Related to Intraoperative

A functional atlas is created by plotting three-dimensionally al¬ located neurophysiological data on the 3-D anatomic atlas. Sections from the atlas, their angle of rotation on the 3-D axis, and positions are freely selected. The category of data to be dis¬ played and the filtering parameters and their ranges are selected according to the type of functional atlas to be created. Since each of 0.5-mm atlas plates consists of 2-D coordi¬ nates, one can create 3-D coordinate data by the addition of 0.5-mm step coordinates in the direction of a line perpendicular to the atlas plates except for the horizontal plates, which are not aligned with the plane of the AC-PC axis and therefore require additional conversion coordinates. For simultaneous display of the anatomic atlas with functional data, the 3-D coordinates of each should be three-dimensionally processed in exactly the same manner. Since 3-D processing for each plate of the anatomic atlas often varies, three-dimensionally placed func¬ tional data have to be assigned to the topographically closest anatomic atlas with which the data are to be displayed; that is, the data have to be selected so that their coordinates on an axis perpendicular to the anatomic plate used for their display are within ±0.25 mm of those of that atlas plate.

Neurophysiological Studies or the Surgical Procedure

A Three-Dimensional Functional Atlas

Basic Patient Information Not Directly

The clinical parameters used primarily for filtering neurophysi¬ ological data are (1) basic demographic and clinical data, (2) preoperative and postoperative symptomatology, and (3) intraoperatively obtained anatomic data, especially in the vicinity of the target. Basic clinical data that potentially influence the organiza¬ tion of the neurophysiological atlas include age, gender, diag¬ nosis, age at onset of disease, basic neurology, heredity, his¬ tory of previous toxic reactions, and central nervous system (CNS) infection. Pre- and postoperative data are obtained outside the operat¬ ing room, usually in the outpatient clinic, most conveniently with the use of a laptop-type personal computer. Patients are evaluated periodically in the outpatient department with re¬ spect to the physical examination scale, functional disability scale, complication scale, psychometric tests, and so on. These data are used for the assessment of both immediate clinical re¬ sponse and long-term follow-up results after surgery. Although these data cannot be correlated directly with intraoperative physiological data, when these data are processed, the immedi¬ ate and long-term effects of surgery can be correlated with the site of the therapeutic ablative lesion or deep brain stimulation (DBS) electrode site and with the neurophysiological data col¬ lected in the vicinity of the target.

As an example, a computer-processed functional atlas display¬ ing sensory and motor responses obtained intraoperatively by electrical stimulation of human subcortical structure is pre¬ sented. The clinical material was collected from 19 parkinson¬ ian patients and from 3 patients with tremor and with thalamic and pseudothalamic pain, respectively. They underwent a total of 29 stereotactic procedures. Various target areas, nuclei ventralis-oralis posterior (Vop) and ventralis intermedius (Vim) of thalamus for parkinsonism and tremor, and posterior limb of the internal capsule and nucleus ventralis posterolateralis (VPL) for deafferentation pain were approached via frontal burr holes. For each stereotactic procedure one to three trajec¬ tories were explored, and for each trajectory stimulation was conducted at several points over a 3- to 5-mm interval in the vicinity of the target, using a bipolar, coaxial semimicroelec¬ trode whose tip diameter was approximately 50 p.. Stimulation was done with 2-mA constant current square-wave pulses at frequencies ranging from 5 to 90 Hz and pulse widths ranging from 0.1 to 0.5 ms. The modality and somatotopic representations of these re¬ sponses were coded, computer processed, and displayed to¬ gether with the 3-D atlas data to create a functional atlas. Stimulation sites are indicated by an alphanumeric code cor¬ responding to the response modality (Fig. 30-3A and B).

Chapter 30/Computerized Stereotactic Atlases

Although the geographic freedom of location of the exploring electrode is limited and therefore the trajectories are more or less confined to the vicinity of the ventrolateral nuclear group of the thalamus, it is apparent that the stimulation points from which sensory responses were elicited were located not only in the lateral portion of the Vim and VPL nuclei but also were considerably ventroposteromedial in the subthalamic area; motor responses were elicited primarily in the Vop and Vim nuclei. Similar displays based on the somatotopic distri¬ bution of stimulation responses (not shown) indicated that the majority of these responses were referred to the face, hand, or upper limb.

DISCUSSION The Two Types of Three-Dimensional Atlas: Serial Two-Dimensional and True Three-Dimensional Since virtually all data obtained during stereotactic surgery are correlated with points that are widely distributed on a 3-D coordinate system and almost always are simultaneously dis¬ played with an anatomic atlas that serves as the anatomic land¬ mark, the computer-stored atlas should have wide choices of 3-D display. Currently, basically two forms of 3-D atlas are available for this purpose: (1) a serial 2-D atlas and (2) a true 3-D atlas in the form of 3-D voxel data. Because of its capability for multiplanar display, the true 3-D atlas has the potential for a far greater variety of display modalities than does the 2-D serial atlas. A true 3-D anatomic atlas is capable not only of producing detailed multiplanar anatomic sections but also of displaying various images, including 3-D dissection and sites of surgical simulation.22 In a serial 2-D atlas, the display planes are limited to the planes defined by the original anatomic atlas: coronal, sagittal, and horizontal. Furthermore, anatomic structures dis¬ played by the serial 2-D anatomic atlas on one of three planes—coronal, sagittal, and horizontal—may not be threedimensionally completely matched with those in the two other planes. The procedure for fitting individual anatomic organization as visualized by CT or MRI into a 3-D atlas is different for the two types of 3-D atlases. In the case of the serial 2-D atlas, re¬ construction involves 2-D data processing only and is con¬ ducted exclusively on the plane defined by the original atlas, and so 3-D image data must be reformatted to match the plane of the original standard atlas. For the true 3-D standard atlas, volume-to-volume recon¬ struction between two sets of 3-D voxel data (i.e., a true 3-D standard atlas and individual thin-slice CT or MRI imagebased 3-D voxel data) is required and the detailed outlines of parcellated substructures from the standard 3-D voxel anatomic atlas are three-dimensionally reconstructed to form a customized 3-D voxel individual atlas. Even when customiza¬ tion is to be performed using 2-D image data (when thin-slice 3-D voxel image data are not available), 3-D standard atlas data, instead of CT or MRI data, can be reformatted so as to be aligned with a given image plane for customization. In this sit¬ uation, reconstruction in any single plane involves modifica¬

255

tion of the entire set of 3-D voxel data from a standard anatomic atlas. It is apparent that the algorithms involved in processing the two different types of computer-stored atlases are totally differ¬ ent. A simulated 3-D standard atlas consisting of a series of 2-D atlas plates at reasonably short intervals, although incapable of multiplanar display, is capable of various forms of simulated 3-D display.18 20 Since it consists basically of a stack of 2-D plates, the necessary processing of the atlas data and their dis¬ play do not involve complicated software and execution of the program can be expected to be instant. Because of relatively light demand for the necessary software and hardware despite the reasonably appealing display modes that can be provided, the simulated 3-D atlas, despite some drawbacks, seems to be currently the most practical atlas type to be used as a computerstored basis for a computerized system dedicated to stereotactic functional neurosurgery. In the case of the true 3-D atlas, one is dealing with 3-D data processing that requires complicated time-consuming software programming and powerful hardware for instant execution and display of the results. In fact, image processing, even with the use of a sophisticated computer, may not be fast enough.22 However, it is very likely that in the near future technical ad¬ vances will overcome these problems. Because of its capability for multiplanar display and simulated 3-D surgical and anatomic dissection, the true 3-D voxel data atlas will probably become the mainstay for a computer-stored basic atlas for use in stereotactic functional neurosurgery.

FUTURE PROSPECTS As was discussed above, thin-slice CT and MRI data them¬ selves constitute a “true individual” atlas in the form of 3-D voxel data. However, since subnuclei and detailed parcellation of the thalamus and other subcortical structures cannot be visu¬ alized, a customized form of a histology-based standard atlas constructed from an autopsied brain is used. However, this customized form of computer-stored atlas, in the form of serial 2-D atlas pixels or 3-D voxel data, is still a “hypothetical individual” atlas, since most of the pixel and voxel data are derived from interpolation from standard anatomic atlas material; histological architecture for detailed anatomic parcellation has never been verified for the pixel or voxel data used. In this context, the ideal form of computer atlas would be a truly 3-D one in the form of 3-D voxel data obtained by an ex¬ tensive histological cytoarchitectural study of thin slices from a “normal” autopsy brain. If pre- and/or postmortem and postfix¬ ation thin-slice CT and MRI data are available, brain fixation artifacts can be corrected and eliminated by comparison of his¬ tological slices with CT or MRI images; it then becomes possi¬ ble to make a detailed histology-based 3-D voxel atlas with each voxel three-dimensionally correlated with CT or MRI im¬ ages.23 This means that histology-based anatomic 3-D voxel data, which are the foundation for the delineation of minutely parcellated structures, are directly linked to CT and MRI voxel data. Therefore, in theory, if one correlates two sets of thinslice CT and MRI voxel data, one from a standard brain and another from the individual patient’s brain, histology-based standard 3-D anatomic voxel data can be three-dimensionally

256

Part 1/Stereotactic Principles

transformed to match the 3-D anatomic organization of the in¬ dividual brain, thus constituting 3-D customization of a stan¬ dard 3-D voxel atlas.

References

Similarly, using the reverse procedure by transforming an individual CT- or MRI-based 3-D voxel atlas backward into a standard or “normal” 3-D voxel histological atlas, the 3-D co¬ ordinates on a “true individual” atlas can be transformed to those on a standard anatomic atlas as a 3-D volume standard¬ ization of individual 3-D voxel CT and MRI data. In other words, mediated by CT- or MRI-based 3-D voxel data, the three-dimensionally allocated voxels (or 3-D coordinates) of a histology-based standard brain atlas and those of the individual patient’s brain can be reciprocally transferred regardless of in¬ dividual anatomic variations. Thus, when neurophysiological data are to be stored in the computer, the site where physiologi¬ cal data are obtained is referred to an appropriate voxel (3-D coordinates) on the image data of the individual patient and can be further referred to the corresponding 3-D voxel of a standard brain atlas. This will create a unique situation in which each voxel of ei¬ ther the standard or the individual 3-D voxel atlas is designed to represent a 3-D coordinate and store all three modalities of data related to that site: CT or MRI, histological, and intra- or perioperatively obtained neurophysiological or clinical data. In addition, each 3-D voxel (or 3-D coordinate) from the individ¬ ual patient can be reciprocally referred to its counterpart in the voxel system of the standard atlas. As a result, a voluminous quantity of intra- and periopera¬ tive neurophysiological and clinical data from any patient, regardless of age, gender, and race, and pathological and physiological data from any institution can be referred to and accumulated in the 3-D voxels (or 3-D coordinates) of a stan¬ dard (or reference) 3-D voxel atlas, thus creating a huge 3-D voxel data library. Conversely, computer-stored data can be retrieved with appropriate filtration and transferred to and dis¬ played with a customized histology-based atlas and/or indi¬ vidual CT- or MRI-based voxel data for intraoperative use. Thus, if the computer systems of various institutions are linked on-line with a standardized communication protocol and data format, accumulation and retrieval of data will be ef¬ ficiently accomplished. The real benefits of this system may be found in the 3-D display of computer-stored functional or anatomic data. Since each 3-D voxel is able to store virtually all modalities of data that can be related to the 3-D coordinates of a stan¬ dard anatomic atlas, a wide range of 3-D volume displays of different varieties of data modalities is readily available. In particular, if a large enough body of functional data is accu¬ mulated in this 3-D voxel system, voxels containing specific functional data may form a 3-D volume and 3-D display of specific functional or neurophysiological information with or without a simultaneous 3-D volume display of CT or MRI or histology-based anatomic organization; various forms of simulated anatomic approaches or dissections may also be possible. This type of 3-D voxel-based database system may be fur¬ ther extended to handle other information, including that derived from neurohistochemistry,23 positron emission tomog¬ raphy (PET), single-photon emission computed tomography (SPECT),24 and therefore can be an invaluable tool not only for stereotactic functional neurosurgery but also for teaching and research in a wide spectrum of the neurosciences.

1.

Schaltenbrand G, Bailey P (eds): Introduction to Stereotaxis with an Atlas of Human Brain. Stuttgart: Thieme, 1959.

2.

Bertrand G, Oliver A, Thompson CJ: The computer brain atlas: Its use in stereotaxic surgery. Trans Am Neurol Assoc 98:233, 1973. Giorgi C, Broggi G, Garibotto G, et al: Three-dimensional neu-

3.

roanatomic images in CT-guided stereotaxic neurosurgery. AJNR 4:719-721, 1983. 4.

Hardy TL, Koch J, Lassiter A: Computer graphics with computerized tomography for functional neurosurgery. Appl Neurophysiol 46: 217-226, 1983.

5.

6.

Hardy TL, Smith JR, Brynildson LRD, et al: Magnetic resonance imaging and anatomic atlas mapping for thalamotomy. Stereotact Fund Neurosurg 58:30-32, 1992. Kali BA, Kelly PJ, Goerss S, Frieder G: Methodology and clinical ex¬ perience with computed tomography and a computer-resident stereo¬ tactic atlas. Neurosurgery 17:400-407, 1985.

7.

Kelly PJ, Kail G, Goerss S: Stereotactic CT scanning for biopsy of in¬ tracranial lesions and functional neurosurgery. Appl Neurophysiol 46:193-199,1983.

8.

Shabalov VA, Kazamovdkaya MI, Bordkin SM, et al: Functional neu¬ rosurgery using 3-D computer stereotactic atlas. Acta Neurochir Suppl (Wien) 58:65-67, 1993.

9.

Tasker RR, Hawrylyshun P, Organ LW: Computer mapping of brain¬ stem sensory centers in mm. J Neurosurg 44:458—164, 1976. Tasker RR, Organ LW, Hawrylyshyn P: The Thalamus and Midbrain

10.

of Man: A Physiological Atlas Using Electrical Stimulation. Springfield, IL: Charles C Thomas, 1982. 11.

Bertrand G, Jasper H, Wong A, Mathews G: Microelectrode record¬ ing during stereotaxic surgery. Clin Neurosurg 16:328-355, 1969.

12.

Fukamachi A, Ohye C, Narabayashi H: Delineation of the thalamic nuclei with a microelectrode in stereotaxic surgery for parkinsonism and cerebral palsy. J Neurosurg 39:214-225, 1973. Hardy TL, Bertrand G, Thompson CJ: The position and organization of motor fibers in the internal capsule found during stereotactic surgery. Appl Neurosurg 42:160-170, 1979.

13.

14.

Hardy TL, Bertrand G, Thompson CJ: Organization and topography of sensory responses in the internal capsule and nucleus ventralis caudalis found during stereotactic surgery. Appl Neurophysiol 42: 335-351, 1979.

15.

Ohye C, Saito A, Fukamachi A, Narabayashi H: An analysis of the spontaneous rhythmic and non-rhythmic discharges in the human thalamus. J Neurol Sci 22: 245-259, 1974.

16.

Yoshida M: Electrophysiological characterization of human subcorti¬ cal structures by frequency spectrum analysis of neural noise (field potential) obtained during stereotactic surgery. Appl Neurophysiol 50: 471-472, 1987.

17.

Yoshida M: Electrophysiological characterization of human subcorti¬ cal structures by frequency spectrum analsyis of neural noise (field potential) obtained during stereotactic surgery: Preliminary presenta¬ tion of frequency power spectrum of various subcortical structures. Stereotact Fund Neurosurg 52:157-163, 1989.

18.

Yoshida M: Neurophysiological atlas created by mapping of clinical responses elicited on electrical stimulation of the human thalamus. Stereotact Fund Neurosurg 58:39-44, 1992. Tasker RR, Dostrovsky JO, Dolan EJ: Computerized tomography (CT) is just as accurate as ventriculography for functional stereotactic thalamotomy. Stereotact Fund Neurosurg 57:157-166, 1991. Yoshida M: Creation of a three-dimensional atlas by interpolation from Schaltenbrand-Bailey’s atlas. Appl Neurophysiol 50:45-48, 1987. Kazarnovskaya MI, Borodkin SM, Shabalov VA, et al: 3-D computer model for subcortical structures of human brain. Comput Biol Med 21:451—457, 1991.

19.

20. 21.

22. 23. 24.

Tiede U, Bomans M, Hoehne KH, et al: A computerized three-dimen¬ sional atlas of the human skull and brain. AJNR 14:551-559, 1993. Hirai T, Jones EG: A new parcellation of the human thalamus on the ba¬ sis of histochemical staining. Brain Res Rev 15:1-34, 1989. Greitz T, Bohm C, Holte S, Eriksson L: A computerized atlas: Construction, anatomical content, and some applications. J Comput Assist Tomogr 15:26-38, 1991.

PART

2

IMAGE-GUIDED STEREOTAXIS

Section

4

Imaging for Stereotaxis

CHAPTER

31

RADIOGRAPHY IN STEREOTACTIC SURGERY

Chang Rak Choi

Magnification is affected by the distance from the x-ray source to the patient’s head and the distance from the patient’s head to the x-ray film. It is important to minimize this effect in stereotactic radiographs. To achieve this, x-ray tubes should be tightly collimated, a constant distance from the x-ray tube to the patient’s head must be maintained, and the x-ray cassette grid must be attached as close as possible to the patient’s head. The x-ray generator used in stereotactic surgery must be suffi¬ cient, and the duration of exposure long enough.8 The magnifi¬ cation factor is calculated to assure excellent definition by us¬

Stereotactic surgery began in 1908, when Horsley and Clarke designed a stereotactic apparatus for animal experiments.1-4 However, there were problems in applying their principles to humans because of variability between the cerebral structure and the landmarks of the skull.2 In 1947, Spiegel and Wycis developed a practical human stereotactic apparatus similar to Horsley and Clarke’s design.2,5 Target localization for outlining the ventricular system with contrast medium was introduced. The anterior and posterior commissures or the foramen of Monro and the posterior com¬ missures and the connecting intercommissural line were com¬ monly used at internal cerebral landmarks.2 The ultimate purpose of the stereotactic system is to deliver a probe into an accurately calculated site, and it is mandatory to identify the proper anatomic target. Under these principles, instruments that can fix a constant focal point have been developed. It is absolutely necessary to identify the landmarks on the x-ray film in the three-dimensional XYZ axes after fixation of the stereotactic apparatus to the patient’s head. The skull must be rigidly fixed to the stereotactic apparatus, and identifiable structures should be technically and radiologically measured without error. To achieve this, accurate x-ray collimation is

ing the formula (DPR - DP) Measured distance between two reference points on x-ray — actual distance between the reference points Magnification factor = (MF)

True distance (TD) DPR

necessary. The typical anteroposterior (AP) and lateral films must be precisely aligned (Fig. 31-1). On the AP view, the basal ring or probe guide should appear at an exact right angle to the base of the stereotaxic apparatus.6,7 On the lateral view, the center of the x-ray tube should be accurately aimed at the target point through the rifle telescope or a similar alignment device. In our setup, there must be an 8-ft distance from the central point of the fixed stereotactic device to the x-ray tube on the AP view and a 10-ft distance on the lateral view.7 Even if the radiologi¬ cal procedure is performed to maintain these distances, precise localization of the stereotactic target, calculation of the frame coordinates, and confirmation of probe placement are neces¬ sary in stereotactic surgery. Three factors—magnification, parallax, and patient position errors (tilt and rotation, etc.)—must be considered at the time of radiological examination because of radiological character¬ istics for measurements to be accurate.8 Because the x-ray beam diverges radially from the point source, the greater the distance from the central x-ray beam, the greater the magnification.

actual distance between points (AD) DPR - (DPR X MF) TD + (TD X MF)8

Calculating the XYZ coordinates of the target point in stereotactic surgery can easily be done with computed tomog¬ raphy (CT) or magnetic resonance imaging (MRI). When the x-ray central beam from the x-ray source accu¬ rately intersects the zero point of the coordinate axis of the stereotactic device in the AP and lateral views and is rectangu¬ larly maintained, the operation can be easily performed. To es¬ tablish the proper alignment for performing simple and easy stereotactic surgery, right and left reticules should be accu¬ rately superimposed on the lateral view and AP reticules should be superimposed on the AP view. Poor alignment can occur when rotation or displacement of the x-ray tube causes parallax or when the tube is too far or close. Rotation can occur when the patient’s head is not placed centrally in the stereotactic device. Tilting can occur when the horizontal plane of the frame is distorted. Rotational errors can be corrected by adjusting the midline of the line connecting both auditory canals at accurate right angles to the crista galli. X-ray examination is indispensable in the preoperative ori¬ entation and the application of the targeting apparatus.

261

262

Fart 2/Image-Guided Stereotaxis

Figure 31-1. Two x-ray tubes are arranged at right angles, forming AP and lateral extensions of the unit with the beams aligned to converge at the focal point.

Depending on the device used, radiographic identification of the base ring of the stereotactic device fixing the skull forms the basis of the calculations. Subcortical target structures can¬ not be seen on simple x-rays. X-ray imaging through intraoper¬ ative pneumoventriculography or positive-contrast ventricu¬ lography is necessary for visualization of the ventricular landmarks. When one uses the Riechert-Mundinger apparatus, which is used by the author, the target point is located by referring to the three coordinates of the base ring:

length is measured on the x-ray film. The shorter the distance from the x-ray tube to the x-ray plate, the longer the length of the ruler as seen on the x-ray film, as a reflection of greater magnification. When the x-ray film shows 10.8 cm, in the case of a 10-cm metal ruler, the radiological magnifying rate is 10/10.8 = 0.926.6 Accordingly, the actual length can be calcu¬ lated by multiplying by this magnifying rate. We first identify whether the patient’s head is fixed in the stereotactic apparatus without tilting on the AP and lateral views by means of simple skull x-ray examination. After iden¬

1.

2.

3.

The vertical coordinate, determined from the lateral film, is the vertical distance from the base ring to the target point. I he horizontal coordinate, also determined from the lat¬ eral film, is the distance from the interauricular plane of the base ring to the target point. I he frontal coordinate is the lateral distance from the sagit¬ tal plane of the base ring to the target point (Fig. 31-3).

tification with the simple x-ray film, a burr hole is made 4 cm anterior to the right coronal suture and 2 cm lateral to the mid¬ line. Then ventricular tapping is done by targeting the right nasion and the contralateral orbit, and an air or Conray ven¬ triculogram is taken to demonstrate the third ventricle (Figs 31-2 and 31-3). The primary reference line is the line connecting the ante¬ rior and posterior commissures, which corresponds anatomi¬

Magnification must be considered in the measurement of the actual size of the cerebral structures. When one takes the xray, a 10-cm metal ruler is placed within the field, and the

cally to the hypothalamic sulcus.111" The anterior commissure corresponds to the posterior lower border of the foramen of Monro, and the posterior commissure can be easily identified

Chapter 31/Radiography in Stereotactic Surgery

263

by calcification of the pineal gland or the habenular commis¬

from the middle point of the anterior commissure-posterior commissure line to the lower border of the lateral ventricle.6 The frontal coordinate point corresponds to the ventricular width. This is the distance from the intersection of the lateral contour of the lateral ventricle and the caudate contour to the midline.6 In all these measurements, the enlargement of the ventricle or the difference between a model brain and the patient’s brain must be calculated. It must be remembered that on x-ray, dis¬ tortion and magnification have complex effects. For localization of the target point, the author performs di¬ rect ventriculostomy and then demonstrates the ventricular sys¬ tem with infusion of Conray, which allows a good demonstra¬ tion of the anterior commissure and the third ventricle without major complications. After a good demonstration of the third ventricle, the target point is decided by calculation of target coordinates. Occasionally the patient shows side effects, such as nausea and vomiting, after the Conray ventriculogram. In this case, the pa¬ tient is given a diazepam injection, and when the patient is suf¬ ficiently sedated, the next procedure is continued. In some cases, a comparative analysis of Conray ven¬ triculography and angiography is performed simultaneously. Conray ventriculography is the standard method for accu¬ rate demonstration of intracerebral landmarks and the basic method of stereotactic surgery.

sure11 or its relationship to the aqueduct. The second reference line is the height of the thalamus, which is the vertical distance of a perpendicular line drawn

References

Figure 31-2. Stereotactic ventriculography showing that the catheter tip is located at the foramen of Monro. Lateral view showing the third ventricle and the anterior and posterior commissures (AC and PC).

1.

Bosch D: Stereotactic Techniques in Clinical Neurosurgery. New

2.

York: Springer, 2, 1986, pp 9-41. Heilbrun MP: Stereotactic surgery, in Gildenberg PL (ed): Stereotactic Neurosurgery. Baltimore: Williams & Wilkins, 1988,

3. 4. 5. 6.

7. 8.

9.

10. 11.

Figure 31-3. Anteroposterior view showing the midsagittal plane of the cerebrum.

vol 2, pp 1-16. Horsley V, Clarke RM: The structure and function of the cerebellum examined by a new method. Brain 31:45—125, 1908. Tasker RR: Stereotactic surgery, in Rengachary SS, Wilkins RH (eds); Neurosurgery. New York: McGraw-Hill, 1985, pp 2465-2481. Spiegel EA, Wycis HT: Pallidothalamotomy in chorea. Arch Neurol Psychiatry 64:295-296, 1950. Krayenbuhl H, Maspes PE, Sweet WH: Stereotaxic surgery for treatment of Parkinsons syndrome, in Riechert T (ed): Progress in Neurological Surgery. Basel: S. Karger, 1973, vol 5, pp 1-77. Todd EM: Stereotaxy. Southgate, California: Temtwells, 1972. Kelly PJ: Principles of stereotactic surgery, in Youmans JR (ed): Neurological Surgery, 3d ed, Philadelphia: Saunders, 1990, pp 4183M226. Bertrand CM: A pneumotaxic technique for producing localized cerebral lesions and its use in the treatment of Parkinson’s disease. J Neurosurg 15:251-264, 1958. Cooper IS: Parkinsonism: Its Medical and Surgical Therapy. Springfield, IL: Thomas, 1961. Brierley JB, Beck E: The significance in human stereotactic brain surgery of individual variation in the diencephalon and globus pallidus. J Neurol Neurosurg Psychiatry 22:287-298, 1959.

*

..

tf

CHAPTER 32

CT SCANNING IN STEREOTACTIC NEUROSURGERY

Marwan I. Hariz

tumor or abcess. It also may be a particular area of the brain that has to be assessed in relation to visualized ventricular land¬ marks, as in the case of the ventrolateral thalamus and the posteroventral pallidum. Hence, it is the geometric exactitude in performing the scanning and the accuracy of measurement and calculation of the coordinates on the CT image that distinguish a stereotactic CT study from other CT scans. Therefore, all pos¬ sible sources of error that may interfere with the requirements for accuracy of a stereotactic CT study should be accounted for, if not eliminated.

Since the beginning of human stereotactic surgery in 1947,' the radiological study has been a prerequisite for the existence of such surgery. Furthermore, the radiological study has always constituted an integral part of the surgical procedure. It was the limitations of conventional radiology (plain x-ray, ventriculog¬ raphy, and arteriography) that for a long time established the limits of what could be achieved with stereotactic surgery. In 1973, Hounsfield2 published a method for computerized transverse axial scanning that earned him a Nobel Prize in 1979. This method, which became known as computed tomog¬ raphy (CT), has revolutionized all of neurosurgery, including stereotactic neurosurgery. CT introduced a new coordinate lan¬ guage that had to be adopted by stereotactic neurosurgeons3: The anteroposterior direction became Y instead of the previous X, the dorsoventral direction became Z instead of Y, and the lat¬ eral direction became X instead of Z. CT provided an infinite number of diagnostic and therapeutic possibilities, mainly in morphological stereotaxis, which today is the main stereotactic procedure in most countries. In the last two decades technological progress has provided CT machines with much faster data acquisition time, the possi¬ bility of thinner scans, and improved image resolution. This, together with the worldwide availability of CT scanners, has contributed to the spread and popularization of stereotactic methodology not only among an increasing number of neuro¬ surgeons but also for an increasing number of neurosurgical ap¬ plications. A prerequisite for CT-guided stereotactic neurosurgery is the adaptation of the scanning method and the stereotactic frames to each other. This chapter describes the general princi¬ ples for performing stereotactic CT scanning. A brief review of various techniques combining CT and stereotaxis is presented, and the main clinical applications of those techniques are reviewed.

CT Scanners Modern CT scanners of the third or fourth generation (the term generation is used to distinguish the various methods of data acquisition in CT)4 provide fast scanning and data acquisition time, a possibility of obtaining slices down to 1.0 to 1.5 mm in thickness, improved image resolution, and increased mechani¬ cal accuracy. The matrix of a modern CT scanner typically con¬ tains 512 by 512 pixels (picture elements), with a pixel size around or less than 0.5 mm. Compared with earlier scanners with an 80 by 80 matrix of 3-mm pixels, it is obvious that the modern CT per se permits highly accurate measurement on each single image provided that other parameters, such as win¬ dow setting, field of view, density or contrast resolution, and slice thickness, are appropriate for the actual structure that is to be measured or calculated. Computed tomography is user-friendly and patient-friendly. If the scanner is not being used for other diagnostic purposes, some stereotactic surgical procedures may take place inside the gantry. Intraoperative CT scanning has been used by some workers to guide a probe into the brain and document, almost in real time, the accuracy in reaching the target as well as other effects of the surgery on the brain.5’6 Some workers who feel a need for both maximum accuracy and continuous verification of each surgical step in a stereotactic procedure before, during, and immediately after the completion of the surgery have in¬ stalled a “therapeutic” CT scanner completely dedicated to pre-, intra-, and postoperative stereotactic scanning.6

GENERAL PRINCIPLES While a routine CT examination is performed for diagnostic purposes, a stereotactic CT study is a localization procedure and in itself constitutes a crucial step in the surgical procedure. The localization procedure requires that a structure in the cra¬ nium that eventually will be surgically targeted be delineated and defined in relation to a coordinate system. This intracranial structure may be a readily “seen” pathology, as in the case of a

Stereotactic Frame The general requirements of any head-containing system are to provide well-visualized artifact-free fiducials or landmarks on 265

266

Part 2/Image-Guided Stereotaxis

every relevant CT slice in the stereotactic CT study. Besides, the relationship of these external landmarks to the head must be constant during the whole CT scanning and between the CT study and the subsequent surgery. The number of visible land¬ marks on each CT slice may vary according to the frame sys¬ tem used; however, a minimum of three is required to define a zero origin for the anteroposterior Y and lateral X coordinates on the slice. The accuracy of measuring the height Z coordinate increases considerably if the stereotactic frame contains a fidu¬ cial that permits the assessment of the dorsoventral position of the brain target independent of the accuracy of movement of the CT couch and thus without relying on the accuracy of the Scoutview (see below). Finally, it is also an advantage in terms of minimizing measurement error that the external landmarks of the frame are as close as possible to the head, that is, as close as possible to the intracranial structure in which coordinates are to be measured.

Immobilization of the Patient Unlike conventional radiography, a CT study lasts for a pro¬ longed period. In routine CT scanning, the immobility of the head is important to avoid movement artifacts on the CT pic¬ ture. In stereotactic CT scanning, the immobility of the head in relation to the frame and the CT couch is absolutely mandatory, because the scanning usually is performed with very thin slices and because at least one of the target coordinates, that is, the height coordinate Z, is sometimes based on the primary posi¬ tion of the head at the beginning of the scanning. To achieve strict immobility of the head of a nonanesthesized cooperative patient during the entire stereotactic CT scan, one must secure the head to a frame with skull pins or screws and rigidly fix the frame to the CT couch. The discomfort of the patient should be kept to a minimum, and the patient should be able to tolerate the frame. Nonrigid fixation using noninvasive frames or interfaces also has been used7 10 and can achieve ade¬ quate immobilization of the head with sufficient cooperation by the patient during the CT study. A careful explanation of the stereotactic CT procedure, combined if needed with slight se¬ dation, will allow most patients to achieve acceptable immobil¬ ity of the head. In 1970, Nashold11 stated that the success of stereotactic surgery depends, among other factors, on the coop¬ eration of the patient, and this applies even more in patients who are undergoing a stereotactic CT imaging study.

Scanning Plane and Alignment Conventional axial CT scanning is most often performed with a scanning plane parallel to Reid's base line, to the orbitomeatal line, or to the skull base in general.1213 In stereotactic CT scan¬ ning, it is the geometry of the stereotactic frame that dictates the angulation of the gantry and hence the plane of the scan¬ ning. Most CT machines allow a gantry angulation ±25 de¬ grees from the vertical. Therefore, the patient’s head, with the frame on, should be aligned so that the scanning plane, within the angulation range of the gantry, coincides with and is paral¬ lel to the base ring, base plate, or zero plane of the frame.14"16 Some frame systems require that the coordinates of the base ring be made to coincide with the coordinates of the CT gantry; that is, the center of the base ring must coincide with the center

of the gantry.16 However, stereotactic systems that use various N-shaped, Z-shaped, or V-shaped localizers do not require any specific alignment of the head and frame in relation to the gantry.3-17-22 In some frameless stereotactic scanning techniques, such as the Gildenberg-Kaufman method,23 the gantry is always at 90 degrees. These methods usually require additional conven¬ tional radiograms to transfer the plane and level of the CT scanning onto the radiograms for target definition at surgery.

Scan Thickness Even though an axial stereotactic CT scan containing the target generally also provides the X and Y coordinates of the target in relation to any reference structure, the dorsoventral Z coordi¬ nate is not easy to obtain accurately.24-26 This coordinate depends mainly on the thickness of the CT slice24-29 and the ac¬ curacy of the movements of the CT couch along its long axis.29-31 Even the accuracy in calculating the volume of a rela¬ tively small brain pathology is dependent on the thickness of the CT slice, because the volume of the voxel, that is, the im¬ pact of the partial volume effect on the boundaries of the pathology, can be reduced by examining thinner slices.29 However, the spatial resolution of the CT image is known to decrease with thinner scans, because thinner sections have a more unfavorable signal-to-noise ratio than do thicker slices. This can be improved by increasing the degree of contrast dif¬ ference between the lesion and the surrounding brain. The con¬ trast resolution of the image also can be improved by using longer scan times, but this unfortunately prolongs the duration of the scanning and increases the radiation dose to the patient. In most stereotactic CT studies, however, since the main goal is to obtain coordinates of a brain target that are as accu¬ rate as possible, scanning in thin slices prevails. Typically, con¬ trast-enhanced overlapping slices 5 mm or less in thickness are required, and for functional stereotactic purposes, it is recom¬ mended that the scanning be performed with at least 2-mm contiguous slices or 1,5-mm-thick slices with a 0.5-mm interscan space. Furthermore, if a sagittal or coronal reformatting of the ax¬ ial image is desirable, the image resolution of such a reformat¬ ted image is greatly enhanced if the axial scanning has been performed with thin contiguous or slightly overlapping slices. However, it must be stressed that a reformatted or recon¬ structed image almost never equals the resolution of an axial one and always carries an increased risk of measurement error caused by geometric distortion. Therefore, it is inappropriate to use the reformatted image as the only calculation in very small brain structures.

INTERSCAN SPACING While the thickness of the CT slice is determined by the colli¬ mating of the roentgen beam, the interscan spacing is deter¬ mined by the movement of the CT couch along its long axis. When, for instance, an area of the brain is to be scanned with 1.5-mm-thick slices with a 0.5-mm interscan spacing, the step¬ wise movements of the CT couch must be exactly 2 mm for each slice. If the movement calibration of the CT couch is not accurate, there is a great danger of inaccuracy of the dorsoven-

Chapter 32/CT Scanning in Stereotactic Neurosurgery

tral Z coordinate of the target. This issue has sometimes been neglected, especially in the early years of CT-guided stereo¬ taxis, when several workers derived the Z coordinate from the Scoutview or from the height of the CT slice containing the tar¬ get in relation to the level of the scan containing the base ring of the frame16'32 33 or in relation to an arbitrary zero level when frameless stereotactic scanning was used.23 However, it has been shown by this author and by others24,29-31 that the calibra¬ tion of the stepwise movements of the CT couch, even with “modern” CT machines, it not always reliable. Frames with V-shaped, N-shaped, or Z-shaped fiducials3,15,17-19,22,34 accu¬ rately provide the level of any CT scan independent of the movement accuracy of the CT couch.

267

frames and greater than the error attributable to the imaging procedure.

TECHNIQUES OF STEREOTACTIC CT SCANNING The technique used during a CT study depends on whether an invasive stereotactic frame or a noninvasive frame or interface is used and on whether the procedure is being done without the use of a frame.

Techniques Using an Invasive Stereotactic Frame

Measurements and Calculations Even though a CT study does not provoke postural displace¬ ment of the brain,35 small measurement errors are unavoidable. The size of the pixel on the image13,36 represents an inherent source of error, which, however, may be negligible with mod¬ ern CT scanners. The magnification scale displayed on each image is another source of error, since it has been demonstrated that this scale, which is displayed only in the anteroposterior direction, may not be as accurate for measurements in the lat¬ eral direction.30,31,37 Besides, when one is using the cursor point for distance measurement, that point may, on some machines, have an area up to three times the pixel size.30 Finally, the posi¬ tioning of the cursor point on the boundaries of the brain pathology or on the fiducials of a stereotactic frame, as visual¬ ized on the CT image, carries an unavoidable degree of uncer¬ tainty that must be accounted for. Therefore, instead of relying on the computer to calculate coordinates, some authors prefer to do manual calculations on enlarged CT slices, using a ruler, a thin pen, and a minicalculator.7,31 For details concerning the various ways to calculate CT co¬ ordinates for each stereotactic system, the reader is referred to the chapters in this book describing those systems. Generally, there are three ways to perform measurements and calculations of the CT coordinates of a brain target. One may use (1) man¬ ual measurements on enlarged images, sometimes with the help of matching millimeter grids, (2) the software built into the scanner, or (3) a separately provided software dedicated to the stereotactic measurements of a specific system. In some stereotactic systems, all three techniques may be available in conjunction. However, it must be kept in mind that although a given CT machine has proved reliable as far as calibration, accuracy, and software properties are concerned and a given stereotactic frame has proved to be mechanically accurate and compatible with minimal image artifacts, the combination of the two dur¬ ing a stereotactic CT scanning on a “real” patient may result in measurement errors greater than what would be attributable to either one separately. In 1982, Maciunas and coworkers38 pub¬ lished an extensive application accuracy evaluation of the four most commonly used stereotactic frame systems. The study was done on test phantoms scanned stereotactically with a modem CT machine with slice thicknesses from 8 mm down to 1 mm. Even with a 1-mm-thick scan, a mean target error be¬ tween 1.0 and 1.9 mm and a maximal error between 3.1 and 5.0 mm, depending on the frame used, were obtained. The errors were considered greater than the mechanical accuracy of the

The majority of stereotactic CT scanning techniques rely on a stereotactic frame that is rigidly attached to the head of the pa¬ tient with screws or pins in the calvarium. The head ring or base ring of the frame is mounted on the head before the start of the CT study and is kept attached to the head throughout the scanning procedure and until the completion of the surgery. The radiological constraints of the CT technique have required modification, redesign, and reconstruction of “old” frames from the pre-CT era with CT-compatible material to avoid the artifacts they would otherwise provoke on the CT pic¬ ture.3,16,33,39,40 In addition, other new frames were specifically designed to be compatible with CT studies.21,22,41 The material of these frames often consists of alloys based on aluminum, re¬ inforced plastic, or Plexiglas and carbon fiber. In most modem techniques developed specifically for axial scanning, a localizing cylinder or localizing plates or rods are attached to the base ring before the positioning of the patient in the gantry.3,15,18,19,22,34 The patient is then immobilized on the CT couch, using straps or an anchoring system between the frame and the couch. Some CT localizers have three sets of Nshaped, Z-shaped, or V-shaped rods placed anteriorly and later¬ ally on the base ring.18,19,22,34 During scanning, these fiducials are intersected by the x-ray beam and appear on each axial im¬ age as nine separate dots around the head. By measuring the relative distance between the dots, one can define the height as well as the inclination of each CT slice exactly in space in rela¬ tion to the zero level of the frame. A separate computer is needed to calculate the respective coordinates of the target. In systems based on a “gantry-independent” CT localizer, there is no need for a particular alignment of the skull and the frame in relation to the gantry. However, a common characteristic of these CT localizers is that the rods and reference fiducials lie on the very periphery of the CT image, far away from the skull, that is, far from the brain target; this may have an impact on the accuracy of the calculated coordinates.

Techniques Using Noninvasive Stereotactic Frames Some stereotactic CT methods rely on so called CT interfaces, which have been designed as an intermediate, or link, between the CT study and the surgical frame itself.7-9,42,43 The interface is not surgically attached to the head. It may consist of a plaster cap that is molded to the individual patient’s face and head and to which the frame proper or other reference structures are at-

268

Part 2/Image-Guided Stereotaxis

tached. l~ The interface also may consist of a restraining device positioned on the head by pressing it against “natural” anchor¬ age structures, such as the bridge of the nose, the auditory canals, or the upper dentition.7-8-10'43 These methods rely more than do invasive methods on the complete cooperation of the patient to provide immobility of the head during the scanning procedure. Some interfaces include reference structures lying very close to the head, that is, close to the intracranial target.7-14 Some interfaces may be less well tolerated by the patient, pre¬ venting long-duration stereotactic CT scanning unless heavy sedation is used. A noninvasive frame requires that the relation¬ ship between the frame and the head be unchanged not only during the course of the CT study but also upon remounting the frame to the head for the subsequent surgery. If there is good reproducibility of the interface between repeated mountings, this technique permits greater flexibility in scheduling the stereotactic CT scanning in relation to the surgery. Fur¬ thermore, this technique permits a remote postoperative stereo¬ tactic scanning procedure to be performed in exactly the same manner as a preoperative one, several months after surgery, en¬ abling a direct comparison between preoperative and postoper¬ ative stereotactic CT studies.30-31-37

Frameless Stereotactic Techniques Frameless techniques may use needles, wires, or other markers held with tape or glue on a more or less arbitrary area of the scalp to provide an external “landmark.”44^17 Frameless tech¬ niques also may not use external landmarks and rely solely on the bony landmarks shown on the Scoutview to determine the stereotactic position in space of an intracranial target.23-48-51 In the early days of CT-guided stereotaxis, these frameless methods were popular in conjunction with plain x-rays at surgery to assess the position of a brain target to be biopsied or punctured. With the advent of modern image manipulation software, neuronavigators, and other robotic devices, variations of these scanning techniques are reemerging, so far almost only in morphological stereotactic applications.52”55 However, the requirement of immobilization of the patient’s head during scanning and the necessity of a CT study performed with wellknown scanning planes and thin slices remain mandatory even with these frameless techniques.

CLINICAL APPLICATIONS The great majority of stereotactic CT scanning procedures are done for morphological stereotactic purposes: to target a tumor, an abcess, a cyst, or whatever visualized anatomic brain pathol¬ ogy is to be biopsied, punctured, removed by a stereotactic craniotomy, or stereotactically irradiated. A significant propor¬ tion of stereotactic Cl scans, especially in Sweden, are per¬ formed as part of a functional stereotactic procedure, that is, stereotactic surgery for pain, movement disorder, or psychiatricdisorder, in which an ablative lesion or an implantation of a chronic electrode is made in an anatomically “normal” struc¬ ture of the brain. In these cases, the specific subnuclei to be tar¬ geted may not be seen on the C I image, and their position has to be determined in relation to visible internal reference struc¬ tures such as cerebrospinal fluid (CSF) spaces. This issue puts another constraint on the performance of a stereotactic CT study.

CT Scanning

for

Morphological Stereotaxis It is a rule that a stereotactic CT study is performed after a pre¬ vious routine CT study has revealed the brain pathology. Because most brain tumors, abcesses, and so on modify the blood-brain barrier, they are better visualized when intravenous contrast enhancement is used during the diagnostic CT study and the stereotactic CT study, in which the CT scans are gener¬ ally thinner. This makes the visualization of the boundaries of the pathological structure more accurate and even permits a more reliable calculation of its volume. In some stereotactic systems, if the brain lesion is to be punctured, biopsied, or removed through a stereotactic craniotomy, a thin-sliced stereotactic CT scan only through the tumor area may be enough.I5-56-57 However, if the coordinates of the burr hole or craniotomy also have to be stereotactically preplanned, the stereotactic CT scan should include the entire calvarium. This also applies if the brain pathology is to be stereotactically irra¬ diated, as may be the case in arteriovenous malformations, metastases, and other brain tumors, because the subsequent dose planning will take into account the shape and thickness of the bone along the beam directions and trajectories from the ra¬ diation source toward the brain target. Besides, in all cases in which multi-imaging modalities and computerized image ma¬ nipulation are desirable for surgical planning or for roboticaided surgery, it is imperative that the stereotactic CT scan include the whole skull. In these cases, the scanning procedure with thin slices may take a long time.

CT Scanning for Functional Stereotaxis In CT-guided functional stereotaxis, the brain target is usually a tiny subnucleus or part of a nucleus or a tract. These structures cannot be visualized even by the most sophisticated CT scan¬ ner. Instead, the anatomic position of these structures is defined in relation to ventricular landmarks, as is done during conven¬ tional ventriculography. The most commonly used ventricular landmarks are the anterior commissure (AC) and the posterior commissure (PC) of the third ventricle as well as a theoretical line joining the two, the AC-PC line. While ventriculography provides lateral and anteroposterior views of the third ventricle, CT provides an axial view. Therefore, stereotactic CT scanning should be done not only with the thinnest possible scans but also with the scanning plane as parallel as possible to the AC-PC line. One major difficulty has been that the AC-PC line does not "show up” on the CT Scoutview. Both its exact position within the brain and its angulation or inclination in relation to any bony landmarks are subject to individual variations.58 Some au¬ thors have relied on certain bony landmarks that are visible on the Scoutview to determine the scanning plane and approxi¬ mate the dorsoventral area of the scan to include the area of the third ventricle. It has been advocated that the scanning plane that is most “parallel” to the AC-PC line would be the glabellainion plane.5157 M The use of the Twining line, a line between the tuberculum sellae and the protuberantia occipitalis interna, has also been advocated.50 54 Using these bony landmarks, an initial scan of the area of the third ventricle is performed, and if it appears that the AC and PC are visualized on different slices.

Chapter 32/CT Scanning in Stereotactic Neurosurgery

the gantry of the CT machine is reangulated accordingly and the scan is partly repeated. This technique may be timeconsuming and is possible only when gantry-independent CT localizers are used.20,59 In other methods in which the scanning plane and the plane of the AC-PC line can be averaged because of the special de¬ sign of the frame, a superimposition of the CT slice containing one of the commissures onto the CT slice containing the other commissure may be sufficient to measure the length, define the level of the AC-PC line, and assess its inclination in relation to the stereotactic frame.714,30'62 This presupposes that the angle between the scanning plane and the plane of the AC-PC line is not too exaggerated. Some authors have used a reformatted midsagittal image to determine the level of AC and PC.63,64 However, as was stated previously, the resolution of reformatted images is always be¬ low that of axial scans. Besides, reformatted images carry an inherent risk of distortion of the depicted structures that fur¬ ther decreases the accuracy of landmark definition and target calculation. Some workers have used an oblique or horizontal reformatting of 1.5-mm-thick slices through the AC and PC to obtain a “new” axial slice in an attempt to minimize test error.65,66 The pitfalls of stereotactic CT scanning for functional stereotactic procedures include primarily the uncertainty in de¬ termining the height of the Z coordinate of a brain target. This uncertainty is due to the thickness of the CT slice, movement inaccuracies of the CT couch, the geometry of the stereotactic frame, and/or the obliquity between the scanning plane and the plane of the AC-PC line. The source of error in defining a func¬ tional brain target coordinate may also lie in the uncertainty of defining the ventricular commissures on CT. Spiegel and col¬ leagues67 showed in 1952 that the dorsoventral thickness of the AC ranged from 1.5 to 4 mm with a mean of 3 mm. Therefore, even if the CT scan is performed with contiguous 1.5-mm-thick slices, there still may be a risk of error in determining the dorsoventral position of the AC. This risk is theoretically the same for the PC. Since the height of the brain target is defined in relation to the height of the line joining AC and PC, there er¬ rors would produce inaccuracies in the target coordinates in the sagittal plane. Therefore, some authors still prefer to perform ventriculography in addition to a stereotactic CT (and MRI) study to determine a functional brain target.17,68 Others rely solely on the stereotactic CT study and define the AC on the CT slice lying 4 mm below the one depicting the ventralmost part of the foramen of Monro and the PC on the slice just above the one showing the beginning of the aqueduct.7,30,31,62

errors and taking into consideration the fact that a measurement or calculation error at this stage may have serious repercus¬ sions on the results of the surgery and eventually on the patient, the stereotactic CT study is solely the responsibility of the neu¬ rosurgeon. Therefore, it is the surgeon who should be well ac¬ quainted with the scanning technique, including its potentials and pitfalls, as well as with the target coordinate calculation, in addition to the stereotactic frame used. It might be wise to keep in mind the statement made in 1985 by Lars Leksell: “In clinical practice brain imaging can now be divided in two parts: the diagnostic neuroradiology and the pre¬ operative stereotactic localization procedure. The latter is part of the therapeutic procedure. It is the surgeon’s responsibility and should be closely integrated with the operation.”69

References 1. 2. 3. 4.

5.

6. 7.

Computed tomography, more than any other radiological de¬ velopment, has brought stereotactic surgery into a new era. Stereotactic CT scanning has proved to be routinely feasible, and its impact on neurosurgery and neurosurgeons has reached far beyond those who are traditionally “stereotactically oriented.” Whatever the surgical goals, whatever scanning method is used, and whether the surgery is performed in the scanner or in the operating room, a stereotactic CT study constitutes an inte¬ gral part of the stereotactic procedure. It is sometimes the most difficult part of the surgery. Because of its limits and potential

Spiegel EA, Wycis HT, Marks M, Lee AJ: Stereotaxic apparatus for operations on the human brain. Science 106:349-350, 1947. Hounsfield GN: Computerized transverse axial scanning (tomogra¬ phy): I. Description of system. Br J Radiol 46:1016-1022, 1973. Goerss S, Kelly PJ, Kali B, Alker GJ: A computed tomographic stereotactic adaptation system. Neurosurgery 10:375-379, 1982. Drayer BP, Johnson GA, Bird CR: Computed tomography: Recent status, in Wilkins RH, Rengachary SS (eds): Neurosurgery. New York: McGraw-Hill, 1985. vol 1, pp 224-254. Greenblatt SH, Rayport M, Savolaine ER, et al: Computed-tomography-guided intracranial biopsy and cyst aspiration. Neurosurgery 11:589-598, 1982. Lunsford LD, Rosenbaum AE, Perry J: Stereotactic surgery using the “therapeutic” CT scanner. Surg Neurol 18:116-122, 1982. Laitinen LV, Liliequist B, Fagerlund M, Eriksson AT: An adapter for computed tomography-guided stereotaxis. Surg Neurol 23:559-566,

8.

1985. Hitchcock E: Stereotactic-computerized tomography interface device.

9.

Appl Neurophysiol 50:63-67, 1987. Bergstrom M, Greitz T: Stereotaxic computed tomography. AJR

10.

11. 12.

13.

14.

CONCLUSIONS

269

15. 16.

17.

18. 19.

127:167-170, 1976. Sofat A, Rratimenos G, Thomas DGT: Early experience with the GillThomas locator for computed tomography-directed stereotactic biopsy of intracranial lesions. Neurosurgery 31:972-974, 1992. Nashold BS Jr: Stereotactic neurosurgery: The present and the future. Am Surg 36:85-93, 1970. Lang J, Schlehahn F, Jensen HP, et al: Cranio-cerebral tomography as a basis for interpreting computed tomograms, in Lanksch W, Kazner E (eds): Cranial Computerized Tomography. Berlin: Springer, 1976, pp 24-36. Lange S, Golde G: Resolution characteristics of computerized tomog¬ raphy and their impact on quantitative brain diagnosis, in Lanksch W, Kazner E (eds): Cranial Computerized Tomography. Berlin: Springer, 1976, pp 52-55. Laitinen LV: The Laitinen system, in Lunsford LD (ed): Modern Stereotactic Neurosurgery. Boston: Nijhoff, 1988, pp 99-116. Lunsford LD, Leksell D: The Leksell system, in Lunsford LD (ed): Modern Stereotactic Neurosurgery. Boston: Nijhoff, 1988, pp 27-46. Mundinger F, Birg W: The imaging-compatible Riechert-Mundinger system, in Lunsford LD (ed): Modern Stereotactic Neurosurgery. Boston: Nijhoff, 1988, pp 13-25. Kelly PJ: Contemporary stereotactic ventralis lateral thalamotomy in the treatment of parkinsonian tremor and other movement disorders, in Heilbrun MP (ed): Stereotactic Neurosurgery: Concepts in Neurosurgery. Baltimore, Williams & Wilkins, 1988, vol 2, pp 133-147. Heilbrun MP: Computed tomography-guided stereotactic systems. Clin Neurosurg 31:564—581, 1982. Kelly PJ, Goerss SJ, Kail BA: Evolution of contemporary instrumen¬ tation for computer-assisted stereotactic surgery. Surg Neurol 30:204-215, 1988.

270

20.

21. 22.

23.

24.

25. 26.

27.

28.

29.

30.

31.

32.

33. 34.

35.

36.

37.

38.

39.

40. 41.

42.

43.

Part 2/Image-Guided Stereotaxis

Rosenfeld JV, Barnett GH, Palmer J: Computed tomography guided stereotactic thalamotomy using the Brown-Roberts-Wells system for non-Parkinsonian movement disorders: Technical note. Stereotact Fund Neurosurg 56:184—192, 1991. Brown RA: A computerized tomography-computer graphics approach to stereotaxic localization. J Neurosurg 50:715-720, 1979. Couldwell WT, Apuzzo MLJ: Initial experience related to the use of the Cosman-Roberts-Wells stereotactic instrument: Technical note. J Neurosurg 72:145-148, 1990. Gildenberg PL, Kaufman HH, Murthy KSK: Calculation of stereotac¬ tic coordinates from the computed tomographic scan. Neurosurgery 10:580-586, 1982. Alker G, Kelly PJ: An overview of CT based stereotactic systems for the localization of intracranial lesions. Compul Radiol 8:193-196, 1984. Gildenberg PL: Stereotactic neurosurgery and computerized tomo¬ graphic scanning. Appl Neurophysiol 46:170-179, 1983. Zamorano L, Dujovny M, Malik G, et al: Factors affecting measure¬ ments in computed-tomography-guided stereotactic procedures. Appl Neurophysiol 50:53-56, 1987. Hadley MN, Shetter AG, Amos MR: Use of the Brown-Roberts-Wells stereotactic frame for functional neurosurgery. Appl Neurophysiol 48:61-68, 1985. Wyper DJ, Turner JW, Patterson J, et al: Accuracy of stereotaxic lo¬ calization using MRI and CT. J Neurol Neurosurg Psychiatry 49:1445-1448, 1986. Bucholz RD, Ho HW, Rubin JP: Variables affecting the accuracy of stereotactic localization using computed tomography. J Neurosurg 79:667-673, 1993. Hariz MI: A Non-Invasive Adaptation System for Computed Tomography-Guided Stereotactic Neurosurgery (thesis). Umea University Medical Dissertations, New series, no. 269, ISSN 03466612. Umea, Sweden: Umea University Printing Office, 1990. Hariz MI: Clinical study on the accuracy of the Laitinen’s noninvasive CT-guidance system in functional stereotaxis. Stereotact Fund Neurosurg 56:109-128, 1991. Gouda KI, Freidberg SR, Larsen CR, et al: Modification of the Gouda frame to allow stereotactic biopsy of the brain using the GE 8800 computed tomographic scanner. Neurosurgery 13:176-181, 1983. Patil A-A: Computed tomography-oriented stereotactic system. Neurosurgery 10:370-374, 1982. Zamorano I, Chavantes C, Dujovny M, et al: Stereotactic endoscopic interventions in cystic and intraventricular brain lesions. Acta Neurochir Suppl (Wien) 54:69-76, 1992. Tampieri D, Bergstrand G: Postural displacements of the brain—on the feasibility of using CT for determination of stereotactic coordi¬ nates. Neuroradiology 24:167-168, 1983. Bowyer KW, Starmer F, DuBois P: Error sensitivity of computerized tomography guided stereotaxis. Comput Biomed Res 15:272-280, 1982. Hariz Ml: Correlation between clinical outcome and size and site of the lesion in CT-guided thalamotomy and pallidotomy. Stereotact Fund Neurosurg 54, 55:172-185, 1990. Maciunas RJ, Galloway RLJr, Latimer J, et al: An independent appli¬ cation accuracy evaluation of stereotactic frame systems. Stereotad Fund Neurosurg 58:103-107, 1992. Gouda KI, Freidberg SR, Baker RA. et al: Gouda frame redesigned specifically for computed tomographic compatibility. Appl Neurophysiol 49:192-200, 1986. Leksell L, Jemberg B: Stereotaxis and tomography: A technical note. Ada Neurochir (Wien) 52:1-7, 1980. Apuzzo MLJ. Fredericks CA: The Brown-Roberts-Wells system, in Lunsford LD (ed): Modern Stereotactic Neurosurgery. Boston: Nijhoff, 1988, pp 63-77. Greitz T, Bergstrom M, Boethius J, et al: Head fixation system for integration of radiodiagnostic and therapeutic procedures. Neuroradiology 19:1-6, 1980. Kaufman HH, Gildenberg PL: New head-positioning system for use with computed tomographic scanning. Neurosurgery 7:147-149, 1980.

44.

45. 46.

47. 48.

49.

50.

51. 52.

53.

54.

55.

56.

57. 58. 59.

60.

61.

62.

63. 64.

65.

66. 67.

68.

69.

Colombo F, Angrilli F, Zanardo B, et al: A universal method to em¬ ploy CT scanner spatial information in stereotactic surgery. Appl Neurophysiol 45:352-364, 1982. Levy WJ: Simple plastic stereotactic unit in the computed tomo¬ graphic scanner. Neurosurgery 13:182-185, 1983. Patil AA, Woosley RE: Scalp marking of intracranial lesions using computed tomography (CT) images: A technical note. Acta Neurochir (Wien) 80:62-64. 1986. Wester K, Sortland O, Hauglie-Hanssen E: A simple inexpensive method for CT-guided stereotaxy. Neuro-radiology 20:255-256, 1981. Mundinger F, Reinke M-A, Hoefer TH, Birg W: Determination of in¬ tracerebral structures using osseous reference points for computeraided stereotactic operations. Appl Neurophysiol 38:3-22, 1975. Nguyen J-P, Szikla G, Missir O: Fiabilite d’une methode simplifiee de transposition des images TDM: Correlations au reperage st6reotaxique dans 30 cas. Neurochirurgie 28:271-274, 1982. Ohye C, Kawashima Y, Hirato M, et al: Stereotactic CT scan applied to stereotactic thalamotomy and biopsy. Acta Neurochir (Wien) 71:55-68, 1984. Tokunaga A, Takase M, Otani K: The glabella-inion line as a baseline forCT scanning of the brain. Neuroradiology 14:67-71, 1977. Roberts DW, Strohbehn JW, Hatch JF, et al: A frameless stereotaxic integration of computerized tomographic imaging and the operating microscope. J Neurosurg 65:545-549, 1986. Watanabe E, Watanabe T, Manaka S, et al: Three dimensional digi¬ tizer (neuronavigator): New equipment for computed tomographyguided stereotaxic surgery. Surg Neurol 27:543-547, 1987. Ciacci JD, Black KL, Behnke EJ, De Salles AAF: Frameless stereo¬ tactic craniotomy, in De Salles AAF, Goetsch S (eds): Stereotactic Surgery and Radiosurgery. Madison, WI: Medical Physics Publishing, 1993, pp 85-94. Adler JR: Frameless radiosurgery, in De Salles AAF, Goetsch S (eds): Stereotactic Surgery and Radiosurgery. Madison, WI: Medical Physics Publishing, 1993, pp 237-248. Hariz MI, Bergenheim AT, DeSalles AAF, et al: Percutaneous stereo¬ tactic brain tumor biopsy and cyst aspiration using a non-invasive frame. Br J Neurosurg 4:397^406. 1990. Hariz MI, Fodstad H: Stereotactic localization of small subcortical brain tumors for open surgery. Surg Neurol 25:345-350, 1987. Talairach J, David M, Tournoux P, et al: Atlas d Anatomie Stereotaxique. Paris: Masson, 1957. Spiegelmann R, Friedman WA: Rapid determination of thalamic CTstereotactic coordinates: A method. Ada Neurochir (Wien) 110:77-81, 1991. Fox PT, Perlmutter JS, Raichle ME: A stereotactic method of anatom¬ ical localization for positron emission tomography. J Comput Assist Tomogr 9:141-153, 1985. Takase M, Tokunaga A, Otani K. Horie T: Atlas of the human brain for computed tomography based on the glabella-inion line. Neuroradiology 14:73-79, 1977. Hariz MI, Bergenheim AT: A comparative study on ventriculographic and computed tomography-guided determinations of brain targets in functional stereotaxis. J Neurosurg 73:565-571, 1990. Aziz T, Torrens M: CT-guided thalamotorny in the treatment of move¬ ment disorders. Br J Neurosurg 3:333-336, 1989. Jeanmonod D, Thomas DGT: Application of CT-directed stereotaxy in the determination of functional neurosurgical targets in the dien¬ cephalon and cerebral hemisphere. Br J Neurosurg 3:337-342, 1989. Latchaw RE, Lunsford LD, Kennedy WH: Reformatted imaging to define the intercommissural line for CT-guided stereotaxic functional neurosurgery. AJNR 6:429-433, 1985. Hardy TL: Stereotactic CT atlases, in Lunsford LD (ed): Modern Stereotactic Neurosurgery. Boston: Nijhoff, 1988, pp 425-^439. Spiegel EA, Wycis HT, Baird HW: Studies in Stereoencephalotomy: I. Topical relationships of subcortical structures to the posterior com¬ missure. Confin Neurol 12:121-133, 1952. Fox MW, Ahlskog JE. Kelly PJ: Stereotactic ventrolateralis thalam¬ otomy for medically refractory tremor in post-levodopa era Parkinson’s disease patients. J Neurosurg 75:723-730, 1991. Leksell L, Leksell D, Schwebel J: Stereotaxis and nuclear magnetic resonance. J Neurol Neurosurg Psychiatry 48:14-18, 1985.

CHAPTER 33

SPATIAL DISTORTION IN MAGNETIC RESONANCE IMAGING: IMPACT ON STEREOTACTIC LOCALIZATION

Peter A. Hardy and Gene H. Barnett

netic field. The frequency of the radio wave signals is directly related to the strength of the local magnetic field, where the hy¬ drogen atoms are located, and the amplitude is directly related to the density of atoms. Mathematically, the frequency of the signal and the strength of the magnetic field are related as the Larmor equation:

Modem stereotactic neurosurgery relies on spatial information from a variety of computer-processed images, including com¬ puted tomography (CT), magnetic resonance imaging (MRI), digital subtraction angiography (DSA), single photon emission computed tomography (SPECT), and positron emission tomog¬ raphy (PET) to accurately localize points or volumes in space. The spatial fidelity of some of these techniques, such as CT, is determined largely by the position, number, and operating characteristics of detecting sensors and is therefore relatively constant between studies and independent of the specific pa¬ tient imaged. Spatial fidelity in MRI, however, requires that the relationship between position and magnetic field strength be known and, ideally, be linear. Unfortunately, placement of a heterogeneous object, such as a patient’s head or an MRI stereotactic localizer, in the magnetic field of an MRI scanner distorts the linearity of the magnetic field-position relationship in largely unpredictable and potentially significant ways. In this chapter, we present the basic principles of MRI spa¬ tial localization, common forms of spatial distortion affecting MRI, examples of clinically relevant MRI distortion, and strategies to minimize these effects for MRI stereotactic local¬ ization. This discussion focuses on proton MRI, as this tech¬ nique constitutes the basis of most stereotactic MR imaging.

F = yBo

(1)

where y is a constant called the gyromagnetic ratio (which, for hydrogen, is 42.577 MHz/T) and Bo is the magnitude of the applied magnetic field, which is typically measured in Tesla (1 T = 20,000 times the strength of the earth’s magnetic field).4 A signal received from a large sample in a homoge¬ neous field would contain only a single frequency; special techniques must be employed to separate the source of the sig¬ nal intro three dimensions. For each spatial direction, a differ¬ ent encoding technique is used, but each encoding technique requires the application of magnetic field gradients to the sam¬ ple that alter the strength of the magnetic field with position in a linear manner. Because field strength and resonant frequency are linearly related, as shown by Eq. (1), the application of a linear gradient will result in a proportional gradient of reso¬ nant frequencies.

SPATIAL LOCALIZATION IN MAGNETIC RESONANCE IMAGING

Frequency Encoding Frequency encoding is a technique for separating the signal in one dimension—the X direction, for example. For the purposes of understanding the effects of spatial distortion in stereotactic localization, frequency encoding is the most important to dis¬ cuss. Applying a gradient in the X direction while an MR signal is received encodes the position of the signal emitting source in the frequency of its emission (Fig. 33-1A). Decoding the ampli¬ tude and frequencies contained in the received signal through a process called the Fourier transform is equivalent to recon¬ structing a projection of the object along the X direction.5 It is easy to see how any distortion in the homogeneity of the main magnetic field will result in geometric distortion in the

A thorough description of MRI theory is beyond the scope of this chapter. However, certain fundamentals of spatial encoding must be appreciated in order to understand the origin of errors in spatial fidelity. The reader is referred to several excellent re¬ view articles for a thorough description of MRI physics and ar¬ tifacts in general.1-3

Sample Preparation and Spatial Encoding Magnetic resonance images are created from radio waves aris¬ ing from the resonance of hydrogen protons placed in a mag¬

frequency-encode direction (Fig. 33-15).

271

272

Part 2/Image-Guided Stereotaxis

position of an object in the Y direction relies upon recording the rate of phase increase with each step of the applied phaseencode gradient. The rate of phase increase per gradient step depends only upon the incremental increase in the strength of the magnetic field at that location. The incremental increase of the field arises strictly from the step in the phase-encode gradi¬ ent, which, in turn, depends only upon Y position and not upon the strength of the static magnetic field at that location. Thus, a magnetic field that varies in space but not in time does not pro¬ duce geometric distortion in the phase encode direction.

P o s i t i o n

Slice Selection A

P 0

s i t i o n

f— B Figure 33-1. Determination of location in the X direction using frequency encoding. A. The relationship between the resonant frequency (/) of the protons in a linear magnetic field gradient and position (X) is ideally linear. B. Nonlinearities of the frequency—position relationship result in spurious localization of target (X,) compared to actual location (Xa).

Phase Encoding Separating the signal in the orthogonal or Y direction requires a different encoding strategy. In this case, a magnetic field gradi¬ ent is also applied. However, instead of being applied when the signal is received, it is pulsed on momentarily before signal re¬ ception begins. Magnetic resonance signals are complex quan¬ tities and possess, like vectors, both magnitude and phase. The effect of the momentary pulse of a gradient is to alter the phase of the signal, increasing it proportionally to the distance away from the magnet’s center. By applying multiple pulses of grad¬ ually increasing amplitude and receiving a signal for each gra¬ dient amplitude, the shape of the object imaged can be deter¬ mined in the orthogonal direction.5 The nature of phase encoding provides immunity from sim¬ ple geometric distortion in the Y direction. Separation of the

Separation of the signal into the third or Z dimension requires yet another form of encoding. In the simplest method, a slice or slab is excited in a technique called frequency-selective excita¬ tion. In this technique the slice of interest is defined by apply¬ ing a radio frequency (RF) excitation pulse while a gradient is applied in the Z direction. The application of the gradient de¬ fines a continuously varying range of Larmor frequencies. A slice of finite width is excited by including in the RF pulse all frequencies in the spatial range to be excited. Ideally, a flat, rectangular-shaped slice is excited. Imaging a thinner slice to improve the image resolution is accomplished by increasing the strength of the Z gradient while keeping the bandwidth of the RF pulse constant. This approach eventually breaks down for slices of less than approximately 3 mm, since the strength of the Z gradient required usually exceeds the capabilities of the MR imager. An alternative method of slice selection is utilized when slices thinner than 3 mm are required. In this case, a large slab is excited simultaneously by applying a frequency-selective RF pulse. After excitation, a phase-encode gradient, similar to that applied to achieve spatial separation in the Y direction, is ap¬ plied in the Z direction. The Z gradient is pulsed momentarily to phase-encode the signal so that it can be separated in the Z direction. In image reconstruction, a third Fourier transforma¬ tion is employed to extract and separate the signal into the var¬ ious partitions forming the slab. Spatial distortion can arise in the slice-select direction because selection of the region of interest is done with a frequency-selective pulse. Susceptibility-induced field distor¬ tions alter the perfect linear variation of Larmor frequency with position Z. When a frequency-selective pulse is applied in the presence of field distortion, a distorted slice is excited.6 Instead of the rectangular shape hoped for, the distorted slice may have the warped shape of a potato chip. If, however, phase encoding is applied in the Z direction, the partitions extracted have the same immunity to spatial distortion that in-plane phase encod¬ ing enjoyed. The shape of each partition will be perfectly rec¬ tangular provided that the strength of the Z gradient is constant in the Y and X directions. Some distortion can occur at the outer partitions. Additional signal can appear in the front partition originating from the back of the slab. Because of field distor¬ tion, the signal from the back of the slab may not have been en¬ coded properly; consequently, it wrapped around or aliased into the partition on the front of the slab.7 Of the three encoding methods, the greatest distortion arises in the frequency direction, both because it is sensitive to static

Chapter 33/Spatial Distortion in Magnetic Resonance Imaging: Impact on Stereotactic Localization

273

field distortion and because, compared with slice selection, the frequency-encoding gradient is often of lower amplitude. Accurate localization along the frequency axis clearly requires that 1. 2. 3.

The applied magnetic field be homogeneous The frequency-encoding gradient vary linearly in space The section imaged be composed of protons from a single

4.

chemical species The area imaged be free of magnetic field distortion

Manufacturers of MR imagers go to great lengths to satisfy the first two criteria. Field inhomogeneities and gradient nonlin¬ earities are corrected by using shims and electronic compensa¬ tion circuits. Inhomogeneities of the main magnetic field may remain and create distortion, which may be difficult to recog¬ nize. A prudent countermeasure is to perform a global shimming of the field before the stereotactic reference images are made. The scanning of a phantom with recognizable landmarks will display geometric distortion, and these images may be used as a reference for postacquisition correction.68 Last, employing an imaging sequence with relatively high-frequency encoding gra¬ dients will minimize the effects of residual field inhomogeneity. Geometric distortion will also arise from nonlinear gradients or imperfect compensation of eddy currents induced in the mag¬ net by the rapid switching of the gradients. Once again, these ef¬ fects will be manifest in an image of a suitable phantom. Magnetic field distortion will arise in a perfectly uniform magnetic field with the placement of a complex object such as a head or a stereotactic frame in the field. The distortion can be predicted only for simple objects and is difficult to correct for unless the exact distortion is measured separately.9 In a dis¬ torted magnetic field, the linear relationship between position and frequency necessary for reconstructing an accurate image is distorted, potentially resulting in a significant miscalculation of tissue location. An example of this effect is shown in Fig. 33-15.

Metal Artifact Perhaps the most dramatic distortions of MR spatial fidelity are due to the placement of a metal object in the field. Local warp¬ ing of the field will occur as the metal concentrates the mag¬ netic field, as shown in Fig. 33-2. The extent and shape of the distortion are dependent on the size, shape, and composition of the metal object. The resulting field deformities are particularly severe if the metal has a ferrous component, as is the case even with some types of stainless steel. Common sources of metal artifact in MRI of the head include dental amalgams and appli¬ ances, retained neurosurgical hardware such as hemostatic clamps, and shrapnel.10 The local effects of serious metal artifact are obvious. A central area of low signal is surrounded by a zone of prominent spatial distortion that diminishes with increasing distance from the metal. Far away from the metal, the image may appear to return to a spatially accurate image. Unfortunately, the field distortion produced by metal can extend far beyond the areas where distortion is obvious, resulting in subtle yet significant effects in areas of the image that appear normal. For example, when the patient has a dental appliance, images of the brain not

Figure 33-2. Effects of metal artifact due to dental work. Local warping of the field occurs due to concentration of the magnetic field by the metal.

containing that appliance can have significant spatial errors, even though the image may appear entirely normal. A case of frame stereotaxy, where spurious localization due to dental braces occurred is shown in Fig. 33-3A. Spatial distor¬ tion near the mouth is apparent, but the posterior portion of the head appears relatively unaffected, particularly when viewed in a coronal plane, as in Fig. 33-3B. An attempt to target the cen¬ ter of the cyst, however, directed the cannula into the falx, demonstrating a spatial error of more than 2 cm. Similarly, metal dental work shown in Fig. 33-2 created difficulty in ob¬ taining satisfactory registration using scalp fiducials for frame¬ less stereotaxy. In our experience, registration using MRI is routinely less accurate in patients with metal dental work.

Magnetic Susceptibility Artifact Air and tissue have different magnetic susceptibilities—the property of material which affects the strength of the magnetic field both within the tissues and in regions around them. The interfaces and shapes of regions containing tissue and air result in local perturbations in the magnetic field that are often more subtle than metal artifact but are pervasive and largely unpre¬ dictable. Strong magnetic susceptibility artifact (MSA) effects can arise in the region surrounding a cavernous hemangioma, where the hemosiderin deposits can cause significant field dis¬ tortion.11'12 Magnetic susceptibility effects are noticeable in the frequency-encoding direction and are influenced strongly by the particular imaging technique and the strength of its asso¬ ciated frequency-encoding gradient. Ironically, improving the image’s signal-to-noise ratio by reducing the image bandwidth by decreasing the strength of the frequency-encoding gradient will amplify MSA distortions, because the distortion is then

274

Part 2/Image-Guided Stereotaxis

Figure 33-3. A. Severe distortion of the mouth and the face on sagittal ^-weighted MRI due to metal artifact from dental braces. Note the displacement of the anterior fiducials. B. Coronal image of the posterior portion of the same patient. Although the image appears relatively unaffected by the distortion seen in (A), targeting of the center of the ventricular cyst resulted in the probe being directed into the falx—an error of more than 2 cm.

proportionately larger as compared with the strength of the frequency-encoding gradient. This problem illustrates the diverging needs of MR images for diagnosis, where a high signal-to-noise ratio is required, and MR images for stereotac¬ tic surgery, where high spatial fidelity is required.13 An example of MSA is shown in Fig. 33-4A. Here, sagittal images were obtained using a narrow-bandwidth imaging tech¬ nique. Prior to image acquisition, a spatial reference grid was superimposed on the slice imaged, using spatial modulation of magnetization (SPAMM).14 In this image, the grid was applied with high sensitivity to MSA. It is clear that spatial distortion is maximal near the nasopharynx due to the bone-air interface and at the scalp-air interface, where the grid is so distorted that it is difficult to visualize. By increasing the bandwidth of the SPAMM pulses to correspond to the bandwidth of the imaging sequence, we are enabled to see directly the extent of the dis¬ tortion arising from MSA. The distortion remains most obvious at the scalp surface, as in Fig. 33-5. This finding has serious im¬ plications for registration techniques using scalp contours or scalp-affixed fiducials. The design of the stereotactic frame can have effects on geometric accuracy as well. Ideally, the frame will be made of a material such as plastic or aluminum, which minimally dis¬ torts the homogeneity of the main magnetic field. Additionally, the material used in the “N” elements to generate an MR signal should be water-based to avoid chemical-shift artifact. The implications of MSA are particularly serious for frame¬ less stereotaxy that use scalp contours or scalp-affixed fiducials. Figure 33-5 shows field inhomogeneities due to MSA effects.

Note that these errors are again particularly serious at the scalpair interface, which is used for image-digitizer registration. Susceptibility artifact causes much of the spatial error attributed to MRI.

Chemical Shift Another potential source of spatial inaccuracy is the local chemical environment of the protons. Protons in fat have slightly lower resonant frequencies than those in aqueous envi¬ ronments (205 Hz at 1.5 T) because of the influence of the neighboring carbon atoms.' The chemical shifts created by the local environment serve as the basis for MR spectroscopy. Conventional MRI algorithms, however, interpret these fre¬ quency differences as location differences. Because chemical shift affects the resonant frequency, it will, once again, affect spatial encoding in the frequency domain and can be mitigated by increased image bandwidth (i.e., increased gradient strength). As the fat/fluid constitution of the brain is largely ho¬ mogenous, chemical shift is of little practical concern unless fiducials (frame or frameless) are used containing a fatty medium, such as vitamin E or petroleum jelly. In such cases, spurious localization that could be severe in low-bandwidth images would be expected. Errors in fiducial location using fatcontaining tubular localizing tubes can range from 1.5 to 5.5 mm, depending on the frequency encoding gradient strength and the field of view.15 In addition to shifts in the frequencyencode direction, chemical shift also occurs in the slice-select

275

Chapter 33/Spatial Distortion in Magnetic Resonance Imaging: Impact on Stereotactic Localization

Figure 33-4. A. Sagittal images of a normal volunteer made with a low-bandwidth sequence. Before the image data were acquired, a grid of saturated magnetization was superimposed using a frequency selective SPAMM technique. Severe distortions of the grid due to magnetic susceptibility artifact are seen near the nasopharynx, due to the bone-air interface, and at the scalp-air interface. B. Distortion of the grid is minimized by increasing the strength of the gradient used in the SPAMM modulation. Similar improvements can be obtained by increasing the amplitude of the frequency-encoded gradient.

direction. The amount of shift depends upon the amplitude of the slice-select gradient and is typically 1 mm in a 3-mm

if the MRI-derived target is close to the intended target; however, it may be difficult to assure exact correlation if the CT

slice.16

Flow Artifact Accurate localization of vessels is important in trying to avoid passing a probe through a vessel en route to a selected target or in using MR angiography (MRA) to select a target, such as the nidus of a vascular malformation. Unlike fat and susceptibility artifacts, where the greatest error is in the frequency-encoded direction, blood vessel flow produces spatial artifact that is de¬ pendent on both flow and vessel orientation and occurs in the in-plane phase and volume selection directions when the ves¬ sel traverses at an oblique angle with respect to the phaseencode direction.17,18 Flow in the frequency-encode direction results only in a slight blurring of the vessel in the image but not in a geometric distortion.19

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276

Part 2/Image-Guided Stereotaxis

presentation is limited to transverse-slice data or the region has little recognizable anatomic structure on CT. It should be noted that the correlation techniques described here and below are not limited to CT and MRI but may be used with PET, SPECT, and other appropriate modalities. A similar technique of image correlation can be used with frameless techniques by utilizing either multimodality scalp fiducials or object (e.g., scalp or skull) contours, using a best-fit algo¬ rithm to coregister the CT and MRI data. Once the appropriate transformation has produced a one-to-one correspondence be¬ tween voxels of the respective image data sets, several potential methods of correlated display are available. For example, a point determined on a triplanar MRI display (i.e., coronal, sagittal, and transverse images, as shown in Fig. 33-6A) can be displayed on the appropriate triplanar CT display (as shown in Fig. 33-6B). Alternatively, planes of MRI and CT data can be digitally super¬ imposed and displayed to show a combination of these data (Fig. 33-7). This technique, sometimes referred to as fusion, can alert the surgeon to spatial disparities; however, it does not by itself correct for them. The authors prefer to reserve the use of this term for methods that attempt to correct MRI spatial infidelities using data from other techniques, such as CT.20

Figure 33-7. Theoretical means to adjust three-dimensional MR images to conform to certain spatial attributes of CT. After coregistration of the CT and MRI data, the central voxel in both sets is defined as the origin (O) of a vector that then sweeps throughout the data set to its periphery (P). The intersection (I) of the vector and a surface (e.g., ventricle, skull, scalp) is defined for both CT and MRI, and the lengths 01, IP Ol , and IP are therefore defined as in Fig. 33-8. The segments

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3 0.05). A median survival of 6 months af¬ ter radiosurgery for patients with tumor recurrence was remarkable. It clearly shows the efficacy of additional intersti¬ tial radiosurgery after previous surgery and radiotherapy. There was no increased risk of radionecrosis due to the strictly local dose application. Treatment results after external focused-beam radiosurgery using a gamma knife or a linear accelerator are comparable with the results after interstitial radiosurgery, although it must be pointed out that some of these data are based on groups with different treatment strategies.5’8,11’13,14,20’29’50 Available clinical data demonstrate the remarkable ability of external radio¬ surgery to produce sustained local control of brain metastases. The reported overall tumor control rate of 80 to 100 percent was in agreement with our results. The improvement of peritumoral edema, as reported after external radiosurgery, has been observed after interstitial radiosurgery as well.29-50 In accor¬ dance with the multivariate regression analysis, patients profit¬ ing most from interstitial radiosurgery were those who were in good clinical condition, harboring solitary brain metastases without extracerebral organ metastases, and who had experi¬ enced a long time interval between diagnosis of the primary tumor and diagnosis of cerebral metastases. Interstitial radio¬ surgery, however, is a far less invasive treatment modality than craniotomy and tumor resection.

INTERSTITIAL RADIOSURGERY FOR SKULL-BASE TUMORS Meningiomas along the medial sphenoid wing, the petroclival ligament or the cavernous sinus are difficult to remove, and re¬ currences are common. Although microsurgical removal of skull-base tumors involving cranial nerves has become feasi¬ ble, with acceptable morbidity and mortality, radiosurgery has evolved as an alternative treatment.21 To date, experiences with stereotactic irradiation methods for meningiomas of the skull base have been contradictory. Whether microsurgery, stereotac¬ tic fractionated radiotherapy, or stereotactic radiosurgical methods are to be preferred remains an open question. Single¬ shot high-dose focused-beam radiosurgery carries the risk of irreversible damage to cranial nerves. Supported by experimen¬ tal findings and clinical experience, we employed interstitial radiosurgery with a continuous low-dose rate for patients har¬ boring skull-base meningiomas (5 patients) and chordomas (2 patients) with cranial nerve involvement. Treatment volumes ranged from 2 to 11 mL. Average dose to the tumor margin was 6400 cGy. There was no morbidity or mortality. Tumor control was achieved in all patients. Meningiomas responded by evolu¬ tion of a central necrosis and concomitant shrinkage up to 40 percent. The two clivus chordomas responded with significant volume reduction of 68 and 80 percent respectively. None of the patients suffered from further damage to cranial nerves, which is attributed to the 100-fold lower dose rate as compared with single-shot radiosurgery. Interstitial radiosurgery is an al¬ ternative treatment for skull-base tumors when surgery is not advised or is rejected.

597

CONCLUSIONS Interstitial radiosurgery is indicated in the treatment of small, discrete tumors. It can be effectively used to treat circum¬ scribed low-grade gliomas and solitary brain metastases in par¬ ticular, with less invasiveness, dissection of normal brain, and expense than with open surgery. Interstitial radiosurgery im¬ proves the likelihood of local tumor control without the risk in¬ herent in percutaneous radiation treatment. The method of stereotactic interstitial radiosurgery advantageously combines stereotactic precision and accuracy with cost-effectiveness. The investment to establish the method of interstitial radio¬ surgery is but a fraction compared with the investment neces¬ sary for installing focused-beam radiosurgery. The method cannot be applied for AVMs because the insertion of probes is needed. However, with the insertion of probes into tumors, a histological diagnosis is obtained in every case, which forms the legal basis for treatment decisions.

References 1.

2.

3.

Alexander E III, Coffey R, Loeffler JS: Radiosurgery for gliomas, in Alexander E III, Loeffler JS, Lunsford DL (eds): Stereotactic Radiosurgery. New York: McGraw-Hill, 1993, pp 207-218. Anderson LL, Hsin MK, Ing-Yuan D: Clinical dosimetry with 125-1, in George FW (ed): Modern Interstitial and Intracavitary Radiation Cancer Management. New York: Masson, 1981, pp 9—15. Bernstein M, Gutin PH: Interstitial irradiation of brain tumors: A re¬

4.

view. Neurosurgery 6:741-750, 1981. Brenner DJ, Martel MK, Hall EJ: Fractionated regimes for stereotac¬ tic radiotherapy of recurrent tumors in the brain. Int J Radiat Oncol

5.

BiolPhys 21:819-824, 1991. Coffey RJ, Lunsford LD, Flickinger JC: The role of radiosurgery in the treatment of malignant brain tumors. Neurosurg Clin North Am

6. 7.

3:231-244, 1992. Coia LR: The role of radiation therapy in the treatment of brain metastases. Int J Radiat Oncol Biol Phys 23:229-238, 1991. De Angelis LM, Mandell LR, Thaler HT. et al: The role of postopera¬ tive radiotherapy after resection of single brain metastases.

8.

Neurosurgery 24:798-805, 1989. Engenhart R, Kimmig BN, Hover KH, et al: Long-term follow-up for brain metastases treated by percutaneous stereotactic single high-dose

9.

irradiation. Cancer 71:1353-1361, 1993. Fell DA, Leavens ME, McBride CM: Surgical versus nonsurgical management of metastatic melanoma of the brain. Neurosurgery

10.

11.

12.

13.

14. 15.

16.

7:238-242. 1980. Fike JR, Cann CE, Philips TL, et al: Radiation brain damage induced by interstitial 125-1 sources: A canine model evaluated by quantitative computed tomography. Neurosurgery 16:530-537, 1985. Flickinger JC, Bissonette DJ, Lunsford LD: Radiosurgery for solitary brain metastases using the cobalt-60 gamma unit: Methods and results in 24 patients. Int J Radiat Oncol Biol Phys 20:1287-1295, 1991. Flickinger JC: Dosimetry and dose volume relationships in radio¬ surgery, in Alexander E III, Loeffler JS, Lunsford LD (eds): Stereotactic Radiosurgery. New York: McGraw-Hill, 1993. Fuller BG, Kaplan ID, Adler J, et al: Stereotactic radiosurgery for brain metastases: The importance of adjuvant whole brain irradiation. Int J Radiat Oncol Biol Phys 23:413-418, 1991. Galicich JH, Sundaresan N, Thaler HT: Surgical treatment of single brain metastasis. J Neurosurg 53:63-67, 1980. Garcia DM, Fulling KG, Marks JE: The value of radiation therapy in addition to surgery for astrocytomas of the adult cerebrum. Cancer 55:919-927, 1985. Groothuis DR, Wright DC, Ostertag CB: The effect of 1-125 intersti¬ tial radiotherapy on blood-brain barrier function in normal canine brain. J Neurosurg 67:895-902, 1987.

598

17.

18.

19.

20. 21. 22.

23. 24.

25.

26. 27.

28.

29.

Part 3/Stereotactic Radiotherapy

Hoshino T. Rodriguez LA. Cho KG, et al: Prognostic implications of the proliferative potential of low-grade astrocytomas. J Neurosurg 69:839-842, 1988. Kelly PJ, Kail BA. Goerss SJ: Results of computed tomography based computer-assisted stereotactic resection of metastatic intracra¬ nial tumors. Neurosurgery 22:7-17, 1988. Kiessling M. Kleihues P. Gassega E. et al: Morphology of intracranial tumors and adjacent brain structures following interstitial iodine-125 radiotherapy. Ada Neurochir (Suppl) 33:281-289, 1984. Kihlstrom L, Karlsson B, Lindquist C, et al: Gamma knife for cere¬

37. 38.

39.

Philippon J, Clemenceau SH, Fauchon FH, Foncin JF: Supratentorial low-grade astrocytomas in adults. Neurosurgery 32:554-559. 1993. Piepmeier JM: Observations on the current treatment of low-grade astrocytic tumors of the cerebral hemispheres. J Neurosurg 67: 177-181, 1987. Recht LD, Lew R, Smith TW: Suspected low-grade glioma: Is defer¬

40.

ring treatment safe? Ann Neurol 31:431-436, 1992. Sause WT, Crowley JJ, Morantz R, et al: Solitary brain metastasis: Results of an RTOG/SWOG protocol evaluation surgery + RT versus

41.

RT alone. Am J Clin Oncol 13:427—432, 1990. Scanlon PW, Taylor WF: Radiotherapy of intracranial astrocytoma: Analysis of 417 cases treated from 1960 through 1969. Neurosurgery

42.

5:301-308, 1979. Scharfen CO, Sneed PK, Wara WM, et al: High activity iodine-125 interstitial implant for gliomas. Int J Radiation Oncology Biol Phys

braler Metastasen. Nervenarzt 64:108-113, 1993. Krishnaswamy V: Dose distribution around an 125-1 seed source in

43.

tissue. Radiology 125:489-491, 1978. Larsson B: Radiobiological fundamentals in radiosurgery, in Steiner L, Lindquist C, Forster D, Backlund EO (eds): Radiosurgery:

24:583-591, 1992. Shaw EG, Daumas-Duport C, Scheithauer BW, et al: Radiation ther¬ apy in the management of low-grade supratentorial astrocytomas.

44.

Baseline and Trends. New York: Raven Press, 1992. Laws ER, Taylor WF. Marvin BC, Okazaki H: Neurosurgical man¬ agement of low-grade astrocytoma of the cerebral hemispheres.

J Neurosurg 70:853-861, 1989. Sheline GE: The role of radiation therapy in the treatment of lowgrade gliomas, in Little JR (ed): Clinical Neurosurgery. Baltimore:

45.

J Neurosurg 61:665-673, 1984. Leksell L: The stereotaxic method and radiosurgery of the brain. Ada

46.

ChirScand 102:316-319, 1951. Lindquist C. Hindmarsh T, Kihlstrom L, et al: MRI and CT studies of radionecrosis development in the normal human brain, in Steiner L, Lindquist C, Forster D, Backlund EO (eds): Radiosurgery: Baseline

47.

and Trends. New York: Raven Press, 1992. McCormack BM, Miller DC, Budzilovich GN, et al: Treatment and survival of low-grade astrocytoma in adults, 1977-1988. Neuro¬

48.

surgery 31:636-642, 1992. Mehta MP, Rozental JM, Levin AB, et al: Defining the role of radio¬ surgery in the management of brain metastases. Int J Radiat Oncol

49.

bral metastasis. Ada Neurochir (Suppl) 52:87-89, 1991. Kondziolka D, Lunsford LD, Coffey RJ, Flickinger JC: Stereotactic radiosurgery of meningiomas. J Neurosurg 74:552-559, 1991. Kreth FW, Warnke PC, Ostertag CB: Stereotaktische interstitielle Radiochirurgie und perkutane Radiotherapie in der Behandlung cere-

Williams & Wilkins, 1985, pp 563-574. Smalley SR, Laws ER, O’Fallon JR, et al: Resection for solitary metastasis. J Neurosurg 77:531-540, 1992. Smalley SR, Schray MF. Laws ER, O’Fallon JR: Adjuvant radiation therapy after surgical resection of solitary brain metastasis: Association with pattern of failure and survival. Int J Radiat Oncol Biol Phys 13:1611-1616, 1987. Soffietti R, Chio A, Giordada MT, Vasario E: Prognostic factors in well-differentiated cerebral astrocytomas in the adult. Neurosurgery 24:686-692, 1989. Sondhaus CA: 1-125 physical properties, photon dosimetry and effec¬ tiveness, in George FW (ed): Modern Interstitial and Intracavitary Radiation Cancer Management. New York: Masson, 1981, PP 83-101. Stortebecker TP: Metastatic tumors of the brain from a neurosurgical point of view: A follow-up study of 158 cases. J Neurosurg 11:

Biol Phys 24:619-625, 1992. Miralbell R, Balart J, Matias-Guiu X. et al: Radiotherapy for supra¬ tentorial low-grade gliomas: Results and prognostic factors with special focus on tumor volume parameters. Radiother Oncol 27:

50.

84-111, 1954. Sturm V, Kober B, Hover K-H, et al: Stereotactic percutaneous single dose irradiation of brain metastases with a linear accelerator. Int J

31.

112-116,1993. Morantz RA: Radiation therapy in the treatment of cerebral astrocy¬

51.

32.

toma. Neurosurgery 20:975-982, 1987. Ostertag CB. Mennel HD, Kiessling M: Stereotactic biopsy of brain

Radiat Oncol Biol Phys 13:279-282, 1987. Sundaresan N, Galicich JH, Deck MDF, Tomita T: Radiation necrosis after treatment of solitary intracranial metastases. Neurosurgery

30.

33.

34.

tumors. Surg Neurol 14:275-283, 1980. Ostertag CB, Weigel K, Warnke P, et al: Sequential morphological changes in the dog brain after interstitial iodine-125 irradiation. Neurosurgery 13:523-528, 1983. Ostertag CB: Experimental central nervous system injury from im¬ planted isotopes, in Gutin PH, Leibel SA, Sheline GE (eds): Radiation Injury to the Nervous System. New York: Raven Press,

35.

1991. Ostertag CB. Warnke P. Kleihues P, Bigner D: Iodine-125 interstitial irradiation of virally induced dog brain tumors. Neurol Res

36.

6:176-180. 1984. Patched RA. Tibbs PA. Walsh JW, et al: A randomized trial of surgery in the treatment of single metastases to the brain. N Engl J Med 322:494-500, 1990.

52. 53.

8:329-333, 1981. Sundaresan N, Galicich JH, Beattie EJ: Surgical treatment of brain metastases from lung cancer. J Neurosurg 58:666-671, 1983. Turowsky K, Fike JR. Cann CE, et al: Normal brain Iodine-125 radia¬ tion damage: Effect of dose and irradiated volume in a canine model.

54.

Radiology 158: 833—838, 1986. Vecht CJ, Haaxma-Reiche H, Nordijk EM, et al: Treatment of single brain metastasis: Radiotherapy alone or combined with neuro¬

55.

surgery? Ann Neurol 33:583—590, 1993. Vertosick FT, Selker RG, Arena VC: Survival of patients with welldifferentiated astrocytomas diagnosed in the era of computed tomog¬

56.

raphy. Neurosurgery 28:496-501, 1991. Warnke PC, Hans FJ, Ostertag CB: Impact of stereotactic interstitial radiation on capillary physiology. Acta Neurochir (Suppl) 58:85-88, 1993.

CHAPTER

69

INDICATIONS FOR BRACHYTHERAPY

Mark Bernstein

but needed. A radiation dose-response relationship exists for most cancer cells treated by experimental brachytherapy in vitro and in vivo,50 and in humans retrospective nonrandom¬ ized data51 as well as prospective randomized trials52 support a dose-response relationship regarding the radiotherapeutic treat¬

Interstitial brachytherapy is widely used for tumors outside the central nervous system1 and has been used to treat brain neo¬ plasms for over 80 years.2-3 The technique for implantation of radioactive sources was crude until the advent of stereotactic surgery,4-5 which allowed accurate placement of point sources within the brain. However, dosimetry was still crude because imaging remained inferential; the location of structural lesions was inferred from the effects seen on neighboring structures that could be imaged, that is, ventricles (i.e., air and contrast ventriculography) and arteries and veins (i.e., angiography). The modern age of brachytherapy dawned with the advent of positive imaging, or the actual visualization of the exact loca¬ tion and contour of tumors (i.e., computed tomography initially and then magnetic resonance imaging). Sophisticated threedimensional dosimetry could be superimposed on precise image-guided placement of radiation sources, using stereotac¬

ment of these tumors. Additionally, most recurrences occur within the initial treatment volume,53-54 indicating that local control remains the primary challenge in the treatment of these tumors and that therapeutic modalities directed mainly at the initial tumor volume are appropriate. These observations sum¬ marize the rationale for brachytherapy as part of the initial treatment of malignant astrocytomas (including glioblastoma). At present, because of the indisputable benefit of external radiation for malignant astrocytic tumors,55 brachytherapy should be used as a “boost” after conventional therapy consist¬ ing of craniotomy or stereotactic biopsy followed by external fractionated radiation via regional fields to a dose of 50 to 60 Gy in 25 to 30 fractions, with or without concomitant chemo¬ therapy. This scenario represents the situation in which most patients have been treated with brachytherapy for de novo ma¬ lignant astrocytomas.9-24 Whether brachytherapy used in this way actually produces a statistically significant improvement in median survival among patients with de novo malignant as¬ trocytoma is not known but may be clarified by two random¬ ized studies nearing completion: the University of Toronto study7 and that of the Brain Tumor Cooperative Group.8 If brachytherapy is to be used alone as part of the initial therapy for patients with a malignant astrocytoma, that is, without ex¬ ternal radiation, this must initially be done in the setting of an ethically and scientifically sound randomized controlled study. It is clear that randomized studies are required to demonstrate differences between treatment groups, since selection of pa¬ tients alone can have a significant impact on the outcome re¬

tic surgery married to accurate imaging.6 In spite of the physical and mathematical accuracy of brachytherapy, this modality has been applied largely in nonrandomized, often poorly controlled trials, and there are still many questions regarding the true efficacy of this treatment for patients with brain tumors. Only two randomized studies have been conducted, both for newly diagnosed patients with ma¬ lignant astrocytoma (including glioblastoma), and both are nearing completion.7-8 Nonrandomized clinical studies have ex¬ amined the use of brachytherapy for de novo malignant astro¬ cytomas,9-24 recurrent malignant astrocytomas,25-34 de novo low-grade astrocytomas,35-42 de novo and recurrent single metastatic tumors,43-46 and de novo and recurrent extraaxial skull base neoplasms.47-49 This chapter examines the relative indications for interstitial brachytherapy for brain tumors. The conclusions and recom¬ mendations are based on recorded clinical experience, radio¬ biological considerations, and knowledge about the biology, natural history, and response to conventional treatment of the various brain neoplasms that present difficult treatment chal¬ lenges to neuro-oncologists.

gardless of the treatment.56 Patients with a newly diagnosed supratentorial malignant astrocytoma should be considered eligible for brachytherapy only if they have good neurological and functional status, (i.e., Karnofsky score > 70). The enhancing edge of the tumor should be reasonably well demarcated on neurodiagnostic imaging [computed tomography (CT) and/or magnetic reso¬ nance imaging (MRI)] and should have a maximum dimension of < 6 cm. Larger tumors are usually less well demarcated, and larger volumes receiving high-dose radiation are more likely to produce neurological morbidity as a result of swelling from the implant. Tumors producing significant mass effect should be

DE NOVO MALIGNANT ASTROCYTOMA Since the outcome for patients treated conventionally for ma¬ lignant astrocytomas (including glioblastoma multiforme) is so poor, experimental approaches are not only ethically justified

599

600

Part 3/Stereotactic Radiotherapy

reduced surgically before brachytherapy. Tumors with indis¬ tinct boundaries on imaging are inappropriate for brachyther¬ apy because adequate dosimetric planning is not feasible if one cannot discern the borders of the enhancing portion of the tu¬ mor. The tumor should be unilateral and should be confined to the cerebral hemisphere; extension across the midline in the corpus callosum and/or extension caudally into the upper brain stem are indicative of a less favorable tumor biology and can be expected to result in a relatively high incidence of brachytherapy-induced morbidity. Multicentric gliomas should be excluded for a number of reasons, including the fact that there are likely to be other microscopic lesions not seen on imaging that will not be treated and will portend a poor out¬ come for the patient. Tumors in eloquent locations such as dominant thalamus are technically eligible for brachytherapy, but the risk of significant neurological deterioration can be expected to be high, and the opportunity for delayed reoperation, which may be an inte¬ grally important part of treatment with brachyther¬ apy,7,13,16,20,25,26,27,31,57-59 will be unfeasible and/or will be attended by an extremely high risk of neurological morbidity. Reoperation is indicated in up to 50 percent of patients treated with brachytherapy and should be recommended early if a well-circumscribed mass is producing intractable increased in¬ tracranial pressure and/or a focal deficit. Whether such a mass is pure radiation necrosis, recurrent tumor, or a mixture of radi¬ ation necrosis and recurrent tumor (probably the most common situation) is a moot point and one that is difficult to solve preoperatively. Positron emission tomography scanning has been positively correlated with tumor recurrence in patients under¬ going reoperation after brachytherapy60; histological exam¬ ination of surgical specimens usually reveals a mixture of radiation necrosis and identifiable tumor. Reoperation not only may improve the quality of life of the patient by improving neurological function and reducing the steroid requirement but also may prolong survival. Even in the absence of a discrete mass of radiation necrosis, brachytherapy produces significant and prolonged cerebral edema in the majority of patients so treated, and the patient must therefore not have a major con¬ traindication to protracted steroid use (e.g., an active peptic ul¬ cer), at least until a less toxic substitute for corticosteroids is found. At the University of Toronto, approximately 30 percent of patients assessed postoperatively with de novo malignant as¬ trocytoma and glioblastoma satisfy these criteria and are con¬ sidered eligible for brachytherapy.

RECURRENT MALIGNANT ASTROCYTOMA When a malignant astrocytoma recurs after conventional ther¬ apy, survival usually is measurable in terms of a few months if no further therapy is given. Reoperation and systemic chemotherapy offer a relatively modest prolongation of life,61,62 and brachytherapy has therefore been tried in this setting in well-selected patients, with modest but encouraging results.25 14 The indications for brachytherapy in patients with recurrent malignant astrocytoma are similar to those for patients with de novo malignant astrocytoma. The tumor should be ^ 6 cm in its maximum dimension, the recurrence should be solitary (i.e.. not multicentric) and reasonably well circumscribed, and it should not extend into the contralateral hemisphere or upper

brain stem. Lesions productive of significant mass effect are likely to result in an increased neurological deficit after brachytherapy, and cytoreductive surgery should be performed before considering brachytherapy in such patients. The pa¬ tient’s Karnofsky functional status should be ^ 70, since pa¬ tients with malignant brain tumors who are in poor neuro¬ logical condition are well known to do relatively poorly after various treatments, both conventional and experimental.63 The length of the relapse-free interval between initial treatment and recurrence of disease has been shown to be a positive prognos¬ tic variable for therapeutic interventions such as reoperation,61 and this probably reflects a slightly more favorable biology of these tumors; brachytherapy in such a patient would also be ex¬ pected to produce a relatively beneficial palliation. Among all patients with recurrent malignant astrocytoma and glioblas¬ toma evaluated at the University of Toronto, only about 10 per¬ cent fulfill these criteria and are considered eligible for brachytherapy. Hyperthermia has been combined with interstitial brachy¬ therapy for both recurrent and de novo malignant astrocytoma and glioblastoma with modest results and significant morbid¬ ity.64,65 topic is discussed in Chap. 75.

LOW-GRADE GLIOMA Brachytherapy has been used for supratentorial lowgrade gliomas (i.e., astrocytoma, oligodendroglioma, mixed astrocytoma-oligodendroglioma) extensively in Europe,35-42 but a critical examination of the issues does not support a role for brachytherapy in this group of patients. In patients with ma¬ lignant astrocytoma, the benefit of external fractionated radia¬ tion has been incontrovertibly shown in randomized studies to prolong survival.55 The same cannot be said for adult patients with low-grade glioma. A number of retrospective reviews have found conflicting results,66-68 and one cannot conclude that external radiation produces a definite benefit in these pa¬ tients. A number of randomized studies examining the role of radiation in patients with supratentorial low-grade glioma are under way or are being designed, and the neuro-oncological community awaits the results of these studies with interest. At present, the biology and natural history of low-grade gliomas are sufficiently variable and in some cases quite favorable, and many clinicians do not even treat them until clinical and/or imaging progression occurs. Applying a potentially toxic, unproven therapy to a disease with variable biology, often in¬ distinct boundaries on imaging, and an unproven response to conventional fractionated radiation is not scientifically sound. In fact, reports of patients treated with brachytherapy for lowgrade gliomas appear to yield survival results similar to those for patients in series using external radiation or even no radiation.35-42,66"68

METASTATIC TUMORS A modest experience with interstitial brachytherapy in de novo and recurrent brain metastases has accrued.43-*6 Since these tu¬ mors are histologically more circumscribed than are malignant gliomas, the rationale for their treatment with brachytherapy or other focused-radiation techniques is even more compelling than that for malignant astrocytomas. The best conventional treatment of a solitary brain metastasis consists of complete

Chapter 69/Indications for Brachytherapy

surgical resection followed by external fractionated whole brain radiation to doses ranging from 20 Gy in 5 fractions to 50 Gy in 25 fractions.69 With this treatment, the median survival is approximately 40 weeks, but some patients have long-term sur¬ vival or complete control of the brain tumor, with death ensu¬ ing from uncontrolled systemic disease. Because some patients respond so well to conventional therapy, brachytherapy for de novo metastasis is unnecessary and potentially dangerous for the majority of patients with a solitary brain metastasis that is amenable to surgical excision and external radiation. If brachytherapy is used for de novo metastasis, it must be com¬ bined with external fractionated whole brain radiation because of the high incidence of multiplicity of metastatic deposits (seen on MRI or microscopic). The only scientifically justifi¬ able use of brachytherapy for de novo metastatic brain tumors would be as part of a properly designed randomized protocol. Brachytherapy is most appropriate for single brain metastases that recur after conventional therapy. The brain lesion must be solitary and within the cerebral hemisphere; cerebellar tumors are also technically eligible if they do not abut the brain stem. The tumor should be < 6 cm in maximum dimension and should not be associated with significant mass effect; if the lat¬ ter situation occurs, repeat craniotomy for removal of the tu¬ mor should be done before brachytherapy. Systemic disease must be under excellent control, that is, in clinical and radio¬ logical remission with no evidence of disease outside the brain. As with malignant gliomas, the longer the patient has been re¬ currence-free after the initial treatment, the more favorable the tumor’s biology is likely to be and the more likely the patient is to have a beneficial response to brachytherapy.

tant role in highly selected patients with de novo and recurrent malignant astrocytoma, patients with a recurrent solitary brain metastases too large for percutaneous stereotactic radiation, and selected recurrent skull base neoplasms that are not techni¬ cally amenable to percutaneous stereotactic radiation.

References 1.

2. 3. 4.

5.

6.

7.

8. 9.

10.

SKULL BASE TUMORS 11.

There are few data on brachytherapy for skull base tumors, but there is ample evidence that brachytherapy can have a radiologically measurable positive effect on both benign tumors (e.g., meningioma, pituitary adenoma) and malignant tumors (e.g., chordoma, chondrosarcoma) of the skull base, whether treated by high-activity removable seeds or by low-activity permanent implants.4849 This modality has been used for de novo tumors in patients too old or infirm for radical surgery and for recurrent tumors when surgical and/or external radia¬ tion treatment has failed.48,49 There are too few data to draw conclusions or make treatment recommendations, but brachy¬ therapy probably does have a small role to play in the treatment of these tumors, probably only in patients in whom percutane¬ ous stereotactic radiation cannot be used, perhaps because of the anatomy and/or size of the lesion.

12.

13.

14. 15.

Patel FD, Sharma SC, Negi PS, et al: Low dose rate vs. high dose rate brachytherapy in the treatment of carcinoma of the uterine cervix: A clinical trial. Int J Radiat Oncol Biol Phys 28:335-341, 1994. Bernstein M, Gutin PH: Interstitial brachytherapy for brain tumors: A review. Neurosurgery 9:741-750, 1981. Frazier CH: The effects of radium emanations upon brain tumors. Surg Gynecol Obstet 31:236-239, 1920. De Riu PL, Rocca A: Interstitial irradiation therapy of supratentorial gliomas by stereotaxic technique: Long term results. Ital J Neurol Sci 9:243-248, 1988. Talairach J, Ruggiero G, Aboulker J, David M: A new method of treatment of inoperable brain tumours by stereotaxic implantation of radioactive gold: A preliminary report. Br J Radiol 28:62-74, 1955. Ten Haken RK, Diaz RF, McShan DL, et al: From manual to 3-D computerized treatment planning for 125-1 stereotactic brain im¬ plants. Int J Radiat Oncol Biol Phys 15:467^180, 1988. Bernstein M, Laperriere N, Leung P, McKenzie S: Interstitial brachytherapy for malignant brain tumors: Preliminary results. Neurosurgery 26:371-380, 1990. Malkin MG: Interstitial irradiation of malignant gliomas. Rev Neurol (Paris) 148:448^153, 1992. Chin HW, Maruyama Y, Young B, et al: A clinical study with brain brachytherapy for malignant gliomas. Strahlenther Onkol 162: 433^136, 1986. Chun M, McKeough P, Wu A, et al: Interstitial iridium-192 implanta¬ tion for malignant brain tumours: II. Clinical experience. Br J Radiol 62:158-162, 1989. Dyck P, Bouzaglou A, Gruskin P: Stereotactic biopsy and brachyther¬ apy of brain tumours. Neurol Res 9:69-90, 1987. Fontanesi J, Clark WC, Weir A, et al: Interstitial iodine 125 and con¬ comitant cisplatin followed by hyperfractionated external beam irra¬ diation for malignant supratentorial glioma: Preliminary experience at the University of Tennessee, Memphis. Am J Clin Oncol 16: 412-417, 1993. Gutin PH, Prados MD, Phillips TL, et al: External irradiation fol¬ lowed by an interstitial high activity iodine-125 implant “boost” in the initial management of malignant gliomas: NCOG study 6G-82-2. Int J Radiat Oncol Biol Phys 21:601-606, 1991. Kaneko I, Noguchi M, Kogure T, et al: Treatment of brain tumors with iridium-192 seeds. Acta Oncol 27:269-274, 1988. Kumar PP, Good RR, Skultety FM, Leibrock LG: Endocurietherapy of glioblastoma multiforme with iodine-125: Results of treatment.

16.

Radiat Med 5:94—98, 1987. Loeffler JS, Alexander E, Wen PY, et al: Results of stereotactic brachytherapy used in the initial management of patients with

17.

glioblastoma. JNCI82: 1918-1921, 1990. Lunsford LD, Deutsch M, Yoder V: Stereotactic interstitial brachytherapy: Current concepts and concerns in twenty patients.

18.

Appl Neurophysiol 48:117-120, 1985. Montemaggi P, Morganti AG, Smaniotto D, et al: New perspectives in brachycurietherapy of malignant brain tumors: Preliminary report. J

19.

Neurosurg Sci 34: 239-241,1990. Patchell RA, Maruyama Y, Tibbs PA, et al: Neutron interstitial brachytherapy for malignant gliomas: A pilot study. J Neurosurg

SUMMARY Brachytherapy, while a potent adjuvant therapy, has significant toxicity, and unequivocal efficacy remains to be demonstrated for the brain tumors neuro-oncologists encounter frequently. Patients must be well selected, so that the maximum possible benefit accrues to those who are in a position to benefit from the therapy without incurring an undue risk of morbidity. The real challenge may be to identify this subset of patients prospectively. The results of two randomized studies are awaited, and more randomized studies probably will be re¬ quired. Brachytherapy probably will continue to play an impor¬

601

20.

21.

68:67-72, 1988. Prados MD, Gutin PH, Phillips TL, et al: Interstitial brachytherapy for newly diagnosed patients with malignant gliomas: The UCSF ex¬ perience. Int J Radiat Oncol Biol Phys 24:593-597, 1992. Salcman M, Sewchand W, Amin PP, Beilis EH: Technique and pre¬ liminary results of interstitial irradiation for primary brain tumors. J Neurooncol 4: 141-149,1986.

602

Part 3/Stereotactic Radiotherapy

22.

Scharfen CO, Sneed PK, Wara WM, et al: High activity iodine-125 interstitial implants for gliomas. Ini J Radial Oncol Biol Phys 24:583-591, 1992.

45.

Kreth FW, Warnke PC, Ostertag CB: Stereotaktische interstitielle Radiochirurgie und perkutane Radiotherape in der Behandlung zerebraler Metastases. Nervenartz 64:108-113, 1993.

23.

Willis BK. Helibrun MP, Sapozink MD. McDonald PR: Stereotactic interstitial brachytherapy of malignant astrocytomas with remarks on postimplantation computed tomographic appearance. Neurosurgery 23:348-354, 1988.

46.

Prados M, Leibel S, Barnett C, Gutin PH: Interstitial brachytherapy for metastatic brain tumors. Cancer 63:657-660, 1989.

47.

Bernstein M, Gutin PH: Interstitial irradiation of skull base tumours. Can J Neurol Sci 12:366-370, 1985.

48.

Kumar PP, Good RG, Leibrock LG, et al: High activity iodine 125 endocurietherapy for recurrent skull base tumors. Cancer 61: 1518-1527, 1988.

49.

Kumar PP, Patil AA, Leibrock LG, et al: Continuous low dose rate brachytherapy with high activity iodine-125 seeds in the management of meningiomas. Int J Radiat Oncol Biol Phys 25:325-328, 1993. Bernstein M, Gutin PH, Weaver KA, et al: Iodine-125 interstitial im¬ plants in the RIF-1 murine flank tumor: An animal model for brachytherapy. Radiat Res 91:624-637, 1982. Walker MD, Strike TA, Sheline GE: An analysis of dose-effect rela¬ tionship in the radiotherapy of malignant gliomas. Int J Radiat Oncol Biol Phys 51: 1725-1731, 1979. Bleehen NM, Stenning SP: A Medical Research Council trial of two

24.

25.

26. 27.

28.

29.

30.

31.

32.

Zamorano L, Yakar D, Dujovny M, et al: Permanent iodine-125 im¬ plant and external beam radiation therapy for the treatment of malig¬ nant brain tumors. Stereotact Fund Neurosurg 59:183-192, 1992. Bernstein M, Laperriere N, Glen J. et al: Brachytherapy for recurrent malignant astrocytoma. Int J Radial Oncol Biol Phys 30:1213-1217, 1994. Gutin PH. Leibel SA: Stereotaxic interstitial irradiation of malignant brain tumors. Neurol Clin 3: 883-893, 1985. Gutin PH, Leibel SA. Wara WM, et al: Recurrent malignant

50.

gliomas: Survival following interstitial brachytherapy with highactivity iodine-125 sources. J Neurosurg 67:864—873, 1987. Hitchon PW, VanGilder JC, Wen B, Jani S: Brachytherapy for malig¬ nant recurrent and untreated gliomas. Stereotad Fund Neurosurg 59:174-178, 1992.

51.

Kitchen ND, Hughes S, Beaney R, Thomas DGT: Interstitial brachytherapy for recurrent malignant glioma (abstract). J Neurooncol 15:S13, 1993. Larson GL, Wilbanks JH, Dennis S, et al: Interstitial radiogold im¬ plantation for the treatment of recurrent high-grade gliomas. Cancer 66:27-29, 1990. Leibel SA. Gutin PH. Wara WM, et al: Survival and quality of life af¬ ter interstitial implantation of removable iodine-125 sources for the treatment of patients with recurrent malignant gliomas. Int J Radiat Oncol Biol Phys 17:1129-1139, 1989. Lucas GL, Luxton G, Cohen D, et al: Treatment results of stereotactic interstitial brachytherapy for primary and metastatic brain tumors. Int J Radiat Oncol Biol Phys 21:715-721, 1991.

33.

Matsumoto K, Nakagawa M, Higashi H, et al: Preliminary results of iridium-192 brachytherapy for malignant gliomas. Neurol Med Chir {Tokyo) 32:739-746, 1992.

34.

Thompson ES, Afshar F, Plowman PJ: Paediatric brachytherapy: II. Brain implantation. Br J Radiol 62:223-229, 1989. Etou A, Mundinger F, Mohajder M. Birg W: Stereotactic interstitial irradiation of diencephalic tumors with iridium-192 and iodine-125: 10 years follow-up and comparison with other treatments. Child Nerv Syst 5:140-143, 1989.

35.

36.

Frank F, Fabrizi AP, Frank-Ricci R. et al: Treatment of low malig¬ nancy brain neoplasms by means of stereotactic interstitial radiother¬ apy. Appl Neurophysiol 48:121-126, 1985.

37.

Kreth FW, Warnke PC, Ostertag CB: Interstitielle radiochirurgie niedergradiger gliome. Nervenartz 64: 633-639, 1993. Mundinger F, Braus DF, Frauss JK. Birg W: Long-term outcome of 89 low-grade brainstem gliomas after interstitial radiation therapy. J Neurosurg 75:740-746, 1991.

38.

39.

40. 41.

42.

Mundinger F, Weigel K: Indication and results of stereotactic curi¬ etherapy with iridium-192 and iodine-125 for non-resectable tumours of the hypothalamic region. Ada Neurochir Suppl (Wien) 33: 323-330, 1984. Ostertag CB, Kreth FW: Iodine-125 interstitial irradiation for cerebral gliomas. Acta Neurochir (Wien) 119:53-61, 1992. Rougier A, Pigneux J, Cohadon F: Combined interstitial and external irradiation of gliomas. Ada Neurochir Suppl (Wien) 33:345-353. 1984. Szikla G, Schlienger M, Blond S, et al: Interstitial and combined in¬ terstitial and external irradiation of supratentorial gliomas: Results in 161 cases treated 1973-1981. Acta Neurochir Suppl (Wien) 33: 355-362. 1984.

52.

radiotherapy doses in the treatment of grades 3 and 4 astrocytoma. Br J Cancer 64:769-774, 1991. 53.

Bashir R, Hochberg F, Oot R: Regrowth patterns of glioblastoma multiforme related to planning of interstitial brachytherapy radiation fields. Neurosurgery 23:27-30, 1988.

54.

Hochberg FH. Pruitt A: Assumptions in the radiotherapy of glioblas¬ toma. Neurology 30:907-911, 1980.

55.

Walker MD, Alexander E. Hunt WE. et al: Evaluation of BCNU and/or radiotherapy in the treatment of anaplastic gliomas. J Neurosurg 49:333-343, 1978. Florell RC, Macdonald DR, Irish WD, et al: Selection bias, survival, and brachytherapy for glioma. J Neurosurg 76:179-183, 1992. Agbi CB. Bernstein M, Laperriere N, et al: Patterns of recurrence of malignant astrocytoma following stereotactic interstitial brachyther¬ apy with iodine-125 implants. Int J Radiat Oncol Biol Phys 23: 321-326, 1992.

56. 57.

58.

Herman JM, Shetter AG, Rossman K. et al: Reoperation after intersti¬ tial brachytherapy in patients with malignant gliomas. BNI Q 6: 21-29, 1990.

59.

Loeffler JS, Alexander E, Hochberg FH, et al: Clinical patterns of failure following stereotactic interstitial irradiation for malignant gliomas. Int J Radiat Oncol Biol Phys 19:1455-1462, 1990. Valk PE. Budinger TF, Levin VA, et al: PET of malignant cerebral tu¬ mors after interstitial brachytherapy: Demonstration of metabolic ac¬ tivity and correlation with clinical outcome. J Neurosurg 69:830-838, 1988.

60.

61. 62. 63.

64.

65.

66.

67.

43.

Bernstein M. Cabantog A. Laperriere N, Thomason C: Brachytherapy for recurrent single brain metastasis. Can J Neurol Sci 22:13-16, 1995.

68.

44.

Heros DO, Kasdon DL. Chun M: Brachytherapy in the treatment of recurrent solitary brain metastases. Neurosurgery 23:733-737. 1988.

69.

Dirks P, Bernstein M. Muller PJ, Tucker WS: The value of reopera¬ tion for recurrent glioblastoma. Can J Surg 36:271-275, 1993. Kornblith PL, Walker M: Chemotherapy for malignant gliomas. J Neurosurg 68:1-17, 1988. Duncan GG, Goodman GB, Ludgate CM. Rheaume DE: The treat¬ ment of adult supratentorial high grade astrocytomas. J Neurooncol 13:63-72, 1992. Sneed PK, Gutin PH. Stauffer PR. et al: Thermoradiotherapy of re¬ current malignant brain tumors. Int J Radiat Oncol Biol Phys 23: 853-861, 1992. Stea B, Kittelson J, Cassady JR, et al: Treatment of malignant gliomas with interstitial irradiation and hyperthermia. Int J Radiat Oncol Biol Phys 24:657-667, 1992. Philippon JH. Clemenceau SH. Fauchon FH, Foncin JF: Supratentorial low-grade astrocytomas in adults. Neurosurgen1 32: 554-559, 1993. Recht LD, Lew R. Smith TW: Suspected low-grade glioma: Is defer¬ ring treatment safe? Ann Neurol 31:431 -436, 1992. Shaw EG, Daumas-Duport C, Scheithauer BW, et al: Radiation ther¬ apy in the management of low-grade supratentorial astrocytomas. J Neurosurg 70:853-861. 1989. Patched RA, I'ibbs PA. Walsh JW. et al: A randomized trial of surgery in (he treatment of single metastases to the brain. N Engl J Med 322:494-500, 1990.

CHAPTER

70

GOLD SEED BRACHYTHERAPY

Philip L. Gildenberg, Shiao Y. Woo, and Barry M. Berner

The use of stereotactically implanted isotopes for interstitial radiation for treatment of malignant brain tumors is presented in detail elsewhere in this text, so the theory and rationale of brachytherapy per se will not be presented here. The usual methods of brachytherapy involve insertion of multiple cathe¬ ters through the tumor for either temporary1 or permanent2 3 in¬ sertion of radioactive seeds. In some circumstances brachyther¬ apy would be a desirable adjunct to therapy, but the location and/or configuration of the residual or recurrent tumor does not allow catheter insertion, the condition of the scalp after radia¬ tion makes catheter insertion inadvisable, institutional or eco¬ nomic constraints make housing the patient during a severalday period with the isotope inserted difficult, or the patient or physician find it desirable for other reasons to avoid catheter

at the conclusion of a craniotomy,7 which may result in a mal¬ distribution of the dose. Instead of insertion through the cran¬ iotomy incision before it is closed, stereotactic insertion may be done through a single burr hole several days or later after the resection. A particular disadvantage of the short half-life of 198gold is the need to have an immediate supply of gold seed sources. With the steep rate of decay, dose planning must consider the specific hour of implantation, and the strength must be appro¬ priate for implantation at the time of surgery. Another disad¬ vantage is the difficulty of preplanning the site of each seed. Although the general distribution and number of gold seeds are planned on the basis of a routine contrast-enhanced MR scan, the exact seed location is planned after the head ring is in place and the scan done. If a seed were not in the proper position, there is no way to retrieve or move it, but this problem has never arisen. With the program described below, postimplanta¬ tion dosimetry has invariably documented a good dose distrib¬ ution. The recent acquisition of image fusion software, coupled with the use of a GLAD-X system will make it possible to plan seed placement and calculate dose distribution in advance of

insertion. An alternative technique involves the permanent stereotac¬ tic implantation of individual radioactive gold seeds to estab¬ lish a therapeutic dose distribution within the tumor. Although colloidal gold has been used for ventricular or tumor cavity in¬ stallation,45 few reports have discussed the use of permanent implantation of gold seeds for brachytherapy.2 An advantage of the use of l98Au is the short half-life of 2.7 days, which minimizes the time when contact with the patient should be controlled for radiation safety. The short half-life also avoids the risk of the seed migrating through a region of liquefaction necrosis produced by the radiotherapy, since the radioactivity would be minimal by the time necrosis or migra¬ tion would occur. The distribution and amount of radiation ad¬ ministration is comparable to that planned when other isotopes are used, although the time distribution is much different, with a high initial dose rate falling off at a steep slope, which has been reported to be particularly advantageous in higher-grade malignancies.6 The field is confined enough to minimize radia¬ tion exposure of normal brain and minimizes the duration needed to shield the patient from others. Because it is possible to distribute the seeds to obtain smooth dosimetry in a very ir¬ regularly shaped mass, this technique may be used to irradiate residual tumor when a postoperative or late follow-up contrastenhanced magnetic resonance imaging (MRI) scan demon¬ strates residual glioblastoma or midrange glioma in a thin shell adjacent to the resection cavity, a configuration that is often dif¬ ficult to cover with catheters. Stereotactic insertion of individual seeds into defined loci within the tumor is far superior to placing gold seeds manually

the procedure. The preplanning of a stereotactic implant requires informa¬ tion including current computed tomography (CT) and MRI scans with target identification, prescription dose and/or dose rate, permanent versus temporary implant, radionuclide to be used, and activity available. The prescription dose and/or dose rate can be given as either the physical dose resulting from source decay or a biological dose which includes modifiers to the physical dose. The biological dose is more dependent on some of the above variables together with radiobiological data, including mitotic and repair half-lives of the various cell popu¬ lations irradiated. After the dose model is chosen, the planning of source posi¬ tions can begin, and sites for each seed are normally selected relative to target geometry. However, it is necessary to know from which direction, as determined by the neurosurgeon, the sources can be introduced with minimal damage to normal tis¬ sue and what constraints must be introduced to avoid damage to blood vessels or eloquent brain areas. The latter constraints may limit target coverage. An initial estimate for dose calculation is usually done using a uniform arrangement of sources within the target volume. The dose distribution generated, including limiting structures,

603

604

Part 3/Stereotactic Radiotherapy

can then be varied by changing the source locations and/or ac¬ tivities until an acceptable plan is achieved. This approach would be considered a manual iterative process. Algorithmic optimization is a second approach for planning. The process also begins with some initial source distribution within the tar¬ get volume. The dose to each of a set of points which defines the target volume is determined. If the dose to this set of points did not equal the prescription, the algorithm would ideally then be free to specify changes in source number, location, and ac¬ tivity to arrive at a solution. In a practical approach, constraints on what variables are actually subject to change are predefined so that optimization would consider only one or two possibili¬ ties, such as activity and/or number of sources. The process may include limiting doses to normal structures, depending on the algorithm. Irradiation of normal structures in the implanta¬ tion of gold seeds, which have a low tissue penitrance, and sites for each seed can be planned to minimize dose spreading be¬ yond the boundaries of the target volume. Use of planning is beneficial in several ways once the pa¬ tient is in the operating room. First, the location of each seed and general coordinates for the stereotactic implantation are al¬ ready known before entering surgery, which minimizes the op¬ erating time required. Second, although the exact source loca¬ tions are not verified until orthogonal films are taken after surgery, target dose distribution is approached as an optimized process which can include constraints. Third, the cost of sources is minimized by knowing ahead of time the number of seeds and activity to order. The implantation procedure begins in the MR scanning suite in our institution. We use the Cosman-Roberts-Wells (CRW) stereotactic apparatus. An arc-centered system is strongly recommended for this procedure, although our first few implantations were done with the Brown-Roberts-Wells (BRW) apparatus. A contrast-enhanced MR scan is taken in all three planes, usually with 4-mm thick slices and 1-mm gap for a total interslice distance of 5 mm, using the usual protocol for stereotactic surgery. If the seeds are very active and a larger distance between sources is required, the slice thickness can be proportionately larger. The localization of each seed to be implanted takes place at the MRI console and involves the radiation oncologist and the radiation physicist, as well as the neurosurgeon. If none of these are facile with the use of the console, a radiologist or ra¬ diology technician may also be included. The shape of the mass is visualized by the planning team by examination of all three planes of the scan. The distribution of gold seeds is visualized in a configuration resembling the stacking of cannon balls. The number of seeds is determined from a consideration of tumor volume and strength of the seeds. The space between seeds is also a function of the strength of each seed. Each seed must be equidistant from the surrounding seeds to obtain a smooth isodose throughout the tumor mass. This can be accom¬ plished most readily by using the circular cursor on the con¬ sole, the diameter of which is adjusted to represent the strength of each seed, and is usually between one and two centimeters. The stereotactic target where the individual seed is placed is the center of the cursor. Each axial slice represented on the screen demonstrates anterior-posterior (AP) and lateral seed positions and defines the coordinates for each locus on that plane. For instance, if the cursor diameter is 1 cm and the slice

spacing is 5 mm, the ideal distribution on the plane of the slice is achieved by having the circles just touch each other (Fig. 70-1). The voxel addresses that are demonstrated directly when each cursor is deposited represent the X and Y screen co¬ ordinates used to calculate the stereotactic coordinates of each seed target. By depositing each cursor as planning proceeds, a smooth interlocking grid can be developed and visualized on the console. Since the field in three dimensions is a sphere rather than a circle, one can picture that distribution if the slice is looked at from the side. On the adjacent slices, each cursor is positioned at a locus just above each point where the circles do not touch. If demonstrated on the tangential plane, the empty area outside the circles would be covered by the fields of the spheres on the adjacent slices. After the entire field in all slices that visualize the target is covered with such circles, a count is made of the number of sources represented, which should be the same number as the calculated number of seeds to be used. If there are too many circles, the process is repeated with a slightly larger circle cur¬ sor, and if too few the circular cursor is made slightly smaller. When the proper number of loci has been plotted, the stereotac¬ tic coordinate for each cursor is calculated. The gold seed implantation itself occurs in the operating room, with a setup identical to that of a stereotactic biopsy (see Chap. 46). The decision to use general anesthesia or monitored anesthesia care involves the same criteria as for a biopsy. A burr hole is planned at a noneloquent position that allows inser¬ tion of a cannula to all the implantation sites through the same opening without crossing vascular structures. The procedure is identical to biopsy up to the point where the cannula has been inserted to the first target point. We use the same cannula as is used to insert the 2X2 mm forceps in the Gildenberg Stereo-

Figure 70-1. The circular cursor is used to plan the position of each of the gold seeds in a pattern that affords a relatively homogeneous dose distribution (patient RP).

Chapter 70/Gold Seed Brachytherapy

tactic Biopsy Kit (Radionics, Burlington, MA). The cannula is inserted to a position 1 mm before reaching the target point. The obturator is removed. The neurosurgeon steps back, and the radiation oncologist inserts a gold seed to the first site. We use a needle/cannula seed introducer that just fits inside the stereotactic biopsy cannula. It is longer than the biopsy can¬ nula, but a depth stop is used to adjust its length to 1 mm longer than the biopsy cannula, so when it is inserted fully into the biopsy cannula the tip of the introducer lies at the target point, which is I mm beyond the cannula tip. The seed is deposited by advancing the obturator of the seed introducer, and the intro¬ ducer is withdrawn. The biopsy cannula is withdrawn, and the frame is adjusted to the next target point. The angles are read¬ justed so the cannula is inserted from the same burr hole to the new target point. The procedure is repeated until all the gold

605

seeds have been deposited. Following introduction of the last seed, the incision is closed in the usual fashion. After the implant procedure, orthogonal films are taken. Each gold seed is identified on the films, and isodose calcula¬ tion is performed with one of the several commercially avail¬ able computer programs, such as Maxplan. An example of the dose distribution is shown in Fig. 70-2. With experience and planning, satisfactory volume dose distribution around the tar¬ get is achievable. We have implanted gold seeds in glioblastomas in 19 stereotactic procedures in 15 patients. None experienced adverse neurological effect from either the cannula insertion or the radiation. The number of patients is not great enough to analyze statistically whether the use of this technique added to survival, and it is particularly difficult to compare response to the use of radioactive gold seeds to other brachytherapy techniques, but the subsequent course in this group of patients has been comparable to what we have seen in patients treated by brachytherapy with catheter insertion or with stereotactic radiosurgery. Consequently, the use of gold seeds for stereo¬ tactic brachytherapy is a valuable technique to have available for a selected group of patients for whom conventional brachytherapy is inadvisable.

References ].

2. 3.

4. 5.

Figure 70-2.

The postimplantation orthogonal fields are used to plot the actual dose distribution, which corresponds closely to the planned dosimetry (patient VS).

Gutin PH, Leibel SA, Wara WM, et al: Recurrent malignant gliomas: Survival following interstitial brachytherapy with high-activity iodine125 sources. J Neurosurg 67:864-873, 1987. Ostertag CB: Interstitial stereotactic radiotherapy of brain tumors. Wien Klin Wochenschr99.380-3%4, 1987. Fernandez P, Zamorano L, Caspar L, et al: Permanent l25I implant ther¬ apy with concurrent external beam radiation in the up-front treatment of malignant gliomas. Stereotact Funct Neurosurg 1:287-288, 1994. Nagulic M, Nagulic I, Vujnic V: Implantation of radioactive isotopes in intracranial tumors. Acta Chir Jugosl 36:203-218, 1989. Jayle GE, Vola JL, Sedan R, et al: Implantation of radioactive gold into the pituitary gland by the stereotaxic technic in a patient with diabetic

6.

retinopathy. Bull Soc Opthalmol France 65:310-319, 1965. Hosobuchi Y, Phillips TL, Stupar TA, Gutin PH: Interstitial brachy¬ therapy of primary brain tumors. Preliminary report. J Neurosurg

7.

53:613-617, 1980. Larson GL, Wilbanks JH, Dennis WS, et al: Interstitial radiogold im¬ plantation for the treatment of recurrent high-grade gliomas. Cancer 66:27-29, 1990.

CHAPTER

71

LOW-DOSE BRACHYTHERAPY IN THE TREATMENT OF MALIGNANT GLIOMAS

Lucia Zamorano and Laurie Gaspar

In conventional external-beam radiation therapy (EBRT), a radiation dose high enough to kill tumor cells may induce ra¬ dionecrosis in healthy tissue. Similarly, a lower dose may give tumor cells enough of an interval between treatments to repair sublethal cellular damage. Therefore, interstitial brachytherapy provides a way to increase the dose of radiation to a tu¬ mor site while limiting damage to the surrounding normal tissue.1 Brachytherapy refers to short-term interstitial radiation im¬ plantation adjacent to a tumor site or directly into a tumor. Several studies have described the efficacy of using interstitial radiation therapy in the treatment of gliomas.2-4 However, only one patient in four with glioblastoma multiforme (GBM) or anaplastic astrocytoma (AA) is a candidate for brachytherapy, and the incidence of operation for radiation necrosis is high (40 to 49 percent).5-8 Historically, patients with tumors greater than 5 cm in diameter and located in eloquent, deep, or midline ar¬ eas have been excluded from consideration for temporary brachytherapy (approximately 40 to 60 cGy/h) treatment.9 Our treatment protocol with low-dose-rate permanent brachyther¬ apy has three goals: (1) to expand the group of patients that can be treated with brachytherapy to include those with deep, elo¬ quent, or midline tumors, (2) to exploit the radiobiological ad¬ vantages of protracted long-term radiation, and (3) to reduce the incidence of symptomatic radiation necrosis associated with very high levels of irradiation.

Patient Selection Patients were considered appropriate candidates for initial brachytherapy if they had a computed tomography (CT) or magnetic resonance imaging (MRI) scan showing a wellcircumscribed lesion not larger than 7 cm at any diameter of the enhancing rim with no subependymal involvement and a Karnofsky performance status (KPS) equal to or greater than 70.

Treatment Protocol We followed the treatment protocol described below for both primary and recurrent tumor patients. Stereotactic interstitial radiotherapy involves four steps: image data acquisition, stereotactic treatment planning, stereotactic catheter place¬ ment, and catheter loading. Image data acquisition A stereotactic ring was placed on the patient’s head immedi¬ ately before the CT scan [contrast dose, 120 ml of iohexol (Omnipaque) (350 mg I/ml); 2-mm slice thickness] and used as both an external reference system and a fixation device . We also used MRI as a routine planning tool for stereotactic neuro¬ surgery procedures (Fig. 71-1). Stereotactic treatment planning

CLINICAL EXPERIENCE

The target volume consisted of the enhancing rim of the tumor cavity as it was identified on all CT slices. With the assistance

A study was initiated by the first author of this chapter to eval¬ uate the effectiveness of interstitial low-dose-rate permanent brachytherapy in the up-front management of primary brain tumors and recurrent tumors at Henry Ford Hospital in Detroit, Michigan, after 1986 and then at Wayne State University in Detroit after 1991. To reduce the risk of injury to the surrounding normal tissue that is associated with highdose-rate brachytherapy, we used permanent implantation of 125I seeds at a low dose rate of 4 to 7 cGy/h, giving a total dose of 10,000 to 14,000 cGy with concurrent 5000 to 6000 cGy/day EBRT (Table 71-1). The rationale of this protocol was to increase the effectiveness of the low-dose-rate im¬ plant with a concurrent daily “boost” of EBRT by inhibiting the proliferation of tumor cells during protracted low-dose

TABLE 71-1.

125I Permanent Implantation: Cumulative

Dose Rate According to Initial Dose Rate

radiation.8'10,11 607

Days

4 cGy/h

5 cGy/h

6 cGy/h

7 cGy/h

30 60 90 180 270 365

2433 4153 4368 7262 7930 8173

3041 5191 6709 9077 9912 10.216

3650 6229 8051 10.892 11.895 12.260

4258 7267 9393 12.708 13.877 14.303

608

Part 3/Stereotactic Radiotherapy

Postoperative Management and Follow-up The patients were discharged from the hospital the next day. The steroid dose was adjusted as needed, and in general a dose of dexamethasone of 8 mg/day was prescribed during the first 2 months after the implant. After that time, contrast-enhanced CT or MRI was obtained, and if there was no evidence of edema or other undesired effects, patients were completely tapered off the steroids. The patients were followed with clinical evalua¬ tion and a CT or MRI scan every 3 months during the first year after treatment, every 4 months during the second year, and every 6 months thereafter (Fig. 71 -3). The clinical follow-up included KPS, neurological evalua¬ tion, and steroid dependence monitoring. The neurological evaluation used a grading scale of 0 = no deficit, 1 = mild deficit, 2 = moderate deficit, and 3 = marked deficit. Patients were categorized as the same, improved, or worse in the three categories mentioned above.

Survival Analysis

Figure 71-1. MRJ showing a left temporal thalamic lesion. The patient refused surgical debulking, and a stereotactic biopsy was performed that confirmed a malignant AA. Permanent implantation of l25I was performed.

of a three-dimensional (3D) multiplanar treatment planning system (Stereotactic Treatment Planning, Fischer Instrument¬ ation, Freiburg, Germany), a protocol was designed to deliver 5 cGy/h (range, 4 to 7 cGy/h) to the target volume (Fig. 71-2, A through D). The number and trajectory of the catheters and the activity and spacing of the radioactive seeds can be ad¬ justed to an irregular target volume with the aid of computerassisted optimization.

Survival analysis was performed using the log-rank test for univariate evaluation. For two or multivariate analysis, the chisquare test and the Cox proportional hazards regressional analysis were performed. The main goal of the study was to de¬ termine median survival and the probability of survival 12, 24, and 36 months after implantation. Several variables, such as patient age, sex, tumor location, type of surgery, computer-assisted resection, tumor volume, KPS at implant and afterward, implant dose, EBRT dose, and type of second surgery, were categorized in a manner that re¬ flected group differences. The analysis of the data was done us¬ ing the Statistical Analysis System (SAS) statistical package, version 6.07. We used the log-rank test to evaluate differ¬ ences between survival values; it was declared significant at the alpha = 0.05 level. The twenty-fifth, median, and seventyfifth percentiles of mortality with 1-, 2-, and 3-year probability of survival were calculated. Kaplan-Meier survival curves were generated.

Stereotactic placement of the catheter Immediately before surgery, patients received antibiotic, dexamethasone, and anticonvulsant therapy. Under local anesthesia, using a Zamorano-Dujovny (Z-D) localizing unit (Fischer Instrumentation. Freiburg, Germany), the silicone outer catheters of coaxial catheters were placed stereotactically through 5-mm burr holes with C-arm fluoroscopic guidance. Catheter loading Low-activity 12?I seeds (up to 5 mCi) were used. The l25I sources previously loaded into the inner coaxial catheters were inserted into the stereotactically placed outer catheter in the same operative procedure. A metal clip was applied to fix the inner and outer catheters, thus sealing the sources, and the catheters were then glued to bone. The actual catheter geome¬ try is assessed with orthogonal radiography obtained in the op¬ erating suite by using the fiducial markers attached to the stereotactic ring.

RESULTS Primary Malignant Gliomas Between December 1988 and January 1994, we treated 72 pa¬ tients with newly diagnosed malignant gliomas with an l25I per¬ manent implant. There were 37 men and 35 women whose ages ranged from 12 to 79 years (median, 43 years). Forty-five pa¬ tients were diagnosed with AA, and 27 with GBM. There were 43 superficial and 29 deep tumors. The specific locations are shown in Table 71-2. Sixteen patients underwent stereotactic biopsies, and 56 had resection of their tumors. Tumor volume for the entire group averaged 13.2 cm3 (range. 0.3 to 90 cm3) and was 28.00 cm' in the GBM patients (range, 3.3 to 78.8 cm3). The KPS before implantation was 70 to 80 for 37 patients and 90 to 100 for 42 patients. Treatment consisted of perma¬ nent implantation of ,25I delivered in a minimal tumor dose generally of 10,216 cGy (5 cGy/h).

Chapter 71/Low-Dose Brachytherapy in the Treatment of Malignant Gliomas

609

Figure 71-2. A. Axial CT showing the isodose distribution of the margin, 3 and 2 centigrade per hour line. The minimal tumoral dose prescribed was 10,000 cGy at an initial dose rate of 5 cGy/h. Sagittal (B) and coronal (Q views showing the distribution of radiation. D. Dose-volume histogram showing that more than 90 percent of the tumor volume received the prescribed dose.

The preferred sequence was implantation followed by EBRT; nevertheless, because of time of referral or coexisting medical problems, some patients received EBRT before im¬ plantation. Also, some patients refused EBRT and were treated

with implants alone. Thus, the three groups of patients included 45 patients receiving EBRT after the implant, 17 receiving EBRT before implantation, and 10 without EBRT (Table 71-3). The majority of the patients were followed with a 1-year course

610

Part 3/Stereotactic Radiotherapy

of BCNU (carmustine) or, more recently, a combination of chemotherapy and PCV (procabazine, lomustine, vincristine). Survival status was censored up to January 1994. The fol¬ low-up of 72 patients has ranged from 2 to 56 months (mean, 25.7 months). The median survival for the overall group has not been attained; the 1-, 2-, and 3-year survival rates were 83 percent, 72 percent, and 59 percent, respectively (Fig. 71-4). Median survival for GBM was 26.1 months. Median survival for AA has not been attained; the 3-year probability of survival is 64.6 percent. First-, second-, and third-year survivals for AA were 84 percent, 75 percent, and 64 percent, respectively. The 1- and 2-year survivals for GBM were 80 percent and 53 per¬ cent, respectively (Fig. 71-5). The probability of survival in the first, second, and third years with the different modalities of treatment is shown in Fig. 71-6. Longer survival was found in the AA group that did not re¬ ceive EBRT after the implantation of l25I. For the GBM pa¬ tients, we found the best survival rates when EBRT was given after the placement of 125I. The following factors were consid¬ ered good predictors of survival at the 0.05 level: histology, age, location of the tumor, preimplant KPS, and neurological status.

Figure 71-3. Postimplant MRI in the same patient showing a marked response of the tumor. Note the catheter containing the radioactive seeds. Clinically, the mild preoperative dysphasia improved with no additional neurological deficits, and the patient did not receive steroids.

TABLE 71-2.

Permanent Implant of 12SI in Primary Malignant Gliomas (n=72) Overall Survival

Tumor Location Location

No.

Frontal Parietal Temporal Occipital Thalamus Corpus callosum

15 19 23 3 4 8

Total

Figure 71-4. Survival distribution of the overall group of patients treated with permanent implants of l25I seeds in the up¬ front management of malignant gliomas.

72

TABLE 71-3. Comparison of Treatment Modalities Using Permanent Implants and External Radiation Therapy in Primary Malignant Gliomas PI before EBRT

%

PI after EBRT

%

PI without EBRT

Anaplastic astrocytoma Glioblastoma

26

57.8

10

22.2

9

19

70.4

7

25.9

1

3.7

Total

45

62.5

17

23.6

10

13.9

Diagnosis

PI = permanent implant; EBRT = external-beam radiation therapy.

% 20

Total 45 27 multiforme 72

Chapter 71/Low-Dose Brachytherapy in the Treatment of Malignant Gliomas

Permanent Implant of1251 in Primary Malignant Gliomas (n =72) Survival by Histology

Figure 71-5. Survival distribution of primary malignant gliomas by histology; GBM versus AA.

Thirty-five patients required a second surgery, 25 with AA and 12 with GBM. In the AA group, 21 patients were reoper¬ ated on for progressively growing mass lesion, 13 had recur¬ rence of tumor, and 8 had radiation necrosis. In the GBM group, five patients had radiation necrosis and in seven pa¬ tients there was evidence of tumor recurrence. Two patients had infections that required surgical debridement; they re¬ sponded satisfactorily to the treatment and are still alive. In one patient, the catheter was removed to discontinue radiation treatment to avoid further neurological deterioration. One pa¬ tient developed skin necrosis with sepsis and subsequently died of pulmonary embolism.

611

with a median age 47.5 years (range, 13 to 62 years). Fifteen patients were diagnosed with AA, and 17 with GBM. Eight of the 32 patients had previous low-grade gliomas that had be¬ come malignant. Tumor volume averaged 16.9 cm3 for A A (range, 4.3 to 59.0 cm3) and 28.0 cm3 for GBM (range, 3.3 to 78.8 cm3). There were 19 superficial and 13 deep tumors. The KPS before implant was 70 to 80 for 18 patients and 90 to 100 for 14 patients. Twenty-five patients of 32 underwent volumet¬ ric resection before implantation.12 As of February 1994, 17 patients (53 percent) had died, with median survival in the overall recurrent group being 32.6 months (Fig. 71-7). The 1-, 2-, and 3-year survival rates were 80 percent, 67 percent, and 36 percent, respectively. For recurrent AA, the median survival has not been reached; the one-, two-, and 3-year survival rates are 87 percent, 87 percent, and 51 per¬ cent, respectively. For recurrent GBM, the median survival is 20 months after implantation, with 1-, 2-, and 3-year probabilities of survival of 73 percent, 45 percent, and 15 percent (Fig. 71-8).

Permanent Implant of 1251 in Recurrent Malignant Gliomas («= 32) Overall Survival

Recurrent Malignant Gliomas During the same period (1984-1994), 32 patients were treated with brachytherapy for tumor recurrence: 23 men and 9 women

Permanent Implant of1251 in Primary Malignant Gliomas (n=72) Survival by Treatment Modality

Figure 71-7. Survival distribution of the overall group of patients with recurrent malignant gliomas treated with 12:11 permanent implants.

Permanent Implant of1251 in Recurrent Malignant Gliomas (n =32) Survival by Histology

Time (Months)

Figure 71-6. Survival distribution of primary malignant gliomas according to treatment modality: permanent implant before EBRT, permanent implant after EBRT, and permanent implant alone.

Figure 71-8. Survival distribution of the overall recurrent group by histology.

612

Part 3/Stereotactic Radiotherapy

Fourteen patients (nine with AA and five with GBM) had surgery after implantation. Three were operated on for radia¬ tion necrosis (Fig 71 -9A and B), eight for tumor progression, one for a brain abscess, one for catheter exposure, and one for infection. For patients with AA, reoperation was significant; if a patient had no surgery, median survival was 32.6 months. With surgery, median survival has not yet been reached, with p = .03 in favor of those having surgery.

DISCUSSION

median survival of the primary malignant glioma patients has not yet been attained, but the 3-year survival rate is 59 percent; the median survival in patients with GBM was 26.1 months, with a 53 percent survival rate at 2 years. It must be empha¬ sized that this study includes patients with deep or eloquent le¬ sions that would not have been amenable to implantation with a higher dose rate of temporary implants. The same is true for the recurrent group, in which median survival for the overall group was 32.6 months, with a 36 percent survival rate after 3 years. For recurrent GBM, the median survival was 20 months, and for AA, it has not been attained with a 3-year survival rate of 51 percent. These are encouraging results. In addition, the qual¬ ity of survival appears to be very satisfactory in most of the long-term survivors, according to their KPSs, neurological function, and lack of use of steroids (no steroids after 2 months).

Brachytherapy allows a much higher total dose of radiation to be delivered directly to the tumor bed and limits the exposure of adjacent normal brain to this higher concentration of radia¬ tion. Although interstitial brachytherapy appears to be effective in treating primary and recurrent malignant gliomas, it has been studied less extensively in terms of dose rate and optimal temporal parameters. The majority of clinical experience is based on high-activity l25I interstitial implants for gliomas. The survival achieved using very low dose rate l25I implants in the up-front treatment of malignant gliomas reported in this study is comparable to or even better than the results obtained in pa¬ tients treated with temporary high-activity l25I implants; the same is true for recurrent malignant gliomas (Table 71-4). The

The explanation for these encouraging results may be re¬ lated to the fact that the relative efficacy of radiation therapy, especially brachytherapy, depends not only on maximal intratumoral delivery of radiation but also on delivering the radiation in temporal and fractionation patterns that favor more destruc¬ tion of tumor cells and less damage to normal tissue. There are good radiobiological experimental studies to support protracted long-term radiation alone or in combination with high-dose irradiation such as EBRT. Marin and colleagues26 studied the

A

B Figure 71-9. .3. Preoperative MRI showing enhanced lesion in a patient 3 years after an implant for recurrent GBM. B. Postoperative MRI after computer volumetric resection showing a radionecrotic scar with no viable tumor.

Chapter 71/Low-Dose Brachytherapy in the Treatment of Malignant Gliomas

TABLE 71-4.

Brachytherapy Series

Author Mundinger, 198013 Leibel, 1989s

Isotope 125I/I92IR Permanent 125 j

Temporary Chun, 198914

192IR

Temporary Loeffler, 199115 Bernstein, 199016 Gutin, 199117 Selker, 199118 Lucas, 199119

Prados, 19922°

Stea, 19922!

Zamorano, 199222

Scharfen, 199223

Gutin et al. 199224

Malkin, 199225 Zamorano, 199312

613

125 J

Histology GM AA Recurrent GM Recurrent NGM Primary MG Primary AA Primary GM

Median Survival (months)

No. Patients

3-Year Survival

101 123 45 50 20 9 35

17.8% 37.9% 28% 0.8%

11.9 18.9 14.5 15.5 27

Primary MG Recurrent MG Primary GM Primary AA Primary MG

23 18 34 29 55

14 10.3 20.5 36.6 17

Primary /recurrent GM Primary AA Recurrent AA Primary GM Primary AA MG9AA/19 GM

13

10

7 13

28

23 11 20.3 37.3 20.6

25 37

14.1 Not attained

30% (18 months) 70% (18 months) 10% (18 months) 36% (18 months) 22%

Temporary 125 J

Temporary 125 J

Temporary ,92IR 192JR

Temporary

125 J

Temporary l92IR + hyperthermia Temporary 125 J

125 J

Temporary

125 J

Temporary

125 J

125 J

Permanent

Primary MG Temporary Permanent Recurrent MG Temporary Permanent Primary GM Primary NGM Recurrent GM Recurrent NGM

66 67

Primary GM Primary NGM Recurrent GM Recurrent NGM Primary GM Recurrent MG (24GM/12 A A) Primary MG Primary GM Primary AA Recurrent MG Recurrent AA Recurrent GM

34 29 45 50

9.8 9.3 20.5 33.1 52.7 11.4 12.1 18.9 20.5 36.6 12.6 18.9

20 36 72 27 45 32 15 17

22 10 Not attained 26.1 Not attained 32.6 Not attained 20

23 11 106 68

high grade low grade 15% high grade low grade

59% 53% (2 years) 64.6% 36% 51% 15%

AA = anaplastic astrocytoma; GM = glioblastoma multiforme; MG = malignant glioma.

response of GBM cell lines to low-dose irradiation and found that when GBM cell lines were irradiated with single-fraction high-dose-rate radiation (1.1 Gy/min), they were relatively in¬ sensitive to inactivation of colony-forming ability, similar to other GBM cell lines. Initial rates of cell kill with continuous low-dose-rate irradiation (0.075 to 0.49 Gy/h) were low, but at

times greater than 20 h and with dose rates of 0.25 Gy/h or higher, the rate of cell kill increased. Population doubling times for these cell lines were about 24 h, suggesting that cell cycle redistribution may be responsible for the increased sensitivity, with cells accumulating in the G2 and M phases of the cell cy¬ cle. These results suggest that low-dose-rate radiation therapy

614

Part 3/Stereotactic Radiotherapy

(RT) may be effective in treating GBM. Optimization of time intervals between high-dose-rate radiation (EBRT is typically 1.8 Gy in high-dose-rate radiation fractions of 1 to 2 Gy/min) and the dose rates used for GBM may be influenced by these findings, resulting in better integration of continuous low-doserate RT (implants) and high-dose-rate EBRT (fractionated ex¬ ternal beam) into therapeutic programs.27 One hypothesis states that a small dose of high-dose-rate RT used before continuous low-dose RT may sensitize cells to subsequent low-dose-rate radiation. These results also suggest that the isotope half-life chosen specifically to match the growth rate of the tumor should be considered. It is very important to consider how protracted-irradiation modalities such as permanent implanta¬ tion and (even better) radiolabeled antibodies may be used in combination with fractionated high-dose-rate therapy such as EBRT or other high-dose-rate modalities such as remote afterloading to obtain a synergistic effect.27 All these radiobio¬ logical factors may account for the good results obtained in our patients. We calculate the biologically equivalent dose of our perma¬ nent implants to a temporary dose. What dose for a 5-day tem¬ porary implant is equivalent to a permanent l25I implant at an initial dose rate of 0.05 Gy/h? If we assume an alpha/beta ratio of 10 for tumors and 3 for late-reacting normal tissue and also assume that repopulation results in an effective “loss” of 0.4 Gy/day, using time-dose models,28 we find that 10,000-Gy per¬ manent implantation gives a tumor effect equivalent to 5860 cGy delivered by a temporary implant for tumor (assuming 50 cGy/h. a dose similar to that in the temporary brachytherapy series). However, 10,000 Gy would be expected to be slightly more tolerable to normal tissues. The reoperation rate of our patients was 48.6 percent in the primary group and 43.7 percent in the group with recurrent tu¬ mors, very similar to reported series of temporary brachytherapy (Table 71-5). Only 20 percent of the reoperations were due to radionecrosis. Although the reoperation rate after permanent implantation is very similar to that of higher-dose-rate brachy¬ therapy, in our experience, radionecrosis after a permanent im¬ plant is a very well defined fibrotic reaction that is quite differ¬ ent from undefined changes secondary to temporary implants. Many of our patients had areas of enhancement on image stud¬ ies without having symptoms of deterioration; the aggressive approach of early reoperation allows us to detect early recur¬ rences and then begin other treatment options. Future use of functional imaging modalities such as single photon emission

TABLE 71-5.

Reoperative Rate after Brachytherapy

Author

Reoperative Rate

Leibel5 Bernstein16 Prados20

MG 49% MG 21.7% GM 46% AA 56% MG 40% MG 43% Primary MG 48.6% Recurrent MG 43.7%

Sharfen23 Malkin25 Zamorano12

AA = anaplastic astrocytgoma; GM = glioblastoma multiforme; MG = malignant glioma.

computed tomograpy (SPECT) and positron emission tomog¬ raphy (PET) may help decrease the reoperation rate.29 Radionecrosis is both an adverse consequence of irradiation and a somewhat desired effect. Arbit and coworkers30 studied viable glioma cells after brachytherapy and found that cells from treated tumors formed small colonies of 50 to 100 cells each. Those cells grew slowly and degenerated within 14 to 21 days. One should also consider that radionecrosis may influ¬ ence the radiation distribution in a permanent implant. Herbold and coauthors31 studied the influences of radionecrosis arising during interstitial radiation of brain tumors with 125I, l92Ir, or 19sAu. The necrosis has a higher density than normal tissue as a result of radiation-induced changes in tissue composition as well as mineral deposits, with a diameter up to 1 cm around the single seeds. The higher density and changed chemical compo¬ sition compared with homogeneous normal tissue lead to in¬ creased absorption of radiation around the necrosis that results in a lower dose rate in the surrounding tissue. The formation of necrosis during treatment with higher-energy radiation such as |yTr (340 keV) or l98Au (400 keV) may be neglected during therapy planning, as the dose rate is ultimately affected less than 2 percent. If low-energy radiation such as l25I (28 keV) is used, the dose rate can be reduced by more than 30 percent. In this case, the influence of the necrosis on dose distribution, at least for permanent 125I implantation, may not be negligible. Many issues need to be investigated further to extend the benefits of permanent implants in the management of primary brain tumors, such as the use of a radiation sensitizer, or lowdose cisplatin or 5-bromo-2-doxyuridine (BrdUR). In vivo work suggests that the combination of a radiation sensitizer and low-dose-rate radiation may sensitize tumor cells more than normal brain, thus improving the therapeutic ratio. McLaughlin and colleagues32 found that an established glioma line (U-251) incubated with BrdUR at 12 cGy/h led to cell survival equiva¬ lent to that of cells subjected to 100 cGy/h, which the authors concluded was probably independent of a G./M cell block. Normal brain does not incorporate BrdUR, and so the combi¬ nation of this with an implant could result in an improved ther¬ apeutic ratio. There is little clinical experience with radiation sensitizers used concurrently with implants. Hyperthermia can also be used as a sensitizer with brain implants.21 There has been recent interest in treating malignant gliomas with radiosurgery.33 Ling and colleagues34 performed calcula¬ tions based on the linear-quadratic model to assess the biologi¬ cally effective doses (BEDs) of tumor and normal tissue in the stereotactic irradiation of brain tumors with radioactive im¬ plants or radiosurgery techniques. A figure of merit is defined to be the ratio of tumor to normal tissue BED expressed in units of Gy 10/Gy3. These comparisons indicate a clear radiobiologi¬ cal advantage for brachytherapy unless the radiosurgery is de¬ livered in a large number of fractions. The differences in dose uniformity and in the volume of normal tissue encompassed by the high-dose regions also may influence the clinical results.

CONCLUSION At the moment, stereotactic brachytherapy appears to be the most effective adjuvant for increasing survival in patients with primary or recurrent malignant gliomas. Continuous advances in computerized optimization, imaging techniques, selection of

Chapter 71/Low-Dose Brachytherapy in the Treatment of Malignant Gliomas

isotope, and combination with other adjuvants such as hyper¬ thermia and radiosensitizers and a better understanding of the temporal synergism between high and low dose rates may im¬ prove the clinical results. The survival achieved with very low dose rate 125I implants in the up-front treatment of malignant gliomas is comparable to or even better than the results obtained in patients treated with temporary high-activity l25I implants. The rationale of this approach involves the addition of a daily “boost” of EBRT to the protracted long-term radiation delivered by the per¬ manent implant. This daily boost makes it possible to reach the critical dose rate required in fast-growing tumors such as GBM while minimizing the risk of radionecrosis. The need for EBRT in treating AA is questionable if one considers the excel¬ lent results obtained in the group treated with permanent implants alone. Technical details such as the use of 3D dosimetry become critical, especially in deep lesions, allowing optimization of the radiation distribution (maximal radiation to tumor volume and reduction of the dose to the surrounding normal brain). Lesions involving midline and eloquent areas are amenable to implan¬ tation with the dosimetry proposed in this chapter. Short time of hospitalization, no need for isolation after surgery, and lower cost are other advantages of permanent implants. Although this is a small population study, the results strongly suggest that permanent implants can be an effective model of treatment of primary malignant brain tumors, and should be further evalu¬ ated and optimized.

12.

13.

14. 15.

16.

17.

18.

19.

20.

21.

22.

23.

References 1. 2.

3.

4.

5.

6.

7.

8.

9. 10.

11.

Bernstein M, Gutin PH: Interstitial irradiation of brain tumors: Areview. Neurosurgery 9:741-750, 1981. Salazar OM, Rubin P, Feldstein ML, Pizzutiello R: High dose radia¬ tion therapy in the treatment of malignant gliomas: Final report. Int J Radiat Oncol Biol Phys 5:1733-1740, 1979. Walker MD, Strike TA, Sheline GE: An analysis of dose-effect rela¬ tionship in the radiotherapy of malignant gliomas. Int J Radiat Oncol Biol Phys 5:1725-1731, 1979. Walker MD, Alexander E Jr, Hunt WE, et al: Evaluation of BCNU and/or radiotherapy in the treatment of anaplastic gliomas. J Neurosurg 49:333-343, 1978. Leibel SA, Gutin PH, Wara WM, et al: Survival and quality of life af¬ ter interstitial implantation of removable high-activity iodine-125 sources for the treatment of patients with recurrent malignant gliomas. Int J Radiat Oncol Biol Phys 17:1129-1139, 1989. Loeffler JS, Alexander E III, Wen PY, et al: Results of stereotactic brachytherapy used in the initial management of patients with glioblastoma. JNCI 82:1918-1921, 1990. Loeffler JS, Alexander E 111, Hochberg FH et al: Clinical patterns of failure following stereotactic interstitial irradiation for malignant gliomas. Int J Radiat Oncol Biol Phys 19:1455-1462, 1990. Zamorano L, Yakar D, Dujovony M, et al: Permanent iodine-125 im¬ plant and external beam radiation therapy for the treatment of malig¬ nant brain tumors. Stereotact Fund Neurosurg 59:183-192, 1992. Florell RC, MacDonald DR, Irish WD, et al: Selection bias, survival and brachytherapy for glioma. J Neurosurg 76:179-183, 1992. Zamorano L, Yakar D, Dujovny M, et al: Permanent iodine-125 im¬ plant and external beam radiation therapy for the treatment of malig¬ nant brain tumors. Stereotact Fund Neurosurg 59:183-192, 1992. Zamorano L, Dujovny M, Yakar D. et al: Multiplanar image-guided stereotactic brachytherapy with iodine-125, in Dyck P, Bouzaglou A (eds): Neurosurgery: State of the Art Reviews. Philadelphia: Hanley & Belfus, 1989, pp 95-103.

24. 25.

615

Zamorano L, Nolte L, Jiang C, Kadi M: Image-guided neurosurgery: Frame-based and frameless approaches, in Rengachary SS, Wilkins RH (eds): Neurosurgical Operative Atlas. Park Ridge, IL: American Association of Neurological Surgeons, 1993, vol 3, pp 403M22. Mundinger F: Die interstitielle Radioisotopenbestrahlung von Hirntumoren mit vergleichenden Langzeitergebnissen zur Rontgentiefentherpit. Acta Neurochir (Wien) 11:89-109, 1964. Chun M, McKeough P, Wu A, et al: Interstitial iridium-192 implanta¬ tion for malignant brain tumors. Br J Radiol 62:158-162, 1989. Loeffler J: Stereotaxic radiosurgery for metastases and malignant gliomas. Second Symposium on Stereotactic Treatment of Brain Tumors, New York, February 28-March 1, 1991, pp 45M6. Bernstein M, Laperriere N, Leung P, McKenzie S: Interstitial brachytherapy for malignant brain tumors: Preliminary results. Neurosurgery 26:371-380, 1990. Gutin PH, Prados MD, Phillips TL, et al: External irradiation fol¬ lowed by an interstitial high activity iodine-125 implant “boost” in the initial treatment of malignant gliomas: NCOG study 6G-82-2. Int J Radiat Oncol Biol Phys 21:601—606, 1991. Selker RG, Eddy MS, Arena V: Pittsburgh brachytherapy experience. Second Symposium on Stereotactic Treatment of Brain Tumors, New York, February 28-March 1, 1991, pp 23-24. Lucas GL, Luxton G, Cohen D, et al: Treatment results of stereotactic interstitial brachytherapy for primary and metastatic brain tumors. Int J Radiat Oncol Biol Phys 21:715-721, 1991. Prados MD, Gutin PH, Phillips TL, et al: Interstitial brachytherapy for newly diagnosed patients with malignant gliomas: The UCSF ex¬ perience. Int J Radiat Oncol Biol Phys 24:593-597, 1992. Stea B, Kittelson J, Cassady JR, et al: Title treatment of malignant gliomas with interstitial irradiation and hyperthermia. Int J Radiat Oncol Biol Phys 24:657-667, 1992. Zamorano L, Bauer-Kirpes B, Dujvony M, Yakar D: Dose planning for interstitial irradiation, in Kelly P (ed): Computers in Stereotactic Neurosurgery. Cambridge: Blackwell, 1992, pp 280-291. Scharfen CO, Sneed PK, Wara WM, et al: High activity iodine-125 interstitial implant for gliomas. Int J Radiat Oncol Biol Phys 24:583-591, 1992. Sneed PK, Gutin PH, Prados MD, et al: Brachytherapy of brain tu¬ mors. Stereotact Fund Neurosurg 59:157-165, 1992. Malkin MG: Interstitial irradiation of malignant gliomas. Rev Neurol

26.

(Paris) 148:448^153, 1992. Marin L, Smith C, Langston M, et al: Response of glioblastoma cell lines to low dose rate irradiation. Int J Radiat Oncol Biol Phys

27.

2L397M02, 1991. Williams J, Zhang Y, Dillehay L: Sensitization processes in human tumor cells during protracted irradiation: Possible exploitation in the

28. 29.

30.

31.

32.

33.

34.

clinic. Int J Radiat Oncol Biol Phys 24:699-704, 1992. Orton C: Recent developments in time-dose modelling. Australas Phys Eng Sci Med 14:57-64, 1991. Alexander E III, Loeffler JS, Schwartz RB, et al: Thallium-201 technetium-99m HMPAO single-photon emission computed tomography (SPECT) imaging for guiding stereotactic craniotomies in heavily ir¬ radiated malignant glioma patients. Ada Neurochir (Wien) 122:215-217, 1993. Arbit E, Shapiro JR, Fiola M, et al: The significance of morphologi¬ cally viable glioma cells found at the time of operation after intersti¬ tial brachytherapy. Neurosurgery 32:105-110, 1993. Herbold G, Hartmann GH, Lorenz WJ: The influence of mineralising radionecrosis on the dose distribution in interstitial radiation therapy of brain tumours. Radiother Oncol 25:12-18, 1992. McLaughlin P, Mancini W, Stetson P, et al: Halogenated pyrimidine sensitization of low-dose-rate irradiation in human malignant glioma. Int J Radiat Oncol Biol Phys 26:637-642, 1993. Coffey RJ, Lunsford LD, Bissonette D, Flickinger JC: Stereotactic gamma radiosurgery for intracranial vascular malformations and tu¬ mors: Report of the initial North American experience in 331 pa¬ tients. Stereotact Fund Neurosurg 54, 55:535-540, 1990. Ling CC, Chui CS: Stereotactic treatment of brain tumors with ra¬ dioactive implants or external photon beams: Radiobiophysical as¬ pects. Radiother Oncol 26:11-18, 1993.

CHAPTER

72

FRACTIONATED HIGH-DOSE-RATE BRACHYTHERAPY FOR GLIOMA

Shiao Y. Woo, Walter H. Grant, Philip L. Gildenberg, E. Brian Butler, Barry Berner, L. Steven Carpenter, Hsin H. Lu, W. Sam Dennis, J. Kam Chiu, and Lois Friedman

The benefit of surgical resection and postoperative external-beam radiotherapy in the treatment of high-grade gliomas has been well documented in clinical trials.1 However, for the majority of pa¬ tients, while the treatment prolongs life, the therapy is not cura¬ tive and the tumor usually recurs at or adjacent to the primary site.2 Currently, the total external-beam radiation dose that can be delivered safely without causing severe morbidity to the normal brain surrounding the tumor is still too low to sterilize the tumor. Since the probability of significant radiation-induced neurological morbidity is a function of the total dose of irradiation as well as of the volume of brain irradiated, the morbidity could theoretically be lowered by reducing the volume of brain irradiated using the technique of brachytherapy. Conventionally, the isotopes used for brain brachytherapy have been iodine 125, iridium 192, and gold 198, which deliver a low-dose-rate (LDR) irradiation at 40 to 50 cGy per hour. The term low dose rate is used in contrast to the usual high-dose-rate (HDR) external-beam irradiation at 150 to 300 cGy per minute. Studies using brachytherapy for recurrence or for residual primary high-grade gliomas after surgery and ex¬ ternal-beam irradiation have demonstrated prolongation of me¬ dian survival and acceptable morbidity.3,4 It is, however, known that the biological effect of LDR irradiation is different from that of HDR irradiation. Most of the biological studies done in past decades used HDR teleradiotherapy. HDR brachytherapy iridium 192 sources are now available, making it possible to investigate the combined effect on brain of the biology of HDR irradiation and the physics of brachytherapy technique. At the Baylor College of Medicine, the Methodist Hospital, and St. Luke’s Episcopal Hospital, we have developed a pilot program and a phase I protocol to study fractionated HDR brachytherapy for recurrent glioblastoma. In the study, we at¬ tempted to follow the principles of fractionated HDR radiother¬ apy and at the same time minimize the volume of irradiation by

mm in diameter. The small diameter of this source allows the source to be passed through a small 21-gauge needle.

CATHETER SYSTEM The catheters are placed into the tumor using a CRW headframe and stereotactic technique under magnetic resonance imaging (MRI) guidance. A standard silicone rubber catheter employed for LDR brachytherapy is used. This type of catheter, however, is not suitable for an HDR source because the surface tends to grab the source wire instead of allowing for a smooth catheter. We therefore place a flexi-needle made of Hitrel polyester inside the silicone rubber catheter. The flexineedle is glued into position. The open end of the flexi-needle has a special connector for attachment to the HDR unit.

TREATMENT PLANNING A major advantage of HDR brachytherapy is that the planning computer runs an optimization routine to alter the dwell time at various source locations to generate a dose distribution pattern prescribed by the operator. There is therefore a degree of flexi¬ bility in treatment planning that allows the neurosurgeon to find the safest route to insert the catheters into the tumor with¬ out placing the catheters strictly parallel to and at fixed dis¬ tances from one another. By altering the dwell time of the vari¬ ous source positions, one can in general overcome the nonideal placement of the catheters and still generate isodose curves that follow the shape of the tumor.

IMPULSE WAVE

using a brachytherapy technique.

A concern of the neurosurgeon is the possibility of tissue injury arising from the motion of the wire traveling at 13 cm/s as it enters the brain. As part of the preclinical study, force gener¬ ated by the wire motion was measured by using an accelerome¬ ter weighing 2.5 g. The measurements showed a maximum force less than 1 g in 1.3 s for the nickel-titanium wire. This

HDR UNIT The HDR unit we used contains a nominal 10-curie iridium 192 source that is 1 cm in length and is sealed in a wire 0.57

617

618

Part 3/Stereotactic Radiotherapy

force was considered to be far below the threshold for brain injury.

PHASE I STUDY From July 1992 to September 1993, 11 patients with recurring glioblastoma were entered into the phase I study. Three dose levels were used: (1) 2500 cGy (two patients), (2) 4000 cGy (four patients), and (3) 5000 cGy (five patients). We used 250 cGy per fraction, delivered twice per day, 8 h apart, over 8 to 15 days. Morbidity was assessed by using the Radiation Therapy Oncology Group (RTOG) central nervous system toxicity score during treatment, by infectious event, and by developing radi¬ ographically and/or pathologically proven brain necrosis on fol¬ low-up, as well as the serial Karnofsky Performance Scale and steroid dose requirement. Overall, the treatment was very well tolerated. No significant morbidity was encountered during treatment of the 2500-cGy and 4000-cGy groups. However, three of the five patients who received 5000 cGy had a transient increase in seizure and a transient change in mental status. Two patients had scalp wound infections. Most of the patients were steroid-dependent, although one patient was able to come off steroids for 2 months and another came off steroids completely. One patient in the 2500-cGy arm, two patients in the 4000-cGy arm, and two patients in the 5000-cGy arm developed the radi¬ ographic and clinical appearance of necrosis, and in all but one patient extensive necrosis with some tumor cells was found dur¬ ing reoperation. Survival ranged from 2 months to 16 months, with four patients still surviving.

CONCLUSION Fractionated HDR brachytherapy for high-grade glioma is fea¬ sible and tolerable. The flexibility of the treatment-planning program gives the neurosurgeon a degree of freedom to choose the route of insertion of the catheter with the hope of avoiding major vessels and eloquent parts of the brain. The result of the phase I study suggests that a suitable dose for a future phase II study is 4000 cGy in 16 fractions over 1.5 weeks. Other areas that could be investigated with this tech¬ nique include the combination of HDR brachytherapy with ex¬ ternal-beam radiotherapy as a primary treatment of glioma and the combination of radiosensitizers and HDR fractionated brachytherapy.

References 1.

Walker MD, Green SB, Byar DP. et al: Randomized comparisons of ra¬ diotherapy and nitrosoureas for the treatment of malignant gliomas af¬ ter surgery. N Engl J Med 303:1323-1329, 1980.

2.

Garden AS, Maor MH, Yung WK, et al: Outcome and patterns of fail¬ ure following limited-volume irradiation for malignant astrocytomas. Radiother Oncol 20:99-110, 1991.

3.

Leibel SA, Gutin PH. Wara WM, et al: Survival and quality of life after interstitial implantation of removable high-activity Iodine-125 sources for the treatment of patients with recurrent malignant gliomas. Int J Radial Oncol Biol Phys 17:1129-1139, 1989.

4.

Prados MD, Gutin PH, Phillips TL, et al: Interstitial brachytherapy for newly diagnosed patients with malignant gliomas: The UCSF experi¬ ence. Int J Radial Oncol Biol Phys 24:593-597, 1992.

CHAPTER

73

INTERSTITIAL RADIOSURGERY

G. Rees Cosgrove and Nicholas T. Zervas

Shortly after the discovery of radium in 1898, Curie suggested to Danlos that that radioactive isotope could be inserted di¬ rectly into a tumor, resulting in a beneficial effect.1 Since that time, interstitial irradiation has been used in many different or¬ gan systems for the treatment of neoplasia. With the introduc¬ tion of stereotactic techniques in neurosurgery, it became possi¬ ble to place radioactive sources accurately into brain tumors, and the term brachytherapy (therapy at short range) was intro¬ duced to differentiate this procedure from standard long-range external radiation treatment (teletherapy). At the same time, radiosurgical techniques using focused external beams were de¬ veloped for the treatment of small intracranial lesions. In both instances, the therapeutic objective is to deliver a high dose of radiation to a discrete, well-defined volume with minimal ex¬ posure to the surrounding brain structures. This chapter describes the use of a miniature lowenergy x-ray generator that can be placed stereotactically into intracranial tumors to deliver a single fraction of high-dose in¬ terstitial radiation in less than an hour. The physical character¬ istics of this novel intracranial radiosurgical device are de¬ scribed, along with the preliminary experience in 10 patients as well as possible future clinical applications.

DEVICE DESCRIPTION The Photon Radiosurgery System (PRS) is a miniature lowenergy x-ray source that can deliver a prescribed therapeutic

radiation dose directly to small brain lesions.2 The underlying technology was developed by Photoelectron Corporation of Waltham, MA, and was tested by researchers at the Massachusetts General Hospital, Harvard Medical School, and the Massachusetts Institute of Technology. The device weighs 3.8 lb and is designed to be compatible with current stereotac¬ tic frames. It is powered by a 9.6-V rechargeable nickelcadmium battery with a step-up converter that can amplify the voltage supplied by the battery to 40 kV. An internal electron gun creates a 40-pA electron beam 0.5 mm wide that is accel¬ erated through a high-voltage field (range, 15 to 40 kV in 5-kV increments). The beam next passes through deflection coils to control the beam position and then travels down an evacuated magnetically shielded rigid probe 3 mm in diameter and 100 mm in length (Fig. 73-1). At the probe tip, the electron beam strikes a thin gold foil target (0.5 |x), producing a spectrum of x-ray photons whose effective energies are in the range of 10 to 20 keV. The gold foil is thick enough to stop the electrons but thin enough to allow the x-rays generated to pass through. The last 20 mm of the probe tip is constructed from beryllium, which is transparent to these low-energy x-ray photons. The x-rays are emitted from the tip in a spherically symmetrical pattern, resulting in a dose rate in tissue of up to 120 Gy per hour at a 10-mm radius. Since over 99 percent of the energy created by the electron collisions with the gold foil is in the form of heat and less than 1 percent is generated as x-rays, it is important to exclude hyperthermia as a possible tumoricidal

Figure 73-1. Internal diagram of the PRS demonstrates high-voltage (HV) converter components and the electron gun (x-ray tube). Electrons are accelerated through the high-voltage field and pass through beam deflectors before traveling down the evacuated probe shaft to strike a gold foil target at the tip.

619

620

Part 3/Stereotactic Radiotherapy

factor. The power of the electron beam was therefore limited to keep the temperature at the tumor margin at less than 40°C. Because the photons generated by the PRS are low-energy, their absorption characteristics are different from those of typi¬ cal brachytherapy sources. These “soft x-rays” are attenuated rapidly within tissue, and a dose decline rate of approximately 1/R3 is obtained instead of the 1/R2 seen with standard higherenergy interstitial irradiation sources. The resultant 30 percent dose reduction per millimeter of unit tissue creates an ex¬ tremely steep dose falloff (Fig. 73-2), allowing as much as 35 Gy/h to be administered to a 30-mm-diameter lesion with a minimal dose to the scalp and a safe dose rate to personnel more than 2 m away from the probe when it is inserted in a patient. Background exposure has generally been measured at

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T3 3 D = 75 degrees to 4> = -75 degrees. Thus, each degree of couch rotation corre¬ sponds to 2 degrees of gantry rotation. Several successive posi¬ tions through which the gantry and the couch move during the complete stereotactic irradiation procedure are shown in Fig. 82-3, starting (A) with the gantry and couch angles of 30 de¬ grees and 75 degrees, respectively, and proceeding through (B) 90 degrees and 45 degrees, respectively, (C) 180 degrees and 0 degrees, respectively, (D) 270 degrees and —45 degrees, respectively, and (£), stopping with the gantry at 330 degrees and the couch at —75 degrees. During the stereotactic irradiation procedure, the radiation beam always points toward the isocenter, which is in the target volume. The beam entry trace on the patient’s head, however, exhibits a peculiar trace (baseball seam) (Fig. 82-4). Points A, B, C, D, and E on the beam entry trace correspond to beam en¬ try locations for the gantry and couch angles given in Fig. 82-3, A through E, respectively. Note that all the points of the beam entry lie in the upper hemisphere of the patient’s head; this re¬ sults in all the beam exit points lying in the lower hemisphere. This means that in dynamic irradiation, even though all beams intersect at the target volume and the gantry travels almost a full circle (300 degrees), there never is a parallel-opposed beam

722

Part 3/Stereotactic Radiotherapy

Figure 82-2.

Patient on treatment couch with the OBT stereotactic frame and target localization plates.

situation to degrade the steepness of the dose falloff outside the target volume. Dynamic irradiation provides dose falloffs outside the target volume similar to those of the multiple converging arcs tech¬ nique1213 and the gamma unit.14 However, in comparison with multiple converging arcs techniques, the dynamic technique represents a more elegant and less demanding approach to stereotactic irradiation if the LINAC is in excellent mechanical condition and an automated couch rotation link with the gantry rotation as well as appropriate treatment-planning hardware and software are available. The tumor dose rates achieved in the arc therapy mode on our LINAC are on the order of 1 Gy/min to 5 Gy/min. Given these rates and the target doses used in stereotactic irradiation, which are in the range of 10 Gy to 25 Gy for single-session ir¬ radiations, a typical treatment session lasts 10 to 30 min per isocenter used. Fractionated treatments with prescribed target doses on the order of several Gy last only a few minutes per each isocenter.

Radiation Protection Irradiation of tissues outside the target volume directly by the primary beam, through scatter from the primary beam, and through leakage from the LINAC head is of concern because of the potential for somatic (cancer induction) and genetic effects, especially in treating benign lesions in young patients. On our LINAC, the surface doses produced in dynamic stereotactic ir¬ radiation by the primary beam are less than 1 percent of the tar¬ get dose, obviating concern about epilation. The low surface dose results from the skin-sparing effect of the 10-MV mega¬ voltage beam combined with the large surface area over which the beam entry points are spread. In situations where the radia¬ tion beam pattern passes through the lens of the eye. which is at a depth of about 5 mm, the lens dose exceeds the surface dose and amounts to about 2.5 percent of the target dose. For cur¬ rently used target doses, this is well below the cataract forma¬ tion threshold and therefore is not of much concern.

Measured scatter and leakage doses to various radiosensi¬ tive organs of a typical patient are similar for dynamic stereo¬ tactic irradiation7 and the gamma unit,14 amounting to 0.2 percent of the target dose at the thyroid, 0.06 percent at the breast, and 0.02 percent at the gonads. Thus, for a typical target dose prescription of 25 Gy in the treatment of intracranial vas¬ cular disorders, the patient receives 0.05 Gy to the thyroid, 0.015 Gy to the breast, and 0.005 Gy to the gonads. Although these are not negligible doses, the risks that they will cause so¬ matic or genetic defects are much lower than the risks to the patient of leaving the disease untreated. The doses quoted above are for single-isocenter treatments and do not hold true in treatments with multiple isocenters. The surface dose in multiple-isocenter treatments generally re¬ mains the same as in the one-isocenter case except that the dose is spread out over a larger surface area. The dose to the eye lens resulting from multiple isocenters is unlikely to be af¬ fected by more than one beam trajectory; however, the possi¬ bility that two or more trajectories will cross the lens should be considered and the crossover should be avoided with care¬ ful treatment planning. The scatter and leakage doses to radia¬ tion-sensitive organs exhibit a cumulative effect in treatments with multiple isocenters. The larger the number of isocenters, the higher the dose to radiation-sensitive organs and the asso¬ ciated risk of somatic and genetic effects. This should be kept in mind when treatment plans with a large number of isocen¬ ters are proposed.

TREATMENT PLANNING General Considerations Treatment planning with stereotactic irradiation is in certain re¬ spects simpler and in other respects more complicated than treatment planning with standard radiotherapy. For example, the treatment fields used in stereotactic irradiation are circular and have very small diameters; therefore, corrections for oblique beam incidence generally are not required. Tissue

Chapter 82/Dynamic Stereotactic Irradiation: Physical Aspects, Treatment Planning, and Clinical Applications

723

Figure 82-3.

Several successive positions through which the gantry and the couch move during the dynamic stereotactic irradiation procedure. Gantry and couch angles: A, 30 degrees and 75 degrees, respectively; B, 90 degrees and 45 degrees; C, 180 degrees and 0 degrees; D, 270 degrees and —45 degrees; and E, 330 degrees and —75 degrees.

180

0| = 30° | = 75°

0 = 90° 4) » 45°

0 = 180° = 0°

0 = 270° 70, weeks

% Local Failure

% Neurological Deaths

43 40 40 49

34 38 36 36

NS 20 11 11

33 29 17 18

NOTE: The patients in the two radiosurgery studies fit the eligibility criteria employed by the University of Kentucky study. NS = not stated.

Stereotactic radiation techniques (brachytherapy and radio¬ surgery) have been incorporated as techniques to “boost” fulldose external-beam radiation (-6000 cGy). Stereotaxy allows escalation of the total dose of radiation to areas of greatest tu¬ mor cell density (enhancing regions on CT and MRI) without irradiating excessive volumes of normal brain tissue immedi¬ ately outside the target volume.44 Stereotactic irradiation pro¬ vides an adjunct to local (larger static) field irradiation; alone, it cannot be expected ultimately to control nonfocal or infiltrating disease processes.45 Uncontrolled prospective studies (Table 84-7) from the University of California at San Francisco (UCSF) and the .(CRT suggest that high-activity l25I brachytherapy results in significantly improved survival.46-47 The encouraging results from the brachytherapy experiences of UCSF, JCRT, and the Brain Tumor Cooperative Group (BTCG) led us to consider ra¬ diosurgery as a technique tor focal dose escalation in malignant glioma patients.45 Since the dose distributions of radiosurgery and brachytherapy are similar, they therefore appear to have the same potential for improving survival. A summary of results of each boost technique is presented in Table 84-10, which shows that median survivals measured from the time of diagnosis are 11 to 22 months. Reoperation to remove symptomatic radiation necrosis, recurrent tumor, or both was often required with either boost technique.52 Brachy¬ therapy doses were prescribed according to institutional proto¬ cols and were not dependent on target volume. Radiosurgery doses were prescribed according to protocol and were based on lesion location and volume.

toma multiforme treated with either brachytherapy (32 pa¬ tients) or radiosurgery (86 patients) at the JCRT between December 1985 and July 1993.53 Median tumor volumes were 10.1 cm- and 29 cm' for radiosurgery and brachytherapy, re¬ spectively. Initially, brachytherapy was recommended for these recurrent tumors, with radiosurgery being reserved for smaller tumor volumes or tumor in nonimplantable sites. However, with further experience, radiosurgery became the preferred treatment except with larger or irregularly shaped tumors. Twenty-one patients (24 percent) treated with SRS were alive with a median follow-up of 17.5 months. Median actuar¬ ial survival for all patients treated with radiosurgery was 10.2 months, measured from the time of treatment at recurrence. Twelve- and 24 month survivals were 45 percent and 19 per¬ cent, respectively. Younger age and smaller tumor volume were predictive of longer survival. Survival was unrelated to tumor dose, interval after initial diagnosis, and need for reoperation. Comparison of results between patients treated with radio¬ surgery and those who received brachytherapy indicated simi¬ lar survival. Nineteen patients (22 percent) required stereotactic reopera¬ tion after radiosurgery compared with 14 (44 percent) in the brachytherapy group. Actuarial risk for reoperation was 33 per¬ cent at 12 months and 48 percent at 24 months after radio¬ surgery compared with 54 percent and 65 percent, respectively, after brachytherapy (p = .195) Patients undergoing reoperation after brachytherapy survived longer than did similar patients not undergoing reoperation. Survival after SRS was independent of reoperation status. An example of the radiographic results after radiosurgery for a glioblastoma is shown in Fig. 84-4.

Recurrent glioblastoma Radiosurgery and brachytherapy have also been used in pa¬ tients with recurrent glioblastoma (Table 84-11). We recently completed an analysis of 118 patients with recurrent glioblas¬

TABLE 84-10.

Newly diagnosed malignant gliomas Typically, patients considered “eligible" for radiosurgery boost protocols have a Karnofsky Performance Scale (KPS) above 70

Stereotactic Radiation Boost for Primary Glioblastoma Multiforme

Institution

Boost Technique

Boost Dose,* Gy

No. Patients

UCSF46 BTCGt40 Harvard47 Wisconsin50 Harvard51

l25I brachytherapy l25I brachytherapy l25I brachytherapy Radiosurgery Radiosurgery

52.9 60 50.0 12.0 12.0

106 125 56 50 69

*Median dose to tumor periphery. t87% of patients had glioblastoma multiforme: others had anaplastic astrocytoma.

Median Survival, months 22 16 18 11 19.7

Reoperation Rate, % 38 50 64 10 38

Chapter 84/Clinical Experience with LINAC Radiosurgery

percent, radiographically discrete tumors measuring less than 4 cm in greatest diameter, and no evidence of subependymal spread. In our experience, only 20 percent of patients with newly diagnosed glioblastoma meet the eligibility criteria for boost protocols involving radiosurgery or brachytherapy. More aggressive initial surgery may increase the number of eligible patients. We recently reviewed our experience at JCRT using radio¬ surgery as an adjunct to surgery and full-dose external-beam

753

radiotherapy.51 Between May 1988 and April 1994, 69 patients (median tumor volume, 9.3 cm3) with glioblastoma were treated using radiosurgery (median dose, 1200 cGy) within 4 weeks of external-beam radiotherapy (5940 cGy in 33 fractions). To be eligible, patients had to have a KPS of 70 percent or greater, a tumor volume less than 4 cm3, and no evidence of multifocality or subependymal spread. Chemotherapy was not part of the formal protocol although six patients received postradio¬ surgery chemotherapy at the referring physician’s request. These

Figure 84-4. A. Stereotactic CT scan obtained for radiosurgery planning. The patient is a 31-yearold man with recurrent right frontal glioblastoma multiforme. Brachytherapy was recommended, but the patient refused. He was treated with 1650 cGy prescribed to the 85 percent isodose line. B. Follow-up CT scan done 3.5 months after radiosurgery showing increased enhancement and edema. The patient underwent stereotactic resection of the enhancing lesion. C. Histological sections demonstrated necrotic tissue sharply demarcated from adjacent areas of gliosis. D. At follow-up 3 months after reoperation, the patient was asymptomatic off steroids, and this CT revealed decreased edema and enhancement.

754

Part 3/Stereotactic Radiotherapy

TABLE 84-11.

Stereotactic Radiation for Recurrent Glioblastoma Multiforme

Institution

Boost Technique

Dose,* Gy

Harvard53 UCSF46 Harvard53

l25I brachytherapy l25I brachytherapy Radiosurgery

50 64.4 13.0

No. Patients 32 66 86

Median Survival, months

Reoperation Rate, %

11.5 12 10

44 38 22

^Median dose to tumor periphery.

patients represented approximately 20 percent of the glioblas¬ toma patients evaluated for the protocol. Patients were followed at 3-month intervals with complete neurological examinations and CT/MRI studies. Functional MRI and/or dual isotope (tech¬ netium 99m and thallium 201 Cl) single photon emission com¬ puted tomography (SPECT) studies were often used to differen¬ tiate tumor recurrence from radiation necrosis.54 55 The median survival for the whole group measured from the time of pathological diagnosis was 19.7 months (range, 6 to 60 or more months). Reoperation was required for progressive symptomatic mass effect in 38 percent of these patients. At the time of reoperation, most patients were found to have a combi¬ nation ot “treated” tumor cells and necrosis. In a multivariate analysis, younger age [p = .011) and higher dose (p = .045) were the only factors predicting prolonged survival. Patients who underwent a reoperation for symptomatic mass effect en¬ joyed an improved quality of life and were maintained on lower doses of steroid support. However, reoperation alone did not confer an improvement in survival (p = .952). A more de¬ tailed analysis of the role of reoperation is required. The treatment of patients with malignant gliomas with com¬ bination lull-dose external-beam radiotherapy and radiosurgery boost results in superior overall median and 2-year survival in comparison with external-beam radiotherapy alone (in patients with similar prognostic features). In addition, the results of ra¬ diosurgery appear similar to those reported from BTCG, UCSF, and JCRT using l25I brachytherapy, with less attendant morbid¬ ity (Fig. 84-5). In summary, radiosurgery and brachytherapy produce simi¬ lar survival rates in recurrent and newly diagnosed patients with glioblastoma.52-53 The development of symptomatic radia¬ tion necrosis requiring prolonged steroid support and reopera¬ tion is the same for both stereotactic radiation techniques. Ihus, radiosurgery is a more appealing technique than brachytherapy in the management of highly focal malignant gliomas because it is a noninvasive single-day procedure.

Pediatric Brain Tumors The delivery ol precisely localized radiation that spares the de¬ veloping nervous system makes radiosurgery particularly ap¬ pealing for children with benign and malignant brain tumors.56 Even with aggressive therapy, many children with central ner¬ vous system (CNS) tumors die because of the inability to estab¬ lish local control. A recent study from the Children’s Hospital in Boston showed that 5-year freedom from progressive dis¬ ease in patients with completely resected ependymoma and postoperative radiotherapy was 75 percent compared with

0 percent for patients with postoperative gross residual tumor who received radiotherapy.57 Because of the markedly reduced survival rates for patients with radiographically apparent post¬ operative or posttherapy residual disease, many centers are in¬ vestigating the use of radiosurgery as a boost for these patients on institutionally approved protocols.58,59 The early results from the JCRT (56 patients) indicate that local control can be achieved in the majority of patients with focally recurrent ependymoma and medulloblastoma but that most patients eventually succumb to disseminated CNS dis¬ ease.60 Reoperation after radiosurgery for symptomatic mass effect was common (50 percent) in children treated for recur¬ rent posterior fossa ependymoma. This was not the case for children with medulloblastoma, whose radiobiological behav¬ ior is similar to that of patients with metastatic tumors, with a very low reoperation rate. The Pediatric Oncology Group (POG) is conducting a pilot study (protocol 9373) using radiosurgery for children with re¬ current or metastatic intracranial tumors. Children with recur¬ rent lesions 30

36 166 107 19 13 24

No. with Weakness 1 8 16 4 3 10

more on the estimated length of nerve irradiated than on the tu¬ mor dose or tumor volume. Hemifacial spasm induced by the treatment was seen in 2 percent (11 of 530) of the Stockholm patients. It was not a har¬ binger of facial weakness. It started 2 to 11 months after the treatment and was always temporary. The only exception was a 34-year-old female with a 1.8-cm tumor in whom the spasm started 2 years after the GKR and showed slow gradual pro¬ gression over several years. The tumor size remained com¬ pletely unchanged, but because of the spasm, the patient had the tumor removed 11 years after the radiosurgery.29 The relative importance of the different factors influencing facial nerve function after GKR is not clear. The gradually in¬ creased accuracy that has accompanied improved imaging techniques and dose-planning systems and some reduction in the dose has contributed to reducing the risk of temporary fa¬ cial nerve dysfunction to 5 to 10 percent and more recently to less than 2 percent.14

Trigeminal Nerve There was one patient with a slight temporary facial hypoesthesia in the earliest 1969-1974 series of nine patients. The inci¬ dence was 30 percent (12 of 40 patients) in the period 1975-1980, with a reduction to 8 percent (6 of 71) in 1989-1990. This delayed trigeminal neuropathy appeared on average 6.8 months (range, 1 to 19 months) after the treatment. The Pittsburgh group reported delayed trigeminal nerve dysfunction in 32 percent (21 of 66 patients) during the first 3 years of operation.19 Currently, less than 2 percent of the pa¬ tients are affected by this disturbance, which is almost invari¬ ably slight.14 The factors of importance for the development of trigeminal neuropathy seem to be the same as those involved in causing facial nerve dysfunction. There are, however, a few differences. For obvious anatomic reasons, the trigeminal root is at risk of developing spontaneous signs of compression and neuropathy related to the radiosurgical treatment only when the tumor has an intracranial diameter of approximately 15 mm or more. The fifth nerve also shows less of a propensity to recover than does the facial nerve. This was especially evident in four early pa¬ tients with total or subtotal loss of trigeminal nerve function in 1975 and 1976.20 No improvement could be detected in these patients, and one of them actually developed deafferentiation pain. Slight to moderate trigeminal dysfunction was usually re¬

% with Weakness 2 5 15 21 23 42

No. with EMG Only 1 9 13 1 0 0

% with EMG Only 2 5 12 5 0 0

versible even if careful examination sometimes revealed minute signs of facial sensory disturbance up to several years after the treatment.

Cochlear Nerve Unilateral tumors When GKR was presented as a new technique, relatively little attention was paid to hearing and its preservation. Early studies frequently showed initial preservation followed by gradual hearing loss over a period of a few to several years after the treatment.30 Most of this loss tended to occur in the first year, possibly indicating delayed cochlear nerve injury induced by the treatment, especially when higher radiation doses were used. With a more protracted, gradual deterioration over sev¬ eral years, degenerative changes in the cochlear nerve and the organ of Corti that were secondary to cochlear nerve degenera¬ tion and were initiated by the tumor and not halted by the treat¬ ment were the more likely mechanisms.31 A third type of reac¬ tion—an immediate marked impairment of cochlear nerve function—was seen in a small number of patients. Such sudden deafness within 24 h of radiosurgery occurred in a total of 0.7 percent (3 of 452) of patients with unilateral tumors and 2.2 percent (3 of 136) of patients with NF2 tumors. As for microsurgical techniques, the requirements and ex¬ pectations have gradually increased, and today, with up to a 95 percent growth control rate of acoustic tumors and a clinical in¬ cidence of facial neuropathy less than 2 percent, hearing preservation has become a factor of increasing importance. In contrast to microsurgery, it does not take a lot of extra effort and time to plan the treatment to optimize the chance of pre¬ serving hearing. In a recent study, 20 acoustic tumor patients with use¬ ful hearing, defined as Gardner-Robertson class I or II (Table 90-2), remained in those classes in 45 percent of cases 1 and 2 years after radiosurgery.32-33 No further hearing loss was ob¬ served beyond 2 years. In our 1989-1990 series, among a total of 71 patients, 16 had hearing corresponding to Gardner-Robertson class I or 11 before the treatment, 75 percent (12 of 16 patients) 1 year later, and 60 percent (9 of 15) 2 years after the treatment. Three of these 16 patients (19 percent) had class III hearing 1 and 2 years after the radiosurgery. More recent results have shown that hearing tends to remain relatively unchanged over the first

Chapter 90/Gamma Knife Radiosurgery for Acoustic Neurinomas

TABLE 90-2. Hearing Classification According to Gardner and Robertson

Class

Pure Tone Average (dB), 0.5,1.0, 2.0 kHz

Speech Discrimination Score, %

I II III IV V

0-30 31-50 51-90 91-maximum loss No response

70-100 50-69 5^19 1^1 No response

841

(range, 4 to 72 months). There was no useful hearing (class V) in the other two ears. Four ears in class III all remained stable throughout this period. We have found it useful to create a dose plan for NF2 acoustic tumors in which the dose maximum (“hot spot”) in the tumor is moved away from the center, usually posteriorly (Fig. 90-4). Also, a somewhat lower general dose level is prescribed, usually 10 Gy to the periphery with a maximum of 20 Gy at the center. The rationale is to minimize the risk of hearing loss induced by the treatment and consequently give the patient a longer period of stable hearing. The disadvantage is the probably somewhat higher risk of lack of response of the tumor.

source: Modified from Gardner and Robinson.32

Tinnitus 2 years after the treatment in 70 to 75 percent of patients with unilateral tumors. Forty-four patients with unilateral tumors treated between 1991 and 1994 with hearing corresponding to class I or II had hearing in the same classes in 75 percent (33 of 44 patients) 1 year later. Among the 17 patients with 2-year follow-up results available, 71 percent (12 of 17) had hearing corresponding to class I or II. These results probably are corre¬ lated to improved imaging and dose-planning accuracy, which have allowed an increasingly tight fit between the configuration of the radiation and the target. Dexamethasone 2 to 4 mg two to four times per day for a week, tapering to zero over the following week or longer as re¬ quired, was frequently effective in arresting and improving the symptoms of delayed cochlear nerve dysfunction induced by the treatment.

NF2

TUMORS

NF2 tumors constitute a special problem. Whereas the seventh and eighth nerves are confined to the tumor surface in unilat¬ eral cases, the fascicles of these nerves sometimes cross straight through the tumor in NF2 neurinomas.34 The implica¬ tion of this is obviously that the radiation dose in the central part of a unilateral tumor is relatively unimportant in regard to cranial nerve function, whereas an overly high central dose may induce hearing loss in NF2 tumors even if the dose to the periphery is “normal” or below normal. Early experiences in the preservation of hearing in NF2 pa¬ tients were unrewarding, with hearing loss frequently to com¬ plete deafness occurring in most of these patients. In a consec¬ utive series of 20 NF2 patients with 24 tumors treated in Stockholm from 1969 to 1984, impairment of hearing occurred in 18 ears with any degree of hearing before treatment. Eight of these ears became completely deaf. The Pittsburgh group had similar experiences in its 19 NF2 tumors, with none of the five ears with Gardner-Robertson class I to II hearing before radio¬ surgery remaining in the same classes after the treatment and only two of them remaining in class III.26 The tumors were treated with a radiation dose of 14 to 20 Gy (median, 18 Gy) to the periphery and a maximum of 28 to 40 Gy (median, 33 Gy) to the center. Fourteen of the patients with NF2 tumors treated in Stockholm from 1989 to 1994 had some amount of hearing be¬ fore treatment, in nine ears corresponding to GardnerRobertson class I to II. Hearing remained stable within these classes in seven ears (78 percent) an average of 24 months later

Tinnitus is a common symptom of retrocochlear disease in acoustic tumor patients. Sometimes there is no or only very lit¬ tle concomitant hearing loss. The tinnitus normally remains un¬ affected by radiosurgery, although some patients claim that they experienced improvement within a few years of the treat¬ ment. Whether this is a real decrease of intensity or an adap¬ tation to a stable condition cannot be assessed easily. Approximately 1 percent of these patients experienced a clini¬ cally important increase in tinnitus after radiosurgery.

Vestibular Nerve Little documentation exists concerning the effect on vestibular nerve function of GKR. On inquiry, a majority of acoustic tu¬ mor patients admitted having some balance disturbance before the treatment. The complaint was usually that of a tendency to veer while walking or a short period of vertigo-disorientation when turning the head too fast. Few of these patients seemed to have problems of significant clinical importance, and they usu¬ ally were able to ski or ride a bicycle without difficulty. On caloric testing and electronystagmography, the vestibular nerve function tended to deteriorate after radiosurgery.35 In the Stockholm material, in a total of six patients (after approxi¬ mately 1 percent of the procedures), the treatment induced marked to severe temporary (from a week up to several months) aggravation of the balance disturbance. The Pittsburgh group found some imbalance-ataxia in 62 percent (58 of 92) of acoustic tumor patients before treatment.19 Among these patients, 22 percent reported that their symptoms were worse and 14 percent reported that their balance had im¬ proved after radiosurgery. Ten patients in the same study with normal preoperative balance reported worsened balance after radiosurgery.

Peritumoral Reaction A peritumoral reaction characterized by low-attenuation signal changes on CT and T,-weighted MRI and high signal changes on T..-weighted MRI was seen in 7 percent (18 of 255) of these patients from 1980 to 1990, when CT generally was used for follow-up. A reaction was detected in 4 percent (7 of 159 pa¬ tients) in 1991 through 1994, when the more sensitive MRI had become the standard follow-up imaging technique, but the radi¬ ation dose was generally lower and the imaging and dose plan¬ ning were more accurate. The onset of these postradiosurgical

842

Part 3/Stereotactic Radiotherapy

Figure 90-4. Gadolinium-enhanced -weighted axial MRI with superimposed dose plans (Leksell GammaPlan) for (A) a 2.2-cm right-sided unilateral acoustic neurinoma and (B) a 2.5-cm left-sided acoustic neurinoma in a patient with NF2. (A) A dose of 12 Gy was prescribed to the 40 percent isodose line corresponding to the tumor margin for the unilateral tumor. Also included are the 60 percent and 80 percent isodose levels. (B) For the NF2 tumor, a dose of 10 Gy was prescribed to the 50 percent isodose line at the tumor periphery. The 70 percent and 90 percent isodose levels are added to show that the radiation dose to the anterior and midportion of the tumor was kept low to reduce the risk of injury to any intratumoral cochlear nerve fibers in that area. Each cross corresponds to one isocenter (“shot”): 12 in A and 30 in B. The crosses “outside” the tumor are located within the tumor volume at other levels. Note for each case the precise correspondence between the selected isodose line and the margin of the tumor.

changes occurred on average 5.9 months (median, 6 months; range, 1 to 10 months) after the treatment. This reaction usually involved the middle cerebellar peduncle and the cerebellar hemisphere and less often involved the pons. This peritumoral reaction sometimes is referred to as edema, swelling, or parenchymal changes adjacent to the tumor.19 The increasing incidence empirically seems to be related to higher radiation dose and larger tumor volume, although no statistically signifi¬ cant correlations were found by the Pittsburgh group. There was no doubt a high incidence of changes in the Stockholm material in the mid-1970s, when very high radiation doses were used. Similarly, there was no incidence when the tumors were small or completely or mainly intracanalicular, when the radiation dose to the peduncle and the pons clearly was low. However, other factors are involved in determining the inci¬ dence of peritumoral reactions. The type of imaging is of spe¬ cial importance. T2-weighted MRI is much more sensitive in detecting even such subtle reactions than is ^-weighted MRI or CT. T2-weighted MRI is in fact so sensitive that small changes are frequently subclinical. With larger volume and ex¬ tension, which rarely occur with today’s dose-planning strate¬ gies, the patient may experience some temporary dizziness and balance disturbance. For the same reason, the development of hydrocephalus is not induced by today’s limited peritumoral re¬

actions, since they need to be extensive to obliterate the cere¬ brospinal fluid (CSF) pathways.

CSF Circulation Impairment of the CSF circulation, resulting in hydrocephalus and necessitating a shunt operation, may occur because of me¬ chanical blockage or changed quality of the CSF induced by the tumor. Some of these tumors caused a marked (up to 15fold) increase in the CSF protein concentration that was as¬ sumed to interfere with CSF reabsorption. Other mechanisms, so far unknown, were possibly also involved, since not all pa¬ tients had elevated protein levels and few tumors were large enough to block the CSF pathways mechanically. The maxi¬ mum intracranial tumor diameter ranged between 1.4 and 3.7 cm (median, 2.6; mean, 2.5 cm) in these patients. Hydro¬ cephalus directly or indirectly caused by the tumor was seen in 9.2 percent (40 of 434) of the patients: 3.0 percent (13 of 434) was in men and 6.2 percent (27 of 434) was in women. More than half of these patients (24 of 40) required a shunt before the radiosurgical procedure. Hydrocephalus also may develop after swelling of tissues induced by the radiosurgical treatment adjacent to the tumor. Such a peritumoral reaction, which was extensive enough to

Chapter 90/Gamma Knife Radiosurgery for Acoustic Neurinomas

block the CSF circulation and require the insertion of a shunt, occurred in 1.4 percent (6 of 434) of the patients.36

Pain The disabling headaches sometimes noted after microsurgery, especially with the suboccipital-retrosigmoid approach, have not been observed after GKR. Another not rare but sometimes overlooked complaint in acoustic tumor patients is the sensation of local “pressure” or “headache” in or around the external auditory canal on the af¬ fected side. The exact incidence is not well known. Some 10 percent of our patients seemed to experience this sponta¬ neously before treatment. After GKR, approximately 10 per¬ cent more of the patients developed a period of pressure or, less frequently, sharp pain in or around the ear, usually starting 1 to 3 months after the treatment and lasting for several weeks up to a few months. Standard analgesics usually gave adequate pain relief, although steroids (dexamethasone) sometimes were added with good effect. The mechanism responsible for this pain is not known. It may be induced by irritation of pain fibers in the dura.

GAMMA KNIFE RADIOSURGERY VERSUS MICROSURGERY Microsurgery for acoustic tumors has reached a high level of perfection, especially in the hands of a relatively small group of skillful and experienced neurosurgeons and neurootological surgeons. To reach acceptance, any alternative to microsurgery should offer similar results in terms of tumor control and/or eradication and preservation of cranial nerve function. Additional features should make it a better choice than micro¬ surgery for different groups of patients. Most modern microsurgical series have had a rate of com¬ plete tumor removal close to 100 percent for small to mediumsize acoustic tumors.37 Radiosurgery offers a rate of growth control of 95 percent for tumors with an intracranial diameter up to 3 cm.23-37 The rate of immediate facial weakness (H-B grade II to VI) after microsurgery in tumors up to 3 cm seems to be approxi¬ mately 50 percent.37 The long-term (usually > 1 year) follow¬ up rate is 0 to 35 percent, correlated to tumor size. The total in¬ cidence of facial weakness after radiosurgery is currently less than 5 percent at experienced centers.14 Postoperative trigeminal dysfunction that was not present before is rarely mentioned in microsurgical literature. In a re¬ cent study from a center of excellence, permanent postopera¬ tive trigeminal symptoms occurred in 11 percent of the pa¬ tients.37 Like facial weakness, new facial numbness after radiosurgery is becoming increasingly rare, with an incidence currently of less than 5 percent and approaching 0 percent.14 Preservation of any degree of hearing in microsurgery has been reported in up to 50 to 60 percent of patients after removal of selected small (usually ^ 1.5 cm) acoustic tumors and in 70 to 80 percent of patients with intracanalicular tumors if the suboccipital/retrosigmoidal or middle fossa approach is used.38-39 The long-term preservation may be less favorable. In patients undergoing GKR, hearing is preserved unchanged or almost

843

unchanged in 75 percent for at least the first couple of years af¬ ter treatment.23,33 Shunt placement is seldom reported after microsurgery. It occurred, however, in 6 percent of the patients in one study.40 Nine percent (9.2 percent) of gamma knife patients had a shunt inserted—5.5 percent before and 3.7 percent after the radio¬ surgery—because of hydrocephalus induced by the acoustic tu¬ mor. Peritumoral swelling caused by the treatment and result¬ ing in hydrocephalus was seen in 1.4 percent of these patients. The risks of CSF leak, intracranial infection, and hemor¬ rhage after microsurgery are eliminated with radiosurgery. The hospital stay is short, usually a day and a night, and the recov¬ ery period is a matter of a few days rather than several months. Most acoustic tumors with a maximum intracranial size up to 3 cm qualify for GKR. Possible exceptions include situa¬ tions when there are signs of increased intracranial pressure, where the choice is between excision of the tumor and radio¬ surgery plus a shunt. The patient’s condition, age, and personal preferences are of importance in making the final decision. In patients with tumors with an intracranial diameter of 2 cm or more and with clinical signs of trigeminal nerve in¬ volvement, on rare occasions the facial numbness is so pro¬ nounced that it is almost painful. In that situation, the trigemi¬ nal nerve must be decompressed without too much delay, and consequently, excision of the tumor usually is a better choice than radiosurgery. Except for local unavailability, there are few reasons why GKR should not be considered instead of micro¬ surgery for most acoustic neurinoma patients, including young and otherwise healthy individuals. The fact that the tumor is literally removed at microsurgery and not at radiosurgery is frequently better accepted by the pa¬ tient than by the surgeon. Traditionally, surgical treatment is defined as successful if the tumor has been removed com¬ pletely. Other standards have to be adopted in evaluating the re¬ sults of GKR. It has sometimes been reported that acoustic tumors that do not respond to radiosurgery and in which microsurgery was se¬ lected as the second treatment were more difficult to remove with preservation of the surrounding nerves and other struc¬ tures.29 The relationship between the tumor and these structures varies within wide limits even without prior radiosurgery. Also, it does not seem logical that radiosurgery should stimulate the formation of scar tissue outside a tumor when a higher dose of radiation to the tumor itself was not enough to induce a response to the treatment. Different surgeons have expressed widely dif¬ fering experiences in this area. The extent to which this is a problem induced by radiosurgery remains to be clarified. A potential risk with radiosurgery, as with any kind of radia¬ tion, is the induction of new tumors in the future. On the basis of clinical data and theoretical considerations, the risk level seems to be extremely low, less than 1 per 1000.37 41 This is hardly a reason to withhold GKR from young individuals who prefer radiosurgery to microsurgery.

CONCLUSION The data in this presentation indicate that approximately 95 per¬ cent of unilateral acoustic neurinomas show signs of growth control after GKR. The nonresponding tumors show up early (5 years after the treatment)

844

Part 3/Stereotactic Radiotherapy

are extremely unlikely to occur. There is no risk of intracranial bleeding or infection as a consequence of the treatment. Disturbance, usually temporary, of facial and trigeminal nerve function occurs in less than 5 percent of these patients. A ma¬ jority of the patients retain unchanged or almost unchanged hearing for several years. Because of the efficacy and low overall risks, GKR is a treatment for medically infirm patients who cannot undergo microsurgery and also for anyone, re¬ gardless of age and general health, who prefers GKR to an open surgical procedure. With few exceptions, acoustic neuri¬ nomas with an intracranial size up to approximately 3 cm are suitable for GKR.

18.

Noren G, Greitz D, Hirsch A, Lax I: Gamma knife radiosurgery in acoustic neurinoma, in Steiner L (ed): Radiosurgery: Baseline and Trends. New York: Raven Press, 1992, pp 141-148.

19.

Linskey ME, Lunsford LD, Flickinger JC, Kondziolka D: Stereo¬ tactic radiosurgery for acoustic tumors. Neurosurg Clin North Am 3:191-205, 1992.

20.

Noren G, Arndt J, Hindmarsh T: Stereotactic radiosurgery in cases of acoustic neurinoma: Further experiences. Neurosurgery 13:12-22, 1983.

21.

Anniko M, Arndt J, Noren G: The human acoustic neurinoma in organ culture: II. Tissue changes after gamma irradiation. Acta Otolaryngol (Stockh) 91: 223-235, 1981.

22.

Noren G: Gamma knife surgery in acoustic neurinomas, in Samii M (ed): Skull Base Surgery. Basel: Karger, 1994, pp 877-879. Noren G, Karlbom A, Brantberg K, et al: Gamma knife radiosurgery for acoustic neurinomas. Neurosurgeons (Tokyo) 14:159-163, 1995. Noren G, Leksell L: Stereotactic treatment of acoustic tumours, in Szikla G (ed): Stereotactic Cerebral Irradiation. Amsterdam: Elsevier/North-Holland, 1979, pp 241-244.

23. 24.

References 25.

Hall EJ: Radiobiology for the Radiologist, 3d ed. Philadelphia: Lippincott, 1988. pp 107-136.

26.

Linskey ME, Lunsford LD, Flickinger JC: Tumor control after stereo¬

1.

House WF, Luetje CM (eds): Acoustic Tumors. Baltimore: University Park Press, 1979, vol 1, pp 25-32.

2.

Leksell L: Hjarnfragment (brain fragments), in Steiner L (ed): Radiosurgery: Baseline and Trends. New York: Raven Press, 1992, pp 263-292.

27.

3.

Leksell L: The stereotaxic method and radiosurgery of the brain. Acta Chir Scand 102:316-319, 1951.

28.

Linskey ME, Flickinger JC, Lunsford LD: Cranial nerve length pre¬ dicts the risk of delayed facial and trigeminal neuropathies after acoustic tumor stereotactic radiosurgery. Int J Radiat Oncol Biol Phys 25:227-233, 1993.

29.

Slattery WH III, Brackmann DE: Results of surgery following stereotactic irradiation for acoustic neuromas. Am J Otol 16: 315-319, 1995.

30.

Hirsch A, Noren G, Anderson H: Audiologic findings after stereotac¬ tic radiosurgery in nine cases of acoustic neurinomas. Acta Otolaryn¬ gol (Stockh) 88:155-160, 1979. Jahnke K, Neuman TA: The fine structure of vestibular end organs in acoustic neuroma patients, in Tos M, Thomsen J (eds): Acoustic Neuroma. Amsterdam: Kugler, 1992, pp 203-207. Gardner G, Robertson JH: Hearing preservation in unilateral acoustic neuroma surgery. Ann Otol Rhinol Laryngol 97:55-66, 1988. Ogunrinde OK, Lunsford LD, Flickinger JC, Kondziolka D: Stereotactic radiosurgery for acoustic nerve tumors on patients with useful preoperative hearing: Results at 2-year follow-up examination. J Neurosurg 80:1011-1017, 1994. Linthicum FH: Unusual audiometric and histologic findings in bilat¬ eral acoustic neuromas. Ann Otol Rhinol Laryngol 81:433-437, 1972. Bergenius J, Hessen L, Perols O, Nor6n G: Vestibular follow-up in acoustic neurinoma patients treated with stereotactic radiosurgery, in Haid CT (ed): Vestibular Diagnosis and Neuro-Otosurgical

3a. Leksell L: Stereotaxic radiosurgery in trigeminal neuralgia. Acta Chir Scand 137:311-314, 1971. 4.

Leksell L: Stereotaxis and Radiosurgery: An Operative System. Springfield, IL: Thomas, 1971.

5.

Wallner KE, Sheline GE, Pitts LH, et al: Efficacy of irradiation for in¬ completely excised acoustic neurilemmomas. J Neurosurg 67: 858-863, 1987.

6.

7.

8. 9. 10.

11. 12.

Andrews DW, Silverman CL, Glass J, et al: Preservation of cranial nerve function after treatment of acoustic neurinomas with fraction¬ ated stereotactic radiotherapy. Stereotact Fund Neurosurg 64: 165-182, 1995.

31.

Mendenhall WM, Friedman WA, Bova FJ: Linear accelerator-based stereotactic radiosurgery for acoustic schwannomas. Int J Radiat Oncol Biol Phys 28:803-810, 1994. Nordn G, Collins VP: Stereotactic biopsy in acoustic tumors. Appl Neurophysiol 43:189-197, 1980. Bergstrom M, Greitz T: Stereotaxic computed tomography. AJR 127:167-170, 1976.

33.

Leksell L, Lindquist C, Adler JR, et al: A new fixation device for the

34.

Leksell stereotactic system: Technical note. J Neurosurg 66:626-629, 1987.

35.

Leksell L: A note on the treatment of acoustic tumours. Acta Chir Scand 137:763-765, 1971. Bachofer CS, Gautereaux ME, Kaack SM: Relative sensitivity of iso¬ lated nerves to “Co gamma rays, in Haley TJ, Snider RS (eds): Response of the Nervous System to Ionizing Radiation. Boston: Little, Brown. 1964, pp 221-242.

32.

36.

13.

DiTullio MV, Malkasian D, Rand RW: A critical comparison of neu¬ rosurgical and otolaryngological approaches to acoustic neuromas. J Neurosurg 48:1-12, 1978.

37.

14.

Nordn G, Greitz D, Hirsch A, Lax 1: Gamma knife surgery in acoustic tumours. Acta Neurochir (Wien) 58:104-107, 1993. Gruskin P, Carberry J: Pathology of acoustic tumors, in House WF,

38.

15.

16. 17.

Luetje CM (eds): Acoustic Tumors. Baltimore: University Park Press, 1979, vol l,pp 85-148. Laasonen EM, Troupp H: Volume growth rate of acoustic neurino¬ mas. Neuroradiology 28:203-207, 1986. Valvassori GE, Guzman M: Growth rate of acoustic neuromas. Am J Otol 10:174-176, 1989.

39. 40.

41.

tactic radiosurgery in neurofibromatosis patients with bilateral acoustic tumors. Neurosurgery 31:829-839, 1992. House JW, Brackmann DE: Facial nerve grading system. Otolaryngol Head Neck Surg 93:146-147, 1985.

Management of the Skull Base. Grafelfing: Demeter, 1991, pp 48-50. Thomsen J, Tos M. Borgesen SE: Gamma knife: Hydrocephalus as a complication of stereotactic radiosurgical treatment of an acoustic neuroma. Am J Otol 11:330-333, 1990. Pollock BE, Lunsford LD, Kondziolka D, et al: Outcome analysis of acoustic neuroma management: A comparison of microsurgery and stereotactic radiosurgery. Neurosurgery 36:215-229. 1995. Glasscock ME III. Hays JW, Minor LB. et al: Preservation of hearing in surgery for acoustic neuromas. J Neurosurg 78:864-870. 1993. Haines SJ, Levine SC: Intracanalicular acoustic neuroma: Early surgery for preservation of hearing. J Neurosurg 79:515-520, 1993. Wiegand DA, Fickel V: Acoustic neuroma—the patient's perspective: Subjective assessment of symptoms, diagnosis, therapy, and outcome in 541 patients. Laryngoscope 99:179-187, 1989. Noren G: Stereotactic Radiosurgery in Acoustic Neurinonms: A New Therapeutic Approach. Thesis, Stockholm, 1982.

CHAPTER

91

RADIOSURGERY FOR PITUITARY TUMORS

Jeremy C. Ganz

croadenomas can be made, because this is a crucial distinction in radiosurgery. The classical definition is that a microadenoma has a diameter of 10 mm or less, while a macroadenoma is more than 10 mm in diameter.5 It will be seen below that there is a distinction between larger and smaller microadenomas. It is difficult to determine an absolute size limit here because, as will be seen, the significance of the size of a microadenoma is also related to the individual anatomic relationships in a partic¬

This chapter describes the use of the gamma knife in the treat¬ ment of pituitary adenomas. This machine is a sophisticated piece of equipment that delivers an exquisitely accurate radia¬ tion dose to a precisely defined volume of tissue in a single session; this is the basis of the definition of radiosurgery.1 The machine uses a cross-firing technique in which 201 narrow collimated beams emanating from 201 cobalt 60 sources placed around the surface of a hemisphere cross each other at a focal point, which is thus surrounded by a region of high ra¬ diation dose.2,3 Outside this region there is a rapid fall in dose and dose rate, because the energy in the individual beams is low. The beams must be narrow to achieve an acceptably steep gradient of falling dose beyond the limits of the target. The location of the target at the focal point is achieved through the use of stereotactic technique. With targets of complex shape, a variety of maneuvers may be employed to sculpt the dose to fit the target; a level of sophistication that only the gamma knife can offer. These maneuvers include blocking some of the beams, using beams with different di¬ ameters, and dividing the dose into multiple shots placed at different locations.4 However, before discussing the role of the gamma knife, there are other matters to consider first. No account of the radiosurgery of pituitary adenomas would be complete without mention of the results of particle beam focused-radiation techniques. Moreover, if the role of radio¬ surgery is to be assessed, an account of the results of micro¬ surgery and medical methods is also necessary, to place the radiosurgical results in perspective. For this to be done before describing the methods of treatment, it is first necessary to consider the aims of radiosurgery.

ular patient.

Macroadenomas The primary aim with macroadenomas is to regain or at least preserve vision.6,7 While radical removal is also a goal, it is al¬ ways a matter of judgment in the individual case as to how far to continue an operation. Once the vis-ual pathways are ade¬ quately decompressed, radicality can increase the risk of surgery, and there are other treatment methods available, in¬ cluding the use of radiation. Adequacy of treatment is judged in relation to pre- and postoperative visual function and imaging studies.

Microadenomas The aim with microadenomas is to remove the tumor, but be¬ cause it is necessary to control the endocrinopathy that resulted in the detection of the tumor, radicality is more important. Happily, this is more achievable for smaller tumors than for larger ones.8-19 The degree of urgency in correcting an en¬ docrinopathy varies according to the type. Untreated Cushing’s disease was said in the older literature to have a mortality of 100 percent over 5 years.20 Moreover, patients with Cushing’s disease are almost invariably subjectively extremely unwell.21 Acromegaly is believed to reduce life expectancy,14,18,21-24 and in addition it produces a variety of distressing symp¬ toms. Microprolactinomas of themselves represent little threat to life but are of great importance in relation to fer¬ tility. Nonetheless, more recent literature has drawn attention to the risk of osteopenia in the presence of persistent hyper¬ prolactinemia.20,25 Adequacy of treatment in these tumors is related far more to correction of the endocrinopathy and preservation of normal pituitary function than to changes

AIMS OF TREATMENT Although it is an oversimplification, there are two main aims of treatment in respect to pituitary adenomas. The first is to re¬ move a neoplastic process whose continued growth can threaten vision, endocrine function, mental function, and in ex¬ treme cases cerebrospinal fluid circulation. The second aim is to control the overproduction of a hormone. While the two aims overlap, particularly in the case of prolactin-producing tu¬ mors, on the whole tumors that present with hormone overpro¬ duction tend to be smaller than are those which do not. For the sake of clarity, a simple division into macroadenomas and mi¬

845

846

Part 3/Stereotactic Radiotherapy

detected on magnetic resonance imaging (MRI) or computed tomography (CT). Indeed, with microadenomas, postopera¬ tive imaging techniques are not easy to interpret in many cases.

The End Point of Treatment The end point of successful treatment after surgery has been indicated to be removal or substantial volume reduction as viewed on computerized imaging techniques or the correction of an endocrinopathy. The end point of radiosurgery is the same in regard to the hormonal disturbance. However, in re¬ gard to tumor volume, cessation of further growth has be¬ come a widely accepted indicator of successful treatment.2,3 This applies particularly to acoustic schwannomas but also to meningiomas and pituitary adenomas. Obviously, tumor shrinkage is preferred, but it is assumed that until the contrary is proved, cessation of further growth means tumor control. Nonetheless, everyone in the radiosurgical field is aware that to be thoroughly reliable, this control must be lifelong. At present it is too early to have a final opinion on this matter. However, there has been no consistent reporting to date of any benign tumor category that shows early cessation of growth followed by recurrence at a later stage. Instead, if con¬ tinued growth is to occur, it tends to be an early process. Thus, the radiosurgical milieu continues with cautious and ever-observant optimism in respect to the significance of its necessarily early findings. Having considered the aims of treatment, the next step is to examine the success of the different treatment methods in achieving these aims. The first technique to merit attention is that of particle beam focused irradiation.

TECHNIQUES OF PARTICLE BEAM FOCUSED RADIATION Pituitary tumors have been treated with focused-radiation techniques since the 1950s. Indeed, the findings with these methods stimulated the application of the gamma knife for the treatment of Cushing’s disease in the 1970s. The ierm fo¬ cused-radiation techniques is used advisedly in that some of the methods employ fractionation, thus falling outside the strict definition of radiosurgery. However, these results are relevant because it could be argued that with a small number of fractions employed, the method has more in common with staged surgery than with traditional radiotherapy. These tech¬ niques involve the use of particle accelerators. Today, by far the greatest number of patients treated with focusedradiation techniques have been treated with either He+ ions or protons. However, the results with these techniques are to some extent difficult to interpret. The major reporting has come from the Lawrence Berkeley Laboratories in California and the Harvard Medical School in Boston. Different tech¬ niques have been used by the two centers. The results are de¬ scribed below for individual endocrinopathies. It should be noted that these results are reported in terms of the en¬ docrinopathies rather than in terms of the effect on the neo¬ plastic process per se.

Cushing’s Disease In Berkeley, a multiple He+ ion beam crossover* technique was employed, with a dose of 50 to 150 Gy in three to five frac¬ tions.3,26-28 Forty of 42 patients are said to have been cured of Cushing’s disease, but there is a lack of precise detail con¬ cerning the endocrinologic basis for cure. Kjellberg,3 using a 160-MeV cyclotron to perform single-session Bragg peak treatment, achieved a 75 percent “cure” after 5 years. Again, the basis for determining cure is not detailed.

Acromegaly Three hundred eighteen patients were treated in Berkeley with the He+ ion beam crossover technique, using four fractions over 5 days with a dose of 30 to 50 Gy.1-3,26,27 Improvement that increased over the subsequent 10 years was achieved in most patients. However, reduction of growth hormone (GH) below a given acceptable normal level has not been recorded. At Harvard, 80 percent of 577 acromegalic patients treated with a single session of proton beams, using the Bragg peak,+ achieved a fall of GH to below 5 ng/ml over 10 years.3 However, the basis for these data is a personal communication, and the dose is not quoted.

Prolactinomas The Berkeley group achieved a normalization of prolactin with focused He+ ion therapy in 12 of 20 patients followed for 1 year, which is a short follow-up.3 The achievement of these techniques should not be underes¬ timated. They represent a huge body of patients, the majority of whom have been clearly improved by the treatment, which has proved to be very safe. The difficulty with assessing the role of these techniques today has to do with changing conceptions of excellence. When the techniques were introduced, they were revolutionary and could have been claimed to represent one of the best alternatives. However, rapid advances in microsurgery in the last two decades have changed the standard by which the treatment of pituitary microadenomas is judged. In this context, the basis for the assessment of an adequate endocrinologic re-

'A crossover technique uses fine beams directed toward a target from dif¬ ferent directions. The individual beams have low energy, so that a region of high radiation dose is achieved only where the beams cross each other. The beams may be all directed at the same time, as in the gamma knife. Alternatively, they may be directed successively to build up the radiation field. This is the technique employed with the linear accelerator (LINAC) and with particle accelerators. It is necessary to use fine beams if a satisfac¬ tory dose fall is to be achieved outside the target volume. ’The Bragg peak technique applies only to particle irradiation techniques. Particles have mass and can decelerate, in contrast with electromagnetic ir¬ radiation, Particle beams have relatively low energy when the particles move at high speed. This means that there is little dose deposition in the tis¬ sues during this part of their passage. However, at a depth within the tissue that is dependent on the energy of the beam, the particles decelerate, and in this region there is a high deposition of the radiation dose within a region called the Bragg peak, after its discoverer. The dose fall outside this region is very sharp along the direction of the beam, though it is less sharp in other directions.

Chapter 91/Radiosurgery for Pituitary Tumors

suit relates to relevant absolute measures of hormone produc¬ tion. Percentage improvement is not accepted as the basis of a successful surgical result. Moreover, successful microsurgery produces an immediate cure. The long delay between treatment and endocrinologic improvement with radiosurgery is not ac¬ ceptable to many referring endocrinologists today. Because of these uncertainties related to particle beam therapy in its cur¬ rent form, the rest of this chapter will concentrate on the use of the gamma knife. However, before this is considered, a short account of the results of other methods is necessary to provide a basis for comparison. This account will also include macro¬ adenomas, which were not included in the description of the particle beam techniques.

RESULTS OF SURGERY WITH AND WITHOUT FRACTIONATED RADIOTHERAPY Macroadenomas Improvement in vision has been consistently reported after transsphenoidal surgery, which is today’s standard.6,29-31 In a representative series of 200 patients with visual disturbance de¬ rived from a larger group of 1000 tumors, the results were 81 percent with improvement, 16 percent unchanged, and 3 per¬ cent with deterioration.6 The aim of tumor control is less well met, being between 50 and 85 percent.29,32,33 This indicates that surgery alone is unsatisfactory in the long term despite the good short-term improvement in visual function, which led to the prophylactic use of radiotherapy in the past. In one of the more recent series involving for the most part tumors more than 2 cm in diameter, there was control of tumor growth in 68 of 70 patients thus treated. The treatment consisted of a threefield technique, delivering an overall 45 Gy in fractions of 1.8 Gy. However, these authors no longer advise prophylactic treatment in view of the reliability and safety of modem imag¬ ing techniques, so that radiotherapy is reserved today for pa¬ tients with proven tumor recurrence. The reasons are not far to seek in view of the frequency of postradiation hypopituitarism, which can be expected in 50 percent of patients in the long term. Other complications have been described but probably are avoidable if the size of the fraction is kept to 1.8 Gy, the total dose does not exceed 45 Gy (there is no evidence of in¬ creased therapeutic advantage with higher doses), and the radi¬ ation technique is optimized to avoid cerebral damage.

Microadenomas The results vary according to the type of microadenoma treated. Each has its own particular problems. In Cushing’s disease, many tumors are deduced from the en¬ docrinologic abnormality without radiological verification. The degree of certainty can be increased by using the invasive tech¬ nique of petrous sinus venous sampling. The determination of postoperative success can be difficult, and the patients require steroid replacement many months after surgery; even up to a year. There is a spread of results, which is in the main related to

847

comparing large with small series. In recent large series, suc¬ cess has been achieved 65 to 85 percent of cases.8,10,11,34,35 In general, failure has been related to invasive tumor, diffuse hy¬ perplasia, and negative findings.8,10,11 There is the definite but slight risk that hypophysectomy may be seen to be required in the absence of positive findings, with concomitant pituitary failure. Otherwise, pituitary failure is rare. Recurrence after successful surgery has been reported in 3.7 to 9.3 percent of cases.11,34-38 Radiotherapy has been disappointing, with success rates seldom exceeding 50 percent and with the risk of pituitary failure unacceptably high. In acromegaly, the specific problems are the larger size of the tumors and the difficulty of defining a cure, a matter that is a persisting source of controversy. Using a postoperative GH level Vv'v;v)VyV/V^V\4«»v v'-^Sv^V / \'^>'Vw*Vv\VY './S',-v‘.s/\a5'-a,j‘ ,*s*^,Av/V/V*v'’yA/S/v—'\f {*JS't*/1

v

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if -yA* /VWWa/'^nA*/

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Stimulating the spinal neuraxis has proved to be a viable treat¬ ment alternative for seemingly disparate neurological prob¬ lems, including the torticollis, trunk and extremity dystonia, spasticity, pseudobulbar dysfunction, and intractable epilepsy. Relief is the result of neuromodulation producing a restorative effect on the neuronal balance in a dysfunctioning nervous sys¬ tem. The underlying disease state is not altered; instead, the symptoms that result from the abnormalities of neurotransmis¬ sion or central processing are treated. The neuroaugmentation and/or attenuation from an electrical field applied to the spinal cord must be accomplished through a diffuse system that is in¬ fluenced by the stimulating electrodes. Such a system would

TABLE 113-10. Complications Observed in 1440 Patients Undergoing Spinal Cord Stimulation ~ ■*■■ ■*■*>*■ V//W*

Complications

Figure 113-17. A grossly abnormal preoperative EEG (upper) from a 15-year-old head injury patient with a spastic left hemiparesis and intractable seizures. After spinal cord stimulation, he not only was relieved of the left-sided spasticity with improved function but has remained totally seizure-free for 11.5 years. The improvement in his EEG (lower) is shown in a recording taken 1 year after stimulation was started. (From Waltz.17)

Mortality Transient cord compression Cerebrospinal fluid leak Pain Electrode displacement Infection Electrode disruption Receiver failure

n

%

0 2 3 10 21 46 122 136

0.0 0.1 0.2 0.7 1.5 3.2 8.5 9.4

Chapter 113/Chronic Stimulation for Motor Disorders

have to possess both ascending and descending elements in light of the significant effect of the electrode polarity on the clinical response. The system most likely to be affected, as we have postulated in the past, appears to be the reticular forma¬ tion. 15~17-31 More recently, Dimitrijevic and Faganel32 have im¬ plicated the reticular formation, which is the main lower center for extrapyramidal motor control. Neurons of the reticular for¬ mation are well suited for stimulation because of longitudinal arrangement between their most caudad and cephalad levels with long axons and numerous collaterals. The spinal cord level at which the reticular formation is stimulated, the polarity, the configuration of the applied electri¬ cal field, and the frequency of stimulation are crucial factors in achieving maximal therapeutic results and must be established on an individual basis. This can be done with the stimulation parameter flexibility afforded by the four-electrode (quadripolar) computerized system. Continued investigation into the possible neurophysiologi¬ cal mechanisms of the brain and spinal cord initiated or altered by SCS seems justified in light of the accumulated observa¬ tions over the past 20 years. More detailed research exploring the neurophysiological mechanisms of the applied field will lead not only to therapeutic specificity of the applied field but also to a more precise delineation of the underlying neuropathophysiological dynamics of these symptoms and disease states.

12.

13. 14.

15. 16.

1099

Dooley DM, Kasprak M, Stibitz M: Electrical stimulation of the spinal cord in patients with demyelinating and degenerative diseases of the central nervous system. J Fla Med Assoc 63:905-909, 1976. Gildenberg PL: Treatment of spasmodic torticollis by dorsal column stimulation. Rev Inst Nal Neurol 10:11-15, 1976. Waltz JM, Pani RC: Spinal cord stimulation in disorders of the motor system. Proceedings of VI International Symposium on External Control of Human Extremities, Dubrovnik, 1978, pp 545-556. Waltz JM, Reynolds LI, Riklan M: Multi-lead spinal cord stimulation for control of motor disorders. Appl Neurophysiol 44:244—257, 1981. Waltz JM: Surgical approaches to dyskinesias, in Marsden CD, Fahn S (eds): Neurology: Movement Disorders. London: Butterworth,

1982, vol 2, pp 300-307. Waltz JM: Computerized percutaneous multi-level spinal cord stimu¬ lation in motor disorders. Appl Neurophysiol 45:73-92, 1982. 18. Waltz JM, Andreesen WH: Multiple lead spinal cord stimulation tech¬ nique. Appl Neurophysiol 44:30-36, 1981. 18a. Waltz JM, Levita E, Riklan M: Psychological effects of spinal cord stimulation. Appl Neurophysiol 44:93-96, 1981. 18b. Waltz JM, Levita E, Sorkin B: Spinal cord stimulation revisited: Psychological effects. Appl Neurophysiol 49:69-75, 1986. 19. Waltz JM: Spinal cord stimulation in the treatment of dystonia. Dystonia Med Res Found Bull 4:2-8, 1980. 20. Waltz JM, Davis JA: Cervical cord stimulation in the treatment of athetosis and dystonia, in Fahn S, Caine D, Shoulson I (eds): Experimental Therapeutics of Movement Disorder. New York: Raven 17.

21. 22.

Press, 1983, pp 225-237. Waltz JM, Andreesen WH, Hunt DP: Spinal cord stimulation and mo¬ tor disorders. PACE Pacing Clin Electrophysiol 10:180-204, 1987. Gildenberg PL: Treatment of spasmodic torticollis by dorsal column

23.

stimulation. Appl Neurophysiol 41:113-121, 1978. Gildenberg PL: Comprehensive management of spasmodic torticol¬ lis: Seminar on spinal cord stimulation, New York, 1980. Appl Neuro¬

24.

physiol 44:233-243, 1981. Barolat G, Myklebust JB, Hemmy DC, et al: Immediate effects of spinal cord stimulation in spinal spasticity. J Neurosurg 62:558-562,

25.

1985. Barolat G, Myklebust JB, Wenninger W: Effects of spinal cord stimu¬ lation on spasticity and spasms secondary to myelopathy. Appl

J Neurosurg 32:560-564, 1970. Sweet WH, Wespic JG: Treatment of chronic pain by stimulation of fibers of primary afferent neuron. Am Neurol Assoc Trans 93:

26.

Neurophysiol 51:29—44, 1988. Barolat G: Epidural spinal cord stimulation in the management of spasms and spasticity in spinal cord injury. Neurosurgery 4:365-370,

4.

103-107, 1968. Wall PD, Sweet WH: Temporary abolition of pain in man. Science

27.

5.

155:108-109, 1967. Melzack R, Wall PD: Pain mechanisms: A new theory. Science

References 1.

2. 3.

Shealy CN, Mortimer JT, Reswick JB: Electrical inhibition of pain by dorsal column stimulation: Preliminary clinical report. Aneslh Analg 46:489-491, 1967. Shealy CN, Mortimer JT, Hagfors N: Dorsal column electroanalgesia.

150:971-979, 1965. Burton C: Seminar on dorsal column stimulation: Summary of pro¬ ceedings. Department of Neurosurgery, Temple University Health Sciences Center, Philadelphia. Surg Neurol 1:285-289, 1973. 6a. Burton CV: Safety and clinical efficacy. Neurosurgery 1:214-215,

28.

6.

29.

1989. Barolat G, Singh-Sahni K, Staas W Jr, et al: Epidural spinal cord stimulation in the management of spasms in spinal cord injury: A prospective study. Stereotact Fund Neurosurg 64:153-164, 1995. Campos RJ, Dimitrijevic MM, Faganel J, Sharkey PC: Clinical evalu¬ ation of the effect of spinal cord stimulation on motor performance in patients with upper motor neuron lesions. Appl Neurophysiol 44: 141-151, 1982. Richardson RR, McLone DG: Percutaneous epidural neurostimula¬ tion for paraplegic spasticity. Surg Neurol 9:153-155, 1978. Siegfried J, Krainick JU, Haas H, et al: Electrical spinal cord stimula¬ tion for spastic movement disorders. Appl Neurophysiol 41:134-141,

1977. Fox JL: Neuropacemaker for relief of intractable pain. Med Ann Dist

30.

8.

Colum 40:577-579, 1971. Hosobuchi Y, Adams JE, Weinstein PR: Preliminary percutaneous dorsal column stimulation prior to permanent implantation. J Neuro¬

1978. 30a. Waltz JM: Promising research. Am Para! Arsoc Prog Res 9:7-11,

9.

surg 37:242-245, 1972. Nashold BS Jr, Friedman H: Dorsal column stimulation for control of pain: Preliminary report on 30 patients. J Neurosurg 36:590-597,

31.

7.

10.

1972. Cook AW, Weinstein SP: Chronic dorsal column stimulation in multi¬

11.

ple sclerosis. NY Stale J Med 73:2868-2872, 1973. Cook AW: Stimulation of the spinal cord in motor neuron disease. Lancet 2:230-231, 1974.

32.

33.

1984. Waltz JM, Scozzari CA, Hunt DP: Spinal cord stimulation in the treat¬ ment of spasmodic torticollis. Appl Neurophysiol 48:324—338, 1985. Dimitrijevic MR, Faganel J: Spinal stimulation for the treatment of movement disorders, in Lazorthes Y, Upton A (eds): Neurostim¬ ulation: An overview. New York: Futura, 1985, pp 147—172. Waltz JM: Spinal cord stimulation in the treatment of neurologic dis¬ orders. Am J Electromed 2:28-29, 1987.

CHAPTER

114

CEREBELLAR STIMULATION FOR MOVEMENT DISORDERS

Ross Davis

Chronic cerebellar stimulation (CCS) applied to the superomedial cortex reduces spasticity and athetoid movements. Eighteen clinics have reported their experiences with 600 cere¬ bral palsy (CP) patients, who constitute 90 percent of those treated with CCS. CP patients have limited capabilities that are interfered with by primitive reflexes, spasticity, and athetoid movements. With CCS, their problems with drooling, speech, respiration, posture, motor performance, gait, joint range of motion, and mood states improve over 3 to 6 months. Radiofrequency (RF)-linked stimulators initially had serious equipment and calibration problems, yet 68 percent of 422 CP patients improved. When totally implantable controlled-current stimulators were used, 86 percent of 178 patients improved. A double-blind study of 20 patients using this implantable stimu¬ lator showed that 12 patients (60 percent) improved when the stimulator was on. When graded for abilities, the seven patients with the highest grades (5 to 8) all improved (99 percent confi¬ dence level). Experience has proved the continued efficacy and safety of CCS given by an implantable controlled-current source at a charge density of 1 to 4 |xC/cm2/phase at 150 to 200 Hz applied intermittently to the superomedial cerebellar cortex.

HISTORICAL REVIEW

stated that a QD of 7.4 is four to five times that required to evoke efferent activity in monkeys. They warned that without careful attention to the charge densities delivered to the cerebellar cor¬ tex, the conducting elements would be destroyed, eventually rendering the implanted cerebellar prosthesis ineffective. This would be expected when using QDs above 10 |xC/cm2/phase. From 1978 to 1981, Bloedel and associates9 examined fe¬ line motoneuron excitability after stimulation of the paravermal area and found that high-frequency stimulation produced profound reduction of the extensor motoneuron reflexes and a lesser reduction of the flexor reflexes; lower-frequency stimu¬ lation produced increased motoneuron excitability. Stimulation also significantly influenced the response of dorsal horn neu¬ rons activated by low-threshold cutaneous afferents. In 1980, Ebner and coauthors10 found that stretch reflexes in spastic monkeys decreased after paravermal area stimulation, depend¬ ing on the stimulus parameters. Stimulation at 50 Hz caused a slight reduction of the reflexes, with a progressively greater re¬ duction occurring with higher frequencies up to 200 Hz, which produced complete reduction. The stimulus charge density had to be above 1.3 |xC/cm2/phase to be effective. Supporting neuroanatomical, physiological, biochemical, and bioengineering studies of clinical series of CCS were pub¬ lished in 1984.11

In 1972, Cooper and associates2 first applied CCS to the human anterior lobe cerebellar cortex to activate the cerebellar in¬ hibitory output in patients with disorders of posture and move¬ ment secondary to stroke and CP and achieved a reduction in

CLINICAL EXPERIENCE Controversies developed in the late 1970s over the varying clinical results reported with CCS in 783 spastic patients with CP (90 percent), stroke, head injuries, asphyxia, and dystonia.12 Table 114-1 shows the results from 18 clinics reporting 600 CP patients of whom 568 (95 percent) were able to be followed, with 414 (73 percent) benefiting from decreased spasticity and increased performance. However, four of these clinics,1518 20'25 using RF stimulators, reported little if any effect on 32 CP pa¬ tients; two studies, each with 8 patients, were doubleblinded.15,25 Until 1979, only RF stimulators were available, and they were used by 17 clinics on 513 patients, 86 percent of whom suffered from CP. Table 114-1A reports 405 patients fol¬ lowed into the early 1980s by 15 clinics, with 276 (68 percent) benefiting. However, if all 513 implanted patients are consid¬ ered. the benefit rate for these 276 patients is 54 percent. The problems leading to the controversy appear to involve (1) the reliability of the available RF stimulators and the failure to cal¬ ibrate and check this equipment, (2) the effectiveness and

muscular hypertonus.

Animal Studies In 1897, Lowenthal and Horsley5 and Sherrington6 stimulated the superior cerebellar cortex of the anterior lobe in decerebrate animals to inhibit rigidity. In 1950, Moruzzi7 stimulated feline cerebellar cortex; high-frequency (200 to 300 Hz) stimulation reduced decerebrate ridigity, whereas low-frequency stimula¬ tion (5 to 15 Hz) increased it. It was not until 1977, 5 years after clinical studies had started and after an estimated 60 to 65 percent of them had been com¬ pleted, that Brown and colleagues1 reported the effects of CCS on monkey cerebellar cortex. They determined that a charge density (QD) [defined as (pulse current X pulse width) / catho¬ dal electrode surface] of 7.4 (xC/cnr/phase and below does not damage the cerebellum. Babb and associates8 also in 1977,

1101

1102

Part 4/Functional Stereotaxis

TABLE 114-1.

Cerebellar Stimulation in 600 Spastic Cerebral Palsy Patients - Improvement

Neurosurgery Centers

No. Patients

Follow-up

Benefit

None

Mild

Moderate/ Marked

19 59 8 5 1 7 13 3 3 1 4

30

3 75

9 4

6 3

11

5

A. Radiofrequency Stimulator Series (70 %)

B.

Allen13 Coopei4 Davis14 Gahm15 Heimburger16 Wong17 Ivan18 Larson19 Manrique20 Penn21 Reynolds22 Smith23 Sukoff24 Whittaker25 Winkelmuller26

3 141 128 8 20 8 12 48 4 14 4 20 2 8 2

3 124 128 8 20 8 12 48 4 14 4 20 2 8 2

RF series total

422

405

274(68%)

3 105 69 15 7 5' 35* 1 11 3 16 2

8 2 131(32%)

54(38%)

92(36%)

Neurolith Stimulator Series (30%) Amin27 Britt' Davis14 Grant28 Lazorthes29

9 1 146(78R) 6(4R) 16(9R)

9 1 131 6 16

9 1 112 5 13

19 1 3

37 3 4

9 1 75 2 9

Neurolith total

178(91 R)

163

140(86%)

23(14%)

44(27%)

96(59%)

600

568

414(73%)

154(27%)

Total: 18 Centers

Note: R = Radiofrequency systems in 513 (86%) patients as initial system; N = Neurolith systems = 87 (15%) patients as initial system; C = combined series = 168 (28%) patients using Neurolith systems. ‘R.H. Britt (Stanford Medical Center, Stanford, CA), personal communication.

safety of cerebellar stimulation, (3) the optimal cortical place¬ ment sites, and (4) the lack of quantitative measurements in the clinical series, particularly the two double-blind studies.15-25

2.

Stimulators 3. Radiofrequency-linked systems The implanted parts of RF systems consist of the radioreceivers connected to two cerebellar electrode pads. The external trans¬ mitter-stimulator was connected to an antenna positioned over the receiver. Three companies supplied the RF systems: Avery Lab, Inc., Farmingdale, NY; Clinical Technology Corp.. Kansas City, MO; and Medtronic Inc.. Minneapolis. Several serious problems with the RF systems were eventu¬ ally recognized: I. Fluctuations of the stimulation levels because of antenna placement and movement, variable skin thickness, and bat¬ tery depletion occurred by the third day.

4. 5.

Radioreceiver malfunction occurred as early as 6 months. In Davis’s series of 256 patients implanted with RF sys¬ tems between 1974 and 1978, 87 (34 percent) systems failed by 1982,1214-30 while 180 (70 percent) systems failed by 1985.31 By 1994, Davis knew of only two patients from his series who were still using these systems. The external RF stimulators were bulky and easily dam¬ aged; the antenna was readily broken, while output fluctua¬ tions were confirmed by Wong and colleagues.17 Skin irritation from taping the antenna and cosmetic con¬ cerns led patients to reject the systems. The pulse amplitude dial scale (0 to 10) on the external transmitter had no direct relationship to the amount of current being delivered to the cortex; only three se¬ ries1417-18 calibrated their RF systems. Most investigators had turned the amplitude dial up until the patients experi¬ enced tingling in the occiput (“threshold”); this meant that the current had to be sufficient to escape from under the electrode pads to stimulate the overlying tentorium. From experience with calibrating equipment at the time of surgery,30 the charge density required to produce this

Chapter 114/Cerebellar Stimulation for Movement Disorders

tingling was at a level of 25 to 30 p,C/cm2/phase. The am¬ plitude dial was then turned from the “threshold” level down to what was called “subthreshold” for CCS therapy, which has been estimated to be in the range of QD 15 to 25. There were serious problems from ignorance of or failure to calibrate the stimulation charge density applied to the cerebellar surface,1'814’30,32 leading to the use of in¬ effective, excessive, or even damaging levels. With QD levels above 4 to 5 or below 0.8 to 1.0, the effects of CCS on spasticity and patient performance stopped,14-17-30-32'33 indicating that a “window effect” was present at a QD range of 1 to 4 p,C/cm2/phase for the production of physi¬ ological improvement.14 Worthwhile benefits on spasticity and performance were lost in four spastic patients in Davis’s RF series14'30’32 when the patients raised stimulation levels above those which were set. They did not regain a benefit until the electrode arrays were moved to adjacent sites. The question of how much these “higher” QD levels affected the results in RF-coupled series through stimulation in the higher ranges with uncalibrated equipment has not been answered.

Totally implantable, CONTROLLED-CURRENT STIMULATOR Because of the above problems with RF-coupled equipment, Davis and associates11’12,14’30 implanted a fully implantable controlled-current pulse generator (Neurolith 601, Neurodyne Corp., Sylmar, CA) in 1979. This device continued to be used until 1996, having been implanted by 12 clinics in 254 spastic

TABLE 114-2.

patients, 99 (39 percent) of them being replacements for failed RF-coupled receivers; a further 155 patients (61 percent) un¬ derwent initial implantation with this device. A 1994 follow-up was done by Davis on 236 (93 percent) of these implanted pa¬ tients; 94 percent had CP, 4 percent dystonia, and 2 percent anoxic brain damage. Thirty-nine (17 percent) have been explanted, 17 (7 percent) because of infection and 22 (9 percent) because of ineffectiveness or equipment problems. Another 17 (7 percent) died from causes not related to the implant (aspira¬ tion, bowel obstruction, pneumonia, cancer, seizure); 80 per¬ cent of these patients were severely impaired and were rated clinical grade 4 or below (Table 114-2A). Of the remaining 178 patients followed, 51 (29 percent) are improved and another 12 (7 percent) are waiting for a re¬ placement unit. Among these 63 (35 percent) patients, CCS has been used for 2 to 20 years, with 71 percent having had stimulation for over 11 years. Table 114-2A categorizes these patients with functioning units into clinical grades, with 85 percent being graded 4 through 8, indicating that they have functional capabilities. The other 115 patients (65 percent) have implants with depleted batteries. Fifty-seven were able to be questioned about why they have not replaced the de¬ pleted battery/stimulator; 19 said it was ineffective, 15 had financial problems, 12 said that the benefits were insuffi¬ cient, 7 had traveling difficulties, 2 had other health prob¬ lems, and 2 had equipment failures. The lithium battery typi¬ cally has lasted about 3.5 years without stimulator failures. Neurolith pulse generators have been implanted in seven U.S. centers under an investigational device exemption from the Food and Drug Administration as well as in three other countries.

Double-Blind Study of 20 Spastic CP Patients

A. Clinical Grade 1. 2. 3. 4. 5. 6. 7. 8. 9.

Points

Bedridden, severe spastic, no function Bedridden, severe spastic, minimal function Wheelchair, severe spastic, minimal hand function Wheelchair, moderate spastic, limited hand function Wheelchair, moderate spastic, good hand function Walking with walker/brace, moderate spastic Walking with crutch/cane, mild spastic Walking without aids, mild spastic Walking without aids, very mild spastic

0 2 5 6 3 3 1 1 0 20

B. Results of Double-Blind Study: CCS on Mode Improved and the Probability That This Distribution Would Occur by Chance (POC) Clinical Grades

No. Patients

2-8 3-8 4-8 5-8 6-8 7-8

20 18 13 7 4 2

source: Adapted from Davis et al.34

CCS on improved No. % 12 12 10 7 4 2

1103

60 66.7 77 100 100 100

POC

25.17 11.89 4.61 0.78 6.25 25.00

95% confidence level 99% confidence level

1104

Part 4/Functional Stereotaxis

Cerebellar electrodes Stimulation of the bilateral superomedial cortices (paleocerebellum) has been proved3-4’12,14 to be the most effective stimula¬ tion site, more effective than the posterior surfaces and the lat¬ eral lobes. The various electrode types, along with their mechanical and charge density effects on the cortical surface morphology, have been reviewed.32 The thinner four-in-line button electrode pads with a posterior expansion to protect the cortex from the entering wires are the safest. Stimulation parameters Utilizing the results from the animal studies detailed above,1-7-8-10 the following parameters have been shown clini¬ cally to be the safest and most effective:14-30-32 frequencies of 150 to 200 Hz, pulse widths of 0.2 to 0.5 ms, and charge den¬ sity in the range of 1 to 4 p,C/cm2/phase applied intermittently for 1 to 8 min on and off.

RESULTS Improvement in patients responding to CCS generally consists of a noticeable reduction of muscle tone and cocontraction, a reduction in athetosis (if present), and an increase in joint range of motion (ROM). These improvements can occur within one or more days of starting stimulation, while the motor skill im¬ provements plateau in 3 to 6 months. Since 90 percent of the reported cases are spastic CP patients, this review focuses on the effects of CCS on this condition by examining the largest qualitative reports, the quantitative studies, and the double¬ blind studies.

Clinically Evaluated Series In the 18 clinics using CCS for 600 spastic CP patients (Table 114-1), 568 patients (95 percent) were able to be followed, with 414 (73 percent) of them benefiting to varying degrees (Table 114-1). If RF stimulators were used, 68 percent of the 405 patients improved (Table 114-1 A). If the Neurolith stimu¬ lators were used, 86 percent of the 163 patients improved (Table 114-1B). No patient has been reported as clinically worse after stimulation. One postoperative death was reported from an extradural hematoma before CCS had been started.4 Infections occurred in the tissues around the implants in 4.4 percent of the patients, or 2.7 percent of the procedures per¬ formed.33 Two major series have been reported. In 1976, Cooper and associates33 studied 50 CP patients, and in 1978, they summa¬ rized their findings,4 reporting a mild to marked reduction of spasticity in 73 percent and of athetosis in 61 percent of 124 CP patients (Table 114-1A). Ambulation and self-care also improved in 50 percent. RF-coupled stimulators were used for a mean of 13.2 months (range, 3 to 39 months), supplying CCS intermittently at 200 Hz with various stimulation levels applied via two eight-button electrode pads to the superome¬ dial cerebellar surface. Upton35 found 30 patients in Cooper’s series to be set at charge densities of 10 to 20 p.C/cm2/phase, and a later group of 34 patients at 5 to 10 p,C/cm2/phase.

In 1984, Davis and associates14 reported a series of 146 spastic CP patients (Table 114- IB) who were divided according to their abilities into nine clinical grades (Table 114-2A) before undergoing CCS. The Neurolith-601 stimulator (QD 1.1 to 1.9) was implanted and connected to eight-button twin-pad elec¬ trodes (Avery) situated bilaterally on the superomedial cerebel¬ lar surface. The results of CCS were assessed by the patient or guardian in regard to whether there was a marked, moderate, mild, or no effect. These evaluations were made 3 years after the institution of use of this system in May 1979. Various de¬ grees of reduction in spasticity occurred in 85 percent of the patients (marked in 25 percent, moderate in 34 percent, mild in 27 percent); 15 percent had less than mild or no effects from stimulation. Athetosis, present in 62 percent of the spastic CP patients; was unaffected in 10 percent, mildly reduced in 42 percent, moderately reduced in 27 percent, and markedly re¬ duced in 21 percent. Drooling and speech improved in 78 per¬ cent of the patients with these problems. Manual skills in 51 patients who were confined to a wheelchair (grades 4 and 5) improved with CCS; 35 percent improved their existing skills, 59 percent developed new hand skills, and only 6 percent showed no improvement. Ambulation was improved in 89 per¬ cent of the patients in grades 6 to 9. Importantly, of the 23 pa¬ tients who were confined to wheelchairs but who had good hand function (grade 5), 9 (39 percent) became able to walk with aids for the first time, while 4 (17 percent) started crawl¬ ing. Overall, clinical evaluation of CCS showed that severely disabled spastic CP patients (grades 1 to 3) become easier to care for, feed, groom, and dress. Moderately severely affected patients (grades 4 and 5) become able to do more with their hands, and one-third were able to commence ambulating with aids or crawling. The mildly affected patients in grades 6 to 9 were able to ambulate better and became more independent. The fully implantable controlled-current stimulator has been more reliable and has yielded more consistent results than has the RF-coupled system. In a 1994 follow-up of 51 patients with functioning Neurolith systems who had used CCS for 2 to 20 years, marked spasticity reduction was reported in 49 percent, moderate in 33 percent, mild in 11 percent, and none in 7 percent. Forty-two patients had athetoid movements, among whom moderate to marked reduction occurred in 69 percent, mild in 12 percent, and none in 20 percent. Moderate to marked improvement was reported in speech in 60 percent, hand coordination in 61 per¬ cent, and drooling in 53 percent.

Quantitative Studies Five clinics have carried out objective measurements after CCS on 60 CP patients. Motor performance Davis’s group36 did quantitative studies on 17 CP patients, us¬ ing a battery of tests (visual motor coordination, static strength, finger dexterity, and gross arm and leg movements and gait changes). Each patient’s performance was evaluated with up to nine comprehensive tests, including as many as 27 measure-

Chapter 114/Cerebellar Stimulation for Movement Disorders

1105

ments. Performance improvements greater than 10 percent oc¬ curred in 52 percent of these patients. Follow-up testing was done on 10 patients, stimulating for 1.5 to 13.5 months (mean = 6.3), and showed that 62 percent had a greater than 10 per¬ cent improvement in performance. The percentage increase in performance with time indicates ongoing progressive benefits. For each patient, the data were statistically ranked. The ranks from the on periods were summed and compared to a predicted sum. Sixteen of the 17 patients were in clinical grades 4 and better, of whom 14 improved. On retesting, of the 10 patients in clinical grade 5 and better, all improved. Allen and associates13 studied three CP patients (clinical grades 3, 7, and 8) with four tests of fine motor control, coordination, and grip strength re¬ peated three times in two patients and twice in one over 6 to 21 months after the institution of CCS; all three patients improved

Upton and coauthors39 examined two CP patients after 7 to 8 years of RF-coupled CCS and noted a significant increase in SSEP within hours to days after the stimulators were turned off and reductions again when they were switched back on. These authors noted no change in the threshold of stimulation over the years of observation. They recommended measuring SSEP suppression by CCS as a “biocalibration” technique for setting the stimulation level for each individual.35 However, they found that 13 of 87 patients’ SSEP were not suppressed by CCS, even though they improved clinically. Nineteen patients had no clinical improvement, of whom 3 showed SSEP sup¬ pression.

in clinical grade over the months.

Upton and associates39 using positron emission tomography (PET) scans, showed reduced glucose metabolism in the cere¬ bral cortex in patients before the institutions of CCS, but when the stimulators were turned on, the PET scans returned to nor¬

Compliance testing Four CP patients underwent compliance testing on both ankles, using a controlled foot plate.37 Nine of the 16 tests (56 percent) improved with stimulation, but the compliance data did not re¬ late well to functional improvement. Penn and coworkers21 did a prospective study of 14 patients over 1 to 44 months, show¬ ing that compliance testing improved in five (56 percent) of the nine tested, with 9 (64 percent) of 14 patients showing an im¬ provement in primitive reflexes; 11 (79 percent) improved in overall functioning. Respiratory function Wong and associates17 examined respiratory muscle coordina¬ tion in five CP patients, recording rib cage and abdominal movement with magnetometers. With CCS, the breathing pat¬ tern was moderately improved in two patients and mildly im¬ proved in the other three. Frequent respiratory infections occur¬ ring in 4 patients prior to CCS disappeared over 12 to 23 months of follow-up, during which CCS was used. Gray and associates37 studied pulmonary function in 10 patients tested with respiratory inductive plethysmography before and after Neurolith CCS. Of the eight patients with abnormal breathing patterns, three progressed to normal after 1 week of CCS, two more became normal after 5 months of CCS, and the remaining three showed marked improvement after 1 week of stimulation. Somatosensory evoked potentials Upton38 examined nine CP patients from Cooper’s series4 and found inhibition and a reduction in the fluctuation of the H re¬ flexes, VI and V2 late responses, somatosensory evoked poten¬ tials (SSEP), and thalamic potential amplitudes after CCS in eight patients. After 1 min of stimulation, these effects per¬ sisted up to 30 min with “rebound” changes after the cessation of stimulation. Wong and associates17 described similar reduc¬ tions in SSEP at a minimum QD range of 0.27 to 0.35 |xC/cm2/phase in three of their six patients. Larson and cowork¬ ers19 tested 46 patients before, during, and after CCS and found a 50 percent reduction of SSEP in 44 patients. Unilateral stimu¬ lation produced bilateral effects, and bilateral stimulation caused a more profound effect.

Positron emission tomography

mal.

Double-Blind Studies Six double-blind studies have been published. Five15'21,22'25,40 used RF-coupled systems on 41 spastic CP patients and were unable to substantiate any clinical and quantitative improve¬ ment of the type described above. McLellan and coworkers40 studied 11 CP patients from Cooper’s RF-coupled series, who received 10 to 20 pC/cnr/phase; all except 1 patient improved clinically over 4 to 26 months of CCS. They used electrophysiological tests of muscle and nerve function without finding acute changes with 24-h on-off cycling. They noted that if stimulation parameters are changed, at least 3, and preferably 10, days should be allowed for any carryover effects to disap¬ pear. Importantly, they found gradual, progressive changes in reflexes in six patients. Whittaker25 reported a double-blind study of 8 patients taken from a series of 17 patients who had been using CCS for 5 to 23 months. No information was given about their previous overall progress. With CCS on or off for 3 weeks, six physi¬ cians were unable to discern any changes in apparent perfor¬ mance; no objective measurements were made. This series did not measure the charge densities that were delivered, and the patients had various combinations of cerebellar electrodes. Reynolds and Hardy22 studied four patients in a blind study without noting any changes that could be correlated with stim¬ ulation. Assessments were made by showing photographs of the patients to nine physicians. Three of the four patients were judged to be moderately improved by those directly involved in their care. They also did not measure the charge densities being delivered. Gahm and colleagues15 reported eight CP patients in a 3month study with alternating monthly periods of stimulation and placebo. They were evaluated by therapists and a neurolo¬ gist, with no correlation with stimulation or trends over time being found. The stimulation levels were recorded as being “threshold,” meaning that the patients felt tingling in the tento¬ rium from the cerebellar electrodes, a level of stimulation that has been found to result in a charge density of more than 25

1106

Part 4/Functional Stereotaxis

|xC/cm2/phase, which can result in damage to the cortex and render the implant ineffective. On testing seven of these pa¬ tients, Davis and Gray30 found that two radioreceivers were malfunctioning and five were not set at proper levels for ade¬ quate stimulation; these findings render the authors’ results un¬ reliable. Penn and associates21 published a 10-patient double-blind study over two 8-week periods, using joint compliance, and ob¬ servational assessments of developmental reflexes and func¬ tional skills. In comparing performance during on and off peri¬ ods, they did not see significant differences. However, the compliance test has been shown to be an inadequate quantita¬ tive test of motor improvement.37 The authors21 wondered whether the effects of CCS over the months may have been ir¬ reversible, interfering with their double-blind study. Their QD stimulation levels were not calculated, and differing cerebellar arrays were used at different sites. In their prospective study21 on 14 patients over 1 to 44 months, 11 patients (79 percent) functioned better with CCS. In a study published in 1989 by Davis and associates,34 3 0 spastic CP patients underwent CCS and participated in a multi¬ center double-blind study with 25 quantitative tests. Implantable Neurolith 601 stimulators (150 pps, 0.5 ms, 1.5 to 2.5 p,C/cm2/phase, 4 min on, 4 min off) with programmable switches were used. The switch was programmed off at the time of implantation and was then programmed on or off at 1, 2, and 4 months and then left on. Twenty-eight of the above pa¬ tients (CCS mean, 5.9 years; range, 2 to 9 years) had their de¬ vices implanted by 10 neurosurgeons in eight U.S. centers to replace depleted stimulators, while 2 patients had the implant as the initial procedure. Each patient was categorized into grades 1 through 9 (Table 114-2A). The study population was composed of 21 males and 9 females whose average age was 19.7 years (range, 8 to 44 years). The clinical grade ranged from 2 to 8. Physical therapists tested the patients in their own areas. Ten patients had to be excluded from the study because of switch, wire, and connector malfunction; refusal to partici¬ pate; or medical reasons, while 20 patients completed the study. The results were analyzed using nonparametric ranking statistics. The 25 tests included 5 of motor performance: hand dynamometry, hand and foot tapping, peg board placement, and rotary pursuit. Joint range of motion (ROM) was measured in seven joints for both active and passive movements. In addi¬ tion, mood profile was tested using a 65-question question¬ naire. Among the 20 patients (Table 114-2B), 12 (60 percent) im¬ proved when the stimulator was on. In the 13 patients in grades 4 (wheelchair, with hand ability) to 8 (walking), 10 (77 per¬ cent) showed improvement with the stimulator on (confidence level of 95 percent). However, the seven patients in grades 5 through 8 all improved when on (99 percent confidence level).

3 to 6 months. The higher the clinical grade of the patient, the greater the probability of improvement. It is important that CCS be given by an implantable, controlled-current source (QD 1 to 4 p,C/cm2/phase at 150 to 200 Hz) applied intermit¬ tently to the superomedial cerebellar cortex for safe, effective, and continuous results.

References 1.

2.

3.

3a. Cooper I, Riklan M, Amin I, et al: Chronic cerebellar stimulation in cerebral palsy. Neurology 26:744—753, 1976. 4. Cooper 1, Riklan M, Tabaddor K, et al: A long-term follow-up study of chronic cerebellar stimulation for cerebral palsy, in Cooper IS (ed): Cerebellar Stimulation in Man. New York: Raven Press, 1978, pp 59-99. 5. 6. 7.

8.

9.

10.

11. 12.

13.

14.

15. 16.

CONCLUSION Cerebellar stimulation reduces primitive reflexes, spasticity, and athetoid movements in 85 percent of CP patients (markedly in 25 percent, moderately in 34 percent, mildly in 27 percent). CP patients who have limited capabilities that are interfered with by spasticity and athetoid movements can be improved by CCS with respect to drooling, speech, respiration, posture, gait, motor performance, joint ROM, and mood states over the first

Brown W, Babb T, Soper H, et al: Tissue reactions to long-term elec¬ trical stimulation of the cerebellum in monkeys. J Neurosurg 47:366-379, 1977. Cooper I, Chighel E, Amin I: Clinical and physiological effects of stimulation of the paleocerebellum in humans. J Am Geriatr Soc 21:40-43, 1973. Allen M, Malik A, Flanigin H: Performance evaluation of four spastic patients using chronic cerebellar stimulation, in Davis R, Bloedel JR (eds): Cerebellar Stimulation for Spasticity and Seizures. Boca Raton, FL: CRC Press, 1984, pp 189-194.

17. 18. 19.

20.

Lowenthal M, Horsley V: On the relations between the cerebellar and other centers. Proc R Soc Lond [Biol] 61:20-25, 1897. Sherrington C: Decerebrate rigidity. J Physiol 22:319-332, 1898. Moruzzi G: Effects at different frequencies of cerebellar stimulation upon postural tonus and myotactic reflexes. Electroencephalogr Clin Neurophysiol 2:463-469, 1950. Babb T, Soper H, Lieb J, et al: Electrophysiological studies of long¬ term electrical stimulation of the cerebellum in monkeys. J Neurosurg 47:353-365, 1977. Bloedel JR, Ebner TJ, Godersky JC, Huang Cl: Physiological mecha¬ nisms underlying the effects of cerebellar stimulation, in Davis R, Bloedel JR (eds): Cerebellar Stimulation for Spasticity and Seizures. Boca Raton, FL: CRC Press, 1984, pp 35-51. Ebner TJ, Bloedel JR, Vitek JL, Schwartz AB: Modification of the stretch reflex in spastic monkeys by cerebellar stimulation in Davis R, Bloedel JR (eds): Cerebellar Stimulation for Spasticity and Seizures. Boca Raton, FL: CRC Press, 1984, pp 89-103. Davis R, Bloedel JR: Cerebellar Stimulation for Spasticity and Seizures. Boca Raton, FL: CRC Press, 1984. Davis R, Barolat-Romana G, Engle H: Chronic cerebellar stimulation for cerebral palsy—five year study. Acta Neurochir Suppl (Wien) 30:317-332, 1980. Allen M, Malik A, Flanigin H: Performance evaluation of four spastic patients using chronic cerebellar stimulation, in Davis R, Bloedel JR (eds): Cerebellar Stimulation for Spasticity and Seizures. Boca Raton, FL: CRC Press, 1984, pp 189-194. Davis R. Kudzma J, Gray E, et al: Graded clinical effects in spastic cerebral palsy groups following chronic cerebellar stimulation, in Davis R. Bloedel JR (eds): Cerebellar Stimulation for Spasticity and Seizures. Boca Raton, FL: CRC Press, 1984, pp 223-239. Gahm N, Russman B, Cerciello R. et al: Chronic cerebellar stimulation for cerebral palsy; A double-blind study. Neurology 31:87-90, 1981. Heimburger R: Cerebellar stimulator implantation, in Davis R. Bloedel JR (eds): Cerebellar Stimulation for Spasticity and Seizures. Boca Raton, FL: CRC Press, 1984, pp 195-201. Wong P, Hoffman J, Froese A, et al: Cerebellar stimulation in the management of cerebral palsy. Neurosurgery 5:217-224, 1979. Ivan L, Ventureyra E, Wiley J, et al: Chronic cerebellar stimulation in cerebral palsy. Surg Neurol 15:81-84, 1981. Larson S, Sances A, Hemmy D, et al: Physiological and histological effects of cerebellar stimulation. Appl Neurophysiol 40:160-174, 1977-1978. Manrique M. Vaquero J, Oya S, et al: Side effects and long-term re¬ sults of chronic cerebellar stimulation in man. Acta Neurochir Suppl (Wien) 30:333-338,1980.

Chapter 114/Cerebellar Stimulation for Movement Disorders

21.

22. 23.

24.

25. 26.

27.

28.

29.

Penn R, Myklebust B. Gottlieb G, et al: Chronic cerebellar stimula¬ tion for cerebral palsy: Prospective and double-blind studies. J Neurosurg 53:160-165, 1980. Reynolds A, Hardy T: Cerebellar stimulation in four patients with cerebral palsy. Appl Neurophysiol 43:114-117, 1980. Smith W: Cerebellar stimulation used in 20 spastic cerebral palsy pa¬ tients, in Davis R, Bloedel JR (eds): Cerebellar Stimulation for Spasticity and Seizures. Boca Raton, FL: CRC Press, 1984, p 207. Sukoff M: Marked reduction of rigidity and opisthotonus using cere¬ bellar stimulation, in Davis R, Bloedel JR (eds): Cerebellar Stimulation for Spasticity and Seizures. Boca Raton, FL: CRC Press, 1984, p 209. Whittaker C: Cerebellar stimulation for cerebral palsy. J Neurosurg 52:648-653, 1980. Winkelmuller W, Seidel BU, Graubner G: Chronic cerebellar stimula¬ tion in cerebral palsy, in Proceedings of the 29th Annual Meeting: Deutsche Gesellschaft fiir Neurochirurgie. Berlin: Springer-Verlag, 1979, pp 191-196. Amin I: The reduction of spasticity, involuntary movements, and seizures using a fully implantable cerebellar stimulator, in Davis R, Bloedel JR (eds): Cerebellar Stimulation for Spasticity and Seizures.

Neurostimulation: An overview. Mt. Kisco, NY: Futura, 1985, pp 213-230. Gyori E, Davis R: Morphological findings in cerebellar folia follow¬ ing chronic cerebellar stimulation in cerebral palsy, in Davis R, Bloedel JR (eds): Cerebellar Stimulation for Spasticity and Seizures. Boca Raton, FL: CRC Press, 1984, pp 109-124. 33. Davis R, Kudzma J, Ratzan K: Management of infected cerebellar stimulation systems. Neurosurgery 10:340-343, 1982. 34. Davis R, Schulman JH, Zib K: Relevant factors for double-blind study of spastic cerebral palsy using cerebellar stimulation, in Davis R, Kondraske J, Tourtellotte WW, Syndulko K (eds): Quantifying Neurologic Performance. Philadelphia: Hanley and Belfus, 1989, pp 114-150. 35. Upton A: Biocalibration of cerebellar stimulation, in Davis R, Bloedel JR (eds): Cerebellar Stimulation for Spasticity and Seizures. Boca Raton, FL: CRC Press, 1984, pp 133-139. 36. Ryan T, Davis R, Gray E: Quantitative study of neurological perfor¬ mance in spastic cerebral palsy patients with chronic cerebellar sti¬ mulation, in Davis R, Bloedel JR (eds): Cerebellar Stimulation for Spasticity and Seizures. Boca Raton, FL: CRC Press, 1984, pp 32.

Boca Raton, FL: CRC Press, 1984, pp 211-213. Grant J, Llewelyn M, Huber M: Cerebellar stimulation for cerebral palsy patients: 5-year study, in Davis R, Bloedel JR (eds): Cerebellar Stimulation for Spasticity and Seizures. Boca Raton, FL: CRC Press,

37.

1984, pp 215-216. Lazorthes Y: Chronic cerebellar cortex stimulation for graded spastic cerebral palsy patients, in Davis R, Bloedel JR (eds): Cerebellar Stimulation for Spasticity and Seizures. Boca Raton, FL: CRC Press,

38.

30.

1984, pp 217-219. Davis R, Gray E: Technical problems and advances in the cerebellar stimulating systems used for reduction of spasticity and seizures.

31.

Appl Neurophysiol 43:230-243, 1980. Davis R: Clinical experience with cerebellar stimulation in the treat¬ ment of spastic cerebral palsy, in Lazorthes Y, Upton ARM (eds):

1107

39.

40.

169-186. Gray E, Davis R, Cohn M: Respiratory and joint compliance changes in spastic patients following chronic cerebellar stimulation, in Davis R, Bloedel JR (eds): Cerebellar Stimulation for Spasticity and Seizures. Boca Raton, FL: CRC Press, 1984, pp 157-167. Upton A: Neurophysiological aspects of spasticity and cerebellar stim¬ ulation, in Cooper IS (ed): Cerebellar Stimulation in Man. New York: Raven Press, 1978, pp 101-122. Upton A, Cooper I, Garnet S. Springman M: Acute and chronic effects of CCS on evoked potentials and PET scans, in Davis R, Bloedel JR (eds): Cerebellar Stimulation for Spasticity and Seizures. Boca Raton, FL: CRC Press, 1984, p 141. McLellan D, Selwyn M, Cooper I: Time course of clinical and physio¬ logical effects of stimulating of the cerebellar surface in patients with spasticity. J Neurol Neurosurg Psychiatry 41:150-160, 1978.

¥

CHAPTER

115

CHRONIC THALAMIC STIMULATION FOR CONTROL OF INVOLUNTARY MOVEMENTS CAUSED BY STROKE OR HEAD INJURY

Takashi Tsubokawa, Takamitsu Yamamoto, and Yoichi Katayama

Stereotactic destructive surgery has been applied to the thala¬ mus or basal ganglia to alleviate various kinds of involuntary movements since the 1950s.1’2 The neurosurgical experience indicated that in the thalamus the effective destructive lesion site was the nucleus ventralis lateralis (VL)3,4 and that the most effective results were obtained in patients with tremor and L-dopa-induced dyskinesia.5 However, other types of involun¬ tary movements, such as hemiballismus, chorea, and athetosis, remained difficult to alleviate,6 particularly involuntary move¬ ments caused by brain damage resulting from cerebrovascular disease or head injury.5 Moreover, it was not always acceptably safe to use thalamotomy for the relief of symptomatic involun¬ tary movements caused by cerebrovascular disease or head injury or for operations on the basal ganglia, and bilateral thal¬ amotomy for bilateral involuntary movements7 was considered particularly risky. As a safer and less invasive treatment, chronic stimulation of the nucleus ventralis intermedius of the thalamus has been applied to control parkinsonian tremor.8-9 The basis of this treatment is the fact that various kinds of involuntary move¬ ments can be improved acutely by high-frequency stimulation applied for physiological localization during procedures such as stereotactic thalamotomy.1011 Since chronic stimulation is re¬ versible if it is ineffective and appears to be safer than tradi¬ tional destructive thalamotomy, tremor and hemiballistic movement induced by stroke or head injury have been treated with chronic thalamic stimulation in our clinic since 1985.1This chapter describes the clinical methods for and the re¬ sults with chronic thalamic stimulation aimed at controlling certain kinds of symptomatic involuntary movements, such as

ter the causative insult. Whenever these symptomatic involun¬ tary movements became more severe during the course of med¬ ical treatment and were accompanied by severe limitation of daily activities, the patients were considered candidates for chronic thalamic stimulation therapy. At that time, the involuntary movement of each patient was evaluated by surface electromyography (EMG) and videotape recording. The neuropsychological state also was assessed by employing a modified mini mental test, which is a common method in our clinic for grading the cognitive state of patients and checking for psychogenic changes. Patients suffering from any psychogenic changes were excluded as candidates. The use of computed tomography (CT) and magnetic reso¬ nance imaging (MRI) was also important in checking the loca¬ tion of the causative pathological lesions induced by stroke or head injury. However, the location and size of the lesions were not employed as criteria for excluding candidates. Instead, the radioanatomic findings were applied to determine how to im¬ plant the electrode exactly into the target and assess the rela¬ tionship between the pathological lesions and the involuntary movements.

SURGICAL PROCEDURE The surgical procedure has two parts: stereotactic insertion of the chronic stimulation electrode into the target and internaliza¬ tion of the entire stimulation system after checking the effects of stimulation during a test period. The first part of the surgery is performed as a conventional stereotactic surgical procedure under local anesthesia with bar¬ biturate administration to suppress the involuntary movement. The patient is placed in a Todd-Wells stereotactic frame. A bunhole is made 2 cm anterior to the coronal suture and 3 cm lat¬ eral to the sagittal suture. Double-contrast ventriculography of the third ventricle is carried out through the frontal burr hole. The anterior and posterior commissures are identified, and the bicommissural line drawn and measured on the ventriculo¬ gram. The target is defined for both tremor and hemiballismus according to the following stereotactic coordinates: 6 to 7 mm in front of the posterior commissure, 14 to 15 mm from the

tremor and hemiballistic movement.

SELECTION OF CANDIDATES Patients suffering from hemiballismus or hemiballistic move¬ ment that was associated with choreoid hyperkinesia caused by hemorrhage or an infarct in the subthalamic nucleus or striatum and those suffering from tremor caused by traumatic or cere¬ brovascular lesions in the basal ganglia received various kinds of conventional medical treatment for the first 2 to 3 months af¬

1109

1110

Part 4/Functional Stereotaxis

midline, and at or 1 mm above the bicommissural line. A flexi¬ ble platinum-iridium electrode with four active terminals at 8mm intervals (multicontact deep brain stimulation electrode; Medtronic Corp, Minneapolis) is implanted. The tip of the electrode is inserted at the target point, that is, nucleus ventralis intermedius (Vim). The third or fourth active terminal of the electrode must be placed in nucleus ventrooralis posterior (Vop). Bipolar stimulation is carried out between the tip of the electrode in Vim and the fourth active terminal in Vop (Fig. 115.1). For the treatment of symptomatic tremor, the tip of the electrode and the second active terminal must both be in Vim and are used for bipolar stimulation between them.12

coronal sactlon

The distal end of the electrode is tunneled under the scalp behind the ear and is connected to a temporary transcutaneous lead to be used for test stimulation for a few days. The scalp is closed and then covered with a transparent sterile plastic sheet. During test stimulation, various intensities and pulse widths of high frequency square wave pulses (60 to 120 Hz) are tested to establish the most effective parameters. When adequate stimulation is applied, the involuntary movement can be con¬ trolled satisfactorily immediately after the stimulation is turned on. The most effective stimulation parameters in our experi¬ ence are a 60- to 120-Hz frequency with a 0.5-ms pulse dura¬ tion applied at a slightly higher stimulation intensity than that of the sensory threshold.12 When the involuntary movement can be controlled by the test stimulation, the receiver system which generates the stimu¬ lation currents when coupled to a radiofrequency (RF) trans¬ mitter is implanted in the subcutaneous space of the anterior thorax as the second part of the surgery (Fig. 115-2). After implantation of the receiver, chronic stimulation is initiated by employing an antenna placed on the skin just over the implanted receiver. The antenna is attached to an RF trans¬ mitter almost the same size as a cigarette box, which is kept in the patient’s pocket. The transmitter can be switched on and off when the patient uses its control panel. In the present series, the Itrel (Medtronic Corp.), which is a totally implantable pro¬ grammable stimulator, was not used. The patient must there¬ fore turn the stimulator on and off according to the diurnal pat¬ tern of the involuntary movement and then turn it off at night.

RESULTS

sagittal sactlon

Figure 115-1. Stereotactic target points for symptomatic tremor and hemiballismus on the Schaltenbrand brain atlas.

Hemiballismus and ballismus with choreoid movement caused by pathological lesions in the subthalamic nucleus or striatum can be stopped or markedly reduced by 60- to 120-Hz stimula¬ tion in all cases, but the most effective stimulation parameters are not the same in all cases. Therefore, the most effective stim¬ ulation parameter must be selected during the test stimulation (Fig. 115-3). At the beginning of stimulation therapy, hemiballismus is stopped completely or is reduced during stimulation. However, as soon as the stimulation is turned off, the EMG reveals that the involuntary movement remains slightly inhibited only for several minutes, after which involuntary movement is observed again (Fig. 115-3). There is no rebound effect when the stimu¬ lation is discontinued. The patient must therefore keep the stimulator on throughout the day to stop the hemiballistic movement completely during the first 3 to 5 weeks after begin¬ ning chronic stimulation therapy (Fig. 115-4). About 1 month after the institution of stimulation therapy, the duration of post¬ stimulation EMG suppression becomes progressively longer, so that the stimulation period each day becomes shorter. However, there is some difference in the stimulation period necessary to achieve a useful everyday life between patients with lesions in the subthalamic nucleus and those with lesions in the striatum (Fig. 115-5). For hemiballismus caused by a le¬ sion in the subthalamic nucleus, a stimulation time of 8 h per day is still necessary 1 year after beginning chronic stimulation therapy, whereas for hemiballismus caused by a lesion in the striatum, the stimulation time can be reduced to 2 to 3 h per day and still help the patient achieve a fruitful everyday life (Fig. 115-5). In the case of hemiballismus caused by stroke or

Chapter 115/Chronic Thalamic Stimulation for Control of Involuntary Movements Caused by Stroke or Head Injury

1111

Figure 115-2. A chronic thalamic stimulation electrode inserted into Vim and a receiver system implanted at the anterior thorax. The electrode is connected to the receiver by a bipolar system. All systems are shown on x-ray.

SURFACE EMG RECORDING (HEMIBALLISM) 5 sec

shoulder

upper extremlty-^|VV\^''^VW^/WWvn/WWVwWVN^WVWW\^^^./WW

lower extremity

V

DBS ON_DBS OFF 111' f 11 _~n| rrrrri _

_riiiirii. irrm 11 _ rn inn.imim _"in r rn i i_rr

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Figure 115-3. Surface EMG in hemiballismus caused by a striatal lesion induced by a stroke. Stimulation was done with 80-Hz, 0.5-ms square wave pulses with an intensity slightly higher than the sensory threshold. All abnormal movements disappeared as shown on the EMG. Involuntary movement occurred just after the stimulation was stopped, but ballistic movement was slightly inhibited, as shown on the EMG during a period of several minutes.

1112

Part 4/Functional Stereotaxis

Figure 115-4. Hemiballismus associated with choreoid movement. Upper: before chronic thalamic stimulation. Lower: 1 month after the application of chronic thalamic stimulation (during application of the stimulation).

Chapter 115/Chronic Thalamic Stimulation for Control of Involuntary Movements Caused by Stroke or Head Injury

hour*

(hemiballlsm)

1113

implanted electrode system. The risk of infection or electrode migration must be taken into account. While some patients complain of paresthesia during stimulation, such adverse ef¬ fects can be controlled by stopping the stimulation, changing parameters, or, in extreme cases, altering the stimulation site. Although continuous long-term deep brain stimulation may theoretically produce neural damage, there was no evidence to suggest that brain damage was induced around the implanted electrodes in our patients and no change in the threshold re¬ quired to induce paresthesias that would suggest pathological changes at the electrode-brain interface, at least during 5 years of follow-up.

MECHANISM OF ACTION Figure 115-5.

Time course of the total stimulation period per day. In the daytime, the patients utilized stimulation in an attempt to achieve a useful everyday life. One week after application of the chronic stimulation, use was almost continuous throughout the daytime, but several months after application, the patients were able to control their involuntary movements with a total stimulation period of 4 to 8 h per day. There was some difference according to the location of the causative lesion. Hemiballismus caused by a subthalamic lesion could not be controlled with a stimulation period less than 8 h, whereas hemiballismus caused by a striatal lesion could be controlled with less than 4 h of stimulation per day.

head injury, VL-thalamotomy achieved complete control in only 36 percent of our patients, but 85 percent of patients using chronic Vim-Vop stimulation were able to achieve excellent control and return to society without serious side effects or complications. No patient deteriorated. Tremors caused by stroke or head injury can be stopped or reduced remarkably in a similar manner to parkinsonian tremor when treated with chronic thalamic stimulation.8 91314 Shortly after the institution of thalamic stimulation, the tremor can be stopped only during stimulation with a very short aftereffect. Nevertheless, the stimulation period necessary per day to stop the tremor completely during the daytime becomes progres¬ sively shorter until at 3 months the stimulation time per day necessary to allow performance of the activities of everyday life decreases to 3 to 5 h without side effects. This decrease in the stimulation period has no relation to the site or pathogene¬ sis of the causative pathological lesion. Chronic Vim stimulation completely stopped tremor caused by cerebrovascular disease or head injury in 75 percent of cases. In the other 25 percent, there was still a beneficial re¬ duction of the tremor. The results are similar to those with VLthalamotomy, but without the side effects and complications of

There is no clear explanation of the mechanism of action by which chronic thalamic stimulation controls tremor and hemi¬ ballismus. In an attempt to explain the control of tremor, Blonde and coworkers14 suggested that the therapeutic effect of high-frequency thalamic stimulation could be related to desyn¬ chronization of the autonomous neuronal activities which syn¬ chronize parkinsonian tremor with the timing and frequency of activity in Vim. In regard to hemiballismus, the stimulation may facilitate inhibitory pathways from the striatum to the globus pallidus that are involved in hemiballistic movement. Such speculations could explain why the effective stimulation frequency of chronic thalamic stimulation must be 60 to 120 Hz and slightly above the sensory threshold and why there is no aftereffect of the stimulation at the beginning of the treatment. The increase in the aftereffect after 1 to 3 months may be caused by the fact that the stimulation induces an increase in regional cerebral blood flow associated with an increase in me¬ tabolism of both glucose and oxygen within the stimulation area, including the pathological lesion site.12 It may also induce neuroplastic effects at the site of the pathological lesion, lead¬ ing to a remarkable increase in synaptogenesis and gangliogenesis day by day.12

CONCLUSION Chronic stimulation therapy for hemiballismus and tremor caused by stroke or head injury is a useful treatment modality without serious complications or side effects and therefore provides a safe and attractive alternative to stereotactic de¬ structive surgery for the alleviation of these involuntary move¬ ment disorders.

References 1.

that procedure. 2.

SIDE EFFECTS AND COMPLICATIONS

3.

No dysarthria, cerebellar impairment, or neuropsychological changes appeared after implantation or during chronic stimula¬ tion, and no serious complications arose from the chronically

4.

Cooper IS, Bravo G: Chemopallidectomy and chemothalamectomy. J Neurosurg 15:244 250, 1958. Hassler R, Riechert T: Indikationen und lokalisations—methode der gezielten hirnoperationen. Nervenarzt 25:411-447, 1954. Kelly PJ, Gillingham F: The long-term results of stereotaxic surgery and L-dopa therapy in patients with Parkinson’s disease: A 10-year follow-up study. J Neurosurg 53:332-337, 1980. Narabayshi H: Stereotaxic VIM thalamotomy for treatment of tremor. Eur Neurol 29(suppl l):29-32, 1989.

1114

Part 4/Functional Stereotaxis

5.

Wester K, Hauglie-Hanssen E: Stereotaxic thalamotomy—experi¬ ences from the levadopa era. J Neurol Neurosurg Psychiatry 53: 427-430, 1990.

6.

7.

Mundinger F, Riechert T. Disselhoff J: Long term results of stereo¬ taxic operations on extrapyramidal hyperkinesia (excluding parkin¬ sonism). Confin Neurol 32:71-78, 1970. Matsumoto K, Schichijo F, Fukami T: Long term follow up review of

8.

cases of Parkinson’s disease after unilateral or bilateral thalamotomy. J Neurosurg 60:1033-1044, 1984. Benabid AL, Poliak P. Louveau A, et al: Combined (thalamotomy and

9.

stimulation) stereotactic surgery of the VIM thalamic nucleus for bi¬ lateral Parkinson disease. Appl Neurophysiol 50:344-346, 1987. Blond S, Siegfried J: Thalamic stimulation for the treatment of tremor and other motor movement disorders. Acta Neurochir Suppl (Wien) 52:109-111, 1991.

10.

Brice J, McLellan L: Suppression of intention tremor by contingent deep-brain stimulation. Lancet 1:1221-1222, 1980.

11.

Tasker RR, Organ LW, Hawrylyshyn PA: The Thalamus and Mid¬ brain of Man: A Physiological Atlas Using Electrical Stimulation. Springfield, IL: Thomas, 1982.

12.

Tsubokawa T: Modern functional stereotaxy. Gildenberg P (modera¬ tor). 60th Annual Meeting of the American Association of Neuro¬ logical Surgeons, San Francisco, 1992.

13.

Tsubokawa T: Chronic stimulation of deep brain structures for treat¬ ment of chronic pain, in Tasker RR (ed): Stereotaxic Surgery. Phila¬ delphia: Hanley & Belfus, 1987, pp 235-356.

14.

Blond S, Caparros-Lefebvre D, Parker F, et al: Control of tremor and involuntary movement disorder by chronic stereotactic stimulation of the ventral intermediate thalamic nucleus. J Neurosurg 77:62-68, 1992.

CHAPTER

116

TRANSPLANTATION TO IMPROVE FUNCTIONS IN THE DISEASED CENTRAL NERVOUS SYSTEM

Fred C. Junn and Andres M. Lozano

TRANSPLANTATION IN THE CENTRAL NERVOUS SYSTEM In adult mammals, there is poor neuroanatomical recovery after injury to the central nervous system (CNS). This limited capac¬ ity for the repair of neurons and their axonal processes con¬ tributes to permanent neurological deficits in patients with in¬ jury or degeneration of the brain and spinal cord. CNS tissue transplantation has permitted a new avenue for the alleviation of such disorders. With advances in neurobiology and our un¬ derstanding of neurological disorders, the possibility of trans¬ plantation as a therapeutic modality has become a reality. In ad¬ dition, neural transplantation has become an invaluable research tool in exploring the development and plasticity of the CNS. This chapter provides a brief synopsis of the factors re¬ sponsible for successful grafting, the mechanisms of graft func¬ tion, and some of the current clinical and experimental uses of transplantation in the CNS for neurological disorders. Transplantation in Parkinson’s disease is discussed only briefly, since it is covered more extensively in Chap. 220.

Important Variables in Successful Grafting Age of donor and host The success of CNS transplants depends on the optimization of several host- and graft-related variables as well as the technical factors involved in graft placement. The developmental age of the donor is an important consideration in neural graft survival. The optimal donor ages are variable and depend on the specific neural substance being collected for transplantation.'^ The op¬ timal windows often coincide with the period of proliferation and migration in neuronal and glial populations. During this time, the mechanical disruption and anoxia incurred during tis¬ sue preparation may be the least harmful.5 Experimental evi¬ dence has shown that the grafted fetal neurons appear to con¬ serve their biological clock, proliferating and developing in a

(PNS). Survival and functional integration of grafted PNS tis¬ sues such as the vagal nodose ganglia,9 superior cervical gan¬ glia,10 and adrenal glands11 from young adult rodents into the host CNS have been well demonstrated. In contrast, the role of host age with respect to graft survival is less clear. Fetal cortical grafts,12 fetal hypothalamic grafts in Battleboro rats,13 and fetal cholinergic and noradrenergic grafts14 showed no host age-dependent differences in graft pro¬ liferation. However, Azmitia and associates15 found that the outgrowth of serotoninergic fibers was less pronounced in older recipients. In general, older recipients had less tolerance for more mature grafts. Donor tissue for transplantation CNS tissue transplants can be broadly separated into homo¬ topic and heterotopic grafts (Table 116-1). Homotopic graft transplantation implies that the tissue transplanted is from the same anatomic and functional area of the donor and the re¬ cipient. Because of the poor viability of mature grafts, most homotopic grafting has been carried out with fetal tissue. Almost every area of fetal brain, from the olfactory neuroep¬ ithelium to the spinal cord, has been transplanted success¬ fully.16 Heterotopic transplantation implies the use of tissue grafts from an anatomic location different from the recipient site. Such grafts are exemplified by mesencephalic or chro¬ maffin cell grafts placed into the striatum for the treatment of

TABLE 116-1.

Sources of CNS Grafts

Homotopic grafts: neural Allografts Xenografts Heterotopic grafts: neural and nonneural Autografts Allografts Xenografts Cells and cell lines Primary cells: astrocytes, Schwann cells, adrenal chromaffin cells Genetically altered cells: astrocytes, fibroblasts Tumor cell lines: PC 12, B16HC29, ACT-20/hENK Neural stem cells

time frame very similar to that in situ.6-7 Bjorklund and Stenevi8 estimated that only about 10 to 30 percent of grafted fetal cortical neurons survive transplantation into the host CNS. The donor age is a less critical factor in the survival of neural grafts from the peripheral nervous system

1115

1116

Part 4/Functional Stereotaxis

Parkinson’s disease (PD). In general, the extent of anatomic and synapse formation tends to be greater in homotopic than in heterotopic grafts.17 The source of the CNS transplant can be autologous, from an individual of the same species that is antigenically distinct (allogeneic), or from a different species (xenogeneic). Further, primary and genetically engineered cells and cell lines, includ¬ ing fibroblasts, tumor cell lines such as PC 12 cells (rat pheochromocytoma), and neural CNS stem cells, are potential sources of graft tissue. For transformed and neoplastic cell lines, it has often been useful to package cells in polymer cap¬ sules to confine and control their proliferation and prevent mi¬ gration while allowing the size-restricted inflow of nutrients and the outflow of synthesized trophic substances. Techniques of transplantation The survival and integration of grafts also depend on transplan¬ tation techniques (for examples, see Refs. 18 through 23). The wide variety of techniques for implanting tissue into the brain or spinal cord (Table 116-2) has been reviewed by Gash and associates.16 Early work relied on simple placement of grafts into cortical slits, with rather poor graft survival. This was per¬ haps due to the insufficient supply of nutrients and trophic sub¬ stances available in the surrounding parenchyma in the first few days after grafting. Transplant revascularization in the rat takes approximately 3 to 5 days.22'24 To overcome this diffi¬ culty, a two-stage grafting technique (implanting into a pre¬ formed cavity) has been employed, with enhancement of graft survival.2 Nieto-Sampedro and colleagues25 suggested that the injured transplantation cavities also secrete neurotrophic sub¬ stances that enhance the survival of grafts. Implantation into the ventricular system has also been per¬ formed. In animal experiments, the lateral, third, and fourth ventricles have been used as a graft bed.26 Injury of ependyma is implicated in better graft survival.26 The intraventricular technique avoids the need for two operations by utilizing the capillary bed of choroid as a source of vascular supply. Both single-stage ventricular grafting and two-stage grafting into a preformed cavity are suitable for larger grafts. However, larger grafts with a smaller surface-to-volume ratio often undergo central necrosis and show less survival than do smaller grafts. With intraventricular placement in particular, there is also the possibility of imprecise graft placement and graft migration. Stereotactic intraparenchymal implantation of tissue grafts offers several advantages, including precise graft placement and enhanced survival. The most successful intraparenchymal

TABLE 116-2.

Current Transplantation Techniques

Single-stage procedures Intraventricular/subarachnoid transplantation; solid, packaged grafts Intraparenchymal transplantation; solid, packaged, suspension (cell or tissue fragment) grafts Two-stage procedure Surgically prepared transplantation cavities: solid, packaged grafts

grafting was pioneered by Schmidt and colleagues.27 In gen¬ eral, tissue pieces are enzymatically digested, mechanically dissociated into cell suspensions, and implanted into the brain parenchyma. Neurons implanted as suspensions show good survival and differentiation.27 Since human brain tissue has marked sensitivity to mechanical dissociation, the most popular implantation method in human trials has been the stereotactic intraparenchymal implantation of small tissue fragments.28'29 In addition, because the area to be reinnervated is often large, the use of multiple grafts has gained popularity in more recent hu¬ man trials. Immunologic reaction While the brain has been thought of as an immunologically privileged site because of a less effective afferent limb of the immune system, recent experiments have shown that tissue re¬ jection does occur in the CNS with both allografts and xeno¬ grafts.30-32 Low immunogenic tissue such as fetal CNS tends to survive longer than does adult peripheral tissue.33 This could be due to tolerance of fetal antigens by the brain immune system, perhaps as a result of the absence of the molecules that trigger rejection in the transplanted cells.34 The role of the blood-brain barrier in the CNS immune reaction is unknown, but the en¬ dothelial tight junctions of brain capillaries may inhibit interac¬ tions between transplanted antigens and immune effector cells. It is not clear whether systemic immunosuppressants are neces¬ sary for the best outcome.

Mechanisms of Graft Function The proposed mechanisms for functional improvement after CNS transplantation (Table 116-3) fall into three categories: (1) replacement of lost neurons and glia, (2) enhancement of neural repair and regeneration, and (3) modulation of altered neural activity. Neural tissue grafts were initially implanted to replace lost neurons and glia, deliver deficient neurotransmitters, and reestablish synaptic connections. The prototypical use of this strategy was in attempts at correction of lost dopaminergic cells in PD patients, using fetal mesencepahlic grafts or adrenal chromaffin cells.

TABLE 116-3. Proposed Mechanisms Responsible for Neurological Amelioration with Transplants Replacement and supplementation Repopulation of missing cells (neurons, glia) Supply of missing neurotransmitters Reestablishment of lost neural connections Regeneration and prevention of degeneration Supply of gene products including trophic factors Neutralization of neurite growth inhibitory factors Bridges: peripheral nerve cables, Schwann cells, biomaterial matrices, embryonic neural tissue Modulation of altered neural activity Augmentation and diminution of neural transmission

Chapter 116/Transplantation to Improve Functions in the Diseased Central Nervous System

Transplanted neurons can produce both specific and nonspe¬ cific host innervation. The degree of integration depends on both the nature and maturity of the graft and the features of the implantation site in the host brain. Lund and Hauschka18 and McLoon and Lund19 showed that grafted fetal retinas sent pro¬ jections only to the area that normally receives retinal fibers— the superior colliculi—and that this innervation was increased when the host eye was enucleated to liberate synaptic fields in the target area. Such specificity in reinnervation also has been demonstrated by grafted monoaminergic and cholinergic neu¬ rons transplanted into the denervated host hippocampus.20 However, there are exceptions to this specificity: Lewis and Cotman21 showed that striatal cholinergic neurons that nor¬ mally do not project to the hippocampus send projections to this target. Transplantation strategies also have been directed at over¬ coming neuronal degeneration and failed axonal regrowth after a CNS injury. Transplantation has been used to increase levels of trophic factors and provide substrates that are permissive for axonal regrowth in attempts to enhance neural regeneration and repair after injury. Thus, various primary cells and tissues, such as Schwann cells35-36 and amnion37-38 or genetically altered neurotrophin-secreting fibroblasts39 and astrocytes,40 have been used to facilitate graft survival when implanted as a cograft or to promote host neurite regeneration. There is also strong evidence that the CNS environment provides negative cues that play an important role in blocking the regeneration of injured axons. At least three neurite out¬ growth inhibitory molecules—NI-35 and NI-250 and myelinassociated glycoprotein (MAG)—have been identified.41-43 The exact mechanism through which these molecules inhibit neu¬ rite outgrowth is unknown. It has been suggested that certain inhibitory molecules may act by triggering a pertussis-sensitive G-protein pathway, with changes in intracellular calcium lead¬ ing to growth cone collapse.44-45 Segments of peripheral nerves have been used as bridges46 to bypass the “unfriendly” CNS en¬ vironment. In addition, the delivery of monoclonal antibodies47 to block inhibitory factors has been shown to promote axonal regeneration of the CNS. Neural transplantation can be used not only for neuroaug¬ mentation to replace lost neural function but also for neuro¬ modulation to modify existing abnormal neural activity. Examples of the use of transplants to provide neuroactive sub¬ stances that modulate neural function can be found in the fields of movement disorders (dopamine), pain (enkephalins), and epilepsy (inhibitory neurotransmitters). In many cases, grafts function in both augmentative and modulatory roles.

Theoretical Therapeutic Applications Some CNS diseases that are amenable to transplantation are summarized in Table 116-4 and discussed below. In general, transplantation is most likely to succeed when there is limited and localized CNS damage. In contrast, a diffuse disease process involving multiple populations of neurons in diverse areas poses more difficulty. Transplants to restore neural functions dependent on the precise point-to-point reconstruction of neural circuitry and synapses would be expected to be less successful than grafts functioning through nonsynaptic mechanisms, such as the sup¬ ply of a deficient transmitter or trophic factor.

TABLE 116-4.

1117

Diseases Potentially Amenable to Grafting

Replacement/regeneration Neurodegenerative Parkinson’s disease Huntington’s disease Alzheimer’s disease Amyotrophic lateral sclerosis Stroke Trauma Brain and spinal cord injury Hormone deficiency Modulation Epilepsy Pain

Parkinson’s disease The development of transplantation technology has been dri¬ ven largely by the use of transplants for the treatment of PD. With the development of a suitable animal model48 of PD, the field of neural transplantation has evolved rapidly into clinical trials. PD is characterized by progressive depletion of striatal dopamine (DA) as a result of loss of dopaminergic neurons in the pars compacta of the substantia nigra. Earlier transplant strategy was aimed at replacing the lost neurotransmitter by transplanting cells capable of producing DA. Behavioral im¬ provement has been observed in animal experiments to a vary¬ ing degree with both adrenal chromaffin cells and fetal mesen¬ cephalic tissue.49 In addition, autologous fibroblasts transfected with the gene for tyrosine hydroxylase (the rate-limiting en¬ zyme in DA synthesis) have been transplanted with encourag¬ ing results.50 In human trials, the most promising benefits have been observed with the transplantation of fetal mesencephalic grafts into the caudate and putamen.51 In view of the vast amount of both clinical and experimental experience in the use of transplantation to treat PD, a more comprehensive review is given in Chap. 220. Huntington’s disease Huntington’s disease (HD) is a familial neurodegenerative dis¬ order characterized by behavioral deterioration, chorea, and de¬ mentia. The caudate and putamen of these patients are involved primarily. Pathologically, there is a loss of intrinsic striatal neu¬ rons and the medium spiny projection neurons, with a diminu¬ tion of striatal gamma-aminobutyric acid (GABA), acetyl¬ choline (Ach), and enkephalin. Striatal DA levels remain largely unaffected. Models of HD have been created in rats52-53 and monkeys54 by excitatory amino acid (EAA) lesioning of the striatum. The extrapyramidal motor abnormalities in such animals have been shown to improve partially after fetal stri¬ atal transplantation.52-54 In addition, there is a protective effect of prior intraparenchymal or ventricular grafts of fetal stria¬ tum55-56 and chromaffin tissues57 on EAA lesions in the stria¬ tum. It has been proposed that in these experiments transplants act as toxin sumps or release neuroprotective/trophic sub¬ stances. Intrastriatal implantation of fetal striatum has also been performed in patients with HD. In 1993, Madraza and col-

1118

Part 4/Functional Stereotaxis

leagues58 implanted the first HD patient, using an open microsurgical approach, with reported arrest in progression and im¬ provement in symptoms. Now that the gene responsible for HD has been identified, it may be feasible to combine genetic engi¬ neering and transplantation strategies to treat the disease mani¬ festations.

Alzheimer’s dementia The dementia associated with Alzheimer’s disease (AD) in¬ volves widespread brain dysfunction. It has been suggested that the loss of neurons and depletion of Ach in the basal nucleus of Meynert (bnm) is important in the pathogenesis of AD. Attempts to supplement this missing neurotransmitter by infus¬ ing Ach into the ventricles have not been generally fruitful.59 Animal models of AD have relied on the observation that the hippocampus receives cholinergic projections from the sep¬ tal area and noradrenergic projections from the locus caeruleus that are implicated in memory and learning.60-61 Several experi¬ ments addressing septal-hippocampal function have involved sectioning of the fimbria-fornix. Loss of neurons in the septal nucleus has been observed in monkeys62-65 and rats66-68 after in¬ terruption of this pathway. In such models, fetal septal, locus caeruleus, and raphe grafts have been shown to reinnervate ap¬ propriate regions of rat hippocampus and restore levels of Ach, noradrenaline (NA), and serotonin.66-69 Septal grafts have also been shown to improve cognitive and learning deficits associ¬ ated with fimbria-fornix lesions in rats and nonhuman pri¬ mates.65-70 Another strategy in the treatment of AD is prevention of fur¬ ther degeneration of neuronal elements through the provision of trophic substances required for cell survival. It has been shown that medial septal cholinergic magnocellular neurons depend on nerve growth factor (NGF) transported retrogradely from the hippocampus through the fornix.62-70 Therefore, trans¬ plantation of living tissues capable of releasing NGF is a ratio¬ nal choice. In fact, in such an experimental paradigm, rescue of septal neurons has been observed in both rats and monkeys af¬ ter the infusion of NGF or the use of peripheral nerve grafts as a continuous source of NGF.68-71 In addition, in a 6-hydroxydopamine lesion model that resembles the pattern of cell loss found in AD, noradrenergic neuronal rescue has been observed in the locus caeruleus with the use of genetically modified fi¬ broblasts that produce neurotrophin-3.72 Such strategies can the¬ oretically be used to prevent the progression of AD and may have a wider use once specific neurotrophic substances for the various neuronal population are identified. Because of the lack of suitable animal models mimicking slow and progressive human degenerative neurological disor¬ ders and the uncertainty of the fate of tissue transplanted into a degenerating diseased brain, the application of these strategies in humans requires further study.

Stroke and trauma Cortical injuries, whether caused by stroke or by trauma, lead to a direct loss of neurons and to indirect effects in other brain areas through anterograde and retrograde neuronal degenera¬ tion. Fetal cortical neurons grafted into infarcted areas have been shown to reduce the thalamic atrophy that occurs after

cortical ablation, presumably by supplying the necessary trophic factors.73-74 An anatomic connection between the trans¬ planted neurons and the host thalamus has been demon¬ strated.75 Further, glucose utilization has increased in the trans¬ planted neurons in the cortex with stimulation of the whiskers,76 a finding that suggests functional integration of the transplant. Whether such transplants improve motor function in the adult nervous system is unknown.77-78 In rats, destruction or removal of the medial frontal or pari¬ etal lobe leads to worsening performance in T-maze alternation tasks.79-80 After transplantation of fetal cortex, the rats showed improved behavior compared with the untreated animals.79 In contrast, fetal cerebellar grafts did not produce improvements, suggesting a donor tissue-specific effect.80 The often large vol¬ umes of tissue loss after a cortical infraction in humans pose an important challenge to the use of transplantation.

Hormone deficiencies The use of tissue grafts in hormone disorders appears promis¬ ing because the cellular requirement is small and the necessity for synapse formation is less critical. The discoveries of the Battleboro rat81 and the hypogonadal mouse82 have provided ideal animal models to test the functional capacity of neural grafts. Battleboro rats, which are genetically deficient in vaso¬ pressin, suffer from chronic diabetes insipidus (DI). When these animals are treated with grafts of fetal preoptic hypothal¬ amus from normal rats (containing vasopressin-positive cells) into the third ventricle, their DI improves.83 This effect is more pronounced when grafting is performed in normal hypophysectomized rats.83-84 Mice genetically deficient in gonadotropin releasing hor¬ mone (GnRH) have hypogonadism and are sterile. When GnRHcontaining neurons from the preoptic nucleus are transplanted to the hypothalamic region in these mice, the mice develop sec¬ ondary sexual characteristics and are able to reproduce.85-86 In addition, the pituitary gland itself can be transplanted to the median eminence of hypophysectomized rats, with survival of pituitary tissue and normalization of blood levels of luteiniz¬ ing hormone, prolactin, and thyroxine.87 On the basis of these encouraging results in animals, the possibility of transplan¬ tation to correct human neuroendocrine disorders should be considered.

Spinal cord In adult mammals, two factors leading to poor neurological re¬ covery from injury or disease in the spinal cord are neuronal loss and lack of regeneration of interrupted axons. The descending projections of brain stem monoaminergic neurons are important in regulating the activity of the intrinsic spinal neurons involved in locomotor and autonomic functions. Embryonic brain stem noradrenergic and serotonergic neurons implanted in the transected spinal cord extend processes up to 2 cm.88-89 These grafts can restore the levels of monoamines in the transected spinal cord with the return of crude reflex loco¬ motive and sexual function90-91 but not discriminatory sensation or fine motor control, which probably requires a more complete reconstruction of spinal circuitry.

Chapter 116/Transplantation to Improve Functions in the Diseased Central Nervous System

Transplants also have been used as a bridge in the interrupted spinal cord and as a source of trophic factors to rescue axotomized neurons.92 Such grafts are associated with a reduction of astrocytic scarring (which may act as a barrier to regenerating axons) at the graft-host interface.93,94 Impressive recovery has been reported with homotopic embryonic spinal cord grafts transplanted into neonatal rats with transected cords.95 In addi¬ tion, tissue grafts capable of secreting ciliary neurotrophic factor to rescue anterior horn cells of the spinal cord have had some success in animal models of amyotrophic lateral sclerosis.96 Transplantation of glia has been used to promote remyelination after a demyelinating process or spinal cord injury. At least two animal models have been used: a focal demyelination model using local application of ethidium bromide and irradia¬ tion97 and a more diffuse model using the shiverer mouse, a ge¬ netic mutant deficient in myelin basic protein.98 In such mod¬ els, transplanted glial cells not only survived but remyelinated the host to a variable degree.99 The transplanted glia could also act by providing cues and trophic support for the host oligoden¬ drocytes.

Epilepsy Epileptiform activity is characterized by the hyperexcitability and synchrony of neuronal discharges.100'101 Decreased GABA levels have been shown in animal kindling models of epilepsy102,103 and in human cortical tissue from patients under¬ going surgical resection of epileptic foci.104 Further, increased GABAergic transmission in the substantia nigra of rodents with kindled epilepsy has been reported to reduce seizure gen¬ eralization.105 Therefore, transplants that produce inhibitory neurotransmitters may be useful in increasing inhibitory neuro¬ transmission and controlling seizure propagation. Transplant strategies designed to increase noradrenaline transmission should also be considered. Lindvall and Bjorklund101 showed that transplants of noradrenergic fetal neurons from the locus caeruleus into NA-depleted hippocampus not only reinnervated the hippocampal formation but protected rats from kindlinginduced seizure activity.

Pain Enkephalins exert a powerful analgesic effect when applied in the region of the periaqueductal gray matter. The process¬ ing of painful sensation in the dorsal horns of the spinal cord has also been shown to be altered by local opioid and cate¬ cholamine levels. Segan and colleagues106,107 demonstrated that adrenal chromaffin cells release both catecholamines and opi¬ oids. Subarachnoid transplantation of chromaffin cells has been shown to reduce pain perception in a rat model of acute pain (tail flick testing).108 Genetically modified cells such as B16F1C29 melanoma cells, which release catecholamine,109 and ACT-20/hENK cells,110 which have been modified to pro¬ duce proenkephalins, ameliorate the acute pain response when transplanted into the lumbar subarachnoid space. Biopolymer encapsulation has been valuable in the packaging of bovine chromaffin cells and genetically altered cells for transplanta¬ tion.111 A European preliminary human trial to treat pain associ¬ ated with malignancy by using biopolymer-encapsulated bovine cells has shown encouraging results.112

1119

FUTURE DIRECTIONS Neural transplantation has provided a new outlook on the treat¬ ment of various neurological disorders. There remain practical and ethical problems of tissue harvesting and handling before implantation. The difficulties can be overcome, at least in part by using cell lines rather than primary tissues. The cell lines can be characterized and manipulated in culture before trans¬ plantation. Cells can be genetically altered to express desirable characteristics and can be grown in large amounts for multiple transplantation. Among the various methods of genetic modifi¬ cation, the introduction of genetic material with retroviral vec¬ tors has been the most widely used technique.113,114 The ideal cells for gene transfer are those which show vigorous survival and stably express transgene product in vivo. Recently identi¬ fied neural stem cells that are present in the periventricular region in adult CNS have opened new possibilities for trans¬ plantation.115 It has become clear that these stem cells are multipotent and can develop into either neuronal or glial lineages, depending on the local microenvironment.1,3 The identification of the signals required to direct the terminal differentiation of these cells along specified paths will be important. In addition, since these stem cells can be made to proliferate in culture, the practical limitation on the amount of cells grafted can be over¬ come. With currently available techniques of genetic manipula¬ tion, stem cells can ultimately be used as custom-packaged transplants that may prove to be powerful tools in future at¬ tempts to treat various neurological disorders.

CONCLUSIONS The rationales for neural transplantation are to supplement defi¬ cient neural functions incurred through degenerative disease processes or traumatic or genetic loss and to modify existing neural function by means of the added effects of engrafted cells and the molecules they secrete. To date, the best results have been obtained when the desired effects could be achieved in neural systems that do not require complex synaptic connections. Future improvements will depend on overcoming the technical problems of transplantation and gaining a better understanding of the neuroanatomical and neurophysiological deficits in neuro¬ logical diseases. Identification of neural stem cells and develop¬ ments in genetic engineering offer exciting possibilities. Neural transplantation remains an important experimental tool with nu¬ merous possible applications. Its clinical use will require contin¬ uous reappraisal.

References 1. 2.

3.

4.

Seiger A, Olson L: Quantification of fiber growth in transplanted central monoamine neurons. Cell Tissue Res 179:285-316, 1977. Stenevi U, Bjorklund A. Svengaard N-AA: Transplantation of cen¬ tral and peripheral monoamine neurons to the adult rat brain: Techniques and conditions for survival. Brain Res 114:1-20, 1976. Kromer LF, Bjorklund A, Stenevi U: Intracephalic implants: A tech¬ nique for studying neuronal interactions. Science 204:1117-1119, 1979. Kromer LF, Bjorklund A, Stenevi U: Intracephalic neural implants in the adult rat brain: I. Growth and mature organization of brain stem, cerebellar and hippocampal implants. J Comp Neurol 218: 433^159, 1983.

1120

5.

6.

7.

8. 9.

10.

Part 4/Functional Stereotaxis

Jilek L: The reactions and adaptation of the central nervous system to stagnant hypoxia and anoxia during ontogeny, in Himwich WA

29.

Lindvall O, Backlund EOM, Fared 1, et al: Transplantation in Parkinson’s disease: Two cases of adrenal medullary grafts to the putamen. Ann Neurol 22:457-468, 1987.

30.

Baker CF, Billingham RE: Immunologically privileged sites, in Kunkel HG. Dixon FJ (eds): Advances in Immunology. New York: Academic Press, 1977, pp 1-54.

veloping transplants. J Comp Neurol 200:213-230, 1981. Wells J, McAllister JP: The development of cerebellar primordia

31.

transplanted to the neocortex of the rat. Dev Brain Res 4:167-179, 1982.

32.

Bjorklund A, Stenevi U, Dunnett SB: Cross-species neural grafting in a rat model of Parkinson's disease. Nature 298:652-654, 1982. Low WC, Lewis PR, Bunch ST: Embryonic neural transplants across a major histocompatibility barrier: Survival and specificity of innervation. Brain Res 262:328-333, 1983. Fuchs HE, Bullard DE: Immunology of transplantation in the central nervous system. Appl Neurophysiol 51:278-296, 1988. Rees RC, Price MR, Baldwin RW: Oncodevelopmental antigen ex¬ pression in chemical carcinogenesis. Methods Cancer Res 18: 99-133, 1979.

(ed): Developmental Neurobiology. Springfield, IL: Thomas, 1970, pp 331-369. Jaeger CB, Lund RD: Transplantation of embryonic occipital cortex to the tectal region of newborn rats: A Golgi study of mature and de¬

Bjorklund A, Stenevi U: Reconstruction of brain circuitries by neural transplants. Trends Neurosci 2:301-306, 1979. Zalewski A: A prolonged survival and trophic function of neurons in homologous transplants of sensory ganglion in vivo. Exp Neurol 30:510-524, 1971. Rosenstein JM, Brightman MW: Some consequences of grafting au¬

33. 34.

tonomic ganglia to brain surfaces, in Sladek JR, Gash DM (eds): Development and Function. New York: Plenum Press, 1984, pp 424-443.

35.

Doering LC: Peripheral nerve segments promote consistent long¬ term survival of adrenal medulla transplants in the brain. Exp Neurol 118:253-260, 1992.

11.

Freed WJ, Morihisa JM, Spoor E, et al: Transplanted adrenal chro-

36.

12.

rnaffin cells in rat brain reduce lesion-induced rotational behavior. Nature 292:937-939, 1983. Hallas BH, Das GD, Das KG: Transplantation of brain tissue in the

Collier TJ, Sladek CD, Gallagher RW, et al: Diffusible factor(s) from adult rat sciatic nerve increases cell number and neurite out¬ growth of cultured embryonic ventral mesencephalic tyrosine hydroxylase-positive neurons. J Neurosci Res 27:394-399, 1990. Seigel GM, Junn F, Gash DM: Neurotrophic effects of amnion ex¬ plants co-cultured with rat mesencephalon. Dev Brain Res 77: 137-139, 1994. Bankiewicz KS, Palmatier M. Plunkett RJ. et al: Reversal of hemiparkinsonian syndrome in nonhuman primates by amnion implanta¬ tion into caudate nucleus. J Neurosurg 81:869-876, 1994.

13.

14. 15.

16.

17.

18. 19. 20.

21.

22.

23. 24.

25.

26. 27.

28.

brain of rat: II. Growth characteristics of neocortical transplants in hosts of different ages. Am J Anat 158:147-159, 1980. Kaplan AS, Coleman PD, Gash DM: A Golgi study of hypothalamic transplants in young and old host rat. Neurobiol Aging 6:205-211, 1985. Sladek JR. Gash DM: The use of neural grafts as a means of restor¬ ing loss associated with aging. Anat Rec 202:178, 1982. Azmitia EC, Perlow MJ, Brennan MJ, Lauder JM: Fetal raphe and hippocampal transplants into adult and aged C57BL/6N mice: A pre¬ liminary immunocytochemical study. Brain Res Bull 7:703-710, 1981. Gash DM, Collier TJ, Sladek JR: Neural transplantation: A review of recent developments and potential application to the aged brain. Neurobiol Aging 6:131-150, 1985. Sanberg PR, Koutouzis TK, Freeman TB, et al: Behavioral effects of fetal neural transplants: Relevance to Huntington's disease. Brain Res Bull 32:493^196. 1993. Lund RD, Hauschka SD: Transplanted neural tissue develops con¬ nections with host rat brain. Science 193:582-584, 1976. McLoon SC, Lund RD: Specific projections of retina transplanted to rat brain. Exp Brain Res 40:273-282, 1980. Bjorklund A, Stenevi U: Reformation of the severed septohippocampal cholinergic pathway in the adult rat by transplanted septal neurons. Cell Tissue Res 185:289-302, 1977. Lewis ER, Cotman CW: Neurotransmitter characteristics of brain grafts: Striatal and septal tissues form the same laminated input to the hippocamus. Neuroscience 8:57-66. 1983. Saltykow S: Versuche fiber Gehirnplantation, zfigleich ein Beitrag zur Kenntriss der Vorgange an den zelligen Gehirnelementen. Arch Psychiatr Nervenkr 40:329-388, 1905. Del Conte G: Einpflanzungen von embryohalem Gewebe ins Gehirn. Beitr Pathol Anat Allg Pathol 42:193-202, 1907. Svendgaard N-AA, Bjorklund A, Stenevi U: Regenerative properties of central monamine neurons as revealed in studies using iris transplants as targets. Adv Anat Embryol Cell Biol 51:1-77, 1975. Nieto-Sampedro M, Manthorpe M, Barbin G, et al: Injury-induced neuronotrophic activity in adult rat brain: Correlation with survival of delayed implants in the wound cavity. J Neurosci 3:2219-2229, 1983. Rosenstein JM, Brightman MW: Intact cerebral ventricles as a site for tissue transplantation. Nature 276:83-85, 1978. Schmidt RH, Bjorklund A, Stenevi U: Intracerebral grafting of dissociated CNS tissue suspension: A new approach for neuronal trans¬ plantation to deep brain sites. Brain Res 218:347-356, 1981. Backlund EO, Granberg PO, Hamberger B, et al: Transplantation of adrenal medullary tissue to striatum in parkinsonism: First clinical trials. J Neurosurg 62:169-173, 1985.

37.

38.

39.

40.

41.

42.

43.

44.

45.

46. 47.

48.

49. 50.

51.

52.

Rosenberg MB, Friedmann T, Robertson RC, et al: Grafting geneti¬ cally modified cells to the damaged brain: Restorative effects of NGF expression. Science 242:1575-1578, 1988. Stromberg I, Wetmore CJ, Ebendal T, et al: Rescue of basal fore¬ brain cholinergic neurons after implantation of genetically modified cells producing recombinant NGF. J Neurosci Res 25:405-411, 1990. Caroni P. Schwab ME: Two membrane protein fractions from rat central myelin with inhibitory properties for neurite growth and fi¬ broblast spreading. J Cell Biol 106:1281-1288, 1988. McKerracher I, David S, Jackson D, et al: Identification of myelinassociated glycoprotein as a major myelin-derived inhibitor of neu¬ rite growth. Neuron 13:805-811, 1994. Mukhopadhyay G, Doherty P. Walsh FS, et al: A novel role for myelin-associated glycoprotein, as an inhibitor of axonal regenera¬ tion. Neuron 13:757-767, 1994. Banddtlow CE, Schmidt MF, HassingerTD, et al: Role of intracellu¬ lar calcium in ni-35-evoked collapse of neuronal growth cones. Science 295:80-83, 1993. Igarashi M, Strittmatter SM. Vartanian T, et al: Mediation by G pro¬ teins of signals that cause collapse of growth cones. Science 259:77-79, 1993. Benfey M, Aguayo AJ: Extensive elongation of axons from rat brain into peripheral nerve grafts. Nature 296:150-152, 1982. Schnell L. Schwab ME: Axonal regeneration in the rat spinal cord produced by an antibody against myelin-associated neurite in¬ hibitors. Nature 343:269-272, 1990. Ungerstedt U, Arbuthnott G: Quantitative recording of rotational be¬ havior in rats after 6-hydroxy dopamine lesions of the nigrostriatal dopamine system. Brain Res 24:485-493, 1970. Lindvall O: Prospects of transplantation in human ncurodegenerative diseases. Trends Neurosci 14:376-384, 1991. Fisher LJ, Jinnah HA, Kale LC, et al: Survival and function of intrastriatally grafted primary fibroblasts genetically modified to pro¬ duce L-dopa. Neuron 6:371-380, 1991. Freeman TB. Olanow CW, Hauser RA, et al: Bilateral fetal nigral transplantation into the postcommissural putamen in Parkinson's disease. Ann Neurol 38:379-388, 1995. Mason ST, Fibiger HC: Kainic acid lesions of the striatum: Behavioural sequalae similar to Huntington's chorea. Brain Res 151:313-329, 1978.

Chapter 116/Transplantation to Improve Functions in the Diseased Central Nervous System

53.

54.

55.

56.

Divac I, Markowitsch HJ, Pritzel M: Behavioral and anatomical consequences of small intrastriatal injections of kainic acid in the rat. BrainRes 151:523-531, 1978. Hantraye P, Riche D, Maziere M, et al: Intrastriatal transplantation of cross-species fetal striatal cells reduces abnormal movements in a primate model of Huntington’s disease. Proc Natl Acad Sci USA 89:4187—4191, 1992. Lu SY, Sanberg PR, Norman AB: Intrastriatal and intraventricular fe¬ tal striatal transplants protect against QA-induced reduction of D1 dopamine receptors in rat striatum. Soc Neurosci Abstr 17:903, 1991. Pearlman SH, Levivier M, Collier TJ, et al: Striatal implants protect the host striatum against quinolinic acid toxicity. Exp Brain Res

75.

76.

77.

78.

1121

Grabowski M, Brundin P, Johansson BB: Fetal neocortical grafts implanted into adult hypertensive rats with cortical infarcts follow¬ ing a middle cerebral artery occlusion: Ingrowth of afferent fibers from the host brain. Exp Neurol 116:105-121, 1992. Grabowski M, Brundin P, Johansson BB: Functional integration of cortical grafts placed in brain infarcts of rats. Ann Neurol 34: 362-368, 1993. Plumet J, Cadusseau J, Roger M; Skilled forelimb use in the rat: Amelioration of functional deficits resulting from neonatal damage to the frontal cortex by neocortical transplantation of fetal cortical tissue. Restor Neurol Neurosci 3:135-147, 1991. Sandor R, Gonzalez MF, Moseley M, et al: Motor deficits are pro¬ duced by removing some cortical transplants grafted into injured sensorimotor cortex of neonatal rats. J Neural Transplant Plast 2:

84:303-310, 1991. Sanberg PR, Emerich DF, McDermott PE, et al: Transplantation of polymer encapsulated bovine adrenal chromaffin cells prevents quinolinic acid induced lesions of the striatum. Soc Neurosci Abstr

79.

17:903, 1991. Madrazzo I, Cuevas C, Castrejon H, et al: The first homotopic fetal homograft of the striatum in the treatment of Huntington’s disease.

80.

59.

GacMedMex 129:109-117, 1993. Harbaugh RE, Roberts DW, Coombs DW, et al: Preliminary report: Intracranial cholinergic drug infusions in patients with Alzheimer’s

81.

60.

disease. Neurosurgery 15:515-518, 1984. Bjorklund A, Stenevi U, Svendgaard N-A: Growth of transplanted monoaminergic neurons into the adult hippocampus along the per-

82.

61.

forant path. Nature 262:787-790, 1976. Bjdrklund A, Kromer LF, Stenevi U: Cholinergic innervation of the rat hippocampus by septal implants is stimulated by perforant path¬

83.

way lesion. Brain Res 173:57-64, 1979. Kordower JH, Fiandaca MS: Response of the monkey cholinergic septohippocampal system to fornix transsection: A histochemical

84.

62.

and cytochemical analysis. J Comp Neurol 298:443^157, 1990. Koiatsos VE, Nauta HJW, Clattervuck RE, et al: Mouse nerve growth factor prevents degeneration of axotomized basal forebrain cholinergic neurons in the monkey. J Neurosci 10:3801-3813, 1990. Kordower JH, Bartus RT, Bothwell M, et al: Nerve growth factor re¬ ceptor immunoreactivity in the nonhuman primate (Cebus apella): Distribution, morphology, and colocalization with cholinergic en¬

85.

Neurosci 76:391-394, 1980. Krieger DT, Perlow MJ, Gibson MJ, et al: Brain grafts reverse hy¬ pogonadism of gonadotrophine-releasing hormone deficiency.

86.

Nature 298:468^171, 1982. Gibson MJ, Krieger DT, Charlton HM, et al: Mating and pregnancy can occur in genetically hypogonadal mice with preoptic area brain

87.

grafts. Science 225:949-951, 1984. Tulpan NB, Zacur HA, Allen GS: Pituitary transplantation: I. Successful reconstitution of pituitary-dependent hormone levels.

57.

58.

63.

64.

65.

66.

67.

68.

69.

70.

71.

72. 73.

74.

zymes. J Comp Neurol 277:465^187, 1988. Ridley RM, Thornley HD, Baker HF, et al: Cholinergic neural trans¬ plants into hippocampus restore learning ability in monkeys with fornix transections. Exp Brain Res 83:533-538. 1986. Nilsson OG. Brundin P, Bjorklund A: Amelioration of spatial mem¬ ory impairment by intrahippocampal grafts of mixed septal and raphe tissue in rats with combined cholinergic and serotonergic de¬ nervation of the forebrain. Brain Res 515:193-206. 1990. Nilsson OG, Shapiro ML, Gage FH, et al: Spatial learning and mem¬ ory following fimbria-fornix transsection and grafting of fetal septal neurons to the hippocampus. Exp Brain Res 67:195-215, 1987. Williams RI, Varon S, Peterson GM, et al: Continuous infusion of nerve growth factor prevents basal forebrain neuronal death after fimbria-fornix transsection. Proc Natl Acad Sci USA 83:9231-9236,

88.

89. 90.

91.

221-233, 1991. Sinson G, Flanint ES, McIntosh TK: A model of fetal neural tissue transplantation into a site of traumatic brain injury. Soc Neurosci Abstr 20:1907, 1994. Maciunas RJ, Tulipan NB, Burns RS, et al: Brain transplantation: State of the ait, in Wilkins RH, Rengachary SS (eds): Neurosurgery Update II. New York: McGraw-Hill, 1991, pp 511-550. Valtin H: Hereditary hypothalamic diabetes insipidus in rats (Battleboro strain). Am J Med 42:814-827, 1967. Cattenach BM, Iddon CA, Charlton HM, et al: Gonadotrophin¬ releasing hormone deficiency in a mutant mouse with hypogo¬ nadism. Nature 269:338-340, 1977. Gash DM, Sladek JR, Sladek CD: Functional development of grafted vasopressin neurons. Science 210:1367-1369, 1980. Gash DM, Sladek JR: Functional and nonfunctional transplants: Studies with grafted hypothalamic and preoptic neurons. Trends

Neurosurgery 16:331-335, 1985. Bjorklund A, Nornes H, Gage F: Cell suspension grafts of noradren¬ ergic locus coeruleus neurons in rat hippocampus and spinal cord: Reinnervaton and transmitter turnover. Neuroscience 18:685-698, 1986. Privat A, Mansour H, Rajaofetra N, et al: Intraspinal transplants of serotonergic neurons in the adult rat. Brain Res Bull 22:123-129, 1989. Mas M, Zahradnik MA, Martino V, et al: Stimulation of spinal sero¬ tonergic receptors facilitates seminal emission and suppresses penile erectile reflexes. Brain Res 342:128-134, 1985. Nygren L-G, Olsson L, Seiger A: Monoaminergic reinnervation of the transected spinal cord by homologous fetal brain grafts. Brain

1986. Richter-Levin G, Segal M: Raphe cells grafted into the hippocampus can ameliorate spatial memory deficits in rats with combined sero¬ tonergic/cholinergic deficiencies. Brain Res 478:184-186, 1989. Low WC, Lewis PR, Bunch SB, et al: Functional recovery following neural transplantation of embryonic septal nuclei in adult rats with

92.

Res 29:227-235, 1977. Bregman BS, Reier PJ: Neural tissue transplants rescue axotomized rubrospinal cells from retrograde death. J Comp Neurol 244:86-95,

93.

1986. Reier PJ, Bregman BS, Wujek JR: Intraspinal transplantation of em¬ bryonic spinal cord tissue in neonatal and adult rats. J Comp Neurol

septohippocampal lesions. Nature 300:260-262, 1982. Kordower JH. Fiandaca MS, Notter MFD, et al: NGF-like trophic support from peripheral nerve for grafted rhesus adrenal chromaffin

94.

247:275-296, 1986. Houle JD, Reier PJ: Transplantation of fetal spinal cord tissue into the chronically injured adult rat spinal cord. J Comp Neurol

cells. J Neurosurg 73:418-424, 1990. Arenas E, Persson H: Neurotrophin-3 prevents the death of adult central noradrenergic neurons in vivo. Nature 367:368-371, 1994. Sharp FR, Gonzalez MF: Fetal cortical transplants ameliorate tha¬ lamic atrophy ipsilateral to neonatal frontal cortex lesions. Neurosci

95.

269:535-547, 1988. Iwashita Y, Kawaguchi S, Murata M: Restoration of function by re¬ placement of spinal cord segment in the rat. Nature 367:167-170,

Lett 71:247-251, 1986. Sorenson JC. Zimmer J, Castro AJ: Fetal cortical transplants reduce the thalamic atrophy induced by frontal cortical lesions in newborn rats. Neurosci Lett 98:33-38, 1989.

96.

97.

1994. Sendtner M. Kreutzberg GW, Thoenen H: Ciliary neurotrophic fac¬ tor prevents the degeneration of motor neurons in mouse mutant progressive motor neuronopathy. Nature 358:502-504, 1992. Blakemore WF, Crang AJ: The use of cultured autologous Schwann cells to remyelinate areas of persistent demyelination in the central nervous system. J Neurol Sci 70:207-223. 1985.

1122

98.

99. 100.

101.

102.

103.

104.

105. 106.

Part 4/Functional Stereotaxis

Gumpel M, Bauman N, Raoul M, et al: Survival and differentiation of oligodendrocytes from neural tissue transplanted into new mouse brain. Neurosci Lett 37:307-311, 1983. Blakemore WF, Franklin RJM: Transplantation of glial cells into the CNS. Trends Neurosci 14:223-227, 1991. Delgado-Escutal AV. Ward AA, Woodbury DM. et al: Basic Mechanisms of the Epilepsies: Molecular and Cellular Approaches. Advances in Neurology. New York: Raven Press, 1986, vol 44. Lindvall O, Bjorklund A: Intracerebral grafting of inhibitory neu¬ rons: A new strategy for seizure suppression in the central nervous system. Adv Neurol 57:561-569, 1992. Loscher W, Schwark WS: Further evidence for abnormal GABAergic circuits in amygdala-kindled rats. Brain Res 420: 385-390, 1987. Emson P, Joseph MH: Neurochemical and morphological changes during the development of cobalt-induced epilepsy in the rat. Brain Res 93:91-110, 1975. Lloyd KG, Bossi L, Morselli PL, et al: Alterations of GABAmediated synaptic transmission in human epilepsy. Adv Neurol 44: 1033-1044, 1986. Iadarola MJ, Gale K: Substantia nigra: Site of anticonvulsant activity mediated by gamma-aminobutyric acid. Science 218:1237-1240, 1982. Segan J, Kemmler JE, Wang FI: Adrenal medullary transplants increase spinal cord cerebrospinal fluid catecholamine levels and re¬ duce pain sensitivity. J Neurochem 56:623-627, 1991.

107.

Segan J, Kemmler JE: Increased levels of Met-enkephalin-like immunoreactivity in the spinal cord CSF of rats with adrenal medullary transplants. Brain Res 502:1-10, 1989.

108.

Segan J, Kemmler JE, Wang H: Adrenal medullary implants in the rat spinal cord cerebrospinal fluid catecholamine levels and reduce pain sensitivity. J Neurochem 56:623-627, 1991. Wu HH, Lester BR, Sun Z, et al: Antinociception following implan¬ tation of mouse B16 melanoma cells in mouse and rat spinal cord. Pain 56:203-210, 1994. Wu HH, McLoon SC. Wilcox GL: Antinociception following im¬ plantation of AtT-20/hENK cells in rat spinal cord. J Neural Transpl Plast 4:15-26, 1993. Lysaght MJ, Frydel B, Gentile F, et al: Recent progress in immunoisolated cell therapy. J Cell Biochem 56:196-203, 1994. Aebischer P, Buchser E. Joseph JM, et al: Xenotransplantation of encapsulated bovine chromaffin cells for the treatment of in¬ tractable pain: A phase I clinical study. Soc Neurosci Abstr 20:1707, 1994,

109.

110.

111. 112.

113. 114. 115.

Sanes JR. Lichtman JW: Neurobiology: From cell line to brain. Nature 356:562-563, 1992. Fredericksen K. Jat PS, Valtz N. et al: Immortalization of precursor cells from the mammalian CNS. Neuron 1:439^148, 1988. Snyder EY, Deitcher DL. Walsh C, et al: Multipotent neural cell lines can engraft and participate in development of mouse cerebel¬ lum. Cell 68:33-51, 1992.

CHAPTER

117

FETAL TISSUE TRANSPLANTATION IN MOVEMENT DISORDERS

Alan Fine and Renn O. Holness

The intracranial grafting of mammalian brain tissue was at¬ tempted as early as 1890 by W. G. Thompson,1 and survival of immature brain tissue allografts was reported by Dunn in 1917.2 Brain tissue transplantation was attempted intermit¬ tently over the following decades; survival of fetal mammalian central nervous system tissue transplanted to the anterior eye chamber was reported in 1924,3 and transplantation to the brain was reported in 1940.4 Neurons and glia of the fetal brain lack major (class I and II) histocompatibility antigens under normal circumstances,5 al¬ though these antigens are expressed on brain endothelia6 and meningeal cells and may be induced in certain glia by inter¬ feron-gamma and other stimuli.5-7 Thus, in contrast to other fe¬ tal tissues,8 grafts of properly prepared fetal neural cells may survive transplantation to an unrelated member of the same species without rejection. Serious efforts to reconstruct a damaged or diseased brain by means of fetal neural transplantation began only after the development of new anatomic marking techniques that permit¬ ted the unambiguous demonstration of graft survival910 and es¬ pecially after the demonstration that grafts could influence host brain function in an animal model of Parkinson’s disease.1112 The principal lesion of Parkinson’s disease is the degenera¬ tion of dopaminergic neurons in the pars compacta of the sub¬ stantia nigra and the subsequent reduction of dopamine release from these cells’ terminals in the corpus striatum. The causes of this degeneration are in most cases unknown, and there is no cure. Although some other brain structures also are affected, most—including the targets of the dopamine fibers—are rela¬ tively spared, making this disorder particularly amenable to re¬ construction by fetal neural transplantation. Indeed, substantial behavioral improvements were obtained when rat fetal dopa¬ minergic brain tissue was implanted into the dopaminedepleted striatum of rats with an experimentally induced form of parkinsonism."-13 These results have been widely confirmed and extended in rodents14 and primates.15-17 Furthermore, hu¬ man fetal dopaminergic brain tissue was found to reduce motor deficits when transplanted to the striatum of immunosuppressed experimentally parkinsonian rats.1819 The mechanisms by which intracerebral fetal neural grafts exert these behavioral effects are not fully understood, but there is evidence that the grafts can supply missing neurotrans¬ mitter or neuromodulator substances not only by ditfuse re¬ lease but by reformation of anatomically appropriate synaptic

connections with neurons in the host brain. In addition, the grafts may produce growth-stimulating factors, stimulate their production by the host brain, influence gene expression and other aspects of the metabolism of host brain neurons, and serve as physical conduits for the regeneration of host brain pathways.20-23 In 1987, clinical trials of human fetal dopaminergic brain tissue transplants were begun in Sweden,24-253 Mexico,26 and England.27 Encouraging results and the absence of major complications have led to the continuation of these trials28-41 and the initiation of similar clinical trials in Cuba,42 Spain,43 the United States,44'48 Canada,49 France,493 China,50 Czecho¬ slovakia,51 and Poland.52 These preliminary clinical trials and their potential implications for application of fetal tissue trans¬ plantation to the treatment of other disorders have been major causes of the current upsurge in public attention and contro¬ versy concerning the use of human fetal cadaver tissue.

TECHNICAL CONSIDERATIONS Experience with open craniotomy for microsurgical implanta¬ tion of adrenal or fetal tissue has indicated that elderly parkin¬ sonian patients withstand major surgery poorly.53 In contrast, surgical treatment of tremor had shown that stereotactic tech¬ niques have a high degree of safety. Therefore, it seemed preferable to attempt grafting procedures in parkinsonian pa¬ tients by using stereotactic means. Stereotactic implantation of adrenal medullary tissue for the treatment of parkinsonism was first attempted by Backlund and associates54 and has since been used by others to place fetal ventral mesencephalic tissue uni¬ laterally or bilaterally into the corpus striatum with minimal complications. Cannula trajectories are generally computed from computed tomography (CT) or magnetic resonance imag¬ ing (MRI) stereotactic coordinates through the use of trigono¬ metric software (e.g.. Arc Angle for Leksell stereotactic appa¬ ratus, Elekta Instruments) (Fig. 117-1). The principal technical differences between the groups at¬ tempting these procedures have involved the construction of injection cannulas; the number and site of targets; the source, preparation, and amount of injected material; and immunosup¬ pression of the recipient. In general, transplanted fetal neurons survive best when taken from embryos shortly after their last cell division but before extensive outgrowth of axons and den-

1123

1124

Part 4/Functional Stereotaxis

VICTl

Figure 117-1. Determination of stereotactic coordinates for tissue implantation. CT scans at 5-mm intervals are made with the headframe in place. Targets are selected at two levels within the striatum and are spaced so that lines linking both anterior (1), both middle (2), and both posterior (3) targets converge toward the surface, anterior to motor cortex and avoiding the midline. Arc angles and injection depths are computed on the basis of these target coordinates.

drites that would be traumatized during dissection; for human fetal dopaminergic neurons of the substantia nigra, this period appears to be mainly between 5 and 8 weeks of gestational age.55,56 Provision must be made to establish the absence of transmissible pathogens in the transplanted material; this ordi¬ narily requires some period of storage until bacteriologic and virological tests are obtained. Thus, Henderson and coworkers57 have used a 20-mm nee¬ dle (0.9 mm in outer diameter, 0.5 mm in inner diameter) to implant 0.52 ml of ventral mesencephalic tissue from a single fetus (11 to 19 weeks of gestational age) stored at 4°C for 5 to 12 h. The tissue was “partially dispersed” by agitation in a volume of approximately 1 ml and injected unilaterally into the caudate; 12 cases were reported with no significant complications. Spencer and colleagues4® have used two to four targets 4 mm apart on an anterior-posterior line bisecting the caudate nu¬ cleus on one side. MRI scans were used to calculate “avascular trajectories” for a l-mtn (outer diameter) needle. Tissue from 7- to 11-week gestational age fetuses was stored in liquid nitro¬

gen for periods up to several months and thawed immediately before implantation; tissue fragments were aspirated into the injection needle without dissociation and extruded along 8-mm tracks. Widner and associates32 have used bilateral putamenal injections spaced 2 weeks apart to treat patients with 1-methyl4-phenyl-l,2,3,6-tetrahydropyridine (MPTP)-induced parkin¬ sonism. For these injections, fresh tissue from three to four fe¬ tuses was enzymatically dissociated in balanced salt solution, final volume 100 pd. A 1-mm (outer diameter) cannula was used to make eight deposits of 2.5 |xl of cell suspension each over a 10- to 14-mm distance. Three injections were made into each putamen. Freed and colleagues46 have made bilateral putamen and caudate injections of fetal ventral mesencephalic tissue during a single operation. Blocks of tissue from one fetus (45 to 55 days of gestational age) were stored for more than 24 h at 10°C in the medium of Kawamoto and Barrett58 before being aspi¬ rated into the injection cannula (0.46- or 0.64-mm outer diame¬ ter). Seven implants of 1.5 to 3.0 jxl. each along a 10-mm track.

Chapter 117/Fetal Tissue Transplantation in Movement Disorders

1125

were made on each side via an elliptical burr hole 3.5 by 1.5 cm. No major complications were reported other than non¬ threatening pneumocephalus. Indications from animal studies suggest that successful cell suspension implantation diminishes with increasing needle di¬ ameter.59 In five cases, we have used nested cannulas to achieve satisfactory rigidity for accurate placement while retaining small dimensions (0.5-mm outer diameter, 0.25-mm inner di¬ ameter) over the distal 3 cm. We inject a total of 100 pi of cell suspension, derived from four to six ventral mesencephalons of 5- to 8-week gestational age fetuses, along three 1.5- to 2.0-cm tracks into the putamen opposite the most severely involved extremities. Tissue is stored from 3 to 7 days at 4°C in the medium of Kawamoto and Barrett58 prior to enzymatic dissoci¬ ation and implantation, to permit testing of adjacent, nondopaminergic tissue for bacterial and mycoplasma contamina¬ tion (Fig. 117-2). A specially designed micrometer advance allows tissue to be injected as the cannula is withdrawn over a 15- to 20-min period; the cannula is then held in place for 5 min, followed by slow withdrawal to prevent the loss of the in¬ jected tissue (Fig. 117-3). Most patients subjected to fetal tissue transplantation have had the procedure done under local anesthesia. We have been impressed with the comfort and safety afforded by neurolept anesthesia or intravenous general anesthesia with the patient intubated. This allows accurate neuroimaging without the ef¬ fects of tremor or dyskinetic movements. The surgical proce¬ dure itself, though simple, requires that the patient be in the same position for 2 or 3 h, and general anesthesia greatly facil¬ itates the process. Among possible operative complications is deep intracere¬ bral hemorrhage caused by the passage of the cannula. It can be

Figure 117-3. Close-up view of the instrument carrier, showing the microsyringe together with the fine screw advance allowing 0.1-mm accuracy in depth, with smooth advance and retraction over a range of approximately 30 mm.

expected that in the future, three-dimensional imaging tech¬ niques superimposing angiographic and CT or MRI informa¬ tion will become widely available. Skull entry can be achieved via a small craniectomy— which has the potential of causing cerebrospinal fluid (CSF) loss leading to undesirable brain shifting during implantation— or, as favored by us, via multiple small drill holes that cause minimal CSF loss (Fig. 117-4). Most reports to date do not specify the patients’ detailed postoperative course. Despite the less invasive nature of stereo¬ tactic implantation (compared with open craniotomy), it must be noted that in the series of Freed and associates46 in which multiple bilateral implants were performed during each opera¬ tion, five patients worsened in the 4 to 6 weeks after surgery. The details of this deterioration are not given, but it may be as¬ sumed to have been induced by the surgical procedure. Bilateral implantation may be safer if performed in a staged fashion, as practiced by Widner and colleagues.32 Figure 117-2. Human fetal ventral mesencephalic neurons used for transplantation. The minute quantity of cell suspension remaining in the loading vial after surgery was grown for 1 week in tissue culture, fixed and stained with antibodies against tyrosine hydroxylase. Dopaminergic neurons, constituting about 10 percent of the total population, are stained brown; other, unstained cells are visible in outline in this differential interference contrast image.

OUTCOME As of February 1995, more than 160 severely afflicted parkin¬ sonian patients were treated by intrastriatal implantation of fe¬ tal ventral mesencephalic brain tissue, usually of 5 to 12 weeks of gestational age, using material from 1 to 16 fetuses per pa-

1126

Part 4/Functional Stereotaxis

the patients and neurologists, was reported to improve both during optimal drug therapy and during drug holiday periods. Three of the 12 patients described by Henderson and asso¬ ciates57 were thought to be significantly improved after 12 months, while 6 had more modest improvements; 3 deterio¬ rated below baseline levels during the period of follow-up. Freed and coworkers46 reported 7 patients followed for 12 to 46 months after transplantation; 6 showed improvements in the Hoehn and Yahr scale from an average of 3.71 to 2.50, while their required drug doses decreased by 39 percent on average. Both immunosuppressed and nonimmunosuppressed patients appeared to improve equally.

Figure 117-4. Operative field with the microsyringe, guide cannula, and needle in place at the end of an injection.

tient. Improvements have been reported in most cases, and in no patient have symptoms been seen to worsen.37-60 Inadequate documentation and lack of standardization have made it diffi¬ cult to evaluate the majority of these claims, and even welldocumented reports have been criticized.603'61 Of particular interest, the improvement of MPTP-induced parkinsonism in subhuman primates after fetal dopaminergic neural transplantation has recently been replicated in humans by Widner and associates.32 Two immunosuppressed patients with severe MPTP-induced parkinsonism displayed a signifi¬ cant and sustained improvement in motor function as well as a reduction in L-dopa requirements over a 2-year period. Striatal uptake of fiuorodopa on positron emission tomography (PET) scans was convincingly increased in both patients, although in the absence of postmortem histology the possibility remains that such PET changes reflect the growth of endogenous rather than transplant-derived catecholaminergic fibers. The response of idiopathic parkinsonism to fetal tissue grafting has been less consistent and dramatic. Most of these patients have not been subjected to rigorous reproducible evaluation. PET imaging has in some cases revealed in¬ creased striatal fiuorodopa uptake after transplantation, but interpretation is subject to the previously mentioned reserva¬ tion. Lindvall and associates25 found no major clinical benefit in two patients who were implanted unilaterally and followed for 6 months; this conclusion was maintained at 18 months.253 By this time one of the patients had reverted to the preopera¬ tive status; the other, while demonstrating significant im¬ provement in electrophysiological, PET, and quantitative clin¬ ical parameters, had not sustained significant functional improvement as revealed by the Hoehn and Yahr scale. Spencer and colleagues48 described three patients with idio¬ pathic Parkinson’s disease in whom unilateral transplantation led to bilateral improvement in motor tasks, as assessed on videotape; function in activities of daily living, as assessed by

Despite these encouraging results, implanted patients with idiopathic Parkinson’s disease remain recognizably parkin¬ sonian and require continued drug treatment. It is fair to say that most of these patients have not been significantly im¬ proved from a practical standpoint. Unfortunately, the varia¬ tions in technique and above all in the thoroughness of clini¬ cal and quantitative assessment make it practically impossible for the different series to be compared objectively. This sit¬ uation will certainly be remedied as more trials using the evaluation methods and criteria recommended by the Core Assessment Program for Intracerebral Transplantation62 are implemented. With more long-term follow-up and further re¬ porting of larger series of cases, it should soon be established whether fetal tissue grafting for Parkinson’s disease is an ef¬ fective form of treatment for late-stage disease that is safe enough to be offered to the less severely afflicted patients who might be expected to benefit more from this form of intervention.

POSSIBLE FUTURE APPLICATIONS OF FETAL TRANSPLANTATION Human fetal sympathetic neurons and adrenal chromaffin cells, which under certain circumstances may synthesize and secrete dopamine, have been transplanted to the striatum of parkinson¬ ian monkeys, but without an effect on the monkeys’ clinical symptoms.63 Fetal adrenal tissue also has been transplanted to the striatum of three parkinsonian patients33-35; the results so far have been disappointing.36 The outcome of fetal ventral mesen¬ cephalic as well as adrenal grafts may be enhanced by the ad¬ ministration of exogenous growth factors.64 Huntington’s disease is a progressive, autosomal dominant inherited disease that is characterized by dyskinesias and men¬ tal deterioration resulting from massive degeneration of striatal neurons, particularly the inhibitory projection neurons that use gamma-aminobutyric acid as a transmitter substance. Although symptoms of the disease generally appear only in the third or fourth decade, newly available genetic markers permit the identification of carrier or afflicted individuals even in utero. There is at present no effective treatment, and death generally occurs by age 50. Studies in rodents65-67 and primates68 have demonstrated that fetal striatal grafts to the lesioned striatum can survive and provide partial functional restitution to the le¬ sioned animal. Here, as in Parkinson’s disease, a clinical trial of human fetal neural transplantation has been initiated on the basis of rodent studies before the publication of primate results69; slight motor improvements in the first patient were re¬ ported after 1 year.

Chapter 117/Fetal Tissue Transplantation in Movement Disorders

Preliminary experimental studies in rodents suggest that at least two other types of neurodegenerative movement disorders—motor neuron disease and hereditary degenerative ataxias—may be amenable to treatment by fetal neural trans¬ plantation.28,70 These progressive, untreatable, and fatal disor¬ ders are characterized by degeneration of spinal motoneurons and cerebellar neurons, respectively. In studies using animal models of these diseases, it has been demonstrated that fetal spinal motoneurons transplanted into the experimentally motoneuron-depleted spinal cord of adult rats can establish anatomic interactions with the host,71,72 while fetal cerebellar Purkinje’s cells transplanted into the cerebellum of Purkinjecell-degeneration mutant mice can establish features of normal cerebellar circuitry.73 An ability of these grafts to induce func¬ tional recovery has not been demonstrated. While most forms of epilepsy are controllable by medica¬ tion, at least 10 percent of patients do not respond adequately; surgical removal or isolation of epileptic foci can control seizures in some of these patients, although the resulting im¬ pairments may be profound. The results of animal experiments suggest that fetal neural transplantation may provide an alter¬ native and less destructive means for the control of medically intractable epilepsy. Enhanced seizure susceptibility in rats caused by genetic abnormalities74 or experimental depletion of forebrain catecholamines75,76 can be suppressed by intracere¬ bral transplantation of fetal catecholamine-secreting neurons. Evidence that rats can be protected from seizures by focal intracerebral microinfusion of drugs that mimic or augment the inhibitory action of gamma-aminobutyric acid77 raises the possibility that permanent protection may be provided by similarly placed transplants of fetal gamma-aminobutyric acid-secretin neurons, although a preliminary attempt has been unsuccessful.78 The results of animal experiments suggest that other neu¬ rological disorders, such as the currently untreatable demen¬ tias of Alzheimer’s disease, advanced Parkinson’s disease, and chronic alcoholism (Korsakoff’s syndrome), may be amenable to appropriate fetal neural transplantation. The pathology of Alzheimer’s disease is conspicuously wide¬ spread, involving many cortical and subcortical brain regions; however, profound degeneration of certain monoaminesecreting pathways, particularly of the acetylcholine-secreting projections from the basal forebrain to the neocortex and hip¬ pocampus, is characteristic of all three disorders79-81 and may be correlated with the extent of cognitive deficits.82,83 Experi¬ mental studies in rats84,85 and monkeys86 have provided fur¬ ther evidence that degeneration of the acetylcholine-secreting projections may contribute to memory impairment in these disorders. Unfortunately, it has not been possible to reproduce the full pathology of these human diseases in experimental animals. Nevertheless, memory impairments resulting from chronic ethanol administration81 or disruption of acetylcholine projections to neocortex86a or hippocampus87 in rats and in monkeys88,89 have been restored by transplantation of fetal neurons of the acetylcholine-producing basal forebrain to the depleted cortex or hippocampus; fetal neural transplantmediated restoration of another monoamine, serotonin, to the depleted rat hippocampus has also ameliorated memory impairments.90,91 There are indications that fetal neural transplantation may play a future role in the treatment of traumatic injury and isch¬

1127

emic or hemorrhagic injury (stroke) to the brain or spinal cord; at present, the consequences of these injuries are largely irre¬ versible. Cortical neuronal degeneration after acute hypoxia in rats has been reported to be reduced by subsequent intracere¬ bral implantation of fetal neocortical tissue,92 and transplants of fetal hippocampal cells into rat hippocampus 1 week after se¬ lective ischemic hippocampal injury can reestablish anatomic and electrical features of the damaged local neuronal cir¬ cuitry.93,94 This potential application of fetal neural transplanta¬ tion is still speculative. Full functional recovery after spinal trauma or another mas¬ sive central nervous system injury would require not only re¬ placement of damaged nerve cells but reformation of long pathways and of the intricate neuronal interconnections neces¬ sary for normal sensory and motor function. Thus, the applica¬ tion of fetal neural transplantation to such injury is speculative. There has, however, been some progress with respect to long¬ distance pathway reconstruction: nerve fiber regrowth through fetal brain and spinal cord tissues may be more extensive than through adult central nervous system tissue, and such fetal tis¬ sue transplants have been used to establish “bridges” for the re¬ formation of long pathways in the lesioned adult rat central nervous system.95,96 Implantation of other permissive substrates for long-range nerve fiber growth, such as peripheral nerve,97 in conjunction with transplants of appropriate fetal neural tissue,98 may in the future facilitate the functional reconstruction of complex brain circuitry. Preliminary observations of the func¬ tional effects of intraspinal implants of fetal monoaminergic brain tissue in rats with spinal cord lesions99,100 raise the possi¬ bility of therapeutic applications of such fetal tissue transplants for the treatment of paraplegia to replace damaged descending monoaminergic projections.101 Progress with respect to the reconstruction of detailed mi¬ croscopic patterns of connectivity has been less encouraging; to date there have been no convincing demonstrations of refor¬ mation of ordered topographic connections in the damaged adult central nervous system by transplanted fetal neurons. Thus, the neurological applications of fetal tissue transplanta¬ tion most likely to be successful in the near future are those in which damage or degeneration affects pathways in which pre¬ cise spatial and temporal patterns of neurochemical release are not essential for function. Fetal tissue transplantation may play a role in the manage¬ ment of chronic pain. Transplants of adrenal medullary tissue—which contains, in addition to catecholamines, endoge¬ nous opioids known to influence central nervous system pro¬ cessing of pain—to pain-processing pathways in the spinal cord and midbrain have produced analgesia in rats.102 Recently, allografts of adult cadaveric adrenal medullary tissue to the spinal subarachnoid space have yielded long-lasting relief from chronic pain in terminally ill cancer patients.103 According to a principal investigator in these transplant studies, human fetal tissue may be more effective than adult cadaveric tissue for these applications (Pappas G, personal communication), which at present are highly speculative.

ACKNOWLEDGMENT Our work on fetal dopaminergic transplantation has been sup¬ ported by grants from the Parkinson Foundation of Canada.

1128

Part 4/Functional Stereotaxis

References 1. 2.

3.

4. 5. 6.

7.

8.

9.

10.

11.

12.

13.

14.

15.

16.

17.

18.

19.

20. 21.

22.

Thompson WG: Successful brain grafting. NY Med J 51:701-702, 1890. Dunn EH: Primary and secondary findings in a series of attempts to transplant cerebral cortex in the albino rat. J Comp Neurol 27:565-582, 1917. Faldino G: Sullo sviluppo dei tessuti embrionali omoplastici innestati nella camera anteriore dell’occhio del coniglio. Arc Scien Biol 5:328-346, 1924. Le Gros Clark WE: Neuronal differentiation in implanted foetal cor¬ tical tissue. J Neurol Psychiatry 3:263-284, 1940. Wong GHW, Bartlett PF, Clark-Lewis I, et al: Inducible expression of H-2 and la on brain cells. Nature 310:688-691, 1984. Mauerhoff T, Pujol-Borrell R, Mirakian R, Bottazzo GF: Differential expression and regulation of major histocompatibility complex (MHC) products in neural and glial cells of the human fetal brain. J Neuroimmunol 18:271-289, 1988. Wong GHW, Bartlett PF, Clark-Lewis I, et al: Interferon-gamma in¬ duces the expression of H-2 and la antigens on brain cells. J Neuroimmunol 7:255-278, 1985. Hofman FM, Danilovs JA, Taylor CR: HLA-DR (Ia)-positive den¬ dritic-like cells in human fetal nonlymphoid tissues. Transplantation 37:590-594, 1984. Olson L, Seiger A: Brain tissue transplanted to the anterior chamber of the eye: I. Fluorescence histochemistry of immature cate¬ cholamine and 5-hydroxytryptamine neurons innervating the rat iris. Z Zellforch 195:175-194, 1972. Das GD, Altman J: Transplanted precursors of nerve cells: Their fate in the cerebellums of young rats. Science 173:637-638, 1971. Perlow MJ, Freed WJ, Hofer BJ, et al: Brain grafts reduce motor abnormalities produced by destruction of nigrostriatal dopamine system. Science 204:643-647, 1979. Bjorklund A, Stenevi U: Reconstruction of the nigrostriatal dopamine pathway by intracerebral nigral transplants. Brain Res 177:555-560, 1979. Bjorklund A, Stenevi U. Dunnett SB, Iversen SD: Functional reacti¬ vation of the deafferented neostriatum by nigral transplants. Nature 289:497^199, 1981. Nadaud D, Herman JP, Simon H, Le Moal M: Functional recovery following transplantation of ventral mesencephalic cells in rats sub¬ jected to 60HDA lesions of the mesolimbic dopaminergic neurons. Brain Res 304:137-141, 1984. Sladek JR, Redmond DE, Collier TJ, et al: Transplantation of fetal dopamine neurons into primate brain reverses MPTP-induced parkinsonism. Prog Brain Res 71:309-322, 1987. Fine A, Hunt SP, Oertel WH, et al: Transplantation of embryonic dopaminergic neurons to the corpus striatum of marmosets rendered parkinsonian by l-methyl-4-phenyl-l,2,5,6-tetrahydropyridine. Prog Brain Res 78:479-489, 1988. Dunnett SB, Annett LE: Nigral transplants in primate models of parkinsonism, in Lindvall O, Bjorklund A, Widner H (eds): Intracerebral Transplantation in Movement Disorders. Amsterdam: Elsevier, 1991. pp 27-51. Stromberg I, Bygdeman M, Goldstein M, et al: Human fetal substan¬ tia nigra grafted to the dopamine-denervated striatum of immunosuppressed rats: Evidence for functional reinnervation. Neurosci Lett 71:271-276, 1986. Brundin P. Nilsson OG, Strecker RE, et al: Behavioral effects of hu¬ man fetal dopamine neurons grafted in a rat model of Parkinson’s disease. Brain Res 65:235-240, 1986. Fine A: Transplantation in the central nervous system. Sci Am 82:52-58B, 1986. Bjorklund A, Lindvall O, Isacson O, et al: Mechanisms of action of intracerebral neural implants: Studies on nigral and striatal grafts to the lesioned striatum. Trends Neurosci 10:509-516. 1987. Segovia J, Meloni R, Gale K: Effect of dopaminergic denervation and transplant-derived reinnervation on a marker of striatal GABAergic function. Brain Res 493:185-189, 1989.

23.

24.

Segovia J, Castro R, Notario V, Gale K: Transplants of fetal substan¬ tia nigra regulate glutamic acid decarboxylase gene expression in host striatal neurons. Mol Brain Res 10:359-362, 1991. Lindvall O. Rehncrona S, Gustavii B, et al: Fetal dopamine-rich mesencephalic grafts in Parkinson’s disease. Lancet 2:1483-1484, 1988.

25.

Lindvall O. Rehncrona S, Brundin P. et al: Human fetal dopamine neurons grafted into the striatum in two patients with severe Parkinson’s disease: A detailed account of methodology and a 6-month follow-up. Arch Neurol 46:615-631, 1989. 25a. Hoffer BJ, Leenders KL, Young D, et al: Eighteen-month course of two patients with grafts of fetal dopamine neurons for severe Parkinson’s disease. Exp Neurol 118:243-252, 1992. 26. Madrazo I, Leon V, Torres C, et al: Transplantation of fetal substan¬ tia nigra and adrenal medulla to the caudate nucleus in two patients with Parkinson’s disease. N Engl J Med 318:51, 1988. 27. Hitchcock ER, Clough CG, Hughes RC. Kenny BG: Transplantation in Parkinson’s disease: Stereotactic implantation of adrenal medulla and foetal mesencephalon. Acta Neurochir Suppl (Wien) 46:48-50, 1988. 28. 29.

30.

31.

32.

33.

34.

35.

36.

37.

38.

39.

40.

41.

Lindvall O: Prospects of transplantation in human neurodegenerative diseases. Trends Neurosci 14:376-384, 1991. Lindvall O, Brundin P, Widner H, et al: Grafts of fetal dopamine neurons survive and improve motor function in Parkinson’s disease. Science 247:574-577, 1990. Lindvall O, Widner H, Rehncrona S, et al: Transplantation of fetal dopamine neurons in Parkinson’s disease: One-year clinical and neurophysiological observations in two patients with putaminal im¬ plants. Ann Neurol 31:155-165, 1992. Sawle GV, Bloomfield PM, Bjorklund A, et al: Transplantation of fetal dopamine neurons in Parkinson’s disease: PET [l8F]6-L-fluorodopa studies in two patients with putaminal implants. Ann Neurol 31:166-173, 1992. Widner H. Tetrud J. Rehncrona S, et al: Bilateral fetal mesen¬ cephalic grafting in two patients with parkinsonism induced by l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP). N Engl J Med 327:1556-1563, 1992. Madrazo I, Franco-Bourland R, Ostrosky-Solis F, et al: Fetal ho¬ motransplants (ventral mesencephalon and adrenal tissue) to the striatum of Parkinsonian subjects. Arch Neurol 47:1281-1285, 1990. Madrazo I, Franco-Bourland R. Ostrosky-Solis F, et al: Neural transplantation (auto-adrenal, fetal nigral and fetal adrenal) in Parkinson’s disease: The Mexican experience. Prog Brain Res 82:593-602, 1990. Madrazo I, Franco-Bourland RE, Aguilera M, et al: Fetal ventral mesencephalon brain homotransplantation in Parkinson’s disease: The Mexican experience, in Lindvall O, Bjorklund A. Widner H (eds): Intracerebral Transplantation in Movement Disorders. Amsterdam: Elsevier, 1991. pp 123-130. Madrazo I: Key issues in intracerebral transplantation in movement disorders, in Lindvall O, Bjorklund A, Widner H (eds): Intra¬ cerebral Transplantation in Movement Disorders. Amsterdam: Elsevier, 1991. p 222. Madrazo I, Franco-Bourland R. Aguilera M. et al: Development of human neural transplantation. Neurosurgery 29:165-177, 1991. Hitchcock ER. Kenny BG, Clough CG, et al: Stereotaxic implanta¬ tion of foetal mesencephalon (STIM): The UK experience. Prog Brain Res 82:723-728, 1990. Hitchcock ER. Kenny BG, Clough CG. et al: Stereotaxic implanta¬ tion of foetal mesencephalon. Stereotact Fund Neurosurg 54, 55:282-289, 1990. Hitchcock ER. Henderson BTH. Kenny BG. et al: Stereotaxic im¬ plantation of foetal mesencephalon, in Lindvall O, Bjorklund A, Widner H (eds): Intracerebral Transplantation in Movement Disorders. Amsterdam: Elsevier. 1991, pp 79-86. Clough CG, Hitchcock ER. Hughes RC, et al: Brain implants in man do not break down the blood-brain barrier to dopamine and domperidone. Brain Res 536:318-320, 1990.

Chapter 117/Fetal Tissue Transplantation in Movement Disorders

42.

43.

44.

45.

46.

47. 48.

Molina H, Quinones R, Alvarez L, et al: Transplantation of hu¬ man fetal mesencephalic tissue in caudate nucleus as treatment for Parkinson’s disease: The Cuban experience, in Lindvall O, Bjorklund A, Widner H (eds): Intracerebral Transplantation in Movement Disorders. Amsterdam: Elsevier, 1991, pp 99-110. Lopez-Lozano JJ, Bravo G, Brera B, et al: Can an analogy be drawn between the clinical evolution of Parkinson’s patients who undergo autoimplantation of adrenal medulla and those of fetal ventral mes¬ encephalon transplant recipients? in Lindvall O, Bjorklund A, Widner H (eds): Intracerebral Transplantation in Movement Disorders. Amsterdam: Elsevier, 1991, pp 87-98. Freed CR, Breeze RE, Rosenberg NL, et al: Transplantation of hu¬ man fetal dopamine cells for Parkinson’s disease: Results at 1 year. Arch Neurol 47:505-512, 1990. Freed CR, Breeze RE, Rosenberg NL, et al: Fetal neural implants for Parkinson’s disease: Results at 15 months, in Lindvall O, Bjorklund A, Widner H (eds): Intracerebral Transplantation in Movement Dis¬ orders. Amsterdam; Elsevier, 1991, pp 69-77. Freed CR, Breeze RE, Rosenberg NL, et al: Survival of implanted fetal dopamine cells and neurologic improvement 12 to 46 months after transplantation for Parkinson’s disease. N Engl J Med 327:1549-1555, 1992. Redmond DE Jr, Leranth C, Spencer DD, et al: Fetal neural graft survival. Lancet 336:820-822, 1990. Spencer DD, Robbins RJ, Naftolin F, et al: Unilateral transplantation of human fetal mesencephalic tissue into the caudate nucleus of pa¬ tients with Parkinson’s disease. N Engl J Med 327:1541-1548,

1992. 49. Fine A, Gaudet P, Flolness RO, et al: Fetal dopaminergic neural transplantation for treatment of Parkinson’s disease: Outcome after one year. Can J Neurol Sci 21(suppl 2):S27, 1994. 49a. Peschanski M, Defer G, N’Guyen JP, et al: Bilateral motor improve¬ ment and alteration of L-dopa effect in two patients with Parkinson’s disease following intrastriatal transplantation of fetal ventral mesen¬ cephalon. Brain 117:487-499, 1994. 50. Blakeslee S: In careful test, Parkinson’s patient shows gains after fetal-cell implant. New York Times. May 2, 1989, p 18. 51. Subrt O, Tichy M, Vlayka V: Grafting of fetal dopamine neurons in Parkinson’s disease. Presented at the Eric K. Fernstrom Symposium: Intracerebral transplantation in movement disorders: Experimental basis and clinical experiences, Lund, Sweden, June 52.

53.

54.

55.

56.

57.

58. 59.

20-22, 1990. Dymecki J. Zabek M, Mazurowski W, et al: Human fetal dopamine cell transplantation in Parkinson’s disease. Presented at the Eric K. Fernstrom Symposium: Intracerebral transplantation in movement disorders: Experimental basis and clinical experiences, Lund, Sweden, June 20-22, 1990. Goetz CG, Olanow CW, Roller WC, et al: Multicenter study of autologous adrenal medullary transplantation to the corpus striatum in patients with advanced Parkinson’s disease. N Engl J Med 320:337-341, 1989. Backlund ED, Granberg PD, Hamberger B, et al: Transplantation of adrenal medullary tissue to striatum in parkinsonism: First clinical trials. J Neurosurg 62:169-173, 1985. Freeman TB, Kordower JH: Human cadaver embryonic substantia nigra grafts: Effects of ontogeny, pre-operative graft preparation and tissue storage, in Lindvall O. Bjorklund A, Widner H (eds): Intra¬ cerebral Transplantation in Movement Disorders. Amsterdam: Elsevier, 1991, pp 163-170. Verney C, Zecevic N, Nikolic B, et al: Early evidence of catecholaminergic cell groups in 5- and 6-week-old human embryos using tyrosine hydroxylase and dopamine-(3-hydroxylase immunocytochemistry. Neurosci Lett 131:121 -124, 1991. Henderson BTH, Clough CG, Hughes RC, et al: Implantation of human fetal ventral mesencephalon to the right caudate nucleus in advanced Parkinson’s disease. Arch Neurol 48:822-827, 1991. Kawamoto JC, Barrett JN; Cryopreservation of primary neurons for tissue culture. Brain Res 384:84-93, 1986. Brundin P: Dissection, preparation, and implantation ot human em¬ bryonic brain tissue, in Dunnett SB, Bjorklund A (eds): Neural

1129

Transplantation: A Practical Approach. Oxford: Oxford University Press, 1992, pp 139-160. 60. Thompson L: Fetal transplants show promise. Science 257:868-870, 1992. 60a. Freed WJ: Fetal brain grafts and Parkinson’s disease. Science 250:1434, 1990. 61. Miletich RS, Bankiewicz KS, Plunkett RJ: Fetal brain grafts and Parkinson’s disease. Science 250:1434-1435, 1990. 62. CAPIT Committee: Langston JW, Widner H, Goetz CG, et al: Core assessment program for intracerebral transplantations (CAPIT). Mov Disord 7:2-13, 1992. 63. Yong VW, Guttmann M, Kim SU, et al: Transplantation of human sympathetic neurons and adrenal chromaffin cells into parkinsonian monkeys: No reversal of clinical symptoms. J Neurol Sci 94:51-67, 64.

65.

66.

67.

68.

69.

70.

71.

72.

73. 74.

75.

76.

77.

78. 79. 80.

81.

1989. Olson L, Backlund EO, Ebendal T, et al: Intraputaminal infusion of nerve growth factor to support adrenal medullary autografts in Parkinson’s disease: One year follow-up of first clinical trial. Arch Neurol 48:373-381, 1991. Deckel AW, Robinson RG, Coyle JT, Sanberg PR: Reversal of longterm locomotor abnormalities in the kainic acid model of Huntington’s disease by day 18 fetal striatal implants. Eur J Pharmacol 93:287-288, 1983. Isacson O, Brundin P, Kelly PAT, et al: Functional neuronal replace¬ ment by grafted striatal neurones in the ibotenic acid lesioned rat striatum. Nature 311:458—460, 1984. Isacson O, Dunnett SB, Bjorklund A: Graft-induced behavioral re¬ covery in an animal model of Huntington disease. Proc Natl Acad Sci USA 83:2728-2732, 1986. Hantraye P, Riche D, Maziere M, Isacson O: An experimental pri¬ mate model for Huntington’s disease: Anatomical and behavioural studies of unilateral excitatoxic lesions of the caudate-putamen in the baboon. Exp Neurol 108:91-104, 1990. Madrazo I, Franco-Bourland RE, Cuevas C, et al: Fetal neural graft¬ ing for the treatment of Huntington’s disease (HD)—Report of the first case. Soc Neurosci Abstr 17:902, 1991. U.S. Congress, Office of Technology Assessment: Neural Grafting: Repairing the Brain and Spinal Cord. OTA-BA-462. Washington, DC: U.S. Government Printing Office, 1990. Nothias F, Horvat J-C, Mira J-C, et al: Double step neural trans¬ plants to replace degenerated motoneurons. Prog Brain Res 82:239-246, 1990. Sieradzan K, Vrbova G: Factors influencing survival of transplanted embryonic motoneurons in the spinal cord of adult rats. Exp Neurol 114:286-299, 1991. Sotelo C, Alvarado-Mallart RM: The reconstruction of cerebellar circuits. Trends Neurosci 14:350-355, 1991. Clough RW, Browning RA, Maring ML, Jobe PC: Intracerebral grafting of fetal dorsal pons in genetically epilepsy-prone rats: Effects on audiogenic-induced seizures. Exp Neurol 112:195-199, 1991. Barry DI, Kikvadze I, Brundin P, et al: Grafted noradrenergic neu¬ rons suppress seizure development in kindling-induced epilepsy. Proc Natl Acad Sci USA 84:8712-8715, 1987. Barry DI, Wanscher B, Kragh J, et al: Grafts of fetal locus coeruleus neurons in rat amygdala-piriform cortex suppress seizure development in hippocampal kindling. Exp Neurol 106:125-132, 1989. Gale K, Iadarola MJ: Seizure protection and increased nerve-termi¬ nal GABA: Delayed effects of GABA transaminase inhibition. Science 208:288-291, 1982. Stevens JR, Phillips I, Freed WJ: Cerebral transplants for seizures: Preliminary results. Epilepsia 29:731-737, 1988. Davies P, Maloney AJF: Selective loss of central cholinergic neu¬ rons in Alzheimer’s disease. Lancet 2:1403, 1976. Mann DMA, Yates PO: Pathological basis for neurotransmitter changes in Parkinson’s disease. Neuropathol Appl Neurobiol 9:3-19, 1983. Arendt T, Bigl V, Arendt A, Tennstedt A: Loss of neurons in the nu¬ cleus basalis of Meynert in Alzheimer’s disease, paralysis agitans

Part 4/Functional Stereotaxis

1130

and Korsakoff’s disease. Acta Neuropathol (Berl) 61:101-108, 82.

83. 84.

85.

86.

1983. Perry EK, Curtis M, Dick DJ, et al: Cholinergic correlates of cog¬ nitive impairment in Parkinson’s disease: Comparison with Alzheimer’s disease. J Neurol Neurosurg Psychiatry 48:413—421, 1985. Collerton D: Cholinergic function and intellectual decline in Alzheimer’s disease. Neuroscience 19:1-28, 1986. Flicker C, Dean RL, Watkins DL, et al: Behavioral and neurochemi¬ cal effects following neurotoxic lesions of a major cholinergic input to the cerebral cortex in the rat. Pharmacol Biochem Behav 18:973-981, 1983. Murray CL, Fibiger HC: Learning and memory deficits after lesions of the nucleus basalis magnocellularis: Reversal by physostigmine. Neuroscience 14:1025-1032, 1985. Ridley RM, Murray TK, Johnson JA, Baker HF: Learning impairment following lesion of the basal nucleus of Meynert in the mar¬

92.

Polezhaev LV, Alexandrova MA: Transplantation of embryonic

93.

brain tissue into the brain of adult rats in hypoxic hypoxia. J Hirnforsch 25:99-106, 1984. Mudrick LA, Baimbridge KG, Peet MJ: Hippocampal neurons transplanted into ischemically lesioned hippocampus: Electro¬ responsiveness and reestablishment of circuitries. Exp Brain Res

94.

95.

96.

87.

88.

89.

90.

91.

ory in a rat model of Alzheimer’s disease. Proc Natl Acad Sci USA 82:5227-5230, 1985. Dunnett SB, Low WC, Iversen SD, et al: Septal transplants restore maze learning in rats with fornix-fimbria lesions. Brain Res 251:335-348, 1982. Ridley RM, Thornley HD, Baker HF, Fine A: Cholinergic neural transplants into hippocampus restore learning ability in monkeys with fornix transections. Exp Brain Res 83:533-538, 1991. Ridley RM, Gribble S, Clark B, et al: Restoration of learning abil¬ ity in fornix-transected monkeys after fetal septal but not fetal hippocampal tissue transplantation. Neuroscience 48:779-792, 1992. Nilsson OG, Brundin P, Bjorklund A: Amelioration of spatial im¬ pairment by intrahippocampal grafts of mixed septal and raphe tissue in rats with combined cholinergic and serotonergic denervation of the forebrain. Brain Res 515:193-206, 1990. Richter-Levin G, Segal M: Raphe cells grafted into the hippocam¬ pus can ameliorate spatial memory deficits in rats with combined serotonergic/cholinergic deficiencies. Brain Res 478:184-186, 1989.

1991. Dunnett SB, Rogers DC, Richards SJ: Nigrostriatal reconstruction after 6-OHDA lesions in rats: Combination of dopamine-rich nigral grafts and nigrostriatal “bridge” grafts. Exp Brain Res 75:523-535, 1989. Houle JD, Reier PJ: Regrowth of calcitonin gene-related peptide (CGRP) immunoreactive axons from the chronically injured rat spinal cord into fetal spinal cord tissue transplants. Neurosci Lett

moset: Modification by cholinergic drugs. Brain Res 376:108-116, 1986. 86a. Fine A, Dunnett SB, Bjorklund A, Iversen SD: Cholinergic ventral forebrain grafts into the neocortex improve passive avoidance mem¬

76:333-342, 1989. Mudrick LA, Baimbridge KG: Hippocampal neurons transplanted into ischemically lesioned hippocampus: Anatomical assessment of survival, maturation and integration. Exp Brain Res 86:233-247,

97.

98.

99.

100.

103:253-258, 1989. David S, Aguayo AJ: Axonal elongation into peripheral nervous sys¬ tem “bridges” after central nervous system injury in adult rats. Science 214:931-933, 1981. Gage FH, Stenevi U, Carlstedt T, et al: Anatomical and functional consequences of grafting mesencephalic neurons into a peripheral nerve “bridge” connected to the denervated striatum. Exp Brain Res 60:584—589, 1985. Privat A, Monsour H, Geffard M: Transplantation of fetal serotonin neurons into the transected spinal cord of adult rats: Morphological development and functional influence. Prog Brain Res 78:155-166, 1988. Foster GA, Brodin E, Gage FH, et al: Restoration of function to the denervated spinal cord after implantation of embryonic 5HT- and substance P-containing raphe neurons. Prog Brain Res 82:247-259.

101. 102.

1990. TesslerA: Intraspinal transplants. Ann Neurol 29:115-123, 1991. Sagen J, Pappas GD: Morphological and functional correlates of chromaffin cell transplants in CNS pain modulatory regions. Ann NY

103.

Acad Sci 495:306-333, 1987. Sagen J, Winnie AP, Wang H, et al: Pain reduction by adrenal medullary transplants in the spinal subarachnoid space of terminal cancer patients. Soc Neurosci Abstr 17:235, 1991.

Section

14

Functional Procedures for Parkinson’s Disease

.'if

1

CHAPTER

118

CLINICAL PATHOPHYSIOLOGY IN PARKINSON’S DISEASE

Allen S. Mandir and Frederick A. Lenz

Stereotactic approaches to the treatment of Parkinson’s disease (PD) include tissue transplantation, chronic stimulation, and, most commonly, lesions of the thalamus and basal ganglia. The goal of these treatments has been to ameliorate the motor man¬ ifestations of parkinsonism, including tremor, rigidity, bradykinesia, and akinesia. Thalamotomy has been most widely used to treat tremor and rigidity and often confers an immediate and long- lasting benefit.1 Pallidotomy may alleviate all parkinson¬ ian motor symptoms2-3 and may result in bilateral benefit from unilaterally placed lesions.4 Advances in the understanding of basal ganglia physiology and pathophysiology in parkinsonism have led to theories about the way in which stereotactically placed lesions diminish the motor manifestations of PD. The basal ganglia “motor cir¬ cuit”5’6 (see Chap. 119) has been studied in parkinsonian pa¬ tients and in monkeys rendered parkinsonian by injection of MPTP (l-methyl-4-phenyl-1,2,3,6-tetrahydropyridine). This chapter describes how these theories apply to human patho¬ physiology in the surgical treatment of parkinsonism.

BASAL GANGLIA CIRCUITRY (MOTOR LOOP) The motor circuit of the basal ganglia includes a direct pathway from the putamen to the internal segment of the globus pallidus (GPi) and an indirect pathway from the putamen to the external segment of the globus pallidus (GPe) and then to GPi via the subthalamic nucleus. In nonhuman primates, GPi-inhibitory (GABAergic) efferents in the motor loop project to neurons of the thalamic nucleus ventral lateral pars oralis (VLo).78 This nucleus corresponds to the ventralis oralis posterior (Vop) in humans. Cortical projections activate these pathways, with a resultant reduction of inhibitory GPi activity via the direct pathway and an increase of inhibitory GPi activity via the indi¬ rect pathway. The motor manifestations of parkinsonism are seen with dys¬ function of the nigrostriatal dopaminergic pathway.9 Dopa¬ minergic projections from the substantia nigra tend to activate the direct pathway (D1 dopamine receptor-mediated) and decrease the activity of the indirect pathway (D2 receptor-mediated). Therefore, the net influence on either path is reduction of the inhibitory influence of GPi on the thalamus. With dopaminergic dysfunction, the inhibition of GPi is diminished. Extracellular

recordings of GPi in parkinsonian patients show increased GPi activity,10 as would be expected from this schema. It is believed that this abnormally increased GPi activity forms the basis for parkinsonian motor symptomatology.

TREMOR Parkinsonian resting tremor results from alternating activation of opposing muscles at a frequency of 3 to 6 Hz at rest. Voluntary activation of the muscles or complete rest (as occurs during sleep) diminishes resting tremor. In monkey models of parkinsonism6'11"13 and in humans, extracellular recordings throughout the thalamus and basal ganglia demonstrate an os¬ cillatory firing pattern of neurons.1014-27 Thalamic neurons in particular have been implicated in the generation of resting tremor. Thalamic recordings in patients with PD have shown oscillatory activity that is significantly correlated with elec¬ tromyographic (EMG) activity during tremor,28 and thala¬ motomy has produced immediate and long-lasting relief of tremor.1’29’30 The common site for thalamotomy has been the nucleus ventralis intermedius (Vim), although the Vop has sometimes been targeted. Thalamic neuronal activity in these nuclei strongly correlates with the EMG activity of resting tremor.28 The oscillatory activity of cells in Vop is probably an effect of GPi influence. As correctly predicted by the model of the basal ganglia motor loop, GPi neurons in parkinsonian patients have increased firing rates.11’31 By virtue of its inhibitory sign, the increased output of GPi in parkinsonism should hyperpolarize the neurons of Vop. On that basis, studies of in vitro guinea pig thalamic cells provide an explanation of thalamic oscilla¬ tions. Depending on their state of depolarization, thalamic neu¬ rons demonstrate two distinct modes of firing: the “transfer” mode and the “oscillatory” mode. Thalamic cells in a sub¬ threshold depolarized state generate action potentials at a con¬ stant rate that is determined by the action potential after hyper¬ polarization.32 Under these conditions, a thalamic neuron receiving a steady depolarizing input will respond by firing a steady rate of action potentials. This is known as the transfer mode, which occurs during the normal waking state. An oscil¬ lating inhibitory (hyperpolarizing) influence from GPi, as seen in parkinsonism, on thalamic neurons in the transfer mode would theoretically result in an oscillatory firing pattern in Vop.

1133

1134

Part 4/Functional Stereotaxis

When in vitro thalamic cells are placed in hyperpolarized states, they are said to be in the oscillatory mode and demon¬ strate different firing characteristics compared with the transfer mode. High-frequency bursts of action potentials occur in the oscillatory mode, mediated by slow time- and voltage-depen¬ dent calcium potentials also known as calcium spikes.3334 A rel¬ ative refractory period after activation of the calcium channels separates bursts of action potentials in this mode. This type of activity also has been demonstrated in humans during sleep (see Ref. 35). In three nonparkinsonian patients undergoing thalamic procedures for pain relief, thalamic neurons demon¬ strated bursting of the type associated in animals with the oc¬ currence of calcium spikes. To explain the characteristic 3- to 6-Hz frequency of resting tremor in parkinsonism, it has been suggested that oscillatory mode thalamic neurons transform pallidal inputs. In this for¬ mulation, pallidal inputs bursting at 12 to 15 Hz1132 are trans¬ formed to the lower frequency of resting tremor by the inherent calcium bursting characteristics with relative refractory peri¬ ods. An alternating hyperpolarizing input from GPi thus would result in thalamic firing at tremor frequency. One might not expect parkinsonian tremor to be related to the oscillatory mode state, since this is thought to occur during sleep, when parkinsonian resting tremor disappears. Perhaps an increase of GPi inhibitory activity in parkinsonism could hyperpolarize Vop neurons and drive them into the oscillatory mode during waking. However, extracellular recordings of Vim tha¬ lamic neurons in parkinsonian patients with resting tremor do not suggest an extracellular pattern of calcium spike activity.3536 Extracellular recordings of 25 cells in Vim and Vop of patients with PD demonstrated that 24 did not have characteristics of calcium spike-associated bursting.35 The suggestion that an increase in GPi tonic activity plays a causative role in generating resting tremor is supported by clin¬ ical improvement in tremor after disruption of GPi efferents in parkinsonian patients.43738 However, other influences may be present in the production of parkinsonian resting tremor. Stereotactic thalamotomy targeting Vim in parkinsonian pa¬ tients also abolishes tremor, although these neurons do not re¬ ceive direct projections of GPi, since Vim is outside the basal ganglia motor circuit. Other contributions to parkinsonian rest¬ ing tremor may result from peripheral inputs. Peripheral inputs affecting tremor may be involved in long loop reflex arcs. Sensory inputs traversing the long loop reflex arc are thought to involve thalamic nuclei projecting to the mo¬ tor cortex, including Vim. Output from the motor cortex is transmitted to the periphery and may account for the longlatency EMG activity that occurs in muscles stretched by im¬ posed joint rotation. The long-latency reflex activity occurs af¬ ter the short-latency spinal reflex (tendon tap) response to joint rotation. Evidence that long loop reflex arcs contribute to longlatency reflex activity comes from studies showing that periph¬ eral inputs reliably activate cells in VPLo39 and that cells in pri¬ mary motor cortex respond to peripheral inputs as if they were involved in the long-latency reflexes.40 Finally, lesions of the motor cortex abolish long-latency reflex activity in muscles acting across the monkey hand.41 In MPTP-treated parkinsonian monkeys, neurons in GPi demonstrate altered responsiveness to peripheral sensory in¬ puts. In turn, the VLo in MPTP-treated parkinsonian monkeys (corresponding to Vop in humans) shows more frequent, less

specific responses to peripheral somatosensory inputs.12 These responses may be related to tremor, as demonstrated by studies in the human thalamus. Cells in Vim and Vop are classified into those which are also activated in response to somatosensory stimulation (combined cells) and those which are not (volun¬ tary and no response cells).42 The activity of cells with and without sensory input often has a concentration of power at tremor frequency that is correlated with EMG activity.43 The activity of a majority of combined and voluntary cells was cor¬ related with and led to tremor.43 The fact that thalamic activity has a phase lead on tremor does not prove that this activity causes tremor. However, the similarities between the tremorrelated activities of combined and voluntary cell types suggest that both cell types with and all types without peripheral inputs are involved in the generation of tremor. Finally, the impor¬ tance of peripheral inputs has been demonstrated by studies of the transfer function linking thalamic and EMG activity.71 These transfer functions show evidence of peripheral input for most cells, even cells that do not respond to sensory stimuli. Alterations in long loop reflex arcs also may be reflected in long-latency reflexes in parkinsonian patients. Long-latency re¬ flexes in these patients demonstrate a fixed, increased gain.44-45 Furthermore, peripheral input producing reflex activity can al¬ ter the phase of tremor.45-48 Dorsal root sections in a parkinson¬ ian patient altered the characteristics of but did not abolish rest¬ ing tremor.49 These findings can be explained by simulations demonstrating that long loop reflexes with increased gain have the potential to oscillate and thus cause tremor.50 Activity in the pallidum or thalamus seems to be involved in the generation of tremor, since lesions in both structures may successfully abolish tremor. This is true as measured clinically by subjective means' or objectively.51 Accelerometer measures of the affected limb before and after thalamotomy in four pa¬ tients showed abolition of tremor even at a sensitive level of movement detection and EMG recordings of the muscles con¬ tributing to tremor.51 The antagonist-agonist alternation of contraction that is char¬ acteristically seen in resting tremor is difficult to understand. Are separate oscillatory loops simultaneously generated out of phase, corresponding to opposite movements? Perhaps thalamic oscillations turn a movement on and off to produce tremor (as in¬ ferred in Ref. 52). A combination of oscillatory activity inherent to the basal ganglia and contributions from sensory input may be required to explain classic parkinsonian resting tremor.

RIGIDITY Parkinsonian rigidity is characterized by an increase in resis¬ tance to the passive movement of a joint that is independent of the rate of movement and exists throughout the movement. Axial and distal musculature may be affected, and cogwheeling may be demonstrated. It has been suggested that the signs of parkinsonian rigidity result from increased tonic activity of cells in GPi projecting to the thalamus. This is consistent with the reported relief of rigidity in parkinsonian patients undergo¬ ing thalamotomy or pallidotomy.'■4-2930 Studies of parkinsonian patients generally find no funda¬ mental change in mechanical muscle properties or shortlatency reflexes.53 Microneuronal recordings of fusimotor ac¬ tivity in PD suggest that la discharges are not increased.54

Chapter 118/Clinical Pathophysiology in Parkinson’s Disease

These findings have led to a theory of a supraspinal contribu¬ tion to parkinsonian rigidity. Evidence of a cortically mediated mechanism of rigidity in PD has been explained by long loop reflexes. As was described above, the long-latency reflex in parkinsonian patients has an increased, relatively fixed gain.53 The EMG response to stretch is thus increased, leading to rigidity or increased resistance to joint movement. Further¬ more, resting EMG activity in PD is elevated, implying tonic motoneuron activity, perhaps cortically mediated. An alternative supraspinal mechanism of parkinsonian rigidity has been proposed by Delwaide and colleagues.55 They suggested that lb intemeurons that normally exert an inhibitory influence on alpha motoneurons are less active in parkinsonian patients. They proposed that this change in lb activity results from changes in basal ganglia output in PD. They implicated a pathway from the basal ganglia projecting to the pontine nu¬ cleus gigantocellularis and the dorsal longitudinal fasciculus of the reticulospinal projections. Rigidity as predicted by these models should be reduced by disrupting altered GPi outflow by means of stereotactic le¬ sions. The effect of pallidotomy in reducing rigidity is sup¬ portive of both cortically mediated and reticulospinally medi¬ ated theories of long-latency reflex pathways. Similarly, the report that dorsal rhizotomy diminishes rigidity in PD49 sup¬ ports both theories of rigidity. The cortical mechanism of long-latency reflexes is supported by the finding that thalamot¬

1135

ficity of GPi neurons that fire in response to limb perturbations has been reported in MPTP-treated monkeys.5’6’11 The alter¬ ations of SMA neuronal activity in the parkinsonian state are also reflected in clinical studies by abnormal cortical “readi¬ ness” (bereitschaft) potentials, abnormal cerebral blood flow studies, and abnormal positron emission tomography (PET) imaging. The readiness or bereitschaftspotential is a negative wave occurring before movement that is thought to reflect activity in the Brodmann’s area 6 and the SMA.65 In parkinsonian pa¬ tients, this potential is consistently reduced in amplitude in comparison with normal controls.65-67 Studies using radioactive xenon also show reduction in the increase in blood flow that occurs in normals during volitional movements. More recently, PET studies have also shown impaired activation of SMA in parkinsonian patients.68,69 After pallidotomy, akinesia and bradykinesia are im¬ proved.4,37 It appears that removal of the increased inhibitory drive of GPi assists in allowing the return of some organization of EMG activity. Conversely, in parkinsonism, thalamotomy has been suggested to increase bradykinesia3 or, in a majority of studies, to have no effect on the speed of movement execu¬ tion.1,51 The improvement in akinesia and bradykinesia70 after subthalamotomy further supports the notion that the increased tonic output of GPi in parkinsonism is responsible for these clinical signs.71

omy abolishes rigidity.

CONCLUSION AKINESIA AND BRADYKINESIA Bradykinesia is defined as the slowed execution of movement, whereas akinesia indicates defective initiation of movement. Both are prevalent in PD and are more evident in the perfor¬ mance of self-initiated movements than in the performance of stimulus-initiated ones. The dysfunction of the dopaminergic system generating these effects in parkinsonism must ulti¬ mately be expressed at the cortical level. The primary motor cortex (MI) is the cortical region most directly involved in pro¬ ducing skilled voluntary movements. It receives prominent projections from the supplementary motor area (SMA), which is implicated in functions of preparation and execution of voluntary movements. GPi influences MI in a large part via thalamocortical relay directed to the SMA, although direct connections from VLo to MI have been demonstrated.56-61 Bradykinesia and akinesia are reflected by prolonged reac¬ tion times (RLTs), prolonged movement times (MLTs), and dis¬ organized EMG activity. Parkinsonian movements lack classic organization of the triphasic burst pattern used to produce bal¬ listic movements.62 This pattern is even more disrupted in selfinitiated compared with stimulus-initiated movements.61 Extracellular recordings in parkinsonian primate MI directly reflect this disorganization.64 It is likely that activity in MI is disrupted in parkinsonism by the abnormal influence of GPi mediated via SMA and VLo. Watts and Mandir provided support for the idea that disrup¬ tion of GPi neuronal firing in the parkinsonian state is reflected at the SMA cortical level.64 One characteristic of SMA neurons in MPTP-treated parkinsonian monkeys is loss of the highly di¬ rectional specificity these neurons demonstrate normally in the period before movements. Reduction of the directional speci¬

Recent studies of the pathophysiology of parkinsonism explain the efficacy of stereotactic lesions that have been employed for four decades in the treatment of PD. Advances in surgical, imaging, and electrophysiological techniques will continue to refine this mode of therapy. These advances, along with the ability to eradicate the motor symptoms of PD, make these minimally invasive procedures attractive to both patients and surgeons. Despite the advancing understanding of the complexities of the basal ganglia, it is clear that most physiological and patho¬ physiological mechanisms are not well understood. The theo¬ ries about and limited understanding of the mechanisms of aki¬ nesia and bradykinesia, tremor, and rigidity in parkinsonism presented in this chapter demonstrate the need for future exper¬ imental investigations of motor physiology. The physiological monitoring carried out during these procedures may contribute to the understanding of movement disorders.

References 1.

2. 3.

4.

Tasker RR, Siqueira J, Hawrylyshyn PA, Organ LW: What happened to VIM thalamotomy for Parkinson’s disease? Appl Neurophysiol 46:68, 1983. Bakay RA, DeLong MR, Vitek JL: Posteroventral pallidotomy for Parkinson’s disease. J Neurosurg 77:487, 1992. Laitinen LV, Bergenheim AT, Hariz MI: Ventroposterolateral palli¬ dotomy can abolish all parkinsonian symptoms. Stereotact Fund Neurosurg 58:14, 1992. Baron M, Vitek JL, Turner R, et al: Lesions in the sensorimotor re¬ gion of the internal segment of the globus pallidus (GPi) in parkin¬ sonian patients are effective in alleviating the cardinal signs of parkinson’s disease. Soc Neurosci Abstr 19:1584, 1993.

1136

Part 4/Functional Stereotaxis

5.

DeLong MR: Primate models of movement disorders of basal ganglia origin. Trends Neurosci 13:281, 1990.

6.

Miller WC, DeLong MR: Parkinsonian symptomatology: Anatomical and physiological analysis. Ann NY Acad Sci 515:287, 1988. Penney JB, Young AB: GABA as the pallidothalamic neurotransmit¬ ter: Implications for basal ganglia function. Brain Res 207:195, 1981. Young AB, Penney JB: Neurochemical anatomy of movement disor¬ ders. Neurol Clin North Am 2:417, 1984.

7. 8. 9. 10.

11.

12.

13. 14.

15. 16.

Hornykiewicz D: The mechanisms of action of L-DOPA in Parkinson’s disease. Life Sci 7:1249, 1974. Vitek JL, Kaneoke Y, Turner R, et al: Neuronal activity in the internal (GPi) and external (GPe) segments of the globus pallidus (GP) of parkinsonian patients is similar to that in the MPTP-treated primate model of parkinsonism. Soc Neurosci Abstr 19:1584, 1993. Filion M, Tremblay L, Bedard PJ: Abnormal influences of passive limb movement on the activity of globus pallidus neurons in parkin¬ sonian monkeys. Brain Res 444:165, 1988. Vitek JL, Ashe J, DeLong MR, Alexander GE: Altered somatosensory response properties of neurons in the “motor" thalamus of MPTP treated parkinsonian monkeys. Soc Neurosci Abstr 16:425, 1990. Lamarre Y: Tremorogenic mechanisms in primates. Adv Neurol 10:23, 1975. Guiot G, Hardy J. Albe-Fessard DG: Delimitation precis des structures sous-corticales et identification de noyaux thalamiques chez l'homme par Telectrophyiologie stereotactic. Neurochirurgie 5:1, 1962. Hardy J, Bertrand C, Martinez N: Activites ceilulaires thalamiques liees au tremblement parkinsonien. Neurochirurgie 10:449, 1964. Alberts WW, Libet B. Wright EW, Feinstein B: Physiological mechansims of tremor and rigidity in parkinsonism. Gonfin Neurol 26:318, 1965.

17.

18. 19.

20.

21.

22.

23.

Jasper HH, Bertrand G: Thalamic units involved in somatic sensation and voluntary and involuntary movements in man. in Purpura DP, Yahr MD (eds): The Thalamus. New York: Columbia University Press, 1966, pp 365-390. Albe-Fessard DG, Arfel G, Guiot G, et al: Thalamic unit activity in man. Electroencephalogr Clin Neurophysiol 25:132, 1967. Li CL, van Buren J: Microelectrode recordings in the brain of man with particular reference to epilepsy and dyskinesia, in Somjen G (ed): Neurophysiology Studied in Man. Amsterdam: Excerpta, Medica, 1972. pp 49-63.

Kelly P, Gillingham FJ: Long-term results of stereotactic surgery and L-dopa therapy in patients with Parkinson’s disease: A ten year follow-up study. J Neurosurg 53:332, 1980.

30.

Ohye C, Hirai T. Miyazaki M, et al: Vim thalamotomy for the treat¬ ment of various kinds of tremor. Appl Neurophysiol 45:275, 1982. Anderson SA: Suppression of cortical spontaneous barbiturate spindles via specific and unspecific spinal pathways. Acta Physiol 69:191, 1967. Steriade M, Jones EG, Llinas RR: Thalamic Oscillations and Signaling. New York: Wiley, 1990.

31. 32. 33. 34.

Lenz FA, Vitek JL, DeLong MR: Role of the thalamus in parkinson¬ ism tremor: Evidence from studies in patients and primate models. Stereotact Fund Neurosurg 60:94, 1993.

36.

Lenz FA, Kwan HC, Dostrovsky JO, Tasker R: Characteristics of the bursting pattern of action potentials which occurs in sensory thalamus of patients with central pain. Brain Res 496:357, 1989.

37.

Laitinen LV. Bergenheim AT. Hariz Marwan I: Leksell’s posteroventral pallidotomy in the treatment of Parkinson’s disease. J Neurosurg 76:53, 1992.

38.

Svennilson E, Torvik A, Lowe R, Leksell L: Treatment of parkinson¬ ism by stereotactic thermolesions in the pallidal region. Acta Psychiatr Neurol Scand 35:358, 1960. Vitek JL, Ashe J, DeLong MR. Alexander GE: Organization of pri¬ mate ventrolateral thalamus: Neuronal relations to active and passive limb movements. Soc Neurosci Abstr 15:287, 1989.

39.

40.

Cheney PD, Fetz EE: Cortico-motoneuronal cells contribute to long latency stretch reflexes in the rhesus monkey. J Physiol 349:249, 1984.

41.

Lenz FA, Tatton WG. Tasker RR: The effect of cortical lesions on the electromyographic response to joint displacement in the squirrel monkey forelimb. J Neurosci 3:795, 1983.

42.

Lenz FA, Kwan H, Dostrovsky JO, et al: Single unit analysis of the human ventral thalamic nuclear group: Activity correlated with movement. Brain 113:1795, 1990.

43.

Lenz FA. Kwan HC, Martin RL. et al: Single neuron analysis of the human ventral thalamic nuclear group: Tremor-related activity in functionally identified cells. Brain 117:531-543, 1994. Tatton WG, Bedingham W, Verrier MC, Blair RDG: Characteristic al¬ terations in responses to imposed wrist displacements in parkinsonian rigidity and dystonia musculorum deformans. Can J Neurol Sci 11: 281, 1984.

44.

Raeva SN: Unit activity of some deep nuclear structures of the human brain during voluntary movements, in Somjen G (ed): Neuro¬ physiology Studied in Man. Amsterdam: Excerpta Medica, 1972, pp 64-78.

45.

Umbach W: Stereotactic macro- and micro-registration in motor dys¬ function and epilepsy, in Somjen GG (ed): Neurophysiology Studied in Man. Amsterdam: Excerpta Medica, 1972, pp 85-94. Bertrand C, Martinez SN, Hardy J, et al: Stereotactic surgery for parkinsonism: Microelectrode recording, stimulation, and oriented sections with a leucotome, in Krayenbuhi H. Maspes PE, Sweet WH (eds): Progress in Neurological Surgery. Basel: Karger, 1973, pp 79-112.

47.

Donaldson IML: The properties of some human thalamic units. Brain 96:419, 1973.

25.

Fukamachi A, Ohye C, Narabayashi H: Delineation of the thalamic nuclei with a microelectrode in stereotaxic surgery for parkinsonism and cerebral palsy. J Neurosurg 39:214, 1973. Hongell A. Wallin G, Hagbarth KE: Unit activity connected with movement initiation and arousal situations recorded from the ventro¬ lateral nucleus of the human thalamus. Acta Neurol Stand 49:681. 1973.

27.

Velasco F, Molina-Negro P: Electrophysiologic topography of the hu¬ man diencephalon. J Neurosurg 38: 204, 1973.

28.

Lenz FA, Tasker RR. Kwan HC, et al: Single unit analysis of the hu¬ man ventral thalamic nuclear group: Correlation of thalamic "tremor cells” with the 3-6 H/ component of parkinsonian tremor. J Neurosci 8:754, 1988.

Jahnsen H, Llinas R: Electrophysiological properties of guinea pig thalamic neurones: An in vitro study. J Physiol 349:205, 1984. Jahnsen H. Llinas R: Ionic basis for the electroresponsiveness and os¬ cillatory properties of guinea-pig thalamic neurones in vitro. J Physiol 349:247, 1984.

35.

Lucking CH, Struppler A, Erbel F, Reiss W: Stereotactic recording from human subthalamic structures, in Somjen GG (ed): Neuro¬ physiology Studied in Man. Amsterdam: Excerpta Medica, 1972, pp 95-99.

24.

26.

29.

46.

48.

Teravainen H, Evarts E. Caine D: Effects of kinesthetic inputs on parkinsonian tremor. Adv Neurol 24: 161, 1979. Renou G, Rondot P. Balhien N: Influence of peripheral stimulation on the silent period between bursts of parkinsonian tremor, in Desmedt JE (ed): New Developments in Electromyography and Clinical Neurophysiology. Basal: Karger, 1973, pp 635-640. Rack PMH, Ross HF: The role of reflexes in the resting tremor of Parkinson’s disease. Brain 109:115, 1986. Stein RB. Lee RG: Tremor and clonus, in Brooks VB (ed): Handbook of Physiology. Section 1: Nervous System. Volume II: Motor Control. Part II. Belhesda. MD: American Physiological Society, 1981, pp 325-343.

49.

Pollack LJ. Davis L: Muscle tone in Parkinsonian states. Arch Neurol Psychiatry 23:303, 1930.

50.

Stein RB. Oguztoreli MN: Tremor and other oscillations in neuro¬ muscular systems. Biol Cybern 22:147, 1976. Oyesika N, Mandir AS, Bakay RAE, et al: Stereotactic thalamotomy for Parkinson’s disease: Quantitative assessment of tremor and bradykinesia before and after surgery. Congress of Neurological Surgeons, 1991.

51.

52.

53.

Pare D, Curro Dossi R. Steriade M: Neuronal basis of the parkinson¬ ian resting tremor: A hypothesis and its implications for treatment. Neuroscience 35:217, 1990. Rothwell JC, Obeso JA. Traub MM. Marsden CD: The behaviour of long-latency stretch reflex in patients with Parkinson's disease. J Neurol Neurosurg Psychiatry 46:35, 1983.

Chapter 118/Clinical Pathophysiology in Parkinson’s Disease

54. 55.

56. 57. 58.

59.

60. 61.

62. 63.

Burke D, Hagbarth KE, Wallin G: Reflex mechanisms in Parkinsonian rigidity. Scand J Rehabil Med 9:15, 1977. Delwaide PJ, Pepin JL, Maertens de Noordhout A: Short-latency au¬ togenic inhibition in patients with Parkinsonian rigidity. Ann Neurol 30:83, 1991. Strick PL: Anatomical analysis of ventrolateral thalamic input to pri¬ mate motor cortex. J Neurophysiol 39:1020, 1976. Schell GR, Strick PL: The origin of thalamic inputs to the arcuate pre¬ motor and supplementary motor areas. J Neurosci 4:539, 1984. Holsapple JW, Preston JB, Strick PL: The origin of thalamic inputs to the “hand” representation in the primary motor cortex. J Neurosci 11:2644, 1991. Kim R, Nakano K, Jayaraman A, Carpenter MB: Projections of the globus pallidus and adjacent structures: An autoradiographic study in the monkey. J Comp Neurol 169:263, 1976. Kuo J-S, Carpenter MB: Organization of pallidothalamic projections in rhesus monkey. J Comp Neurol 151:201, 1973. Hedreen J, Martin LJ, Koliatsos VE, et al: Organization of primate basal ganglia motor circuit: IV. Ventrolateral thalamus links internal pallidum (GPi) and supplementary motor area (SMA). Soc Neurosci

64.

65.

66.

67. 68.

69.

Abstr 14:721, 1988. Hallett M, Marsden CD: Ballistic flexion movements of the human

70.

thumb. J Physiol 294:33, 1979. Watts RL, Mandir AS, Montgomery EB: Neuronal, kinematic and electromyographic characterization of self- and stimulus-initiated

71.

1137

motor tasks in normal and MPTP parkinsonian nonhuman primates. Soc Neurosci Abstr 16:115, 1990. Watts RL, Mandir AS: The role of motor cortex in the pathophysiol¬ ogy of voluntary movement deficits associated with parkinsonism. Neurol Clin North Am 10:451, 1992. Simpson JA, Khuraibet AJ: Readiness potential of cortical area 6 pre¬ ceding self paced movement in Parkinson’s disease. J Neurol Neurosurg Psychiatry 50:1184, 1987. Shibasaki H, Shima F, Kuroiwa Y: Clinical studies of the movementrelated cortical potential (MP) and the relationship between the dentatorubrothalamic pathway and readiness potential (RP). J Neurol 219:15, 1978. Dick JP, Rothwell JC, Day BL et al: The Bereitschaftspotential is ab¬ normal in Parkinson’s disease. Brain 112:233, 1989. Playford ED, Jenkins IH, Passingham RE, et al: Impaired mesial frontal and putamen activation in Parkinson’s disease: A positron emission tomography study. Ann Neurol 32:151, 1992. Jenkins IH, Fernandez W, Playford ED, et al: Impaired activation of the supplementary motor area in Parkinson’s disease is reversed when akinesia is treated with apomorphine. Ann Neurol 32:749, 1992. Bergman H, Wichmann T, DeLong MR: Reversal of experimental parkin¬ sonism by lesions of the subthalamic nucleus. Science 249:1436, 1990. Schnider SM, Kwong RH, Lenz FA, Kwan HC: Detection of feed¬ back in the central nervous system using system identification tech¬ niques. Biol Cybern 60:203, 1989.

CHAPTER

119

PATHOPHYSIOLOGICAL BASIS OF NEUROSURGICAL TREATMENT OF PARKINSON’S DISEASE

Mahlon R. DeLong, Thomas Wichmann, and Jerrold L. Vitek

Recent advances in our understanding of the functional organi¬ zation of the basal ganglia and the pathophysiology of disor¬ ders such as Parkinson’s disease have helped in the develop¬ ment and refinement of surgical approaches to this and related disorders. This progress has been made possible by new anatomic, physiological, and pharmacological techniques and by the development and study of suitable animal models of the human disorders, for instance, the primate MPTP model of Parkinson’s disease. The physiological concepts of normal basal ganglia physiology are still strongly influenced by ex¬ trapolation from data obtained from patients with basal ganglia disorders and from animal models of those diseases. Thus, much more is currently known about the functioning of the basal ganglia in pathological states than under physiological conditions.1"3 Over the last 20 years, it has become clear that the output of the basal ganglia influences a far wider portion of the frontal lobe than was previously thought.4-7 This influence appears to be exerted through a system of functionally segregated basal ganglia-thalamocortical circuits6,8 that arise from and whose output is directed back to specific areas of the frontal lobe. The close functional association between the basal ganglia and cor¬ tical areas implies that the functions of the basal ganglia may be considered largely in terms of their influences on different cortical areas. Furthermore, disturbances in basal ganglia func¬ tion are seen as resulting in abnormal cortical output, which may then lead to movement disorders such as Parkinson’s dis¬ ease. This chapter considers the impairments in Parkinson’s disease in light of newly acquired anatomic data on primates and physiological data on the MPTP-treated primate model of parkinsonism, which has provided an opportunity to study di¬ rectly the changes in neuronal activity in the basal ganglia in this disorder. This brief overview is based in large part on re¬ cent more comprehensive reviews,6,9-11 to which the reader is referred for a more detailed treatment of these topics.

BASAL GANGLIATHALAMOCORTICAL CIRCUITS The basal ganglia receive topographic projections from all ar¬ eas of the cerebral cortex and in turn project their output, via

portions of the thalamus, back onto wide areas of the frontal lobe. The basal ganglia, along with related cortical areas and thalamic subnuclei, may be viewed as components of a family of “basal ganglia-thalamocortical circuits” that are organized and function in a parallel and largely segregated manner.4,8,10 In the monkey, five separate circuits, each taking its origin from and terminating on a specific region of the frontal lobe, have been identified: a “motor circuit” centered on the precentral motor fields, an “oculomotor circuit” centered on the frontal eye fields, two prefrontal circuits centered on the dorsolateral, prefrontal, and orbitofrontal cortex, and a “limbic circuit” on the anterior cingulate and medial orbitofrontal cortex. The cor¬ tical regions involved in each circuit are shown schematically in Fig. 119-1.

Figure 119-1. Frontal lobe targets of basal ganglia output. This figure illustrates schematically the cortical areas that receive the output of the separate basal ganglia-thalamocortical circuits. ACA = anterior cingulate area; DLPC = dorsolateral prefrontal cortex; FEF = frontal eye field; LOFC = lateral orbitofrontal cortex; MC = primary motor cortex; MOFC = medial orbitofrontal cortex; PMC = premotor cortex; SEF = supplementary eye field; SMA = supplementary motor area.

1139

1140

Part 4/Functional Stereotaxis

A basic principle of this scheme is that all the specific cir¬ cuits, although subserving distinctly different functions, are or¬ ganized in a similar manner. For each circuit, a region of stria¬ tum receives input from several functionally and anatomically interconnected cortical areas. Projections from this region of the striatum are then directed via separate output pathways to the internal pallidal segment (GPi) and the substantia nigra pars reticulata (SNr). The output nuclei (GPi and SNr) in turn pro¬ ject to specific portions of the thalamus. Each circuit is par¬ tially closed by subsequent thalamic projections to one of the original cortical areas that supply the striatal input. Below, we focus largely on the motor circuit, since this circuit is most strongly implicated in the pathophysiology of the parkinsonian motor signs that have been relatively accessible to scientific methods. Although it is extremely likely that oculomotor ab¬ normalities in Parkinson’s disease result from abnormalities in the oculomotor circuit and that the emotional-cognitive fea¬ tures of parkinsonism have their source in disturbances of lim¬ bic and associative circuits, substantially less is known about the physiology and pathophysiology of the latter circuits.

MOTOR CIRCUIT The motor circuit has its origin in the motor, premotor, supple¬ mentary motor, and somatosensory areas as well as in the supe¬ rior parietal lobule (Fig. 119-2). Each cortical area projects on the putamen, the principal striatal component of the motor cir¬ cuit. The motor circuit has been shown to be organized somatotopically throughout as a result of topographically organized projections that link the different nuclei (Fig. 119-2). Thus, corticostriatal fibers originating from cortical motor and sensory “leg” areas terminate in a dorsolateral portion of the putamen, fibers from the “face” areas terminate in a ventromedial sector, and fibers from the “arm” areas terminate in a region lying be¬ tween the two. A somatotopic organization of the putamen, the pallidum, the subthalamic nucleus (STN), and the ventrolateral nucleus of the thalamus (VL) has been confirmed in neuro¬ physiological studies as well,12'14 in which the grouping of cells with a response to peripheral input and a relationship to the movement of individual body parts was examined. Evidence for a similar somatotopic organization in the human pallidum has been observed in the course of single-cell mapping studies for pallidotomy.15 The portions of the putamen that receive the sensorimotor input project in turn to specific portions of the external pal¬ lidum (GPe) and GPi. Between the input structure (putamen) and the output structures (GPi and SNr) of the basal ganglia, two major pathways—a “direct” pathway and an “indirect” pathway—have been identified, each arising from separate sub¬ populations of putaminal neurons, as shown in Fig. 119-34.5 The “direct” pathway projects monosynaptically onto the mo¬ tor portions of GPi and SNr, whereas the “indirect” pathway in¬ volves connections between the putamen and GPe and between GPe and STN and a pathway from the STN to GPi and SNr. In addition, there are reciprocal connections between GPe and GPi16 and a direct projection from precentral motor areas onto STN. The intrinsic projections in the direct and indirect path¬ ways are inhibitory, with the exception of that from the STN to GPi and SNr, which is excitatory.1718 Transmission through the direct and indirect pathways is modulated by the dopaminergic

Figure 119-2. Somatotopic organization of the motor circuit. The region of arm representation for each stage of the circuit is shaded. Somatotopy is maintained by virtue of topographically organized connections between these arm areas. The cortical areas that give rise to “open loop” inputs to the arm area of the putamen have horizontal hatching. VAPc = parvocellular ventral anterior nucleus; CM = centrum medianum; Put = putamen. See text and Fig. 119-1 for additional abbreviations.

nigrostriatal projection. Dopamine may have differential ef¬ fects on the activity of the direct and indirect pathways,19 act¬ ing in an overall manner to increase activity in the direct path¬ way and decrease activity via the indirect pathway. Efferents from the sensorimotor region of GPi terminate pri¬ marily in the pars oralis of the VL (VLo), while the VL in turn projects to both the supplementary motor area (SMA) and the motor cortex (MC). The retrograde virus transport technique has been used to demonstrate anatomically segregated outputs from GPi to MC, SMA, and the ventral premotor area.20 This, together with other studies21 demonstrating separate terminal fields of corticostriate projections to the putamen from the same areas, strongly argues for the existence of segregated sub¬ circuits within the larger motor circuit, each related to a differ¬ ent motor and premotor cortical area. Conceivably, each of these subcircuits may play a different role in motor behavior and even in the pathogenesis of specific motor signs in disor¬ ders such as Parkinson’s disease.

THE MOTOR CIRCUIT IN PARKINSON’S DISEASE The effects of dopamine depletion in the basal ganglia, as occurs in Parkinson’s disease, has been studied directly with microelectrode recordings in primates that were rendered parkinsonian by the dopaminergic neurotoxin MPTP2224 and

Chapter 119/Pathophysiological Basis of Neurosurgical Treatment of Parkinson’s Disease

A. Normal

B. Parkinsonism

1141

C. STN lesion

Spinal cord Figure 119-3. Model of the functional anatomy of the basal ganglia-thalamocortical motor circuit. Open arrows = excitatory connections; filled arrows = inhibitory connections. SNc = substantia nigra pars compacta; VL = ventral lateral nucleus of the thalamus. A. Normal. Input (putamen) and output (GPi and SNr) structures of the basal ganglia are connected by direct (D) and indirect (I) projections systems. The indirect pathway involves GPe and STN. Dopamine exerts differential effects on the direct and indirect projections via activation of dopamine D, and D, receptors, respectively. B. Parkinsonism. Changes resulting from the striatal loss of dopamine in the overall activity in individual projection systems are indicated by changes in the width of the arrows. Inactivation of the nigroputaminal projection increases tonic and phasic GPi activity, primarily as a result of overactivity along the indirect pathway. The subsequent overinhibition of thalamocortical circuits may account, at least in part, for all parkinsonian motor signs. C. Effect of STN lesions in parkinsonism. Activation of STN reduces GPi output toward more normal levels, leading to a reduction of parkinsonian motor signs.

indirectly by metabolic studies.25 These studies have demon¬ strated major changes in the output of the motor circuit that have led to a new model of parkinsonian pathophysiology in which all parkinsonian motor signs arise from altered basal ganglia output. According to this model (Fig. 119-35), loss of striatal dopamine leads to excessive inhibitory output from the putamen to GPe, and this results in lower activity of GPe neurons and consequently leads to disinhibition of STN. Increased activity in STN neurons then results in increased excitatory drive on GPi. By contrast, the loss of striatal dopamine appears to decrease activity in the direct pathway and, by disinhibition, to further in¬ crease GPi activity. The negative feedback characteristics of the reciprocal connection between GPe and GPi may further en¬ hance GPi activity. The resulting increase in tonic basal ganglia output is postulated to result ultimately in increased inhibition of the portions of the motor thalamus receiving GPi projections and reduced activity in thalamocortical neurons. Alterations in phasic discharge in basal ganglia neurons also have been ob¬ served in MPTP-treated animals.2223 Phasic responses to pas¬ sive manipulation of individual body parts are enhanced overall, and receptive fields are less specific than normal. The observed

enhanced responses to proprioceptive inputs suggest that the gain of the motor circuit for somatosensory responses is in¬ creased in parkinsonism. Strong rhythmic discharge activity re¬ lated to tremor has been observed in MPTP-treated monkeys.24 Compelling evidence that overactivity in the indirect path¬ way is involved in the development of parkinsonian motor signs was obtained by lesioning of the STN in monkeys that had been rendered parkinsonian with systemic injections of MPTP.26 Based on the model mentioned above, inactivation of the STN, by reducing the excitatory drive on GPi, should ame¬ liorate at least some parkinsonian signs. This prediction was confirmed experimentally. Within minutes after the injection of the excitoxin ibotenic acid into the STN, the contralateral ex¬ tremities showed increased movements. Although the animals developed transient dyskinesias after STN inactivation, pur¬ poseful movements were markedly increased so that the ani¬ mals were again able to feed and groom themselves and ex¬ plore objects of interest. In addition, tremor and rigidity were almost completely abolished in the contralateral limbs. Improvement in overall behavioral altertness, locomotion, and posture was also observed. The effects of ibotenic acid injec¬ tions on parkinsonian motor signs were permanent and re-

1142

Part 4/Functional Stereotaxis

mained until the animals were sacrificed 3 to 5 weeks later. It is noteworthy that the dyskinesias resulting from STN lesions re¬ solved after several weeks. Similar results have been reported with electrolytic lesions or after high-frequency stimulation of the STN in parkinsonian monkeys27 and after injections of ex¬ citatory amino acid antagonists into GPi, which presumably di¬ rectly antagonized the excessive excitatory drive from STN.28 In some of the reports mentioned above, prominent bilateral effects on akinesias were observed after unilateral inactivation of STN. Recently, bilateral improvements in parkinsonian signs have also been observed after pallidotomy for Parkinson’s disease.29 The importance of STN in the develop¬ ment of parkinsonian motor signs is underscored by a clinical case report on a patient whose contralateral parkinsonian motor signs were reversed after the development of hemiballismus af¬ ter a stroke involving STN.30

tion of the “indirect pathway” acts to increase, inhibitory basal ganglia output (via GPi and SNr) onto thalamocortical neurons, which in turn modulate the activity of precentral motor areas. The tonic inhibitory basal ganglia output onto thalamocortical cells appears to suppress movement, whereas phasic reductions of basal ganglia output, time-locked to movement, may act to facilitate the later phases of cortically initiated voluntary motor acts. Given the late onset of pallidal discharge in relation to movement compared with cortical motor areas, output from the basal ganglia is probably less involved in the initiation than in the execution of movement. The magnitude of phasic responses may be important in the scaling of planned or ongoing move¬ ments. This model implies that changes in tonic or phasic basal ganglia output should have effects on motor performance. The postulated dual mode of operation of the motor circuit in facilitating cortically initiated movements and suppressing

Further evidence for the importance of increased basal gan¬ glia output in the development of parkinsonism comes from studies in human patients undergoing stereotactic surgery for Parkinson’s disease. Moreover, it has been found that GPi neu¬ ronal activity is increased over that in GPe in human Parkinson’s disease patients just as it is in MPTP-treated mon¬ keys.15 It has been found that lesions of the caudoventral GPi can reverse akinesia, rigidity, and tremor.31-32 The early report by Svennilson and associates31 and later reports by Laitinen and coworkers32 and Baron and colleagues33 emphasized the impor¬ tance of lesioning the caudal portion of GPi, that is, the region of the pallidum that by extrapolation from electrophysiological motor maps in monkeys and direct mapping in humans would appear to correspond to the motor circuit portion of GPi. Taken together, the data from experimental studies in animals and ob¬ servations in humans strongly support the hypothesis that all the major parkinsonian motor signs depend on increases in tonic and phasic output from the sensorimotor territory of the GPi. From the proposed pathophysiological model and the previ¬ ously mentioned data, it would appear logical that lesions of GPi (pallidotomy) in parkinsonian subjects not only might have beneficial effects on parkinsonian signs by directly lower¬ ing GPi output but also should, based on the proposed hyperki¬ netic circuit model, result in dyskinesias by acutely disinhibiting the thalamus. Contrary to the prediction of the model, dyskinesias have not been reported in either series of patients undergoing pallidotomy.3132 In our experience, however, tran¬ sient dyskinesias of the contralateral limbs are frequently ob¬ served acutely during and after pallidotomy (unpublished observations). Although one might expect that these pallidal lesions in humans or primates would result in significant move¬ ment abnormalities as a result of the loss of the postulated highly specific facilitation of cortically initiated movements and inhibition of “competing" movements, this has not in fact been reported. While inconsistent with the predictions of the model, these data may be taken to suggest the development of compensatory changes in subsequent stages of the “motor cir¬ cuit,” possibly at the thalamic level.

other competing movements is difficult to defend in light of the striking lack of significant long-term effects of STN and GPi le¬ sions on voluntary limb movements in both humans and mon¬ keys. The dramatic reversal of parkinsonian akinesia and bradykinesia after lesions of the STN or GPi provides strong ev¬ idence for the role of excessive pallidal output in the production of hypokinetic signs, and the appearance of dyskinesia in asso¬ ciation with lowered basal ganglia output in hyperkinetic disor¬ ders is well documented. The inference, however, that the nor¬ mal function of the basal ganglia in voluntary movement lies between these two extreme pathological states is difficult to maintain. It seems likely that our concept of normal basal gan¬ glia function in movement has been excessively influenced by the pathophysiological consideration and that the normal func¬ tion of the motor circuit is not some simple middle ground be¬ tween that observed in hypo- and hyperkinetic disorders. The changes in basal ganglia output in parkinsonian and dyskinetic subjects could produce significant behavioral effects through a number of mechanisms, none of them necessarily re¬ flecting the loss of normal basal ganglia function. Indeed, although Parkinson’s disease generally has been considered prototypical of basal ganglia dysfunction, the behavioral deficits observed in this disorder may equally well reflect ab¬ normal cortical and possibly brain stem function. For instance, bradykinesia may not indicate a direct role of the basal ganglia in movement initiation or execution but may result from func¬ tional inactivation of cortical areas that are directly involved in those processes. STN or GPi lesions may free the cortex and brain stem from the excessive inhibitory output.

ROLE OF THE MOTOR CIRCUIT IN MOVEMENT According to the prevailing model of basal ganglia function, activation of the direct pathway acts to reduce, whereas activa¬

PATHOPHYSIOLOGICAL BASIS OF PARKINSONIAN MOTOR SIGNS We now consider in greater detail possible links between the previously discussed activity changes in the basal ganglia cir¬ cuitry in primate models of movement disorders and the motor disturbances seen in parkinsonian patients.

Akinesia The role of the loss of dopamine in the development of akinesia is attested to by the fact that dopamine blockers (e.g., neurolep¬ tics) induce akinesia and dopaminergic drugs (L-dopa, apomorphine, bromocriptine) reverse it. In parkinsonism, dopamine

Chapter 119/Pathophysiological Basis of Neurosurgical Treatment of Parkinson’s Disease

depletion is greatest in the putamen, implying that dysfunction of the motor circuit may be particularly relevant in the develop¬ ment of akinesia.34 This is further supported by positron emis¬ sion tomography (PET) studies of preclinical and clinical parkinsonian patients,35 in whom reduced putaminal 18F-dopa uptake has consistently been the earliest sign of striatal dopamine deficiency. The finding that STN26 or GPi lesions31,32 can reverse akine¬ sia strongly indicates that akinesia results from excessive basal ganglia output. Moreover, the recent finding that selective inac¬ tivation of the motor territory of STN and GPi reverses akine¬ sia suggests that the motor circuit is strongly implicated in the production of akinesia. Increased tonic inhibition of thalamo¬ cortical neurons by increased basal ganglia output in parkin¬ sonism may render the precentral motor areas less responsive to other inputs that normally are involved in initiating move¬ ments or may interfere with “set” functions that are highly de¬ pendent on the integrity of basal ganglia pathways.5 In accor¬ dance with this, preparatory activity in SMA in MPTP monkeys is reduced compared to normal.36 Finally, PET stud¬ ies37 have shown that akinesia in human parkinsonian patients is associated with failure to activate the anterior cingulate cor¬ tex and SMA. This deficit was reversed by the administration of the dopamine agonist apomorphine.38 Components of akinesia also may result from damage to other dopaminergic projection systems, innervating “limbic” or “associative” basal ganglia-thalamocortical circuits or even damaging nondopaminergic brain stem nuclei (e.g., the locus caeruleus25). For example, dopamine loss in associative (cau¬ date nucleus) or limbic areas of the basal ganglia (nucleus accumbens and parolfactory gyrus) may parallel the development of akinesia,39 and in rats, dopaminergic transmission in the nu¬ cleus accumbens (the ventral striatum in primates) mediates dopamine agonist-induced locomotion.40

Bradykinesia Although the term bradykinesia is sometimes used inter¬ changeably with akinesia, it is used here in the simple sense of slowness of movement, reflecting several disturbances of movement execution. Thus, parkinsonian subjects fail to gener¬ ate adequate initial bursts in the agonist muscle on electromy¬ ography (EMG),41 perform movements of large amplitude at low velocities, often in a segmented manner with multiple small-amplitude movements42 and with a range of scaling of the magnitude of the initial agonist burst which is reduced compared with normal patients.43 In parkinsonian patients, movement times are out of proportion when simple movements are performed sequentially or simultaneously compared with the case when they are performed alone.44,45 The pathophysiological basis of bradykinesia remains un¬ certain. Conceivably, the increased tonic inhibition of thalamo¬ cortical neurons by excessive output from GPi could reduce the overall responsiveness of cortical mechanisms. Changes in the phasic discharge of basal ganglia output neurons may be in¬ volved in the development of bradykinesia as well. With an ex¬ cessively high level of tonic discharge in GPi neurons, it is pos¬ sible that superimposed phasic reductions in activity that occur during movement execution are not transmitted faithfully to the cortex, resulting in a reduced range of neuronal amplitude changes and scaling of movement. Increased gain in the motor

1143

circuit may lead to nearly maximal phasic responses even with movements of small amplitude; thus, the grading of phasic re¬ sponses in GPi may be reduced, and this may reduce the range of velocities permitted by basal ganglia output. Although active movements have not been studied in detail in the MPTP model, the enhanced responses observed during passive movements suggest the possibility that increases in discharge during active movement may actually be enhanced, thus acting to reduce thalamocortical facilitation of movement and slow movements.

Rigidity Rigidity has long been argued to be due to increased alphamotoneuron excitability;46 however, the mechanisms that lie behind this abnormality remain uncertain. As one possibility, abnormalities in la afferents have been suspected in this regard. Although dorsal root section has been reported in at least one subject to abolish parkinsonian rigidity,47 various studies have not detected abnormalities in la afferent fiber activity.48 As an alternative, fixed, abnormally high reflex “gain” in longlatency reflexes (LLRs) may account for the abnormal alphamotoneuron excitability in parkinsonian patients. The abnor¬ mal phasic responses generated in the basal ganglia of MPTP-treated primates22,23 could be responsible for increased LLR production (acting through the motor circuit projection to SMA) or may reflect abnormally large inputs to the striatum from the motor or somatosensory cortices that are engaged in LLR production and whose altered responsiveness may result from increased tonic output from GPi. The finding that rigidity does not correlate with the magnitude of LLRs in parkinsonian patients in the “on” and “off’ states, however, argues against a role of these reflexes in rigidity.49 A more recent hypothesis attributes rigidity to the reduction of autogenic inhibition on the spinal level. The results of Delwaide and coauthors50 in patients with parkinsonism sug¬ gest that lb intemeurons are less active in parkinsonian subjects than in normal individuals, leading presumably to disinhibition of alpha-motoneurons. The authors suggested that this abnor¬ mality may be due to alterations in basal ganglia output that are mediated via the basal ganglia outputs to the pedunculopontine nucleus (PPN) and the nucleus reticularis gigantocellularis and the reticulospinal projection leading to increased inhibition onto lb intemeurons.

Tremor The pathophysiological basis of the characteristic 4- to 5-Hz tremor at rest in Parkinson’s disease is not well understood. In the past, the thalamus was considered to be the principal candi¬ date for tremor generation, since surgical lesions in the thala¬ mus [principally the ventralis intermedius nucleus (Vim)] abol¬ ish the tremor of Parkinson’s disease. In addition, recordings of neuronal activity in the thalamus during these thalamotomies have revealed oscillatory bursting discharge patterns of Vim neurons associated with tremor. It is important to note that the Vim portion of the thalamus does not receive direct projections from GPi51 and appears to receive principally cerebellar input. However, from recent animal data, it has become clear that al¬ terations in the basal ganglia may play a much larger role in tremor than was previously thought.52 The discrepancy with the

1144

Part 4/Functional Stereotaxis

above-mentioned Vim lesioning data in humans could conceiv¬ ably be resolved, assuming that these lesions actually lessen pallidal outflow fibers en route to their target movements in Vim. In animals, it is difficult to induce tremor that faithfully re¬ produces the tremor of Parkinson’s disease. Even in most MPTP-treated monkeys, tremor is a rather inconsistent sign. An exception to this rule appears to be African green monkeys,26 in which MPTP leads to parkinsonian tremor at rest in a high percentage of cases. This species dependence may be partly accounted for by differences in the vulnerability of sub¬ populations of the dopaminergic neuron pool. Dopaminergic cells projecting to GPi may play a significant role in this re¬ gard,53 because parkinsonian patients and MPTP-treated African green monkeys have a more severe dopaminergic deficit in GPi than do MPTP-treated macaque monkeys.54 Of course, species differences may also be explainable by differ¬ ential involvement of nondopaminergic midbrain nuclei.55 As was pointed out earlier, changes in basal ganglia activity are likely to be important for tremor development, because sur¬ gical interruption of pallidal outflow by disruption of pallidal efferent fibers or by lesions of GPi can produce lasting relief of tremor in parkinsonian patients31-56-57 and because inactivation of STN in MPTP-treated monkeys markedly reduces tremor.26 Tremor could be due to oscillatory (phasic) activity in the basal ganglia themselves or to increased tonic basal ganglia output, promoting oscillatory activity in the thalamus. In monkeys, lesions of the substantia nigra frequently in¬ duce bursting discharge patterns in GPi, with bursts typically occurring at a frequency of 12 to 15 Hz2258-59 in rhesus mon¬ keys that do not show overt tremor and at 4 to 8 Hz in African green monkeys that show tremor of the same frequency.23-24 Similar bursting patterns were obtained by intracellular record¬ ings from GP in brain slices from adult guinea pigs when the recorded cells were abruptly depolarized from a hyperpolarized membrane potential.60 In parkinsonian patients undergoing stereotactic thalamotomy, cells discharging at frequencies close to the parkinsonian tremor frequency have been detected in the areas of the thalamus that receive input from the basal ganglia.61 Taken together, these findings suggest that neurons in the basal ganglia per se are capable of producing burst discharges inde¬ pendent of peripheral somatosensory input and that such bursts may occur at the parkinsonian tremor frequency of 3 to 5 Hz. Increased tonic output from GPi and SNr to the thalamus also may play a role in tremor. It has been proposed that hyperpolarizing inputs to the thalamus from SNr and GPi may pro¬ mote bursts in thalamocortical cells.62-63 This tendency for rhythmic oscillation of thalamocortical neurons may be en¬ hanced by periodic bursting in the reticular nucleus of the thal¬ amus during moments of immobility. Finally, the increased gain in the motor circuit may, by way of its feedback character¬ istics, also have a powerful tremorigenic effect.64-65

served behavioral disturbances result in part from abnormal ac¬ tivity in the cortical targets of basal ganglia- thalamocortical pathways. The diversity of motor, cognitive, and emotional signs and symptoms of Parkinson’s disease becomes more eas¬ ily understood when it is considered within the framework of this circuit model. Motor symptoms such as rigidity, bradykinesia, akinesia, and dyskinesias are believed to reflect disrup¬ tion of the motor circuit and the activity of the precentral motor fields. Similarly, oculomotor deficits may result from dysfunc¬ tion of the oculomotor circuit and frontal eye fields and certain cognitive deficits, and frontal release may reflect dysfunction in association circuits and the prefrontal cortex. Clarification of the intrinsic circuitry of the basal ganglia, in particular the opposing influences of the direct and indirect pathways on basal ganglia output, have helped us understand the basis of hypokinetic disorders, which appears to lie in in¬ creases in tonic and phasic basal ganglia outflow resulting from loss of the dopaminergic innervation supply of the basal gan¬ glia. New therapeutic strategies, including drug treatment, transplantation approaches, and stereotactic lesioning proce¬ dures, should aim primarily to reduce excessive basal ganglia outflow.

References 1.

Albin RL, Reiner A, Anderson KD, et at: Striatal and nigral neuron subpopulations in rigid Huntington’s disease: Implications for the functional anatomy of chorea and rigidity-akinesia. Ann Neurol 27:357-365, 1990.

2.

DeLong MR: Primate models of movement disorders of basal ganglia origin. Trends Neurosci 13:281-285, 1990. DeLong MR: Overview of basal ganglia function, in Mano N, Hamada I, DeLong MR (eds): Role of the Cerebellum and Basal Ganglia in Voluntary Movement. New York: Excerpta Medica, 1993, pp 65-70.

3.

4.

5.

6.

7. 8.

9.

10.

11.

SUMMARY AND CONCLUSION Advances in our understanding of the functional organization of the basal ganglia have helped clarify the role of those struc¬ tures in behavior and in the pathophysiology of Parkinson’s disease. The segregated circuit model predicts that the ob¬

12.

DeLong MR. Georgopoulos AP: Motor functions of the basal ganglia, in Brookhart JM, Mountcastle VB, Brooks VB, Geiger SR (eds): Hand¬ book of Physiology. The Nervous System: Motor Control. Bethesda: American Physiological Society, 1981, vol II. pp 1017-1061. Alexander GE, Crutcher MD: Functional architecture of basal ganglia circuits: Neural substrates of parallel processing. Trends Neurosci 13:266-271, 1990. Alexander GE. Crutcher MD, DeLong MR: Basal ganglia-thalamocortical circuits: Parallel substrates for motor, oculomotor, “pre¬ frontal” and “limbic” functions. Prog Brain Res 85:119-146, 1990. Kemp JM, Powell TPS: The cortico-striate projection in the monkey. Brain 93:525-546, 1970. Alexander GE, DeLong MR, Strick PL: Parallel organization of func¬ tionally segregated circuits linking basal ganglia and cortex. Annu Rev Neurosci 9:357-381, 1986. Miller WC, DeLong MR: Parkinsonian symptomatology: An anatomical and physiological analysis. Ann NY Acad Sci 515: 287-302, 1988. Alexander GE, DeLong MR, Crutcher MD: Do cortical and basal ganglionic motor areas use “motor programs" to control movement? Behav Brain Sci 15:656-665, 1992. Wichmann T, DeLong MR: Pathophysiology of parkinsonian motor abnormalities, in Narabayashi H. Nagatsu T, Yanagisawa N. Mizuno Y (eds): Advances in Neurology. New York: Raven Press, 1993, vol 60. pp 53-61. Alexander GE, DeLong MR: Microstimulation of the primate neo¬ striatum: II. Somatotopic organization of striatal microexcitable zones and their relation to neuronal response properties. J Neuro¬ physiol 53:1417-1430. 1985.

Chapter 119/Pathophysiological Basis of Neurosurgical Treatment of Parkinson’s Disease

13.

Crutcher MD, DeLong MR: Single cell studies of the primate putamen: I. Functional organization. Exp Brain Res 53:233-243, 1984.

14.

DeLong MR, Crutcher MD, Georgopoulos AP: Primate globus pallidus and subthalamic nucleus: Functional organization. J Neuro¬ physiol 53:530-543, 1985. Vitek JL, Kaneoke Y, Turner R, et al: Neuronal activity in the internal (GPi) and external (GPe) segments of the globus pallidus (GP) of parkinsonian patients is similar to that in the MPTP-treated primate model of parkinsonism. Soc Neurosci Abstr 19:1584, 1993.

15.

16.

17.

18.

19.

20. 21.

22.

23.

24.

25.

26.

27.

28.

Hazrati LN, Parent A, Mitchell S, Haber SN: Evidence for intercon¬ nections between the two segments of the globus pallidus in pri¬ mates: A PHA-L anterograde tracing study. Brain Res 533:171-175, 1990. Kita H, Kitai ST: Efferent projections of the subthalamic nucleus in the rat: Light and electron microscope analysis with the PHA-L

35. 36.

37.

38.

method. J Comp Neurol 260:435-4-52, 1987. Smith Y, Parent A: Neurons of the subthalamic nucleus in primates display glutamate but not GABA immunoreactivity. Brain Res

39.

453:353-356, 1988. Gerfen CR, Engber TM, Mahan LC, et al: D1 and D2 dopamine re¬ ceptor-regulated gene expression of striatonigral and striatopallidal neurons. Science 250:1429-1432, 1990.

40.

Hoover JE, Strick PL: Multiple output channels in the basal ganglia. Science 259:819-821, 1993. Alexander GE, Koliatsos VE, Martin LJ, et al: Organization of pri¬ mate basal ganglia “motor circuit”: I. Motor cortex (MC) and sup¬ plementary motor area (SMA) project to complementary regions within matrix compartment of putamen. Soc Neurosci Abstr 14:720, 1988. Miller WC, DeLong MR: Altered tonic activity of neurons in the globus pallidus and subthalamic nucleus in the primate MPTP model of parkinsonism, in Carpenter MB, Jayaraman A (eds): The Basal Ganglia II. New York: Plenum Press, 1987, pp 415—427.

sonian patients are effective in alleviating the cardinal signs of Parkinson’s disease. Soc Neurosci Abstr 1993. Kish SJ, Shannak K, Hornykiewicz O: Uneven pattern of dopamine loss in the striatum of patients with idiopathic Parkinson’s disease. N Engl J Med 318:876-880, 1988. Brooks DJ: Detection of preclinical Parkinson’s disease with PET. Neurology 41(suppl 2):24—27, 1991. Watts RL, Mandir AS: The role of motor cortex in the pathophysiol¬ ogy of voluntary movement deficits associated with parkinsonism. Neurol Clin North Am 10:451^169, 1992. Playford ED, Jenkins IH, Passingham RE, et al: Impaired mesial frontal and putamen activation in Parkinson’s disease: A positron emission tomography study. Ann Neurol 32:151-161, 1992. Jenkins IH, Fernandez W, Playford ED, et al: Impaired activation of the supplementary motor area in Parkinson’s disease is reversed when akinesia is treated with apomorphine. Ann Neurol 32:749-757, 1992. Pifl C, Bertel O, Schingnitz G, Hornykiewicz O: Extrastriatal dopa¬ mine in symptomatic and asymptomatic rhesus monkeys treated with l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP). Neurochem Int 17:263-270, 1990. Pijnenburg AJJ, Van Rossum JM: Stimulation of locomotor activity following injection of dopamine into the nucleus accumbens. J Pharm Pharmacol 25:1003-1005, 1973.

41.

Hallett M, Khoshbin S: A physiological mechanism of bradykinesia. Brain 103:301-314, 1980.

42.

Draper IT, Johns RJ: The disordered movement in parkinsonism and the effect of drug treatment. Bull Johns Hopkins Hosp 115:465^180, 1964.

43.

Berardelli A, Dick JPR, Rothwell JC, et al: Scaling of the size of the first agonist EMG burst during rapid wrist movements in patients with Parkinson’s disease. J Neurol Neurosurg Psychiatry 49: 1273-1279,

44.

Filion M, Tremblay L, Bedard PJ: Abnormal influences of passive limb movement on the activity of globus pallidus neurons in parkin¬

1986. Benecke R, Rothwell JC, Dick JPR, et al: Simple and complex move¬ ments off and on treatment in patients with Parkinson’s disease. J Neurol Neurosurg Psychiatry 50:296-303, 1987.

sonian monkeys. Brain Res 444:165-176, 1988. Wichmann T, Bergman H, DeLong MR: Increased neuronal activity in the subthalamic nucleus of MPTP treated monkeys. Mov Disord

45.

5(suppl)l:78, 1990. Mitchell IJ, Clarke CE, Boyce S, et al: Neural mechanisms underly¬ ing parkinsonian symptoms based upon regional uptake of 2-deoxyglucose in monkeys exposed to l-methyl-4-phenyl-l,2,3,6-tetrahy-

46.

739-757, 1986. Marsden CD: The mysterious motor function of the basal ganglia: The Robert Wartenburg lecture. Neurology 32:514-539, 1982.

47.

Pollack LT, Davis L: Muscle tone in parkinsonian states. Arch Neurol

dropyridine. Neuroscience 32:213-226, 1989. Bergman H, Wichmann T, DeLong MR: Reversal of experimental parkinsonism by lesions of the subthalamic nucleus. Science 249:

48.

Psychiatr 23:303-319, 1930. Burke D, Gandevia SC, McKeon B: Monosynaptic and oligosynaptic contributions to human ankle jerk and H reflex. J Neurophysiol 52:

1436-1438, 1990. Aziz TZ, Peggs D, Sambrook MA, Crossman AR: Lesion of the sub¬ thalamic nucleus for the alleviation of l-methyl-4-phenyl-l,2,3,6tetrahydropyridine (MPTP)-induced parkinsonism in the primate.

49.

435^148, 1984. Cody FWJ, MacDermott N, Matthews PBC, Richardson HC: Ob¬ servations on the genesis of the stretch reflex in Parkinson’s disease.

50.

Brain 109:229-249, 1986. Delwaide PJ, Pepin JL, Maertens de Noordhout A: Short-latency au¬ togenic inhibition in patients with parkinsonian ridigity. Ann Neurol

51.

30:83-89, 1991. Schell GR, Strick PL: The origin of thalamic inputs to the arcuate premotor and supplementary motor areas. J Neurosci 4:539-560,

Mov Disord 6:288-292, 1991. Brotchie JM, Mitchell IJ, Sambrook MA, Crossman AR: Alleviation of parkinsonism by antagonism of excitatory amino acid transmission in the medial segment of the globus pallidus in rat and primate. Mov

29.

Disord 6:133-138, 1991. Baron MS, Vitek JL, Bakay RAE, et al: Treatment of advanced Parkinson’s disease by GPi pallidotomy: 1 year pilot-study results.

30.

Ann Neurol 40:355-366, 1996. Sellal F, Lisovoski F, Hirsch E, et al: Contralateral disappearance of parkinsonian signs after subthalamic hematoma. Neurology 42:255,

31.

34.

1145

1992. Svennilson E, Torvik A, Lowe R, Leksell L: Treatment of Parkinsonism by stereotactic thermolesions in the pallidal region: A clinical evaluation of 81 cases. Acta Psychiatr Neurol Scand 35:

32.

358-377, 1960. Laitinen LV, Bergenheim AT, Hariz MI: Leksell’s posteroventral pal¬ lidotomy in the treatment of Parkinson’s disease. J Neurosurg 76:53,

33.

1992. Baron MS, Vitek JL, Turner RS, et al: Lesions in the sensorimotor re¬ gion of the internal segment of the globus pallidus (GPi) in parkin¬

52.

53.

54.

55.

Benecke R, Rothwell JC, Dick JPR, et al: Performance of simultane¬ ous movements in patients with Parkinson’s disease. Brain 109:

1984. Vitek JL, Wichmann T, DeLong MR: Current concepts of basal gan¬ glia neurophysiology with respect to tremorgenesis, in Findley LJ, Roller W (eds): Handbook of Tremor Disorders. New York: Marcel Dekker, 1994, pp 37-50. Bemheimer H, Birkmayer W, Hornykiewicz O, et al: Brain dopamine and the syndromes of Parkinson and Huntington. J Neurol Sci 20: 415-455, 1973. Dacko S, Smith MG, Schneider JS: Immunohistochemical study of the pallidal complex in symptomatic and asymptomatic MPTPtreated monkeys, normal human, and Parkinson’s disease patients (abstract). Neuroscience 16:428, 1990. German DC, Dubach M, Askari S, et al: 1-methyl-4-phenyl-l,2,3,6tetra-hydropyridine-induced parkinsonian syndrome in Macaca fascicularis: Which midbrain dopaminergic neurons are lost? Neuro¬ science 24:161-174, 1988.

1146

56. 57.

58.

59.

60.

Part 4/Functional Stereotaxis

Spiegel EA, Wycis HT: Ansotomy in paralysis agitans. Arch Neurol Psychialr 71:598-614, 1954. Hassler R, Reichert T, Mundinger F, et al: Physiological observations in stereotaxic operations in extrapyramidal motor disturbances. Brain 83:337-350, 1960. Filion M: Effects of interruption of the nigrostriatal pathway and of dopaminergic agents on the spontaneous activity of globus pallidus neurons in the awake monkey. Brain Res 178:425-441, 1979. Filion M, Tremblay L: Abnormal spontaneous activity of globus pal¬ lidus neurons in monkeys with MPTP-induced parkinsonism. Brain Res 547:142-151, 1991. Nambu A, Llinas R: Electrophysiology of the globus pallidus neu¬ rons: An in vitro study in guinea pig brain slices. Soc Neurosci Abstr 180:8, 1990.

61.

62.

Pare D, Curro’Dossi R. Steriade M: Neuronal basis of the parkinson¬ ian resting tremor: A hypothesis and its implications for treatment. Neuroscience 35:217-226, 1990. Buzsaki G, Smith A, Berger S, et al: Petit mal epilepsy and parkin¬ sonian tremor: Hypothesis of a common pacemaker. Neuroscience 36:1-14, 1990.

63.

Llinas RR: The intrinsic electrophysiological properties of mam¬ malian neurons: Insights into central nervous system function. Science 242:1654—1664, 1988.

64.

Schwarz R, Hokelt T, Fuxe K, et al: Ibotenic acid-induced neuronal degeneration: A morphological and neurochemical study. Exp Brain Res 37:199-216, 1979.

65.

Tremblay L, Filion M: Responses of pallidal neurons to striatal stimu¬ lation in intact waking monkeys. Brain Res 498:1-16, 1989.

CHAPTER

120

ANIMAL MODELS OF PARKINSON’S DISEASE

Andre Parent and Pierre-Yves Cote

Animal models are widely used to investigate the pathophysi¬ ology of neurological dysfunctions such as Parkinson’s disease (PD) and Huntington’s chorea. Basic researchers interact with clinicians mostly through the investigation of animal models that are used to study the anatomic, physiological, pharmaco¬ logical, and therapeutic aspects of a given disease. There are no perfect animal models, but some are more suitable than others. The characteristics of a good animal model are reproducibility of the cardinal symptoms of the disease, the response of ani¬ mals to drug therapy, and comparable locations and degree of neuropathologic lesions observed in the model and in the idio¬ pathic form of the disease.

PARKINSON’S DISEASE The anatomic hallmark of idiopathic PD is a progressive loss of neurons in the pars compacta of the substantia nigra (SNc).1-3 These neurons use dopamine as their neurotransmitter and pro¬ vide an important input to the striatum.4 7 Lesions of the nigrostriatal pathway led to the development of the first reliable models of PD.8 Currently, rats lesioned with 6-hydroxydopamine (6-OHDA) and monkeys treated with l-methyl-4phenyl-l,2,3,6-tetrahydropyridine (MPTP) are more widely used than are other models, which include MPTP-treated cats, dogs, sheep, mice, and goldfish. Although 6-OHDA rats show a substantial cell loss in the SNc, MPTP monkeys also exhibit the typical symptoms seen in PD.9 These include (1) resting tremor, which affects the distal parts and to a lesser degree the proximal parts, (2) rigidity, or resistance to passive movements of the limbs, (3) akinesia in motor initiative, kinetic versatility, and strategy of learning, and (4) postural instability, that is, a typical bent posture.10

parkinsonian brains.5 Stereotactic variations in the placement of electrolytic lesions called for a more selective way of lesioning specific neurotransmitter systems in animal studies. This need was satisfied through the use of neurotoxins—mole¬ cules that cause specific cellular death in restricted neuronal populations.

Rat Model of Parkinson’s Disease One of the most widely used animal models to study PD is the 6-OHDA rat. 6-OHDA has a structure analogous to that of dopamine and norepinephrine and, when injected directly in brain tissue or in cerebrospinal fluid, leads to nearly complete destruction of the nigrostriatal pathway.1112 A concomitant de¬ crease in striatal dopamine is observed, but at least 85 percent of this pathway must be altered before motor symptoms ap¬ pear.13 In 6-OHDA rats, however, motor deficits and neuro¬ chemical changes occur shortly after the injection, whereas symptoms in idiopathic PD develop over years.14 Furthermore, damage caused by the introduction of the cannula into sur¬ rounding structures and a possible lack of specific effect on dopaminergic nigral neurons should be taken into considera¬ tion.15 This model is most likely the least expensive one, and it can be obtained quite rapidly compared with primate models. Unilaterally lesioned 6-OHDA rats show a characteristic cir¬ cling as well as other typical behaviors that are enhanced after injections of various dopamine agonists.131617 This model can verify the efficacy of antiparkinsonian drugs and has proved useful in a number of biochemical studies.

Discovery of MPTP At the end of the 1970s, the fortuitious discovery of a novel neurotoxin drastically changed basic research strategies in PD. The toxin, MPTP, a meperidine analogue sold as a new “synthetic heroin,” was taken intravenously by illicit drug users.1819 Those individuals became symptomatic soon after self-injection of the drug, and postmortem analysis of one brain revealed a moderate to severe midbrain neuronal loss com¬ parable to that seen in idiopathic PD.18 Shortly after its identifi¬ cation, MPTP was injected in primates and proved to selec¬ tively affect dopaminergic neurons in the SNc.9’20 Thus, a new era of PD research began.

ANIMAL MODELS OF PARKINSON’S DISEASE The first animal studies of PD were conducted in primates and involved electrolytic lesions stereotactically placed in various portions of the upper brain stem.8 Lesions of the ventromedial tegmental area caused the greatest cell loss in the SNc accom¬ panied by a substantial decrease of dopamine in the striatum.7 Similar decreases in striatal dopamine were reported in human

1147

1148

Part 4/Functional Stereotaxis

Overview of MPTP models There are several MPTP animal models. The MPTP mouse model was developed about a decade ago, and its use yielded important findings on alterations of neurotransmitter recep¬ tors.21’22 However, this model differs from the idiopathic disease because deficits are rapidly induced and are partly reversible. In cats, MPTP injection produces rigidity, akinesia, and pos¬ tural instability, but interestingly, most animals recover a few weeks after the administration of the drug. This intriguing re¬ covery, which is occasionally observed in 6-OHDA rats and MPTP primates, is accompanied by a partial biochemical re¬ covery in the striatum. Striatal depletions of dopamine and its major metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), range from 92 to 99 percent in symptomatic animals compared with controls, and selective cell loss is found in the SNc.23 Altogether, these observations indicate that, despite some limitations, the MPTP-treated cat is an interesting model for PD studies. Sheep, dogs, and even goldfish can be rendered parkinson¬ ian by MPTP administration. Reports using these models are scarce, and very few novel data have emerged from these stud¬ ies.24-26 Sheep require special facilities and are rather large ani¬ mals to handle. Nonetheless, they show pathological abnormal¬ ities in SNc and respond to L-dopa treatment.24 The MPTP dog model is not used extensively, but earlier reports25 emphasized that the degeneration of the nigrostriatal pathway affects pri¬ marily fibers that terminate in one chemical compartment of the striatum, the matrix.27 Recently, a “parkinsonian syndrome” was induced in the goldfish by MPTP injection. The syndrome is characterized by bradykinesia and decreases in dopamine and norepinephrine levels in the forebrain and midbrain. This model is reportedly useful for the screening of novel therapeu¬ tic or neuroprotective drugs.26

in monkeys suggest that there are subtle variations in the de¬ generating patterns at both the SNc and the striatal levels.31-32 MPTP is rapidly oxidized to MPP+ (l-methyl-4-phenylpyridinium), in part by monoamine oxidase-B (MAO-B).33 Pargyline and specific MAO-B inhibitors such as deprenyl (se¬ legiline) are known to block the neurotoxic action of MPTP in primates.34’35 Methylpyridinium specifically enters dopaminer¬ gic neurons through the dopamine reuptake system at the ter¬ minal level. MPP+ is thought to accumulate in mitochondria and interfere with the electron transport chain, leading to a drastic decrease in adenosine triphosphate (ATP) synthesis that presumably causes cell death.33 The “mitochondrial hypothe¬ sis” has received further support from studies showing abnor¬ malities of mitochondrial complex I in the striatum of parkin¬ sonian patients and in the nigral neurons of MPTP monkeys. The “oxidative stress hypothesis” states that disproportion¬ ate amounts of antioxidant defense mechanisms and the processes that generate these cellular oxidants are responsible for the cell death. A role for singlet molecular oxygen has been proposed in PD.36 Singlet molecular oxygen arises from diverse biochemical reactions, including the polymerization of dopamine to neuromelanin.37 Singlet oxygen is a highly reac¬ tive and biologically damaging form of oxygen, react¬ ing strongly with MPDP+, a by-product appearing in the transformation of MPTP to MPP+. It is believed that even if MAO activity is blocked, conversion of MPTP to its neurotoxic products could still take place via singlet molecular oxygen.36 Some aspects of MPTP neurotoxicity are poorly known. Rat SNc neurons, for instance, do not contain neuromelanin, and that may explain the reported resistance of rats to MPTP.38 That resistance also may be due to the presence of high MAO-B ac¬ tivity in rat capillary walls. The formation of MPP+ outside the brain would not allow this charged product to pass the bloodbrain barrier. This field of PD research is the focus of intense investigations.

Primate model of Parkinson’s disease The MPTP monkey model was developed in 1983.9 Baboons, marmosets and cynomolgus, rhesus, and squirrel monkeys, to name a few, can all be rendered parkinsonian by MPTP injection. The drug is injected subcutaneously or intravenously, usually via the internal carotid, which renders primates hemiparkinsonian.28 A detailed protocol for the manipulation and administration of MPTP to primates has been described elsewhere.29 MPTP is usu¬ ally given over a short period of time (days or weeks), and this treatment leads to massive losses of dopaminergic SNc neurons accompanied by a marked decrease of striatal dopamine (Figs. 120-1 and 120-2). All primates are sensitive to MPTP, but some, for example, the marmoset, can recover and do not show varia¬ tions of dopamine receptor density.30

Lesions of the Nigrostriatal Pathway The administration of MPTP to primates rapidly leads to motor impairments. The vast majority of monkeys become akinetic within hours after injection of the neurotoxin. These animals express the typical behavior of parkinsonian patients, being akinetic and rigid and having unstable posture. As in idiopathic PD, motor deficits in MPTP monkeys result from severe degen¬ eration of SNc dopaminergic neurons accompanied by a de¬ crease in striatal dopamine levels.91820 However, recent studies

Treatment of MPTP Primates MPTP-treated monkeys, like parkinsonian patients, respond to ldihydroxyphenylalanine (i.-dopa) treatment by showing marked improvements in their locomotor activities.9-20-39 L-dopa is the precursor of dopamine and constitutes, with dopamine agonists such as bromocriptine, one of the principal therapies given to parkinsonian patients. However, a common side effect of L-dopa therapy is dyskinesia, large-amplitude involuntary movements that generally appear after repeated doses of L-dopa. Dyskinesias develop in a large majority of L-dopa-treated patients and MPTP primates.39-11 The MPTP monkey is particularly useful for devel¬ oping new therapeutic agents that are devoid of side effects. Monkeys treated with MPTP, as opposed to 6-OHDA rats, re¬ spond to drug treatment much as parkinsonian patients do. Certain drugs, such as the D1 dopamine receptor agonist SKF 38393, are effective in 6-OHDA rats but ineffective in MPTP monkeys and human patients.42-*5

Comparisons between the Models and the Clinical Disease Of all PD symptoms, akinesia is the most frequent dysfunction that appears after 6-OHDA or MPTP injections. After a brief

Chapter 120/Animal Models of Parkinson’s Disease

initial phase of excitation, primates injected with the neuro¬ toxin rapidly diminish their locomotor activities.29 The most striking features of MPTP-treated primates are the typical bent posture and the slowness with which they execute movements. In some cases, primates are unable to feed or groom them¬ selves. This reaction is also observed clinically during the late stages of the idiopathic form of the disease.14 Other symptoms of the disease, such as rigidity and postural instability, are more easily and frequently observed in the primate model. Rats do not seem to display rigidity or to have postural problems, but monkeys show resistance to passive movements of their limbs and adopt a typical bent posture. Like their human counter¬ parts, MPTP monkeys become more active after L-dopa treat¬ ment, and the continuous use of this replacement therapy ulti¬ mately leads to the appearance of dyskinesias in the majority of MPTP monkeys.41 The dyskinesias affect primarily limb move¬ ments and almost always appear on the same side as the parkin¬ sonian symptoms. The physiopathology of these dyskinetic movements is poorly understood.46 MPTP monkeys differ from the idiopathic form of PD prin¬ cipally in regard to resting tremor. For unknown reasons, mon¬ keys rarely show resting tremor.47 This phenomenon seems to be species-dependent, as the African green monkey readily de¬ velops resting tremor after MPTP injection, while other species do so less often. It has been proposed that dopaminergic neu¬ rons in African green monkeys have a susceptibility to MPTP neurotoxicity that is different from that of other primates,48,49 but this has to be clarified immunohistochemically. Tremor in¬ duced by MPTP injection in African green monkeys is allevi¬ ated by lesions of the subthalamic nucleus.48 This approach has been considered in humans as a substitute for lesions in ventral tier thalamic nuclei.50 The beneficial effect of subthalamic nu¬ cleus lesions in PD can be explained by the massive excitatory action of this nucleus on the output structures of the basal gan¬ glia, principally the internal pallidum, which strongly inhibits the thalamocortical neurons.51 Similar improvement can be ob¬ tained with a lesion of the internal pallidum itself,52 which re¬ duces the pallidal inhibition on the thalamocortical premotor neurons. These experiments were done in humans after pio¬ neering work in the primate model. Electrophysiological recordings in PD patients undergoing stereotactic surgery re¬ veal that the firing patterns of pallidal neurons are similar to those recorded in MPTP monkeys.53 This is a typical case in which primate animal models play a key role in the develop¬ ment of therapeutic strategies to reduce parkinsonian signs. From the anatomic and biochemical standpoints, all 6OHDA and MPTP models of PD show selective cell loss in SNc accompanied by a decrease in striatal dopamine content (Figs. 120-1 and 120-2). Immunohistochemical studies using antibodies against tyrosine hydroxylase (TH), the rate-limiting enzyme in dopamine synthesis, have shown a dramatic de¬ crease in TH immunoreactivity in the striatum of both human and nonhuman primates (Fig. 120-2), together with variations in the levels of striatal peptide expression.54 The primate globus pallidus is composed of an external (GPe) segment and an in¬ ternal (GPi) segment, the latter being a major output of the basal ganglia. Both segments differ in the chemospecificity of their incoming striatal afferents. Striatal projection neurons are known to utilize gamma-aminobutyric acic (GABA) as a neu¬ rotransmitter, but neurons projecting to the GPi also contain the peptide substance P whereas those projecting to the GPe are en¬

1149

riched with enkephalin.55 Initial studies showed diminished GABA binding in the GPe,56 but current efforts are directed at the assessment of the dynamic changes that occur in striatal peptide expression. In PD, a significant increase in enkephalin immunoreactivity is seen in the GPe and a decrease in sub¬ stance P immunoreactivity is seen in the GPi.54 These changes have been confirmed by in situ hybridization experiments in ro¬ dents and primates. The expression of mRNA coding for sub¬ stance P is reduced in striatal neurons projecting to the GPi, whereas the mRNA for enkephalin is increased in neurons pro¬ jecting to the GPe.57,58 In primates, this enhanced expression occurs only in the so-called sensorimotor territory of the stria¬ tum by virtue of the origin of its cortical afferents.59 The cau¬ date nucleus is, by contrast, part of the associative striatal terri¬ tory.55 This differential modeling in the expression of mRNA for different peptides is said to be regulated by the two different dopamine receptor subtypes (D1 and D2).57 Degneration patterns in SNc of both human and nonhuman parkinsonians are not homogeneous. Neurons in the ventral tier are more severely affected than are those in the dorsal tier (Fig. 120-1).60,61 Furthermore, neurons that are less prone to degen¬ eration contain calbindin, a calcium-binding protein whose specific roles are unknown.60,61 A protective role has been at¬ tributed to calbindin because of its high capacity to buffer in¬ tracellular calcium ions. This remains to be confirmed since in other degenerative pathologies, such as Huntington’s chorea and Alzheimer’s disease, calbindin neurons are destined to die.62,63 Retrograde labeling studies in primates showed that neurons that project to the pallidum are concentrated around the ventral tegmental area, whereas nigrostriatal neurons are lo¬ cated more laterally and ventrally in the SNc.55 In addition, the nigropallidal dopaminergic projection is distinct from and ap¬ pears less sensitive to MPTP than is the nigrostriatal pathway.31 All animal models are not equally representative of the idio¬ pathic form of PD. Hence, no relative sparing of dorsal tier SNc neurons has been observed in nonprimate species. Additionally, 6-OHDA rats do not have spared calbindinpositive SNc neurons and do not show regional peptide mRNA variations in the striatum.

Acute versus chronic MPTP ADMINISTRATION The way MPTP is administered might change in the future be¬ cause of recent data obtained with a model of PD in baboons.32 In these experiments, the neurotoxin was injected chronically over a period ranging from 6 to 22 months to mimic the idio¬ pathic disease, whose onset and development spread over years. One of the aims of this investigation was to verify the possibility that subpopulations of dopaminergic neurons have a differential vulnerability to MPTP toxicity. Even after high cu¬ mulative doses, chronically treated monkeys do not suffer from aphagia or adipsia and are able to feed themselves on a normal diet. Resting tremor was observed a few months after chronic MPTP treatment. The tremor involved first the distal part of the upper limb on one side of the body and then the entire limb, the lower limb on the same side, and finally the four limbs.32 The shorter, acute treatment utilized in most species of monkeys is unlikely to give experimenters the time and opportunity to ob¬ serve resting tremor. Furthermore, monkeys sometimes recover

1150

Part 4/Functional Stereotaxis

j -

Figure 120-1.

Low-power photomicrographs of coronal sections of the intermediate level of the substantia nigra (SN) that are immunohistochemically reactive forTH. A. The SN of a normal cynomolgus monkey on the right side, where numerous cell bodies and bundles of immunoreactive processes are seen in the pars compacta (SNc). Note the TH-immunoreactive processes impinging on the pars reticulata of the substantia nigra (SNr), giving a tortuous border between SNc and SNr. B. A section taken from an MPTP-treated monkey showing a substantial loss of immunoreactive cell bodies and fibers. The cell loss is less important in the dorsal tier of SNc (arrows), which is also the case in idiopathic PD.60 The more medially located ventral tegmental area (VTA) is also relatively spared (arrowheads). The same immunohistochemical and photographic parameters were used for both sections.

Figure 120-2.

Schematic drawings derived from TH-immunoreacted coronal sections taken at the medial third of the striatum. The striatum is anatomically divided into the caudate nucleus (CD) and the putamen (PUT) by the internal capsule (IC). A. The staining of immunoreactive fibers (thin lines) and terminals (dots) in a normal adult cynomolgus monkey. B. The same staining in a moderately denervated MPTP monkey. C. A severely denervated MPTP monkey. Note the decreasing number of fibers and terminals in the dorsolateralmost portion of CD and PUT. The ventral striatum (VS), which includes the nucleus accumbens, is rarely denervated and represents the limbic territory of the striatum.55 OT = olfactory tubercle.

Chapter 120/Animal Models of Parkinson’s Disease

completely from their motor deficits after acute MPTP injec¬ tions.64-66 Interesting anatomic data have been gathered after chronic MPTP treatment in baboons. First, uneven loss of striatal dopamine is noted; the loss is greater in the putamen than in the caudate nucleus and is comparable to patterns of dopamine loss in the striatum of idiopathic PD patients.67 Second, there is a decreasing dorsolateral to medioventral gradient of dopamin¬ ergic fibers in both the caudate nucleus and the putamen. Third, the loss of dopaminergic cells is more severe in the ventral part of the SNc than in the dorsal part, and this is reminiscent of the distribution of calbindin-containing neurons.61 Neurons in the dorsal tier of SNc are relatively spared compared with those in the ventral tier. These results indicate that the sequence of dopaminergic cell loss seen in idiopathic PD may be replicated in primates by injecting MPTP at low doses over a prolonged period. The neurotoxin infused in minute quantities over long periods would therefore induce even more selective nigral

Verhalten bei Erkrankungen des extrapyramidalen Systems. Klin Wochenschr 38:1236, 1960. 6. 7. 8. 9.

10.

11.

12. 13.

dopaminergic cell damage. 14.

CONCLUDING REMARKS Animal models of PD play an important role in basic and clin¬ ical research. While some models, such as 6-OHDA rats, are suitable for screening novel therapeutic agents, the MPTP model seems to date to be the best model for testing drugs suitable for human therapy. For example, transplants of fetal dopaminergic nigral cells into striatum first developed in ro¬ dents led to a successful therapeutic approach in humans.68,69 While the primary causes of parkinsonism are unkown, ani¬ mals models are helpful in the development and trial of ad¬ vanced therapeutic strategies. Since PD is more than a simple one-transmitter dysfunction,70 future studies focused on neu¬ ronal alterations in various chemospecific neuronal systems other than the dopaminergic pathways should be particularly

15.

16.

17.

18.

19.

20.

rewarding.

ACKNOWLEDGMENTS The financial support of MRC of Canada is greatly acknowl¬ edged. We apologize to all contributors whose work served as an inspiration to this concise review but could not be cited be¬ cause of space limitations.

References 1.

2.

3. 4.

5.

Blocq P, Marinesco G: Sur un cas de tremblement parkinsonien hemiplegique symptomatique d'une tunieur du pedoncule cerebral. C R Soc Biol (Paris) 5:105, 1893. Tretiakoff C: Contribution a T etude de l’anatomie pathologique du locus niger de Soemmering avec quelques deductions relatives a la pathogenie des troubles du tonus musculaire de la maladie de Parkin¬ son. These (Paris), 1919. Hassler R: Zur Pathologie des Paralysis agitans und des postenzephalitischen Parkinsonismus. J Psychol Neurol 48:387, 1938. Carlsson A: The occurrence, distribution and physiological role of catecholamines in the nervous system. Pharmacol Rev 11:490, 1959. Ehringer H, Hornykiewicz O: Verteilung von Noradrenalin und Dopamin (3-Hydroxytyramin) im Gehirn des Menschen und ihr

1151

21.

22.

23.

24. 25.

26.

27.

28.

Anden NE, Carlsson A, Dahlstrom A, et al: Demonstration and map¬ ping out of nigroneostriatal dopamine neurons. Life Sci 3:523, 1964. Poirier LJ, Sourkes TL: Influence of the substantia nigra on the cate¬ cholamine content of the striatum. Brain 88:181, 1965. Poirier LJ: Experimental and histological study of midbrain dyskine¬ sias. J Neurophysiol 23:534, 1960. Bums RS, Chiueh CC, Markey SP, et al: A primate model of parkin¬ sonism: Selective destruction of dopaminergic neurons in the pars compacta of the substantia nigra by N-methyl-4-phenyl-l,2,3,6tetrahydropyridine: Proc Natl Acad Sci USA 80:4546, 1983. Barbeau A: Parkinson’s disease: Clinical features and etiopathology, in Vinken PJ, Bruyn GW, Klawans HL (eds): Handbook of Clinical Neurology. Amsterdam: Elsevier, 1986, vol 5, pp 87-152. Thoenen H, Tranzer JP: Chemical sympathectomy by selective de¬ struction of adrenergic nerve endings with 6-hydroxydopamine. Naunyn Schmiedebergs Arch Exp Pathol 261:271, 1968. Ungerstedt U: 6-Hydroxy-dopamine induced degeneration of central monoamine neurons. Eur J Pharmacol 5:107, 1968. Schultz W: Depletion of dopamine in the striatum as an experimental model of parkinsonism: Direct effects and adaptive mechanisms. Prog Neurobiol 18:121, 1982. Hoehn MM, Yahr MD: Parkinsonism: Onset, progression, and mor¬ tality. Neurology 17:427, 1967. Poirier LJ, Bedard PJ, Langelier P, et al: Les circuits neuronaux impliques dans la physiopathologie des syndromes parkinsoniens. Rev Neurol (Paris) 127:37, 1972. Ungerstedt U: Striatal dopamine release after amphetamine or nerve dengeration revealed by rotational behavior. Acta Physiol Scand Suppl 367:49, 1971. Ungerstedt U: Postsynaptic supersensitivity after 6-hydroxydopamine induced degeneration of the nigrostriatal dopamine system. Acta Physiol Scand Suppl 367:69, 1971. Davis GC, Williams AC, Markey SP, et al: Chronic parkinsonism sec¬ ondary to intravenous injection of meperidine analogues. Psychiatr Res 1:249, 1979. Langston JW, Ballard P, Tetrud JW, Irwin I: Chronic parkinsonism in humans due to a product of meperidine-analog synthesis. Science 219:979, 1983. Langston JW, Fomo LS, Rebeit CS, Irwin I: Selective nigral toxicity after systemic administration of l-methyl-4-phenyl-l,2,5,6-tetrahydropyridine (MPTP) in the squirrel monkey. Brain Res 292:390, 1984. Mizukawa K, Ogawa N, Sora YH, Sora I: Alterations of the mus¬ carinic cholinergic (mACh) receptors in the striatum of the MPTPinduced parkinsonian model in mice: In vitro quantitative autoradi¬ ographic analysis. Neurosci Terr 81:105, 1987. Sundstrom E, Fredriksson A, Archer T: Chronic neurochemical and behavioral changes in MPTP-lesioned C57BL/6 mice: A model for Parkinson’s disease. Brain Res 528:181, 1990. Schneider JS, Rothblat DS: Neurochemical evaluation of the striatum in symptomatic and recovered MPTP-treated cats. Neuroscience 44:421, 1991. Hammock BD, Beale AM. Work T, et al: A sheep model for MPTP in¬ duced Parkinson-like symptoms. Life Sci 45:1601, 1989. Hineno T, Mizobuchi M, Hiratani K, et al: Disappear-ance of cir¬ cadian rhythms in Parkinson’s disease model induced by 1-methyl4-phenyl-l,2,3,6-tetrahydropyridine in dogs. Brain Res 580:92, 1992. Pollard HB, Dhariwal K, Adeyemo OM, et al: A parkinsonian syn¬ drome induced in the goldfish by the neurotoxin MPTP. FASEB J 6:3108, 1992. Graybiel AM, Ragsdale CW Jr: Histochemically distinct compart¬ ments in the striatum of human, monkey and cat demonstrated by acetylthiocholinesterase staining. Proc Natl Acad Sci USA 75:5723, 1978. Bankiewicz KS, Oldfield EH, Chiueh CC. et al: Hemiparkinsonism in monkeys after unilateral internal carotid artery infusion of 1-methyl4-phenyl-l,2,3,6-tetrahydropyridine (MPTP). Life Sci 39:7, 1986.

1152

29.

30.

31.

32.

33. 34. 35. 36.

37.

38.

39. 40. 41.

42.

43.

44.

45.

46.

47.

48.

49. 50.

Part 4/Functional Stereotaxis

Bedard PJ, Boucher R. Gomez-Mancilla B, Blanchette P: Primate models of Parkinson’s disease, in Boulton A, Baker G, Butterworth R (eds): Neuromethods. Totowa, NJ: Humana Press, 1992, vol 21, pp 159-173. Temlett JA, Chang PN, Oertel WH, et al: The D[ receptor partial ago¬ nist CY-208243 exhibits antiparkinsonian activity in the MPTPtreated marmoset. Eur J Pharmacol 156:197, 1988. Parent A, Lavoie B, Smith Y, Bedard PJ: The dopaminergic nigropallidal projection in primates: Distinct cellular origin and relative spar¬ ing in MPTP-treated monkeys. Adv Neurol 53:111, 1990. Hantraye P, Varastet M, Peschanski M, et al: Stable parkinsonian syn¬ drome and uneven loss of striatal dopamine fibers following chronic MPTP administration in baboons. Neuroscience 53:169, 1993. Singer TP, Ramsay RR: Mechanism of the neurotoxicity of MPTP. FEBS Lett 274:1, 1990. Langston JW, Irwin I, Langston EB, Forno LS: Pargyline prevents MPTP-induced parkinsonism in primates. Science 225:1480, 1984. Tetrad JW, Langston JW: The effect of deprenyl (selegiline) on the natural history of Parkinson’s disease. Science 245:519, 1989. Chacdn JN, Truscott TG: Chemically induced Parkinson’s disease: III. A study of a possible role of singlet molecular oxygen in Parkinson’s disease. J Photochem Photobiol B 11:261, 1991. Krak I, Lichszteld K, Nichalska F: Evidence for the generation of sin¬ glet molecular oxygen during dopa and dopamine peroxidation. Z Naturforsch [C] 44:39, 1989. Boyce S, Kelly E, Reavill C, et al: Repeated administration of Nmethyl-4-phenyl-l,2,5,6-tetrahydropyridine to rats is not toxic to stri¬ atal dopamine neurones. Biochem Pharmacol 1:1747, 1984. Cotzias GC, Van Woert MH, Schiffer LM: Aromatic amino acids and modification of parkinsonism. N Engl J Med 276:374, 1967. Barbeau A: The use of L-DOPA in Parkinson’s disease: A 20 years follow-up. Trends Pharmacol Sci 2:297, 1981. Bedard PJ, Di Paolo T, Falardeau P, Boucher R: Chronic treatment with levodopa, but not bromocriptine, induces dyskinesia in MPTPparkinsonian monkeys: Correlation with [3H]spiperone binding. Brain Res 379:294, 1986. Amt J, Hyttel J: Differential inhibition by dopamine D-l and D-2 ag¬ onists of circling behavior induced by dopamine agonists in rats with unilateral 6-hydroxydopamine lesion. Eur J Pharmacol 102:349, 1984. Close SP, Marriott AS, Pay S: Failure of SKF 38393 to relieve parkin¬ sonian symptoms induced by l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine in the marmoset. Br J Pharmacol 85:320, 1985. Braun A, Fabbrini G, Mouradian MM, et al: Selective D-l dopamine receptor agonist treatment of Parkinson’s disease. J Neural Transm 68:41, 1987. Rouillard C. Bedard PJ: Specific D-l and D-2 dopamine agonists have synergistic effects in the 6-hydroxydopamine circling model in the rat. Neuropharmacology 27:1257, 1988. Bedard PJ. Gomez-Mancilla B, Blanchette P, et al: Levodopa-induced dyskinesia: Facts and fancy: What does the MPTP monkey model tell us? Can J Neurol Sci 19:134, 1992. Lamarre Y, Dumont M, Joffroy AJ: Le tremblement de type parkinsonien et Taction de Tharmaline: Fails experimentaux et mdcanismes hypothetiques. Arch Hal Biol 111:493, 1973. Bergman H, Wichmann T, DeLong MR: Reversal of experimental parkinsonism by lesions of the subthalamic nucleus. Science 249:1436, 1990. Wichmann T, DeLong MR: Pathophysiology of parkinsonian motor abnormalities. Adv Neurol 60:53, 1993. Tasker RR, Siqueira J, Hawrylyshyn PA, et al: What happened to VIM thalamotomy for Parkinson's disease? Appl Neurophysiol 46:68, 1983.

51.

DeLong MR: Primate models of movement disorders of basal ganglia origin. Trends Neurosci 13:281, 1990.

52.

Baron M. Vitek J, Turner R, et al: Lesions in the sensorimotor region of the internal segments of the globus pallidus (GPi) in parkinsonian patients are effective in alleviating the cardinal signs of Parkinson’s disease. Soc Neurosci Abstr 19:1584, 1993.

53.

Vitek J, Kaneoke Y, Turner R, et al: Neuronal activity in the internal (GPi) and external (GPe) segments of the globus pallidus (GP) of parkinsonian patients is similar to that in the MPTP-treated primate model of parkinsonism. Soc Neurosci Abstr 19:1584, 1993.

54.

Lavoie B, Parent A, Bedard PJ: Effects of dopamine denervation on striatal peptide expression in parkinsonian monkeys. Can J Neurol Sci 18:373, 1991.

55.

Parent A: Extrinsic connections of the basal ganglia. Trends Neurosci 13:254, 1990.

56.

Robertson RG, Clarke CA, Boyce S, et al: The role of striatopallidal neurones utilizing gamma-aminobutyric acid in the pathophysiology of MPTP-induced parkinsonism in the primate: Evidence from [’Hjfiunitrazepam autoradiography. Brain Res 531:95, 1990. Gerfen CR, Engber TM. Mahan LC, et al: D, and D, dopamine recep¬ tor-regulated gene expression of striatonigral and striatopallidal neu¬ rons. Science 250:1429, 1990. Soghomonian J-J, Cote P-Y, Parent A: Preproenkephalin mRNA lev¬ els in the striatum of normal and parkinsonian monkeys. Soc Neurosci Abstr 19:782, 1993. Kiinzle H: Bilateral projections from precentral motor cortex to the putamen and other parts of the basal ganglia: An autoradiographic study in Macaca fascicularis. Brain Res 88:195, 1975. Yamada T, McGeer PL, Baimbridge KG, McGeer EG: Relative spar¬ ing in Parkinson’s disease of substantia nigra dopamine neurons con¬ taining calbindin-D28k. Brain Res 526:303, 1990. Lavoie B, Parent A: Dopaminergic neurons expressing calbindin in normal and parkinsonian monkeys. Neuroreport 2:601, 1991. Seto-Ohshima A, Emson PC, Lawson DEM, et al: Loss of matrix calcium-binding protein-containing neurons in Huntington’s disease. Lancet 1:1252, 1988. Ichimiya Y, Emson PC, Mountjoy CQ, et al: Calbindin-immunoreactive neurons in the nucleus basalis of Meynert in Alzheimer-type de¬ mentia. Brain Res 499:402, 1989. Di Paolo T, Bedard PJ. Daigle M, Boucher R: Long-term effects of MPTP on central and peripheral catecholamines and indolamine con¬ centrations in monkeys. Brain Res 379:286, 1986. Eidelberg E, Brooks BA, Morgan WW. et al: Variability and func¬ tional recovery in the N-methyl-4-phenyl-l,2,3,6-tetrahydropyridine model of parkinsonism in monkeys. Neuroscience 18:817, 1986. Kurlan R, Kim MH, Gash DM: The time-course and magnitude of spontaneous recovery of parkinsonism produced by intracarotid ad¬ ministration of 1-methy 1-4-phenyl-1,2,3,6-tetrahydropyridine to mon¬ keys. Ann Neurol 26:677, 1991. Kish SJ. Shannack K, Homykiewicz O: Uneven pattern of dopamine loss in the striatum of patients with idiopathic Parkinson's disease. N Engl J Med 318:876, 1988. Spencer DD, Robbins RJ, Naftolin F, et al: Unilateral transplantation of human fetal mesencephalic tissue into the caudate nucleus of pa¬ tients with Parkinson’s disease. N Engl J Med 327:1541. 1992. Freed CR, Breeze RE, Rosenberg NL, et al: Survival of implanted fe¬ tal dopamine cells and neurologic improvement 12 to 46 months after transplantation for Parkinson’s disease. N Engl J Med 327:1549, 1992. Agid Y, Javoy-Agid F, Ruberg M: Biochemistry of neurotransmitters in Parkinson's disease, in Marsden CD. Fahn S (eds): Movement Disorders. London: Butterworth. 1987. pp 166-230.

57.

58.

59.

60.

61. 62.

63.

64.

65.

66.

67.

68.

69.

70.

CHAPTER

121

PALLIDOTOMY FOR PARKINSON’S DISEASE

PART

I

THE NEW YORK UNIVERSITY/UNIVERSITY OF CALIFORNIA AT IRVINE EXPERIENCE

Jeffrey D. Gross and Michael Dogali

HISTORY OF SURGERY FOR PARKINSON’S DISEASE

laris via a transventricular approach. First reported in 1942, the procedure came to be known as an ansotomy.7 This approach was ultimately abandoned in favor of a subfrontal one per¬ formed by passing a thermocoagulating electrode through the anterior perforated substance and into the pallidum above the optic tract. In 1951, Meyers published a review of 54 surgical patients who had suffered from a variety of dyskinesias; in the PD patients, both tremor and rigidity were reported to be relieved.8 In 1952, a famous surgical accident occurred while Cooper was attempting a unilateral cerebral pedunculotomy for parkin¬ sonism and unintentionally damaged and subsequently ligated the anterior choroidal artery. When the patient awoke, both tremor and rigidity were absent without accompanying hemiparesis.9 Cooper theorized that an infarction had occurred in the pallidum, and anterior choroidal occlusion soon became a frequently employed procedure in his armamentarium for PD. This procedure ultimately had mixed success, however, be¬ cause of the variability of arterial distribution.10 Narabayashi and Okuma, working in isolated and war-tom Japan, arrived independently at the globus pallidus as a surgical target for treating the symptoms of PD.11 In the 1950s, many authors reported positive results from lesioning a variety of tar¬ gets in the globus pallidus.12-20 Until the much-acclaimed introduction of human stereotaxy by Spiegel and Wycis in 1947,21 procedures such as those de¬ scribed above were accompanied by high mortality and mor¬

Parkinson’s disease (PD) is the movement disorder about which we have collected the largest amount of neuroanatomic, neuropathologic, and physiological data and the one that may be the most responsive to surgical therapy. This therapy has a long, colorful, and occasionally accident-inspired history, with many anecdotally reported positive results. However, it is important to recognize that even today, surgery is done to im¬ prove only the function-related symptoms, not the etiology of the disease. The primary parkinsonian symptoms that most impede the ordinary activities of a patient’s life are rigidity, akinesia, bradykinesia, and tremor. Because of their intractability to medical and surgical therapy, rigidity and akinesia have always provided the greatest clinical challenges in treating PD. Successful relief of parkinsonian tremor was first demonstrated in 1932, when Bucy and Buchanan reported on unilateral subpial resection of cortical areas 4 and 6.1 Other motor pathway surgery for tremor relief continued over the years, including the division of the pyramidal tracts at the upper cervical level2,3 and at the level of the cerebral peduncles.4,5 In all cases, how¬ ever, relief of abnormal and involuntary movements was ac¬ companied by varying degrees of paralysis. The contributions of Meyers to our knowledge in this area cannot be overemphasized; he was the first to focus on the basal ganglia as a surgical target. In 1940, after observing relief of tremor in a patient whose caudate nucleus had lain in the line of resection during a frontal lobotomy, Meyers undertook the treatment of another patient suffering from postencephalitic parkinsonism by excising the anterior two-thirds of the caudate nucleus. He reported satisfactory tremor relief in this case.6 With experience, he discovered that the best results could be obtained by dividing the pallidofugal fibers at the ansa lenticu-

bidity; Meyers experienced a 12 percent mortality rate in his 1942 series. The ability to lesion structures deep in the brain with negligible damage to the surface made possible the surgi¬ cal treatment of PD and other movement disorders on a far broader and safer scale. At the same time, investigation of the chemical and histological bases of movement disorders al¬ lowed the targeting of new anatomic sites and localization with more precision to reduce mortality and morbidity to minimal 1153

1154

Part 4/Functional Stereotaxis

levels. Since then, symptomatic improvement of PD has been reported to accompany stereotactically placed lesions in sev¬ eral sites: globus pallidus (pallidotomy), ventrolateral thalamus (thalamotomy), fields of Forel (campotomy), and posterior sub¬ thalamic region. The globus pallidus was for many years the primary surgical target, but the limitations of radiological localization made sur¬ gical failures common and complications severe. Thus, a tran¬ sition to the thalamotomies began in the middle to late 1950s. This trend increased after a 1956 postmortem discovery by Flassler that he had actually lesioned the thalamus of a patient, demonstrating an “impressive reduction in tremor” after what was thought to be a pallidotomy (the patient died of unrelated causes).22 From a historical perspective, it is important to keep in mind that in the pre-L-dopa era, PD required surgical inter¬ vention at an altogether different clinical stage. In the absence of any real medication, intractable tremor was a major indicator for surgery far earlier than it is today. In 1959, Bravo and Cooper reported that good clinical re¬ sults from large lesions in the vicinity of the pallidum fre¬ quently involved the ventrolateral (VL) nucleus of the thala¬ mus.23 This observation led to further intervention in the thalamus, as did an increasing sophistication in targeting tech¬ niques and lesioning methods that allowed physiological con¬ firmation by microelectrode recordings. These techniques pro¬ vided the means for identifying neurons in the nucleus ventralis intermedius (Vim) that were phase-locked with tremor. Lesions at this level subsequently were found to produce the best re¬ sults for tremor control. However, postthalamotomy patients continued to suffer from persistent postural instability, akine¬ sia, and cognitive and affective dysfunction, although Housepian and Pool believed that these effects occurred more frequently after pallidotomy than after thalamotomy.24'25 Other authors also demonstrated that the accuracy of thalamic lesion placement was somewhat variable.23,26’27 Complications aside, Selby summarized the difference between the thalamic and pal¬ lidal approaches in 1967, reporting that pallidal lesions were better at treating rigidity, while those in the VL nucleus of the thalamus were more effective for tremor.28 The major problem in reviewing the historical literature is the often frustratingly vague terminology used to describe the results. Phrases such as “very satisfactory result,” “significant improvement,” and “good clinical outcome” do not lend them¬ selves to easy or useful comparison. Good scientific justifica¬ tion for the choice of any of the methods used seems to be lack¬ ing. Also, the advent of widespread L-dopa therapy in the 1960s substantially decreased the amount of surgery performed, mak¬ ing it even more difficult to obtain modern data about the vari¬ ous procedures for PD. Only recently have recognition of the long-term failure of L-dopa therapy and the complications with L-dopa-induced dyskinesias and “on-off” fluctuations of these abnormal movements reawakened interest in surgical options. In 1985, Laitinen revived an obscure study that had been published by Svennilson and associates in 1960. It detailed a series of 20 patients with lesions created in the posteroventral globus pallidus, reporting that 19 of them showed improve¬ ment in tremor, rigidity, and bradykinesia.19 The ventral poste¬ rior target of Leksell, the surgeon in this series, was outside what had previously been accepted as the classic target area for pallidotomy. This led Laitinen to reproduce Leksell’s target in a

series of 38 PD patients, 92 percent of whom experienced relief of bradykinesia and rigidity and 81 percent of whom showed relief of tremor.29 Gait and volume of speech improved, and Ldopa-induced dyskinesias and muscle pain were dramatically reduced. The results of this study support contemporary labora¬ tory work undertaken to elucidate the brain’s motor circuitry.

NEUROANATOMY AND PHYSIOLOGY OF PARKINSON’S DISEASE Surgical studies, drug responses, and laboratory work with pri¬ mates have allowed the construction of a biochemical and physiological model, most completely summarized by DeLong and colleagues, that demonstrates the role of basal ganglia function in movement disorders.30 Much of this model ulti¬ mately stems from the observation that self-administration of the selective dopamine neurotoxin 1-methy 1-4-phenyl-1,2,3,6tetrahydropyridine (MPTP) induces a parkinsonian-type state in humans, a realization that led in turn to a model of the disor¬ der in primates.31-37 The MPTP-parkinsonian primate model parallels human PD in many of its behavioral, neurochemical, and neuropathological characteristics. While primates with MPTP-induced parkinsonism recover some motor functions over time and while discrepancies exist between the neu¬ ropathological features of PD in different species, MPTPinduced primate parkinsonism has provided a considerable amount of insight into the workings of human PD. In this model, parallel segregated influences originate from the sensorimotor and association cortex, pass through the basal ganglia, and return via thalamocortical pathways. Alexander and coauthors38 described a so-called motor circuit within a larger, functionally segregated neuronal loop. The circuit con¬ sists of corticostriate, striopallidal. pallidofugal, and thalamo¬ cortical fibers; the loop contains both a “closed” portion and an “open” portion, with the closed circuit being the area of pri¬ mary concent in regard to PD. The putamen serves as the striatal input region of the motor circuit. The various somatotopically distinct cortical inputs, al¬ though continuous within the “motor” putamen, have neverthe¬ less been shown to have nonoverlapping connections.39 The putamen gives rise to direct and indirect pathways. The direct path terminates in the posterior and ventrolateral two-thirds of the internal segments of the globus pallidus (GPi), and in caudolateral regions it terminates within the pars reticularis of the substantia nigra. The indirect path projects to the caudal and ventrolateral two-thirds of the external globus pallidus (GPe). Dopaminergic input is excitatory to the direct pathways and in¬ hibitory to the indirect pathways. The overall effect within this circuit is an augmentation of cortically initiated motor activity. The anatomic motor circuitry through the basal ganglia per¬ mits a focusing of neuronal activity for “fine-tuning" of corti¬ cally initiated movements. Montgomery and Bucholz demon¬ strated the activation of neurons from both the motor cortex and the putamen during the initiation phase of movement.40 Putamenal neuronal units in different locations are active only during the execution phase of the same movement. These find¬ ings suggest a role for basal ganglia motor circuitry in the pro¬ gramming and initiation of internally generated movements.

Chapter 121/Pallidotomy for Parkinson’s Disease: Part I

The administration of MPTP in primates causes a depletion of putamenal dopamine, thus enhancing neural transmission through the indirect pathway and decreasing it in the direct one, as was described above. Ultimately, this inhibits thalamo¬ cortical neuronal activity, resulting in an overall increase in gain and a decrease in selectivity within the basal ganglia motor circuit. Under these conditions, the system becomes more responsive to “noise.” After a certain point, the reduced dopamine level affects the supplementary motor area by caus¬ ing akinesia and an impaired initiation of movement.24 Other experiments in primates with MPTP-induced parkinsonism suggest that there is “functional redundancy” within the striatopallidal circuits and that ablation of no single surgical target or pathway can completely eliminate the dyskinesias associ¬ ated with L-dopa.41 DeLong observed that destruction of the subthalamic nu¬ cleus in MPTP-induced parkinsonian primates was associated with improvement of parkinsonian symptoms.42 Because the major output of the subthalamic nucleus is known to be the GPi (although there is significant output to the pedunculopontine nucleus as well), it became logical once again to focus on the globus pallidus as a surgical target in humans, as Laitinen had done.

AN ONGOING STUDY: MODERN PALLIDOTOMY Surgical Methods In light of Laitinen’s preliminary clinical work and DeLong’s eloquent description of the primate model, our group under¬ took a multidisciplinary study (ongoing at the time of this writ¬ ing) of the effects of ventral pallidotomy on human PD. Patients were divided into a nonsurgical group, an L-doparesponsive group, and an L-dopa-nonresponsive group. The last group consisted of those with striatonigral degeneration (SND), olivopontocerebellar atrophy (OPCA), and corticobasal gan¬ glionic degeneration (CBGD). Each patient underwent exten¬ sive neuropsychological, neurophysiological, and other testing that allowed quantification of a variety of parkinsonian fea¬ tures, including gait and motor functions, balance, rigidity, tremor, cognitive impairment, and a group of abilities that are termed “activities of daily living.”43-55 Subjects were taken off all medication for 12 hr or more (12 HOM) before testing (ex¬ cept for neuropsychological measures) and before surgery. They became markedly immobile (Hoehn and Yahr stage 4 or 5). Patients in the surgery group were also given pre- and post¬ operative magnetic resonance imaging (MRI) and positron emission tomography (PET) scanning and postoperative con¬ frontational visual field analysis within 3 months of surgery. Other authors include juvenile parkinsonism (of Nakashima) as an indication for pallidotomy.56,57 We have not segregated our patient data on the basis of this subtype of PD. Until recently, the method of choice for target localization involved the combined use of a stereotactic frame and ventricu¬ lography. Today, both CT and MR scanning are used in con¬ junction with the stereotactic frame. In our study, a surgical technique based solely on MRI-directed targeting was devel¬ oped. This technique utilizes a Leksell G-frame (Elekta

1155

Instruments, Tucker, GA), with data from MRI digitized and fed to an independent workstation, allowing true correlation of fiducials in space, elimination of magnetic distortion for the de¬ termination of precise coordinates, and application of appropri¬ ate Schaltenbrand and Wahren brain maps.58 Care is taken to place the midline structures in the center of the frame so that the midpoint of the anterior commissure-posterior commissure (.AC-PC) line will lie as close toX = 100, Y = 100, Z = 100 (in Leksell frame coordinates) as possible, minimizing magnetic distortion. In general, this methodology yields an anatomic tar¬ get that lies between 17 and 25 mm lateral to the midline, 6 to 8 mm below the AC-PC line, and 2 to 3 mm anterior to the midcommissural point. Our patients have had same-day targeting or delayed target¬ ing with stereotactic frame reapplication. Some have required retargeting after trajectories proved unsatisfactory. Patients are asked to refrain from ingesting anti-PD medications the evening before surgery. They are admitted the morning of surgery in the “off’ state and are only lightly sedated for the procedure. Surgical access is gained with a 3.5-mm skin punch and a 3-mm twist drill in the same plane as the X coordinate (i.e., lat¬ eral to the midline), at an angle between 40 and 70 degrees to the AC-PC line. An electrode with a 1.1- by 3-mm exposed tip is used to carry out impedance measurements 1 cm from the cortical surface to a depth of 15 to 20 mm. Microelectrode re¬ cordings are made from 15 mm above the target to 2 to 3 mm below it. One to two trajectories are carried out in each patient. Extracellular action potentials are amplified with a DAM-80 AC amplifier (World Precision Instruments, Sarasota, FL) and are simultaneously recorded using standard recording tech¬ niques (—6 dB at 300 and 10,000 Hz), together with a descrip¬ tive voice channel on magnetic tape. When the tip of the micro¬ electrode reaches the globus pallidus, cellular activity is recorded and coordinates are calculated. Spikes that are clearly separable from background noise at a ratio greater than 2:1 are analyzed. Microelectrode recording is continued as long as cell firing is observed to delineate the depth of the globus pallidus. These data are utilized both in planning the lesion and in somatotopically mapping the GPi. Each cell group is assessed for any change in frequency of firing during voluntary and passive upper and lower extremity movements. As the microelectrode passes from the external pallidum to the internal segment, a silent zone is encountered. Highamplitude, high-frequency irregular discharges are characteris¬ tic of the GPi.59 Inhibition and activation of particular cells during active and passive range of motion testing allow somatotopic mapping of GPi. These cellular activities have been confirmed by other authors.60 As the electrode exits GPi, en¬ countering the ansa lenticularis, the cellular activity is dimin¬ ished and changes only briefly as the optic tract is entered. Electrical stimulation is performed before lesioning with a radiofrequency electrode (Radionics TM; 3-mm exposed tip and 1.1 mm in diameter) with a pulse duration of 0.2 ms, 5- and 50Hz trains, and intensities of stimulation up to 10 V. This is done to prevent injury to the internal capsule and optic tract and often elicits contralateral hand contraction in some subjects and nonformed scintillating scotomata in the contralateral visual field in others. If these symptoms occur with stimulations below 3 V, the electrode is moved 1 mm and the process is repeated.

1156

Part 4/Functional Stereotaxis

A test lesion is made at the target site at 70°C for 20 s. During this time, the patient is asked to report any visual, un¬ usual, or unexpected sensory or motor phenomena. Proprio¬ ception and appreciation of light touch and pinprick also are

ing room and lasting 2 to 4 h. One immediately developed ipsi¬ lateral chorea persisting for several minutes, and several also experienced immediate transient bilateral chorea. Such phe¬ nomena have been seen by other surgeons performing palli¬

tested. If the test lesion causes no abnormal motor sensory or visual changes, a definitive lesion is made at the initial depth of the target at 80°C for 80 s. Additional overlapping lesions are then made at 80°C for 80 s at 2-mm intervals along the elec¬ trode trajectory, resulting in between 3 and 10 cylindrically shaped lesions, depending on the patient's pattern of neuronal

dotomies.63 Most patients evidenced an immediate euphoria lasting 1 to 7 days. The average length of hospitalization was 4 days, with all patients returning to their usual activities within 10 days. Other reported clinical results approach our success rate, which has exceeded that of fetal grafting for the relief of

activity. Stimulation near the internal capsule is often manifest by hand and face contracture, and optic tract stimulation can be recognized when patients report phosphenes in the contralat¬ eral visual field. These symptoms can help guide lesioning in GPi. Thus, our lesions are customized to each individual’s GPi somatotopism on the basis of our cellular recordings.

Neurophysiological Results Initially, 12 right-handed patients were studied with single-cell recordings. During movements of contralateral (but not usually ipsilateral) limbs, there were changes in cellular discharge fre¬ quency that appeared to be temporally related to movement cy¬ cles. A small number of units (2 percent) discharged nearly equally in relation to ipsilateral and contralateral limb move¬ ments. For example, in one patient, ipsilateral and contralateral lower extremity extension produced the same degree of firing recorded by an electrode in the right pallidum. Among the first 12 right-handed patients, 6 were explored on the right hemisphere and 6 on the left. Five of them demon¬ strated cells responsive to finger movement: four in the left GPi and one in the right. There were 13 finger-responsive cells in the six left GPi’s studied but only one in the six explored on the right, which yields a statistically significant difference (chisquare = 10.26,p = .0035). This observation suggests possible hemispheric specialization, with greater left pallidal represen¬ tation of the dominant hand.59,61 The somatotopic organization of the internal segment of the globus pallidus has not escaped attention. Cellular recordings in patients are similar to those in primate experiments,59 and this information is used to customize our neuroablative maneuvers. Other authors have reported the differences in cellular activ¬ ity according to symptoms.60 lacono and colleagues60 reported a correlation between high-frequency neuronal activity and hy¬ perkinetic symptoms (tremor, rigidity, dyskinesia) in patients who were typically L-dopa-responsive. Conversely, patients manifesting hypokinetic symptoms (akinesia, autonomic symp¬ toms) typically demonstrated low-frequency neuronal activ¬ ity.60 Others believe that cellular activity is a function of age. with younger patients having higher-frequency activity.62 Further research is needed to sort out these details ol the GPi.

the symptoms of PD.64'65 Postoperative stereotactic MR1 has confirmed the location of all lesions to within ± 1 mm of the intraoperatively deter¬ mined target, with the exception of one patient. Lesion volume in all cases was calculated at between 60 and 90 mm3, with a mean of 75 mm3. Surgical patients in this series have shown a significant ob¬ jective improvement in quantitative measurements of motor functions related to parkinsonism at 1 week and at 3, 6, 9 and 12 months postoperatively. At the time of writing, their scores on the Unified Parkinson’s Disease Rating Scale (UPDRS) have improved by a mean of 54 percent. Core Assessment Program for Intracerebral Transplantation (CAP1T) subtest scores (except gait) have improved in the contralateral limb by a mean of 33 percent, while ipsilateral limb scores have im¬ proved by a mean of 17 percent. Gait scores have improved by a mean of 24 percent. Nonsurgical control subjects have shown no statistically significant improvement in quantitative measurements during the course of the study. All surgical patients with dyskinesia ex¬ amined in the “on” state have demonstrated a virtually com¬ plete resolution of drug-induced contralateral chorea-kinetic dystonia. The “on” and “off” states have both improved, with decreased dyskinesia in the former and decreased bradykinesia. gait difficulty, rigidity, and tremor in the latter. However, pa¬ tients who suffered fluctuations related to L-dopa preoperatively have continued to manifest fluctuations in their hypoki¬ netic symptoms postoperatively. At 6 months postoperatively, there have been no statistically significant changes in the neuropsychological status of surgical patients and no difference between patients receiving dominant and those receiving nondominant hemispheric lesions. At 12 months postoperatively, surgical patients have demonstrated no statistically significant change in mean doses of anti-PD med¬ ications. Others have demonstrated lasting clinical results from pallidotomy with follow-ups approaching 10 years.66 Our data on the long-term success of posteroventral pallidotomy are in¬ complete, and we plan to continue collecting data for as long as possible. Excellent results reported after pallidotomy done specifically for juvenile parkinsonism have already been re¬ ferred to.4156 Although an initial postpallidotomy euphoria is common, we have not been convinced of a placebo effect associated with our treatment.67 The use of the objective measurements we have de¬ scribed will help remove the doubts of skeptics regarding the utility of pallidotomy for the disabling symptoms of PD.6*

Clinical Results Over 90 patients have undergone pallidotomy, with no mortal¬ ity. Among these patients, 90 percent have experienced im¬ provement of rigidity and bradykinesia immediately after le¬ sioning. even while still in the operating room. Several demonstrated transient bilateral chorea beginning in the operat¬

Results of Imaging Supplementary use of PET scanning has shown glucose hyper¬ metabolism on each side of the brain. The degree of this hyper-

Chapter 121/Pallidotomy for Parkinson’s Disease: Part I

1157

metabolism was demonstrated to have a statistically significant correlation with the contralateral body side most affected by the disease (i.e., the body side contralateral to that on which the globus pallidus was lesioned).69 The unoperated side typically demonstrated higher than normal metabolism, but not as high as on the operated side. Thus, PET data have served as confir¬ mation of the clinically based choice of the side of the body most affected by L-dopa-responsive PD in each case. PET scanning has also indicated that glucose metabolism in the brain appears to be markedly diminished from preoperative levels on the side ipsilateral to the pallidotomy and extending over a volume of brain much greater than what could be ac¬ counted for by the volume of the surgical lesion. As has been con¬ firmed in other studies, this expanded area coincided with the re¬ gion subtended by the frontal projections from the basal ganglia, including the premotor and supplementary motor cortices.59'69’70,71 Furthermore, the disinhibition of pallidothalamocortical influ¬ ence by pallidotomy has been demonstrated with PET, allowing reactivation of these motor decision-making areas.70 Lehman and associates72 reported a detailed study of pre- and postpallidotomy MRI. They reported that the lesion volume and location were factors that influenced the clinical outcome. The lesion in the brain of their patients was morpho¬ logically confirmed postmortem (the patient died of a pul¬ monary embolus). Thus, accurate stereotactic planning, as well as physiological localization, is necessary to achieve the de¬ sired clinical outcome with accuracy.

the symptoms of PD but also details and quantifies its effective¬ ness more comprehensively than has any previous study. As of this writing, 56 patients with suitable follow-up have shown a statistically significant improvement in measurements of parkinsonian-related features (made at 12 HOM), including bradykinesia, rigidity, resting tremor, and ambulation difficulty, as well as resolution of medication-induced contralateral dyskinesias. Although pallidotomy may not be as effective as thalamot¬ omy for complete tremor alleviation, tremor has been reduced in all affected patients. Further, speech impairment, which often complicates thalamotomy,73 was not seen even in patients undergoing dominant hemisphere pallidotomy. Also, while im¬ pairment of balance may complicate thalamotomy, pallidotomy improved balance and ambulation as well as bradykinesia. Overall, there has been no significant change in the mean daily dose of antiparkinsonian medication compared with base¬ line. However, the “barrier” of contralateral dyskinesia has been lifted, allowing patients to tolerate the same dose or a mildly increased dose of medication, alleviating their symp¬ toms without inducing contralateral dyskinesia. Additionally, there has been no evidence that unilateral pal¬ lidotomy impairs cognition. One study suggested that cognitive verbal performance is improved after pallidotomy.74 Current data collection from patients undergoing staged and simultane¬ ous bilateral pallidotomies is incomplete; however, others have reported success without increased morbidity and mortality.60 One report advocated simultaneous bilateral pallidotomies for juvenile parkinsonism, since symptoms in this subclass of PD

Complications

tend to be bilateral early.57 Four surgical patients in our study had been diagnosed as suffering from atypical forms of PD: two with SND, one with OPCA, and one with CBGD. They have shown no significant changes in quantitative measurements, except for one patient (SND) who manifested mild gait improvement. The therapeutic failure of pallidotomy in atypical parkinsonism may result from the primary basal ganglia pathophysiology reflected in hypometabolism of the lentiform nucleus.75 However, some pa¬ tients who had responded poorly to L-dopa treatment responded well to pallidotomy,60,76 indicating a gap in our knowledge of the neurophysiology of PD and its various forms. Rigidity has been shown to improve with ansotomy, ventral pallidotomy, and combinations of the two,7,21,125,77-80 but ventral pallidotomy interrupts the majority of pallidofugal fibers pass¬ ing through this area, accounting for the improvement after an¬ sotomy.81'85 The bilateral distribution of pallidofugal fibers also may explain the improvement on the ipsilateral side.63 Such ip¬ silateral improvement in quantitative measurements of motor function, especially in regard to balance and gait, underscores the bilateral effects of unilateral basal ganglia lesions. It should be emphasized again that indications for surgery in PD, and perhaps even the disease itself, were very different in the pre-L-dopa era. Present-day indications include tremor and rigidity when they are the only signs of the disease or when they persist despite pharmacological therapy as long as they still clearly interfere with the professional and social life of a patient. Surgery is also indicated in those who respond well to medica¬ tion but nonetheless develop intense abnormal movements. More specifically, our ongoing study may suggest that the best candidates for stereotactic ventral pallidotomy should ex¬ hibit the following clinical characteristics: (1) bradykinesia and

The following description of recorded complications specific to stereotactic pallidotomy is similar to that reported in many se¬ ries. The most common complication is a homonymous hemianopia contralateral to the optic tract involved.60’63,66 Some of these hemianopias are temporary and are related to perilesioning edema. Central scotomas also have been reported.66 Occasional contralateral facial paresis has been noted and is typically transient. This complication is related to the proxim¬ ity of the internal capsule and may rarely be associated with dysarthria.63,66 Dysarthria has also been associated with the combination of contralateral thalamotomy and pallidotomy.66 More profound contralateral hemiparesis is rare but sometimes is temporarily present as a result of pallidotomy.63,72 One seizure was reported to be due to temporal lobe edema from a GPi lesion.66 Bilateral pallidotomies have not been reported to cause a greater rate of complications than do unilateral pallidotomies,60 but the potential for cognitive impairment must be considered. A report of ipsilateral foot apraxia associated with ipsilateral thalamotomy and pallidotomy has been published.66 Complications not particularly related to pallidotomy that have been observed include cortical and subcortical hema¬ tomas,60 abscesses,60 and one stroke (1 week postoperatively).66 There was one report of a death from pulmonary embolus in an ambulatory patient.63

Discussion of Results The response of patients in this series not only corroborates ear¬ lier reports that ventral pallidotomy is an effective treatment for

1158

Part 4/Functional Stereotaxis

rigidity greater than that seen in tremor-predominant parkin¬ sonism, (2) greater degree of parkinsonian symptoms and “on” dyskinesia on the same side of the body, (3) severe on-off fluc¬ tuations in response to a small amount of antiparkinsonian medication (less than 500 mg/day of L-dopa), (4) bradykinesia and rigidity persisting in the lower body despite upper extrem¬ ity “on” dyskinesia, and (5) hypermetabolic corpora striata on fluorodeoxyglucose (FDG) PET scan. Contraindications to pallidotomy include those for stereo¬ tactic surgery in general: uncontrolled systemic arterial hyper¬ tension causing risk of intraoperative bleeding and hydro¬ cephalus interfering with anatomic correlation during target localization. In addition, there are contraindications specifi¬ cally related to PD, such as preoperative evidence of psycho¬ logical abnormalities, L-dopa-unresponsiveness, and significant dysphagia that may lead to fatal aspiration. It must be made clear to patients that surgery will not alter the course or progress of PD and is intended only for the con¬ trol of disabling symptoms. Under no circumstances should they entertain the belief that surgery can cure the disease, al¬ though it may provide a substantial improvement in the quality of their lives. Some researchers have reported bilateral chronic stimula¬ tion of the ventroposterolateral pallidum for relief of the symp¬ toms of PD.63'86 Although the preliminary results are good, our neuroablative maneuvers using advanced localization with imaging and cellular recordings, are simpler and are accompa¬ nied by minimal side effects and avoid the risk of and need for maintenance of indwelling equipment.87 Acute stimulation of anterior pallidal regions, not the ventroposterolateral pallidum, has been shown to eliminate PD symptoms.88 The clinical util¬ ity of these findings remains unclear, however, as the stimula¬ tory and ablative targets seem to be dissimilar. Other studies have confirmed the effects of variations in le¬ sion location.68 The best clinical results are obtained with the lesion placed close to the optic tract near the posterior limb of the internal capsule. Lesions centered more anteriorly are asso¬ ciated with less successful results. Medially placed lesions are less likely to reduce dyskinesias. Tremor is not well controlled if the lesion is too dorsal. Our experience concurs with these admonitions. Hypotheses regarding the changes in neurochemistry re¬ lated to PD and to pallidotomy have been published.89 It is thought that rebalancing the increased glutaminergic GPi out¬ put is the main effect of pallidotomy, with L-dopa indirectly suppressing the subthalamic nucleus. Other, less obvious neurochemical interactions may partially explain the effect of pallidotomy.89

physiological models and provide data for the performance of bilateral ablative surgery. We have not combined thalamotomy and pallidotomy, but a combination of functional targets may one day be evaluated, along with the combination of chronic stimulation and neuroab¬ lation. Other functional targets for PD have been considered, in¬ cluding the subthalamic nucleus.90 Less invasive approaches have been evaluated for functional targets, such as the use of ra¬ diosurgery. Rand and colleagues described a series of patients who underwent gamma knife pallidotomy or thalamotomy made with 4-mm collimators.91 Lurther studies will be forthcoming. The application of computer-aided cellular recording analy¬ ses will make the procedure easier and more precise. Computer data fusion of multiple informative tests such as PET, MRI, and neurophysiological data will aid in more precise and limited le¬ sion customization. Reduction of MRI distortion will also play a role in the increasing accuracy of stereotaxis. The improve¬ ment of functional MRI of cortical and subcortical areas may also play a unique role in functional surgery of the motor sys¬ tems and warrants further investigation. Additional physiologi¬ cal knowledge of pallidal neurons and their unknown functions will contribute to improvements in patient evaluation and the surgical procedure. Stereotactic posteroventral pallidotomy can be safely and successfully performed to limit the disabling features of PD in selected patients. This refinement of an established neurosurgi¬ cal procedure will bolster the armamentarium of functional neurosurgeons worldwide.

References 1. 2. 3. 4. 5. 6. 7.

8.

9. 10.

CONCLUSION 11.

The application of modern imaging and localization technology has allowed the evaluation and refinement of precision lesioning in the posteroventral pallidal target for L-dopa-responsive PD. We have been encouraged by the clinical results and have improved our understanding of neuronal motor circuits. Further observations, experience, and variation in technique will cer¬ tainly allow advancement in the functional neurosurgery of the motor systems. Bilateral simultaneous recordings of pallidal and thalamic structures will also aid the reformation of motor

12.

13.

14.

Bucy PC, Buchanan DN: Athetosis. Brain 55:479. 1932. Putnam T: Treatment of unilateral paralysis agitans by section of the lateral pyramidal tract. Arch Neurol 44:950-976, 1940. Oliver LC: Surgery in Parkinson's disease: Division of lateral pyra¬ midal tract for tremor. Lancet 1:910-913, 1949. Walker AE: Cerebral pedunculotomy for the relief of involuntary movements. J Ner\> Ment Dis 116:766-775, 1952. Broager B: The surgical treatment of Parkinsonism. Acta Neurol Scand 39:181-187, 1963. Meyers R: Surgical procedure for postencephalitic tremor, with notes on the physiology of premotor fibers. Arch Neurol 44:455-457, 1940. Meyers R: Surgical interruption of the pallidofugal fibers: Its effect on the syndrome of paralysis agitans and technical considerations in its application. N Y State J Med 42:317-325, 1942. Meyers R: Surgical experiments in the therapy of certain “extrapyramidal" disease: A current evaluation. Acta Psychiatr Scand 67:1-42, 1951. Cooper IS: Surgical occlusion of the anterior choroidal artery in Parkinsonism. Surg Gynecol Obstet 99:207-219, 1954. Cooper IS: Clinical results and follow-up studies in a personal series of 300 operations for Parkinsonism. J Am Geriatr Soc 4:1171-1181, 1956. Narabayashi H, Okuma T: Some comtemplations on the role of the globus pallidus in Parkinsonism. Brain Nerv 6:157-161, 1955. Baird HW 111, Chavez M, Adams J, et al: Studies in stereoencephalatomy: VII Variations in the position of the globus pallidus. Con/in Neurol 17:288-299, 1957. Bertrand C, Martinez N: Basal ganglia versus cortieo-spinal tract le¬ sions: Their relative importance in the relief of tremor and rigidity. Rev Can Biol 20:365-375. 1961. Fiinelon F, Thidbault F: R

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3 6 months

Upper limb ataxia 8% (transient) Contralateral 17% hypalgesia Thermoanalgesia 33% contralateral lower limb Ipsilateral upper limb 33% ataxia syndrome Ataxia 8% Contralateral hypalgesia ?

Ataxia or paresis Corneal reflex lost Dysesthesia Contralateral hypalgesia

44% 5% 5% some

2-33 months

88 57

25 23

total 72 76

1-13 years

4 5

the floor of the fourth ventricle, obex, and dorsum of the brain stem. With the odontoid process used as a reference point for the determination of the midline in the posteroanterior film, a separate guide needle is passed through the skin 4 cm from the midline under radiographic control and directed to the trigemi¬ nal tract at or just below the obex on the side of the pain. An electrode is passed through the guide needle into the cere¬ brospinal fluid (CSF) and the into the medulla oblongata, aim¬ ing at a point 2 to 3 mm in front of the roof of the fourth ventri¬ cle. The monitoring of electrical impedance allows the moment of contact of the electrode with the nervous structures to be identified, and electrical stimulation confirms the location of the electrode. The lesion is performed with radiofrequency cur¬

rent."^ In 1989, Kanpolat and associates89 described the method of freehand percutaneous trigeminal nucleotractotomy under computed tomography (CT) control. Later, a few papers on this technique were published.89-91 Special electrodes were developed for this procedure.92 In patients with craniofacial cancer pain, trigeminal tracto¬ tomy is very effective even when pain is present in the sensory areas of the seventh, ninth, and tenth cranial nerves, with an improvement rate of 80 percent88-90 being expected with the procedure. The results of the treatment of trigeminal neuralgia and atypical neuralgia were disappointing.88 Postoperative ipsilateral ataxia occurs frequently but usu¬ ally is transient.49 88 Contralateral thermoanalgesia is observed

Chapter 140/Various Functional Procedures for Pain: Part II

TABLE 140-II-3. Author Fox49

Fox88

Kanpolat et al92

1397

Results and Complications of Freehand Trigeminal Tractotomy Results, %

Etiology Cancer Postherpetic neuralgia Trigeminal neuralgia Anesthesia dolorosa Posttraumatic Cancer Postherpetic neuralgia Atypical neuralgia Trigeminal neuralgia

8 2 1 1 1 14 2 1 1

Cancer Trigeminal neuralgia

5 14

in 25 to 33 percent of these patients.49-88 Dysarthria and Homer’s syndrome are rare. Fever is very common.49 The per¬ cutaneous method is free of mortality (Table 140-H-3).

CAUDALIS DREZ LESIONS In 1971, Hosobuchi and Rutkin22 developed the method of open trigeminal tractotomy using radiofrequency current. The technique of open multiple radiofrequency lesions of the sub¬ nucleus caudalis was described by Nashold and associates93 and Siqueira.58 Later, many authors published papers describ¬ ing their experiences with this technique68-70-87-94-96 under the name of nucleus caudalis DREZ lesions. The procedure is per¬ formed with the patient prone and under general anesthesia and with magnification. Through a small suboccipital craniectomy and C1-C2 laminectomy, the tonsil is elevated and the obex is visualized. The caudal subnucleus of the trigeminal spinal nu¬ cleus occupies the triangular area between the dorsolateral sul¬ cus and the emerging points of the accessory nerve. At the level of the C2 root, the subnucleus caudalis blends within the poste¬ rior horn of the spinal cord and is covered dorsolaterally by a thin layer of the descending trigeminal tract. Near the obex, it is covered by a layer of the external arcuate and dorsal spin¬ ocerebellar fibers. It is widest in the rostral area and tapers caudally until it joins the spinal DREZ of C2. A series of rostrocaudal and mediolateral radiofrequency lesions at 75 to 80°C for 15 s are made using an electrode with a 1.5- to 2-mm tip ex¬ posure covering all of the subnucleus caudalis region.68 The rostral, upper lesions are placed 5 mm below the obex.5 Based on an anatomopathological case,45 it was concluded that the technique of just one line of radiofrequency lesions proposed by Siqueira58 is safer than that proposed by Nashold and coworkers.93 As the caudalis subnucleus merges with the dorsal hom of the C2 root and extends rostrally for 20 mm and has a fusiform configuration with the diameter ranging from slightly more than 2 mm caudally to 1.1 to 1.4 mm at C1 and the obex, a single row of lesions should be enough to destroy the subnu¬ cleus caudalis externally from the C2 rootlets rostrally in line with the DREZ97 (Fig. 140-II-4). Relief of or significant improvement in suffering was ob¬ served in 53 to 94 percent of the patients with facial pain treated with open trigeminal nucleotomy during a short follow¬

Complications Homer’s syndrome Dysarthria (transient) Contralateral hypalgesia Ataxia (transient)

88 0 0 0

8% 8% 25% 100%

Fever Almost all 6% Ataxia 16% Hiccoughs Contralateral lower limb 30% analgesia

80

up after caudalis DREZ lesions.32-68-97 As with other ablative procedures, the success rate is higher in the immediate postop¬ erative period than after long-term follow-up, some loss of the initial benefits effect occurs over time.68 The overall success falls to 58 percent after a mean follow-up of 9.8 months. It appears that the patient’s description of the pain may be useful in predicting the postoperative results. According to Bernard and associates68 better results are observed in cases of sharp or burning pain than in cases of dull pain. They observed that 41 percent and 55 percent of patients with sharp and burn¬ ing pain, respectively, improved after the procedure, in contrast to 24 percent with dull pain. This was confirmed by others.73-95 The correlation between the preoperative sensory deficit and the effectiveness of the operation is controversial.68 The results seem to be less satisfactory in patients with greater compro¬ mise of the afferent fibers. Better results were also observed when pain involved one or a few divisions of the trigeminal nerve and when it did not extend beyond the trigeminal divi-

main sensory nucleus

Figure 140-II-4. Open trigeminal DREZ nucleotomy. Radiofrequency lesions are placed along the pars caudalis of the spinal trigeminal nucleus below the level of the obex.

1398

Part 4/Functional Stereotaxis

sions. Bernard and associates68 observed good results in 75 per¬ cent of patients with pain within one trigeminal division, 50 percent of patients with pain over two divisions, and 38 percent of patients when all trigeminal divisions were involved. The duration of the pain did not affect the final results.68 The number of patients with trigeminal neuralgia reported treated by caudalis DREZ lesions is small. Trigeminal neural¬ gia improved in just 20 to 66 percent of the patients of Bernard and associates.68-86 Trigeminal nucleotractomy is also effective for the treatment of facial dysesthesias (anesthesia dolorosa),97 but the number of cases reported is small.22-70-87 Pain related to traumatic trigeminal neuropathies can also be alleviated.70-93-94 Facial pain resulting from surgical procedures was improved in 33.3 percent of the patients of Bernard and associates.68 Improvement occurred in 66 to 100 percent of patients with postherpetic neuralgia,31-32-68-70-87-97 with the best long-term re¬ sults occurring in this group. There are, however, reports of bad results with this procedure in the treatment of that condition.22 There are few papers about the results of caudalis DREZ le¬ sions for the treatment of central pain caused by vascular le¬ sions of the brain stem. Sampson and Nashold78 performed the procedure in two patients with facial pain resulting from infarc¬ tion of the brain stem. In one patient, complete alleviation of pain was observed, and in the other, partial improvement oc¬ curred. Gorecki and Nashold97 observed improvement in four patients with facial pain associated with cerebral stroke. This author tried the procedure in one patient with facial pain asso¬ ciated with brain stem infarction without success. The long¬ term success rate of the nucleus caudalis DREZ operation is lower for cancer pain than for certain other types of facial pain; initial improvement in almost 100 percent of the patients fell to 40 to 60 percent some months after the procedure20-70-93-95 (Table 140-11-4). The morbidity rate of the procedure is low.95 The radiofre¬ quency lesions not only involve the subnucleus caudalis, the descending tract, and the ascending projections to other trigem¬ inal nuclear structures and the midbrain and thalamic nuclei but also may extend medially and ventrally into nearby struc¬ tures.45 The complications are related to injury to the nearby structures of the spinal cord and medulla. Ipsilateral paresis is related to involvement of the corticospinal tract caused by le¬ sions that are too deep, contralateral hypalgesia to lesions of the spinothalamic tract, and ataxia to damage to the spinocere¬ bellar tracts and posterior columns.31-97 Open caudalis DREZ lesions result in more complications than does stereotactic nucleotractotomy. Extension of analgesia into the area of the C1 root is very common31; contralateral thermoanalgesia occurs in 17 to 25 percent of these patients.22-87 Ataxia is also very fre¬ quent, affecting the upper and lower limbs of 30 to 39 percent of these patients68-70 and the upper limb only in 17 to 61 per¬ cent." 1168 70 7X94,7g8 The use of electrodes specially designed for nucleotractotomy96-98 or of an ultrasound needle may re¬ duce the complication rate even when the lesions are placed at high levels.11 The incidence of ipsilateral upper limb or upper and lower limb dysmetria fell from 74 percent to 39 percent97 when a special angled electrode was used. Motor deficits were described in a few cases.45-87 Brown-Sequard syndrome, eleventh nerve palsy, hemiparesis,45 CSF leak, meningitis, pneumonia, myocardial infarction, and intraoperative stroke have also been described with caudalis DREZ lesions.68-70

Deaths are rare.45-97

PONTINE STEREOTACTIC TRIGEMINAL NUCLEOTRACTOTOMY In 1987, Flitchcock and Teixeira59 described pontine stereotac¬ tic trigeminal nucleotractotomy. Under stereotactic conditions, with the patient in a sitting position, the fourth ventricle is out¬ lined by positive ventriculography. Using the fastigial line as a reference, the target point was a point located 5 to 10 mm from the midline, from 1 mm posterior to 6.6 mm anterior to the floor of the fourth ventricle, and from 10.5 mm rostral to 1.2 mm caudal to the fastigial line. Through a burr hole placed parasagittally to the target in the ipsilateral suboccipital region, an electrode is introduced and directed to the target point. Electrical stimulation is performed, with stimulation of the tar¬ get point resulting in ipsilateral facial paresthesias, stimulation of the trigeminal quintothalamic tract in contralateral facial paresthesias, stimulation of the trigeminal motor nucleus in contraction of the ipsilateral masseter muscle, stimulation of the facial nucleus in contraction of ipsilateral facial muscles, and stimulation of the vestibular nucleus in an ipsilateral buzzing sensation. A radiofrequency lesion is made, and the sensibility of the face is evaluated (Fig. 140-11-5). Facial analgesia after tractotomy is incomplete in distribu¬ tion and degree.6-97-99 This is attributed to incomplete tract section40-57-99 or to representation of the oral and perioral areas rostrally within the trigeminal sensory complex, rostral to the subnucleus caudalis.99 As medullary tractotomy has a quantita¬ tive rather than a qualitative effect on pain sensation, the reduc¬ tion of the overall central summation of afferent inputs in the trigeminal nucleus results in hypalgesia.40 These are the rea¬ sons for lesioning the most rostral levels of the trigeminal de¬ scending tract and nuclear complex, especially for the treat¬ ment of perioral, perinasal, and oral pain.59

CONCLUSION Trigeminal nucleotractotomy is an additional option for the treatment of intractable facial pain. In addition to the classic in¬ dications, available data suggest novel ones, highlighting the special significance of lesioning or the subnucleus caudalis. The results are encouraging, especially in patients with cancer pain and deafferentation states in the areas of the fifth, seventh, ninth, and tenth nerves.89 Postherpetic neuralgia and malignant orofacial pain are the most common indications for the proce¬ dure.79-81 The procedure can be performed by different surgical tech¬ niques. Currently, a single radiofrequency lesion made stereotactically or freehand (trigeminal nucleotomy)22-25-74 and multi¬ ple radiotrequency lesions of the primary and secondary afferent neurons (trigeminal caudalis DREZotomy)58-68 are most often used. The main difference between the two proce¬ dures is that destruction of the entire length of the subnucleus caudalis is possible only with the latter. The concept that the ef¬ fect of DREZotomy parallels the completeness of destruction

Chapter 140/Various Functional Procedures for Pain: Part II

TABLE 140-II-4.

Author Hosobuchi and Rutkin22

Nashold et al93

Bernard et al68

Ishijima et al87

Bernard et al70 19886

Rossitch et al95 Sampson and Nashold78 Abdennebi et al.94 Grigoryan et al31

Nashold et al.98 Gorecki and Nashold97

1399

Results and Complications of Caudalis DREZ Lesions

Result, %

Etiology 3 1 1 1

100 100 100 100

Cancer 1 Postherpetic neuralgia 8 Traumatic fifth nerve 9 neuropathy Cancer 3 Postherpetic neuralgia 7 3 Trigeminal neuralgia Dental operations 3 2 Glaucoma 1 Anesthesia dolorosa Total Postherpetic neuralgia 2 Postherpetic neuralgia + 1 anesthesia dolorosa 1 Anesthesia dolorosa

78

Cancer Atypical Postherpetic neuralgia Anesthesia dolorosa

Cancer Trigeminal neuralgia Postherpetic neuralgia Anesthesia dolorosa Postdental procedure Glaucoma Trauma Postamygdalectomy Salivary calculus Cancer Brain stem lesion

4 5 9 3 3 1 1 1 1 5 2

Postherpetic neuralgia Atypical facial pain Postherpetic neuralgia Cancer

2 9 4 1

Postherpetic neuralgia Atypical facial pain Anesthesia dolorosa Stroke Facial trauma/surgery Headache Multiple sclerosis Trigeminal tumor Trigeminal actinic neuropathy

8 8 5 4 4 1 1 1

100 71 66 100 100 100 94-58 100 100 Improved

25 20 67

Recurrence, % 100 100 100 0

Follow-up, months 4-15 Mean, 8 12 2

Complications Upper limb ataxia + contralateral analgesia (transient)

17%

24

Ment Dis 33:174-208, 1954.

11.

Taren JA, Kahn EA: Anatomic pathways related to pain in face and neck. J Neurosurg 19:116-121, 1962.

12.

Olzewski J: On the anatomical and functional organization of the spinal trigeminal nucleus. J Comp Neurol 92:401^113, 1950.

Chapter 140/Various Functional Procedures for Pain: Part II

13.

14.

Sessle BJ: Trigeminal nociceptive and non-nociceptive neurones brain stem intranuclear projections modulation by orofacial periaquedutal grey and nucleus magnus stimuli. Brain Res 170:547-552, 1979. Azerad J, Woda A, Albe-Fessard D: Physiological properties of neu¬ rons in different parts of the cat trigeminal sensory complex. Brain

15.

Res 246:7-21, 1982. Darian-Smith I, Yokota T: Cortically evoked depolarization of trigeminal cutaneous afferent fibers in the cat. J Neurophysiol

16.

29:170-178,1966. Brodal A: Central course of afferent fibers for pain in facial, glos¬ sopharyngeal and vagus nerves. Arch Neurol Psychiatr 57:292-306,

17. 18.

1947. Kerr FWL: Facial, vagal and glossopharyngeal nerves in the cat: Afferent connections. Arch Neurol 6:264-281, 1962. Brodal A, Szabo T, Torvik A: Corticofugal fibers to sensory trigemi-

40. 41.

42.

43.

44. 45.

nal nuclei and nucleus of solitary tract: An experimental study in the 19.

cat. J Comp Neurol 106:527-555, 1956. Kerr FWL: Structural relation of the trigeminal spinal tract to upper cervical roots and the solitary nucleus in the cat. Exp Neurol

46.

1401

Denny-Brown D, Yanagisawa N: The function of the descending root of the fifth nerve. Brain 96:783-814, 1973. Shigenaga Y, Chen IC, Suemune S, et al: Oral and facial representa¬ tion within medullary and upper cervical dorsal horn in the cat. J Comp Neurol 243:388—408, 1986. Hochfield S, Gobel S: An anatomical demonstration of projections to the medullar dorsal horn (trigeminal nucleus caudalis) from ros¬ tral trigeminal nuclei and the contralateral caudal medulla. Brain Res 252:203-211, 1982. Sessle BJ, Greenwood LF: Inputs to trigeminal brain stem neurons from facial, oral tooth pulp and pharyngolaryngeal tissues: I. Responses to innocuous and noxious stimuli. Brain Res 117:221-226, 1976. Hodge CJ Jr, King RB: Medical modification of sensation. J Neurosurg 44:21-28, 1976. Spiegelmann R, Friedman WA, Ballinger WE, Tedeshi H: Anatomic examination of a case of open trigeminal nucleotomy (nucleus cau¬ dalis dorsal root entry zone lesions) for facial pain. Stereotact Fund Neurosurg 56:166-178, 1991. Raney R, Raney AA, Hunter C: Treatment of major trigeminal neu¬ ralgia through section of the trigeminospinal tract in the medulla.

20.

4:134-148, 1961. Kerr FWL: Spinal V,h nucleolysis: Intractable craniofacial pain. 47.

21.

Surg Forum 17:419—421, 1966. Kerr FWL, Olafson RA: Trigeminal and cervical volleys. Arch Neurol 5:69-76,1961. Hosobuchi Y, Rutkin B: Descending trigeminal tractotomy: Neurophysiological approach. Arch Neurol 25:115-125, 1971. Wall PD, Taub A: Four aspects of trigeminal nucleus and a paradox.

48.

Am J Surg 80:11-17, 1950. Harrison F, Corbin KB: Oscillographic studies on the spinal tract of the fifth cranial nerve. J Neurophysiol 5:465^482, 1942. MacKinley WA, Magoun HW: The bulbar projection of the trigemi¬

49.

nal nerve. Am J Physiol 137:217-224, 1942. Fox JL: Intractable facial pain relieved by percutaneous trigeminal

J Neurophysiol 25:110-126, 1962. Broton JG, Rosenfeld JP: Rostral trigeminal projection signal peri¬ oral facial pain. Brain Res 243:395—400, 1982. Schvarcz JR: Stereotactic trigeminal tractotomy. Confin Neurol

50.

22. 23. 24. 25. 26. 27.

28. 29.

37:73-77, 1975. Stewart WA, King RB: Fiber projections from the nucleus caudalis of the spinal trigeminal nucleus. J Comp Neurol 121:271-286, 1963. Young RF, Perryman KM: Neuronal responses in rostral trigeminal brain-stem nuclei of macaque monkeys after chronic trigeminal trac¬ totomy. J Neurosurg 65:508-516, 1986. McKenzie KJ: Trigeminal tractotomy. Clin Neurosurg 2:50-70, 1955. Young RF: Effects of trigeminal tractotomy on dental sensation in

51. 52.

Boston: Little Brown, 1966, pp. 351-363. Olivecrona H: Tractotomy for relief of trigeminal neuralgia. Arch

54.

Neurol Psychiatr 47:544—654, 1942. Hitchcock E: Stereotactic trigeminal tractotomy. Ann Clin Res

55.

2:131-135, 1970. Hamby WB, Shinners BM, Marsh LA: Trigeminal tractotomy. Arch

humans. J Neurosurg 56:812-818, 1982. Young RF, Perryman KM: Pathways for orofacial pain sensation in the trigeminal brain-stem nuclear complex of the macaque monkey.

56.

31.

J Neurosurg 61:563-568, 1984. Grigoryan YA, Slavin KV, Ogleznev KY: Ultrasonic lesion of the trigeminal nucleus caudalis for deafferentation facial pain. Acta Neurochir (Wien) 131:229-235, 1994. Mosso JA, Kruger L: Spinal trigeminal neurons excited by noxious thermal stimuli. Brain Res 38:206-210, 1972. Nord SG, Ross GS: Responses of trigeminal units in the monkey bulbar lateral reticular formation to noxious and non-noxious stimu¬ lation of the face: Experimental and theoretical considerations.

57.

33.

34.

35.

36.

37. 38. 39.

Brain Res 58:385-399, 1973. Gordon G, Landgren S, Seed WA: The functional characteristics of single cells in the caudal part of the spinal nucleus of the trigeminal nerve of the cat. J Physiol (bond) 158:544—559, 1961. Arvidson J, Gobel S: An HRP study of the central projections of pri¬ mary trigeminal neurons which innervate both pulp in the cat. Brain Res 208:1-16, 1981. Gerard MW: Afferent impulses of the trigeminal nerve: The in¬ tramedullary course of the painful, thermal and tactile impulses. Arch Neurol Psychiatr 9:306-338, 1923. Mattews B, Baxter J, Watts S: Sensory and reflex responses to tooth pulp stimulation in man. Brain Res 113:83-94, 1976. Grant FC: Discussion on trigeminal tractotomy. Clin Neurosurg 2:69-70, 1955. Eskine CA, Rowbotham FG: Late changes in the brain stem following trigeminal tractotomy. Arch Neurol Psychiatr 62:493-502, 1949.

12:297-311, 1949. Kune Z: Treatment of essential neuralgia of the 9“' nerve by selec¬ tive tractotomy. J Neurosurg 23:494—500, 1965. Kune Z: Significance of fresh anatomic data on spinal trigeminal tract for possibility of selective tractotomies, in Knigton RS, Dumke PR (eds): Pain: Henry Ford Hospital International Symposium.

53.

30.

32.

tractotomy. JAMA 218:1940-1941, 1971. Falconer MA: Intramedullary trigeminal tractotomy and its place in the treatment of facial pain. J Neurol Neurosurg Psychiatry

58.

59. 60. 61.

Surg 57:171-177, 1948. Schvarcz JR: Spinal cord stereotaxic techniques for trigeminal nu¬ cleotomy and extralemniscal myelotomy. Appl Neurophysiol 41:99-112, 1978. Grant FC: Complications accompanying surgical relief of pain in trigeminal neuralgia. Am J Surg 75:4247, 1948. Siqueira JM: A method for bulbospinal trigeminal nucleotomy in the treatment of facial deafferentation pain. Appl Neurophysiol 48:277-280, 1985. Hitchcock E, Teixeira MJ: Pontine stereotactic surgery and facial nociception. Neurol Res 9:113-117, 1987. Guidetti B: Tractotomy for relief of trigeminal neuralgia: Observations in 124 cases. J Neurosurg 7:499-508, 1950. Grant FC, Weinberger LM: Experiences with intramedullary tracto¬ tomy: IV. Surgery of the brain stem and its operative complications.

62.

Arch Surg 42:747-754, 1941. Grant FC: Surgical methods for relief of pain. Bull NY Acad Med

63.

19:373-385, 1943. Kune Z: Vertical trigeminal partial nucleotomy. Adv Pain Res Ther

64.

3:325-329, 1979. Plangger CA, Fischer J, Grunert V, Moshsenipour I: Tractotomy and partial vertical nucleotomy for treatment of special forms of trigem¬ inal neuralgia and cancer pain of face and neck. Acta Neurochirurg

65.

Suppl (Wien) 39:147-150, 1987. Anderson L, Black RG, Abraham J, Ward AA Jr: Neuronal hyperac¬ tivity in experimental trigeminal deafferentation. J Neurosurg 35:444-452, 1971.

1402

Part 4/Functional Stereotaxis

65a. Grant FC, Groff RA, Lewy FH: Section of the descending spinal

83.

root of the fifth cranial nerve. Arch Neurol Psychiatr 498-509, 1940. Grant FC, Weinberger 1M: Experiences with intramedullary tractot¬ omy: Relief of facial pain and summary of operative results. Arch Surg 42:681-692, 1941.

84.

66.

67.

Penzholz FI, Menzel J, Hagenlocher HU: Results of surgical treat¬

68.

ment of idiopathic trigeminal neuralgia using different operative techniques (a cooperative study). Adv Neurosurg 3:320-327, 1975. Bernard EJ, Nashold BS Jr, Caputti F: Clinical review of nucleus caudalis dorsal root entry zone lesions for facial pain. Appl Neurophysiol 51:218-224, 1988.

69.

Moffie D: Late results of bulbar trigeminal tractotomy: Some re¬ marks on recovery of sensibility. J Neurol Neurosurg Psychiatry 34:270-274, 1971.

70. 71.

Bernard EJ Jr, Nashold BS Jr, Caputti F, Mossy JJ: Nucleus caudalis DREZ lesions for facial pain. Br J Neurosurg 1:81-92, 1987. Crue BL, Todd EM, Carregal EJA, Kilham O: Percutaneous trigem¬ inal tractotomy. Bull LA Neurol Soc 32;86-92, 1967.

72.

Schvarcz JR: Tractolisis trigeminal estereotaxica. Bol Asoc Arg Neurocir 13:31, 1972.

73.

Teixeira MJ: A lesao do trato de Lissauer e do como posterior da sub-

74. 75. 76.

stanica cinzenta da medula espinal e a estimulaqao eletrica do sistema nervoso central para o tratamento da dor por desaferentaqao. Ph.D. Thesis. Faculdade de Medicina of University of Sao Paulo, 1990. Todd EM, Crue BL, Carregal EJA: Posterior percutaneous tractot¬ omy and cordotomy. Confin Neurol 31:106-115, 1969. Hitchcock ER, Schvarcz JR: Stereotaxic trigeminal tractotomy for post-herpetic facial pain. J Neurosurg 37:412-417, 1972. Crue BL, Carregal EJA, Felsoory A: Percutaneous stereotactic ra¬

85.

78.

79. 80.

81.

82.

Crue BL, Lasby V, Kenton B, Felsoory A: Needle scope to stereotactic frame for inspection of cystema magna during percutaneous radiofre¬ quency trigeminal tractotomy. Appl Neurophysiol 39:58-64, 1976/77. Sampson JH, Nashold BS: Facial pain due to vascular lesions of the brain stem relieved by dorsal root entry zone lesions in the nucleus caudalis: Report of two cases. J Neurosurg 77:473-475, 1992. Hitchcock E: Stereotactic spinal surgery. Neurol Surg 433:271-279 1977.

Hitchcock E: Electrophysiological exploration of the cervicomedullary region. Proceedings of a Symposium held in Paris at the Faculte des Sciences, July 1971. Amsterdam: Excerpta Medica, International Congress Series 253, pp 237-245.

86.

Black R: Trigeminal pain, in Crue BL (ed): Pain and Suffering. Springfield, IL: Thomas, 1970, pp 119-137.

87.

Ishijima B, Shimoji K, Shimizu H, et al: Lesions of spinal and trigeminal dorsal root entry zone for deafferentation pain. Appl Neurophysiol 51:175-187, 1988.

88.

Fox JL: Percutaneous trigeminal tractotomy for facial pain. Acta Neurochir (Wien) 29:83-88, 1973.

89.

Kanpolat Y, Deda H, Akyar S, et al: CT-guided trigeminal tractot¬ omy. Acta Neurochirurg (Wien) 100:112-114, 1989.

90.

Kanpolat Y, Akyar S, Caglar S: Diametral measurements of the up¬ per spinal cord for stereotactic pain procedures: Experimental and clinical study. Surg Neurol 34:478-483, 1995.

91.

Kanpolat Y, Caglar S, Akyar S, Temiz C: CT-guided pain procedures for intractable pain in malignancy. Acta Neurochir Suppl (Wien) 64:88-91, 1995.

92.

Kanpolat Y, Cosman ER: Special radiofrequency electrode system for computed tomography-guided pain-relieving procedures. Neurosurgery 38:600-603, 1996.

93. 94.

diofrequency trigeminal tractotomy with neurophysiological record¬ ings. Clin Neurol 34:389-397, 1972. 77.

Westrum LE: Changes in the synapses of the spinal trigeminal nu¬ cleus after ipsilateral rhizotomy. Brain Res 11:706-709, 1968. Schvarcz JR: Stereotactic trigeminal nucleotomy for dysesthesic fa¬ cial pain. Adv Pain Res Ther 3:331-333, 1979.

95.

Nashold BS Jr, Caputi F, Bernard E: Trigeminal DREZ: Caudalis nuclear lesions for relief of facial pain. Neurosurgery 19:150, 1984. Abdennebi B, Bouatta F, Bougatene B: Nucleotomie du noyau spinal do trijumeau: A propos de deux nevralgies trigeminales posttraumatiques operees. Neurochirurgie 39:231-234, 1993. Rossitch E Jr, Zeidman SM, Nashold BS Jr: Nucleus caudalis D.R.E.Z. for facial pain due to cancer. Br J Neurosurg 3:45^19, 1989.

96.

Young JN, Nashold BS, Cosman ER: A new insulated caudalis nu¬ cleus D.R.E.Z. electrode: Technical note. J Neurosurg 70:283-284, 1989.

97.

Schvarcz JR: Post-herpetic craniofacial dysesthesiae: Their manage¬ ment by stereotactic trigeminal nucleotomy. Acta Neurochir (Wien) 38:65-72, 1977.

Gorecki JP, Nashold BS: The Duke experience with the nucleus cau¬ dalis DREZ operation. Acta Neurochir Suppl (Wien) 64:128-131, 1995.

98.

Schvarcz JR; Craniofacial postherpetic neuralgia managed by stereotactic spinal trigeminal nucleotomy. Acta Neurochirurg Suppl (Wien) 46:62-64, 1989.

99.

Nashold BS Jr, El-Naggar AO, Ovelman-Levitt J, Muwaffak A: A new design of radiofrequency lesion electrodes for use in caudalis DREZ operations. J Neurol 80:1116-1120, 1994. Young RF. Oleson TD. Perryman KM: Effect of trigeminal tractot¬ omy on behavioural response to dental pulp stimulation in the mon¬ key. J Neurosurg 55:420-430, 1981.

Hitchcock ER, Tsukamoto Y: Physiological correlates in stereotactic spinal surgery. Acta Neurochir Suppl (Wien) 21:119-123, 1974.

CHAPTER

141

PERCUTANEOUS LOWER CERVICAL CORDOTOMY

Paul M. Lin

Percutaneous cervical cordotomy at the C1-C2 level was found to be effective in relieving cancer pain in patients whose life expectancy was limited.1-2 The percutaneous high cervical cor¬ dotomy technique requires the insertion of a needle electrode through the lateral aspect of the neck, between the arch of the atlas and the lamina of the second cervical vertebra, and ad¬ vancement to the anterolateral surface of the spinal cord. The lesion is made with a radiofrequency generator through a shielded electrode that passes through the needle. Respiratory impairment associated with high cervical cor¬ dotomy has been well documented.3-5 It has been shown that the fibers descending to the respiratory musculature lie exceed¬ ingly close to the lateral spinothalamic tract at the higher cervi¬ cal level.6-7 Belmusto and associates8 reported a peculiar type of paralysis of involuntary respiration with preservation of voluntary respiration activity in patients who had undergone bilateral high cervical anterolateral cordotomy. These patients could breathe adequately while awake, but “during a period of natural sleep, respiratory efforts become ineffective and require assistance.” We attempted 21 percutaneous high cervical cordotomies at the C1-C2 level in 17 patients, using a technique similar to that described by Rosomoff and coworkers.2’9 All four patients who had undergone bilateral procedures died from respiratory fail¬ ure during sleep (“Ondine’s curse”). To avoid the respiratory complication of paralysis of involuntary reflex-mediated respi¬ ration, an anterior transdiscoidal percutaneous approach to the lower anterolateral cervical cord was devised, producing a lesion of the spinothalamic tract below the emergence of the phrenic nerve fibers (C4) that control diaphragmatic respiratory movement (Fig. 141-1). With this approach, we were able not only to protect involuntary respiratory function but also to re¬ duce the risk of postoperative motor and sphincter paralysis. We believe that some form of selective segmental cordotomy can be achieved (Fig. 141-2).

TECHNIQUE The electrode complex consists of a standard uninsulated 3-in. 18-gauge thin-walled lumbar puncture needle through which a steel wire stylet 0.016 in. in diameter is inserted. The stylet pro¬ trudes 3 mm beyond the point of the needle and is insulated with Teflon, except for the last 2 mm. Two different types of stylets can be used interchangeably. One is straight, and the

•

•

%

V

/ •

'-■V.

Figure 141-1. Schematic drawing of the anterior approach for low cervical percutaneous cordotomy. The needle is inserted from the opposite side of the neck between the carotid sheath and the trachea-esophagus complex. It enters the disk space obliquely to avoid the anterior spinal artery and the corticospinal tract.

other has a curve at the end so that the lesion can be made at a point 1 to 2 mm medial or lateral to the alignment of the needle (Fig. 141-3). A 500-kHz radiofrequency generator with its output con¬ tinuously variable between 0 and 12 W is employed for lesion production. The current is monitored on an incorporated milliampmeter. The patient is placed supine on a stretcher with the head rest¬ ing on a Franklin head unit and immobilized by a standard head clamp. The anterior portion of the neck is antiseptically prepared and draped. The skin, subcutaneous tissues, and prevertebral fascia are infiltrated with a local anesthetic. The 18-gauge thinwalled spinal needle is inserted medial to the carotid sheath and lateral to the trachea and esophagus at a point about 2.5 to 5 cm above the sternoclavicular joint on the side opposite the in¬ tended lesion. With palpation with the needle tip, either the C5-C6 or the C6-C7 disk space is identified radiologically and entered. The needle is directed diagonally through the disk

1403

1404

Part 4/Functional Stereotaxis

Figure 141-3. The needle and electrodes used for a cervical percutaneous cordotomy. Note the curved electrode compared with the straight electrode (far right).

Figure 141-2. Targeting of selective cordotomy on the basis of the anatomic distribution of the dermatomal variations in the anterior and the lateral spinothalamic tracts. A. For thoracic pain, the target point is 4 mm from the midline and 8 mm from the back of the cord. B. For sacral pain, the target point is 8 mm from the midline and 5 mm from the back of the cord.

space, aiming toward the target point in the opposite anterolat¬ eral quadrant of the cord. This oblique angle is desirable to avoid injury to the corticospinal tract and the anterior spinal artery if overpenetration occurs. The placement of the needle is determined by repeated anteroposterior and lateral Polaroid roent¬ genograms. and appropriate corrections, either linearly or of an¬ gulation, can be made by withdrawing the tip of the needle into the disk space. Simple stereotactic angulation calculation can predetermine the eventual end point (Figs. 141-4 and 141-5). Anteroposterior and lateral x-rays are taken with an overhead

Figure 141-4. Mathematical calculation of the effect of the angle of insertion on the lateral deviation as seen on the anteroposterior film and the increased depth of penetration as seen on the lateral film.

Chapter 141/Percutaneous Lower Cervical Cordotomy

Artgle

1405

MM

o.co

o.ie

10

20

0.36

30

o,sa

40

0,54

’

Figure 141-5. Expected lateral deviation of the electrode on the anteroposterior film with 1 -mm penetration in depth as seen on the lateral view, varying with the angle or degree of penetration of the needle as measured through a protractor resting on the midline of the chin.

or portable unit, and so the patient’s head need not be moved during the procedure. Although the intervertebral disk affords adequate immobi¬ lization of the needle, fine adjustments can be made by main¬ taining firm manual pressure on the hub of the needle, after

Figure 141-7. The posterior plane of the cervical cord is visualized by a line connecting the anterior bony margins of the laminae.

which the electrode will glide slightly along or away from the bevel of the needle. An adjustment of more than 2 mm may re¬ quire complete withdrawal of the needle from the disk space and reinsertion. The stability afforded by the transdiscoidal in¬ sertion is sufficient to avoid the need for any mechanical stage or needle holder. When the tip of the needle emerges from the posterior por¬ tion of the intervertebral disk, the dura is encountered. It is ad¬ visable to use a sharp new needle, because in this area, the dura may be more difficult to penetrate than it is in its lateral and posterior portions. Sometimes it is necessary to perforate the dura first with a stylet from a slightly longer lumbar puncture needle. On rare occasions, a distinct pop can be felt as the dura is penetrated. When the tip of the needle is in the subarachnoid space, free flow of spinal fluid occurs. Ten ml of air is then injected through a two-way stopcock, and the anterior surface of the spinal cord is visualized with lateral Polaroid roentgenograms, as in an air myelogram (Fig. 141-6). The posterior surface of the cord is identified by a line connecting the anterior bony sur¬ face of the laminae (Fig. 141-7). The target point is determined by the intended area of anal¬ gesia (Fig. 141-2). To produce a segmental area of analgesia in the lower cervical and upper thoracic dermatomes, the tip of the electrode should enter the cord 4 to 6 mm from the midline, as determined by bisecting the interpedicular line (Fig. 141-8). To produce lumbosacral analgesia, the tip of the electrode should be positioned more laterally, 8 to 9 mm from the mid¬

Figure 141-6. When the needle has pentrated the dura, 10 ml of air is injected into the subarachnoid space. The anterior surface of the spinal cord is visualized.

line (Fig. 141-9). Only the most anterior border of the cord is seen in the lat¬ eral projection, and this represents the portion of the cord near¬ est the midline. When the target is near the midline, the tip of the electrode should lie about 5 mm below the projected ante-

1406

Part 4/Functional Stereotaxis

V—i-1

Figure 141-8. The midpoint of the cord is identified by bisecting the interpedicular line.

rior surface. When the target is more lateral, the actual anterior surface of the cord is more posterior than the apparent anterior surface as seen on the lateral projection with air enhancement in the subarachnoid space. Indeed, when the intended sacral fibers are interrupted, the target is just anterior to the dentate ligament (Fig. 141-10), which lies half way between the pro¬ jected anterior surface of the cord and the anterior surface of the lamina (Fig. 141-8). Gildenberg and colleagues10 advocated the use of imped¬ ance monitoring to detect penetration of the spinal cord using a coaxial electrode, as there is a distinct and detectable change in the impedance between the fluid-air subarachnoid space and the cord tissue. The needle electrode used is a bipolar system with one lead of the radiofrequency generator attached to the needle and the other attached to the protruding stylet wire. The lesion is pro¬ duced by repeated applications of small amounts of current, testing for areas of analgesia and for motor function after each application of current. A satisfactory level usually is obtained with the use of 4.8 W, usually a 40 percent setting of the 12-W maximum output of Radionics generator Model RFG-2A, which produces 60 to 100 mA. The current is first applied for 15 s and then for successively longer periods, depending on the response to each application. The analgesic effect of the current is immediate or appears within a few minutes. To enlarge or alter the area of the analgesia that is produced, the depth of the electrode or the position or angulation of the electrode tip should be changed rather than depending solely on changing the intensity or duration of the current application. The discomfort experienced by the patient during the pro¬ duction of the lesion is less than in radiofrequency percuta-

Figure 141-9. A and B. Anteroposterior roentgenograms with the needle in position, showing the straight tip pointing laterally (A) and the curved tip electrode pointing mesially (B). The electrode is 6 mm from the midpoint as measured by bisecting the interpedicular line.

neous cervical cordotomy done through the lateral approach at the C1-C2 interspace. This probably occurs because the heated electrode is not near the emerging posterior nerve root. The postoperative morbidity from the procedure is negligible, al¬ though there may be mild headache from air in the subarach¬ noid space. Pain secondary to penetration through the disk space is surprisingly minimal, but occasionally there is an an¬ noying pain in the ipsilateral upper extremity that lasts for a tew days. This procedure usually is done on one side during one sitting. If necessary, a lesion on the opposite side is made a week later.

Chapter 141/Percutaneous Lower Cervical Cordotomy

1407

sional nonnarcotic oral medication; fair, diminished pain still requiring either oral or parenteral analgesics; and poor, no improvement. The average age of the patients in this series was 58 years. All but four patients suffered from intractable pain from metastatic carcinoma. The follow-up of these patients lasted from 2 weeks to 7 months. Among the 21 patients who had procedures performed at the C1-C2 level, 14 patients (67 percent) had excellent results and 4 (19 percent) had good ones, for a total of 18 (86 percent) with satisfactory pain relief. In two patients (9 percent) the re¬ sult was fair; in only one patient (5 percent) was there a poor

Figure 141-10. Lateral x-ray of a C3-C4 percutaneous cervical cordotomy showing the tip of electrode at the midpoint of the thickness of the cord (dentate ligament).

RESULTS In an earlier series of 60 percutaneous cervical cordotomies done on 42 patients from 1965 to 1967, 21 procedures were done on 17 patients at the C1-C2 level and 39 were done on 25 patients by the anterior transdiscoidal technique described above.9 There were 12 bilateral procedures, 4 done at the C1-C2 level and 8 done at the lower cervical level on one side combined with a lesion at the C1-C2 level on the contralateral side. Relief of pain was classified as follows: excellent, complete relief of pain; good, slight residual pain requiring only occa¬

Figure 141-11. Percutaneous cervical cordotomy at the C6-C7 level resulting in complete analgesia and relief of pain below T4. A postmortem specimen shows an electrocoagulation lesion well placed at the anterolateral quadrant on the right side.

result. Among 39 procedures at the lower cervical level 16 (41 per¬ cent) results were excellent and 18 (33 percent) were good, for a total of 29 (74 percent) with satisfactory alleviation of pain. Seven procedures (18 percent) gave fair relief, and three (7 per¬ cent) gave relief classified as poor. Since percutaneous cervical cordotomy at the lower cervical levels is admittedly a more dif¬ ficult procedure than that done at the C1-C2 level, it is not sur¬ prising that most of the unsatisfactory results were found in the early patients. The results became better with a learning curve of about a dozen cases. This was best illustrated by the follow¬ up series. Of 190 procedures (42 bilateral) done with the lower cervical technique, 79 percent had a satisfactory result. Complications in this later, larger series showed motor weak¬ ness in the arm in 20 patients (9.5 percent) and in the leg in 29 patients (15 percent). Most weakness improved with physiotherapy. In the percutaneous procedure, even though it was done with radiological, physiological, and accurate stereotactic con¬ trol, the results seen in the postmortem examinations were mixed (Figs. 141-11 through 141-14). Bladder retention in patients who had no sphincter difficulty before the procedures occurred in 5 patients operated on at the C1-C2 level (26 percent), while only 1 of a total of 39 patients operated on through the anterior lower cervical approach had transient urinary incontinence. In the later series of 190 pa-

1408

Part 4/Functional Stereotaxis

Figure 141-12. An example of a mesial anterolateral spinothalamic cordotomy that penetrated deeper than was intended. Note the destruction of the anterior horn cells associated with an inevitable paresis of the upper extremity. Note the deviation of the anterior fissure, which is either the cause of the mesial lesion or a result of the traction from the gliosis of the lesion.

tients, no bladder dysfunction was noted after unilateral cordo¬ tomy. However, in the bilateral group (42 patients), temporary bladder dysfunction was noted in 10 patients (25 percent). In the entire series, there were four deaths from respiratory failure at night during sleep. All occurred after the upper cervi¬ cal technique, and none after the lower percutaneous anterior cervical cordotomy.

DISCUSSION Mullan and associates,1 Rosomoff and colleagues,2 and Tasker" were correct in their contention that percutaneous cervical cor¬

dotomy is advantageous in relieving intractable pain in patients who are debilitated by terminal disease and cancer. Arguably, the morphine pump is as effective in relieving intractable pain, but for individuals who need to be fully alert so that the seda¬ tive side effects of morphine are not an option, a percutaneous cervical cordotomy may still be considered. Anterior percutaneous cervical cordotomy at the lower cer¬ vical level has a distinct advantage over the high cervical tech¬ nique in that the possible complication of paralysis of involun¬ tary respiration can be avoided. In recent years, with careful preoperative and perioperative blood gas monitoring and sup¬ portive respiratory therapy when needed in an intensive care setting. Tasker" and Mullan12 have found that the respiratory

Figure 141-13. Four postmortem specimens of percutaneous lower cervical cordotomies. Specimens in B and C suggest injury to the corticospinal tract.

Chapter 141/Percutaneous Lower Cervical Cordotomy

1409

Figure 141-14. Four postmortem specimens. A shows extension of the lesion into the corticospinal tract and the anterior horn cells. B, C, and D show satisfactory percutaneous cervical anterolateral cordotomy.

complications associated with C1-C2 level percutaneous cor¬ dotomy could be substantially reduced or eliminated. In our experience, operation at the C1-C2 level is techni¬ cally easier to perform than at the lower cervical level and ap¬ pears to produce a higher percentage of satisfactory relief of pain. However, the incidence of the complications of respira¬ tory failure, motor weakness, dysesthesia, and bladder inconti¬

References 1.

2. 3.

nence was lower at the lower level. 4.

CONCLUSION The following conclusions can be drawn: 1.

2.

3.

Percutaneous cervical cordotomy is useful for the relief of intractable pain, especially in a debilitated terminal patient who wants to remain alert. The complication of respiratory embarrassment after high cervical percutaneous cordotomy stimulated the new per¬ cutaneous approach to the lateral spinothalamic tract at a lower cervical level below the outflow of the phrenic nerves (C4). The results of percutaneous cordotomy at the upper C1-C2 level offer a slightly better chance for relief of pain, but the lower transdiscoidal cervical approach has proved to be safer and less likely to be complicated by undesirable or fa¬ tal respiratory side effects.

5. 6. 7. 8.

9. 10.

11.

12.

Mullan S, Hekmatpanah J, Dobben G, et al: Percutaneous, in¬ tramedullary cordotomy utilizing the unipolar anodal electrolytic sys¬ tem. J Neurnsurg 22: 548, 1965. Rosomoff HL, Brown CJ, Sheptak P: Percutaneous radiofrequency cervical cordotomy: Technique. J Neurnsurg 23:639, 1965. Belmusto L, Brown E, Owens G: Clinical observations on respiratory and vasomotor disturbance as related to cervical cordotomy. J Neurosurg 20:225-232, 1963. French LA: Cordotomy in the high cervical region for intractable pain. Lancet 73:283-287, 1953. Peet MM, Kahn EA, Allen SS: Bilateral cervical chordotomy for re¬ lief of pain in chronic infectious arthritis. JAMA 100:488-489, 1933. Nathan PW: Results of antero-lateral cordotomy for pain in cancer. J Neurol Neurnsurg Psychiatry 26:353-362, 1963. Nathan PW: The descending respiratory pathway in man. J Neurol Neurnsurg Psychiatry 26:487-A-90, 1963. Belmusto L, Woildring S, Owens G: Localization and patterns of po¬ tentials of the respiratory pathway in the cervical spine in the dog. J Neurnsurg 22:277-283, 1965. Lin PM, Gildenberg PL, Polakoff PP: An anterior approach to percu¬ taneous lower cervical cordotomy. J Neurnsurg 25:553, 1966. Gildenberg PL, Zanes C, Flitter MA: Impedance monitoring device for detection of penetration of the spinal cord in anterior percutaneous cervical cordotomy: Technical note. J Neurnsurg 30:87, 1969. Tasker RR: Percutaneous cordotomy: The lateral high cervical tech¬ nique, in Schnidek H, Sweet W (eds): Operative Neurosurgical Techniques, 2d ed. New York: Grune & Stratton, 1988, pp 1191-1205. Mullan S: Stereotactic cordotomy, in Youmans J (ed): Neurological Surgery. Philadelphia: Saunders, 1973, pp 1746-1753.

CHAPTER

142

SPINAL CORD SURGERY FOR PAIN MANAGEMENT

Philip L. Gildenberg

Spinal cord surgery for the management of pain has, through the years, mainly concerned the lateral spinothalamic tract, al¬ though more recently there has been concern for the gate into that tract and another central pain tract, as well. The earliest and most popular procedure generally advocated for pain man¬ agement and used primarily until very recently was anterolat¬ eral cordotomy. The lateral spinothalamic tract conducts mainly acute pain and temperature sensation. Fibers originate in the dorsal root entry zone. They may ascend one or more segments before de¬ cussating in the anterior white commissure to ascend in the an¬ terolateral quadrant, on the side opposite the input, where it lies just posteromedial to the fibers of the spinocerebellar tract. There is considerable clinical evidence, however, that the decussation may variably occur in many segments above the input segment1 and that many fibers may not cross in the spinal cord, but only after brain stem levels have been reached.2,3 Fibers are somatotopically arranged, with decussating axons lying on the medial edge of the tract at each spinal cord level. Consequently, as the tracts ascend, the most lateral and poste¬ rior fibers represent the lowest portion of the body, and the more medial and anterior fibers represent one or two levels (or more) below the segment under study. In the highest cervical levels, the most anteromedial fibers represent the upper extrem¬ ity and neck. There is some evidence that fibers representing temperature sensation tend to lie somewhat posterior to those subserving pain sensation.4 Thalamic projections of the spinothalamic system in man are more complex than the classical description would sug¬ gest.5 The ascending fibers tend to contribute collaterals to the multisynaptic gray matter in the midbrain and medial thalamus, those areas projecting to the limbic affective part of the brain. Those few spinothalamic fibers that arrive at the thalamus are distributed primarily in the ipsilateral ventral posterolateral nu¬ cleus and bilaterally in intralaminar nuclei.6 The former may represent discriminative acute pain and the latter the “suffer¬ ing” that is associated with clinical pain.7 The current status of our knowledge about the anatomic and neurophysiological connections has been reviewed by Willis.5 Surgical section of the lateral spinothalamic pathway, called anterolateral cordotomy, produces a loss of pain sensation on acute noxious stimulation starting one or several levels below the spinal interruption. Even though a single pin prick may not be appreciated as being sharp, sometimes repeated pin stick

stimulation can be appreciated.8 Loss of deep pain sensation is somewhat less consistent9 and is more nearly correlated with successful pain relief.8 Somatic pain of the body wall or ex¬ tremities may be relieved by such a maneuver but usually not pain of visceral origin. Lesions in the dorsal root entry zone are also used to treat pain of various types. Because persistent pain may continue or resume after an ap¬ parently successful cordotomy, the existence of multisynaptic pain pathways were assumed, in addition to the lateral spinothalamic pathways, even if they were demonstrated only with difficulty by usual anatomic means. These multisynaptic pathways have been classified as the paleospinothalamic and archispinothalamic systems.10,11 Because there are multiple pathways carrying pain information to the brain, it is not un¬ common for pain and/or suffering to persist or to recur after an initially successful cordotomy. The anatomy of the spinothalamic tract was first described by Edinger12 in 1889, but its function was not known. Spiller13 reported in 1905 on a patient in whom pain and temperature sensation in the lower body was lost secondary to bilateral tu¬ berculomas involving the anterolateral quadrants of the spinal cord. Schuller14 demonstrated in monkeys that one could sec¬ tion the anterolateral tracts without causing paralysis, and he coined the term chordotomie for that procedure. The original theory that pain was specifically transmitted by the lateral spinothalamic pathways led Spiller13 early in this century to study loss of pain sensation after section of the anterolateral quadrants of the spinal cord in animals. He persuaded Martin15 to make similar lesions in patients suffering from pain, and they reported the first successful planned anterolateral cordo¬ tomy in 1912. The operation was developed further by Foerster and Gagel16,17 in Europe and Frazier18 in America and eventu¬ ally became the most commonly performed neurosurgical pro¬ cedure for the treatment of pain. Surgical cordotomy, usually at the thoracic area,9,19,20 be¬ came a standard neurosurgical procedure. It required a laminectomy, however, in a group of patients who were often too debilitated to tolerate such a procedure. Usually it was done with the patient under general anesthesia, so it was not possible to monitor the location or extent of the lesion during surgery, except in the rare case done under local or regional anesthesia.9 This led Mullen and colleagues21 to develop a percutaneous technique whereby a radioactive strontium needle was passed

1411

1412

Part 4/Functional Stereotaxis

into the anterolateral spinal canal at the C2 level, where it was brought into contact with the spinal cord for a sufficient time to produce a lesion of the spinothalamic tract. The procedure was simplified and modified by Rosomoff and coworkers,22 who used a similar approach, but they produced the lesion with a ra¬ diofrequency electrode, providing an immediate lesion and bet¬ ter control over the location and extent of the lesion. A problem with interrupting the anterolateral quadrant at that level, how¬ ever, is that fibers concerned with respiration run in the antero¬ lateral spinal cord down to the C3 level.23 Consequently, when

was elaborated further to include additional concepts of the mechanism of the emotional (limbic) contribution to pain per¬ ception.34 As the understanding of the pain system became more sophisticated, the use of cordotomy for chronic pain de¬ clined, although it was still used appropriately for cancer pain. The further development of spinal cord35"37 or deep brain stim¬ ulation38-40 for management of chronic pain intruded even more on the use of cordotomy, and the decline was accelerated fur¬ ther by the introduction of implantable spinal morphine pumps.41^13

a cordotomy lesion is made above the C4 level, it includes fibers concerned with respiration, so patients with chest wall cancer pain after a pneumonectomy or patients with bilateral lesions were at risk of sleep-induced apnea.24 The respiratory impairment appears to be an inability to integrate sensory in¬ formation into the respiratory drive, rather than paralysis of the diaphragm, so the patient is able to breathe when awake (but

Meanwhile, there was further elaboration of an additional spinal cord pain pathway. In 1970, Hitchcock44 presented a procedure he called central myelotomy. His stereotactic appa¬ ratus allowed insertion of an electrode through the foramen magnum or into the spinal cord at high cervical levels. He used his stereotactic apparatus to introduce a needle-electrode dorsally to perform high-cervical cordotomy, an elaboration of the percutaneous approach introduced by Mullan and asso¬ ciates21 and Rosomoff and colleagues.22 The electrode was in¬ advertently inserted into the center of the spinal cord at the cervicomedullary junction when one patient suddenly moved as the electrode contacted the pia. The patient had immediate relief of his somatic pain, and the relief lasted when only a small lesion was made at that site. This target was adopted for central myelotomy, and other patients had similar successful relief of pain by the production of a lesion at the high central spinal cord.45,46

may express a vague feeling of apprehension), but respiratory drive fails when the patient falls asleep.25-26 This impairment may be identified by a failure of the awake patient to respond to a hypercapnia challenge on breathing CO,.24 Percutaneous cervical cordotomy was modified by Lin and coworkers25 in 1966 to approach the cord wtih a radiofre¬ quency needle electrode diagonally through an intervertebral disk at lower cervical levels, which made the procedure more difficult but safer, with complete elimination of the risk of res¬ piratory depression. Until the mid-1970s, cordotomy was done for persistent pain regardless of etiology. By that time, however, cordotomy gradually became recognized as much more successful in man¬ agement of cancer pain than chronic pain of benign origin, so its use in the latter was discouraged more and more.27-29 As a natural sequel to the adoption of cordotomy, Greenfield suggested to Armour in 1926 that the spinothalamic fibers could be interrupted bilaterally in selected segments by cutting the spinal cord through the midline, where the only significant axons were the decussating spinothalamic fibers.30 Armour31 successfully relieved the pain of one patient, but the patient died of pneumonia postoperatively, and the project was not pursued. However, a decade later, Putnam32 reintroduced the procedure, and it became accepted. It was soon recognized, however, that there may be very little analgesia, even with good relief of pain. Until the mid-1960s, interruption of the spinothalamic tract with either cordotomy or myelotomy became the standard neu¬ rosurgical management of pain, regardless of type. It gradually became apparent, however, that (1) many patients had no or only temporary pain relief; (2) different types of pain de¬ manded different strategies, that is, acute pain, cancer pain, and chronic pain of noncancer origin; (3) evaluation of psychologi¬ cal attributes was needed as well as the patients’ somatic de¬ scription of pain; and (4) some anatomic explanation must exist for these conflicting observations. It was in 1965 that Melzack and Wall33 presented the gate control theory of pain. This concept reconciled seemingly con¬ flicting results from both experimental studies and clinical ob¬ servations. They proposed that there was a gate at the dorsal root entry zone in the substantia gelatinosa that opened or closed transmisison of pain sensation, depending on whether noxious or nonnoxious stimulation predominated. The concept

Although this procedure could not be done readily without a stereotactic apparatus that allowed this unusual approach, oth¬ ers reported similar success by producing a mechanical lesion at the same site. Through the years, there had been reports of pain relief after conventional lumbosacral commissural myelot¬ omy without detectable analgesia, or reports of pain relief far exceeding the amount of analgesia that could be demonstrated, especially if visceral pain predominated.I9-47-48 The observation suggested that in some patients the spinothalamic fibers may ascend more than only one or two segments before dessicating, an observation consistent with examination of patients after percutaneous cervical cordotomy.3 The observation also sug¬ gested that something else is being interrupted when a myelot¬ omy is performed. The sum of these observations led Gildenberg49 to conclude that a pathway, previously undescribed, ascends at the center of the spinal cord and carries predomi¬ nately visceral pain perception and that interruption of that pathway could relieve such cancer pain. The pathway was as¬ sumed to be multisynaptic, probably incorporated into the cen¬ tral grey. There seemed to be little advantage in interrupting the pathway at the cervicomedullary area, as Hitchcock had done, for patients who had pelvic or perineal pain, which occurred commonly in cancer patients. Mechanical interruption of the central cord at the lumbothoracic level often provided excellent relief of such cancer pain. He recruited Hirshberg to collabo¬ rate in accumulating sufficient independent clinical experience, and they published a series of patients thus treated with “lim¬ ited myelotomy" in 1981.49 Hirshberg provided the spinal cord of one of his patients who had died of cancer to Willis,50 who demonstrated a new pathway that was not polysynaptic but lay at the anterior part of the medial borders of the posterior columns. He further demonstrated in rats that the pathway was associated with visceral pain.50

Chapter 142/Spinal Cord Surgery for Pain Management

TECHNIQUES Surgical Cordotomy The technique of surgical cordotomy has been described numer¬ ous times with many minor modifications,918-20 but the basic ap¬ proach has not changed much since Spiller and Martin’s15 origi¬ nal report in 1912. One representative technique is presented here, although others are equally as safe and effective. A one- or two-segment laminectomy is done at a level at least several seg¬ ments above the pain input, care being taken to recognize spinal cord rather than vertebral levels. Since the T9 level has the most vulnerable vascular supply, it is best to avoid that area. The dura is opened, and the spinal cord is visualized under magnified vi¬ sion. The dentate ligaments above and below the planned inci¬ sion are freed. If there is any traction on the dorsal roots when the cord is rotated, or if they prevent the rotation of the spinal cord, the dorsal roots just above and below the incision are also sectioned. The dentate ligament is grasped by a hemostat or other instrument, and the spinal cord is rotated 45° to expose the anterolateral surface, taking care to rotate the entire cord and not to twist it, so the internal structures retain as close to normal ori¬ entation as possible. A sharp blade is inserted at the origin of the dentate ligament, and an incision is made to a point just medial to the emergence of the most medial fibers of the anterior root, with care to avoid injury to the anterior spinal artery. The inci¬ sion should be deep enough into the cord to transect a pie¬ shaped segment of about 90°, rather than interrupting only the pia and superficial fibers. If the dentate ligament originates far dorsal to the lateral midpoint, the latter should be used to iden¬ tify the posterior margin of the incision to avoid interruption of the corticospinal pathway. It has been reported that approximately half of patients with cancer pain will have total immediate relief and one-fourth will have partial relief, but the remaining one-fourth will have no benefit.51 By the end of 6 months, however, pain will return in approximately one-half of the originally successful patients.52 After unilateral cordotomy for pelvic or abdominal cancer pain, an additional 10 percent or more may have the rapid increase of pain on the side opposite the analgesic side.3,53 The mortality rates vary greatly from one series to the next, particularly in relationship to whether noncancer pain is in¬ cluded. White and Sweet54 report an 8 percent mortality rate in cancer patients after high-thoracic cordotomy, but none when the procedure was done for noncancer pain. They also report a 13 percent risk of lower-extremity weakness after unilateral cordotomy.9

Percutaneous Cervical Cordotomy, C2 The technique of percutaneous cervical cordotomy depends on a cooperative patient and excellent fluoroscopy and has not been modified significantly since the first reports of Rosomoff and colleagues.22,24 It requires a much different orientation than usual neurosurgery, along with attention to detail and patience in working with awake patients in great pain. The patient lies supine with a C-arm radiograph apparatus adjusted to visualize either an AP or lateral view across the base of the skull. On the lateral view, it is not difficult to iden¬

1413

tify the crotch between the posterior arch of C1 and the lamina of C2. The needle is introduced horizontally to a point just an¬ terior to the middle of the canal, care being taken to avoid spearing the spinal cord if the needle advances suddenly on penetrating the dura. The use of a head stand and needle micro¬ drive, such as that designed by Rosomoff, is very helpful. A drop of hyperbaric or other contrast material allows visualiza¬ tion of the dentate ligament, and a small amount of air may out¬ line the anterior surface of the cord. The obturator is removed from the needle and the electrode introduced. The electrode tip is advanced with care to the pia half way between the anterior cord and the dentate ligament. The patient may complain of pain as the pia is touched, and it may be necessary to pierce the pia with a sharp thrust. Impedance may be measured to ensure penetration into the spinal cord.55 Stimulation at approximately 50 Hz can be used to verify proper position within the spinothalamic tract, as evidenced by the projection of sensation to the contralateral body, and the tip of the needle-electrode ad¬ justed accordingly. A very low voltage may be required, and segmental sensation must be differentiated from spinothalamic tract response. The threshold for nerve root sensation is lower, and the sensation is much more painful.20’56 A lesion is made, for instance at 70° to 90° for up to 30 s in increments of 10 s.57 The lesion may be repeated, if necessary. When adequate anal¬ gesia is demonstrated, the electrode is withdrawn. The results after percutaneous cervical cordotomy are simi¬ lar to those after surgical cordotomy, but the complication rate may be significantly less.54 The complication of sleep-induced apnea is significant. Although Krieger and Rosomoff58 recom¬ mend the use of a COz challenge prior to production of lesions on the second side, many neurosurgeons fear that complication sufficiently to avoid bilateral C2 cordotomy completely. In our early percutaneous cervical cordotomy experience, a patient who had a pneumonectomy with ipsilateral recurrent chest wall pain died the second night after the operation; only in retro¬ spect did we realize he had died of sleep-induced apnea. Also, three other patients died after a lesion was produced on the sec¬ ond side. All had had excellent analgesia on the first side and were physiologically stable for at least several days before the second-side lesions were made. Another patient did well the night after a percutaneous cervical cordotomy was done on the second side. It was after the reassuring overnight observation of that patient that two more patients had their procedure, both on the following day. All three patients developed sleepinduced apnea, so all three were on ventilators at the same time. It was then that we recognized that the single contralat¬ eral lesion in the first patient denervated the respiratory sensory innervation from his only remaining lung, and this patient, who was already critically ill, was found dead in bed during the night, without our realizing the cause.25 Within a few weeks, we had moved the lesion down to a lower cervical level.

Lower Cervical Cordotomy The procedure of lower-cervical cordotomy has evolved over several years to the following protocol59-60: The patient is in the supine position with the neck slightly extended, similar to that for a cervical discogram; AP and lateral radiograph tubes are adjusted to provide identical magnification without moving ei-

1414

Part 4/Functional Stereotaxis

ther the patient or the radiograph apparatus or cassettes. The needle is inserted under local anesthesia between the carotid sheath and the tracheoesophageal complex. By pressing on the skin at that site, it is possible to bring the subcutaneous tissues almost in contact with the anterior surface of the vertebral body near the midline. The desired interspace is identified by relating the level of the shoulders with the scout lateral radiograph. The tip of the needle is inserted into the disk, and AP and lateral films are taken. The spinal cord ordinarily rests against the posterior canal in this position, but that may be verified by the instillation of contrast material and/or air as for the C2 cordotomy. The target point depends on the segment representing the pain. The cord is 10 x 20 mm at that level, with the dentate ligament attached at the midpoint on the lateral projection. For pain involving the sacrum or lower extremity, the target is 8 mm lateral and 5 mm anterior to the posterior wall of the canal. For chest pain, the lesion is 3 to 4 mm lateral and 8 mm anterior to the posterior wall. The trajectory is either calculated or determined graphically. If one pictures the cross-section of the neck with the needle just entering the anterior disk, the line between the position of the needle tip and the target represents the hypotenuse of a right triangle. The relative distance representing the base of the tri¬ angle can be measured on the AP film as the distance from the tip of the needle to the target point. The relative distance repre¬ senting the height of the triangle can be measured on the lateral film as the distance from the tip of the needle to the target point. An equivalent triangle can be drawn at the corner of a piece of paper by measuring relative base and height distances along the edge of the paper and connecting those points by drawing the hypotenuse. That paper can then be held by the pa¬ tient’s chin and the needle aligned by eye with the hypotenuse, which will place it on the proper trajectory to hit the target. The needle is advanced along that trajectory until it is locked in its path by the posterior annulus fibrosis and posterior longitudinal ligament. The radiographs are repeated using the same technique, the measurements are repeated, an equivalent triangle is drawn (the angles of the triangle should be identical, even if the length of the sides are shorter), and it is verified that the needle lies along the path of the hypotenuse. When it is in satisfactory trajectory, the needle is advanced into the spinal canal, and the obturator is replaced by the elec¬ trode. The electrode assembly is advanced until both the patient and surgeon recognize that the pia is being touched, and the pia is punctured carefully with a sharp thrust. Films are again taken to ensure that the tip of the electrode is at the proper target point. As with C2 percutaneous cervical cordotomy, penetration of the spinal cord can be verified by impedance measurement. Stimulation, however, is less reliable at lower cervical levels, since root pain at a low threshold is more common and may in¬ terfere with stimulation of the ascending tracts. Results after lower percutaneous cervical cordotomy are equivalent to those after open surgical cordotomy or C2 percu¬ taneous cervical cordotomy. The complication of weakness, however, is higher but of a different nature. Approximately 15 percent of patients have weakness of the ipsilateral hand due to trauma to the emerging motor nerve root. Two-thirds of those cases return to normal within 3 weeks, leaving a 5 percent risk of permanent hand weakness. Most patients are so gratified

about their relief from pain that they accept that problem when it occurs.

Commissural Myelotomy The technique of commissural myelotomy begins like that of surgical cordotomy. The usual patients have bilateral pelvic or lower extremity pain or pelvic visceral pain. The spinal cord is exposed throughout all segments for which pain denervation is intended and perhaps two additional cephalad segments. The spinal level does not correspond to the spinal cord segment, and that must be considered when the multiple-level laminec¬ tomy is planned. Today it is advisable to use an operating microscope to visu¬ alize the spinal cord during the midline section. The arachnoid must be carefully dissected to expose the cord and identify the dorsal vasculature. The midline can be identified by the vessels diving between the posterior columns in the posterior median sulcus. The pia may be firm and require sharp dissection to be¬ gin the dissection. The posterior median septum is a single fi¬ brous layer that lies between the posterior columns, and one can dissect along either side of it to the central canal area. Because the septum is a valuable landmark and because the neural tissue to be separated is friable, I prefer to use a ball dis¬ sector. Earlier techniques recommended sectioning only the posterior commissure, but it is doubtful that structure alone could be adequately identified. With good control over the depth of incision, complete myelotomy may provide a more consistent result. The anterior median septum can first be pal¬ pated and then visualized as the anterior extent of the dissec¬ tion, and the surgeon should not continue beyond that for fear of damaging the anterior spinal artery. Results of midline commissural myelotomy vary greatly from one series to another,19 possibly because of differences in patient selection or differences in technique, with some sur¬ geons sectioning more cranially than others or others perhaps not sectioning deeply enough. There are, unfortunately, many reported undesirable side effects, such as hyperesthesia, dimin¬ ished proprioception, paresthesia or dysethesia of the legs, radicular pain, paresis, or incoordination of gait,19 along with a mortality rate of up to 8 percent.61 Gybels and Sweet19 review the literature and note that there may be a variable amount of analgesia, and sometimes good pain relief is obtained with little analgesia.1'47'48-62,63 Although they declined to explain these results on the basis of under¬ standing of pathways at the time of their writing, my observa¬ tions with limited myelotomy49 and the new findings of Willis50 would account for those discrepancies very well.

Limited Myelotomy The theoretical consideration of a pain pathway ascending in the central spinal cord of Hitchcock’s44 central myelotomy served as the basis for our limited myelotomy,49 where a lesion is made in the center of the spinal cord at only a single segment above the input from the painful areas. For pelvic pain, particular visceral pain of rectal or uterine cancer, the most common indication for limited myelotomy, the lesion is made at the thoracolumber junction of the spinal cord.

Chapter 142/Spinal Cord Surgery for Pain Management

An exposure by making a T9 laminectomy exposes the spinal cord at approximately the T12 level, so all the lumbar and sacral dermatomes are included. The procedure is just the same as for commissural myelotomy but involves only a single level. It has been our custom to move the ball dissector around at the depth of the incision to ensure interruption of adjacent pathways. The success rate of limited myelotomy is comparable to that of commissural myelotomy, but so far no untoward side effects or mortality have been seen.49 Somatic pain may not necessar¬ ily be relieved by limited myelotomy and may require a sepa¬

anterolateral cordotomy at cervical level in man. Pain. 42:23-30, 8. 9. 10. 11.

12.

rate procedure.

13.

Interruption of pain pathways within the spinal cord has proved to be of great help to a number of patients. However, it is per¬ formed less and less, for several reasons. During the last two decades, we have recognized more and more that simple interruption of pain pathways is inappropriate for treatment of most patients with chronic pain (Chap. 136). Such pain is complicated by many physical and emotional fac¬ tors28-64'65 which require a more comprehensive pain manage¬ ment program.66 Selected patients with cancer pain, however, are still candidates for cordotomy or myelotomy, since their prognosis for survival may be too short for recurrence of pain to intervene and since the somatic aspects and localization of their pain are often clearly identifiable.67 Alternative methods of treatment have emerged. Intraspinal administration of morphine with either an external (for preter¬ minal care) or an implanted pump (for patients with a progno¬ sis greater than 3 months) may provide excellent relief of can¬ cer pain with fewer risks. If the cancer progresses to involve the other side or other sites, the pump may be reprogrammed to accommodate the increased pathology. In fact, I have per¬ formed only a few cordotomies (percutaneous or surgical)

14.

since I have begun to implant morphine pumps. I would still advocate limited myelotomy for pelvic visceral pain. It has little enough risk and, if successful, may be more cost effective and require less follow-up care than an implanted

24.

spinal pump.

26.

15.

16.

4. 5. 6.

7.

J Nerv Ment Dis 128:89-114, 1959. Edinger L: Vergleichend-entwicklingsgeschichtliche und anatomis-

Sweet WH, Poletti CE: Operations in the brain stem and spinal canal with an appendix on open cordotomy, in Wall PD, Melzack R (eds): Textbook of Pain. Edinburgh: Churchill-Livingstone, 1984, pp 615-631. Truex RC, Taylor MJ, Smythe MQ, Gildenberg PL: The lateral cervi¬ cal nucleus of cat, dog and man. J Comp Neurol 139:93-104, 1970. Gildenberg PL: Physiologic observations during percutaneous cervi¬ cal cordotomy, in Somjen GG (ed): Neurophysiology Studied in Man. Amsterdam: Excerpta Medica, 1972, pp 231-236. Carpenter MB: Human Neuroanatomy, 7th ed. Baltimore: Williams &

4:121-128, 1889. Spiller WG: The location within the spinal cord of the fibers for tem¬ perature and pain sensations. J Nerv Ment Dis 32:318-320, 1905. Schuller A: Uber operative Durchtrennung der Riichenmarksstrange (Chordotomie). Wien Med Wochenschr 60:2292-2295, 1910. Spiller WG, Martin E: The treatment of persistent pain of organic ori¬ gin in the lower part of the body by division of the anterolateral col¬ umn of the spinal cord. JAMA 58:1489-1490, 1912. Foerster O: Vorderseitenstrangdurchschneidung im Riickenmark zur

19.

Z Neurol Psychiatr 138:1-92, 1932. Frazier CH: Section of the anterolateral columns of the spinal cord for the relief of pain. Arch Neurol Psychiatr 4:137-147, 1920. Gybels JM, Sweet WH: Neurosurgical Treatment of Persistent Pain.

20.

Pain and Headache, vol 11. Basel: Karger, 1989. White JC, Sweet WH: Pain, Its Mechanism and Neurosurgical

18.

21.

Control. Springfield: Charles C Thomas, 1955. Mull an S, Harper PV, Hekmatpanah J, et al: Percutaneous interrup¬ tion of spinal pain tracts by means of a strontium-90 needle. J Neuro-

22.

surg 20:931-939, 1963. Rosomoff HL, Carrol F, Brown J, Sheptak P: Percutaneous radio¬ frequency cervical cordotomy: Technique. J Neurosurg 23:639-644,

23.

25.

27.

3.

eral cordotomy. Adv Pain Res Ther 3:921-926, 1979. White JC, Sweet WH: Pain and the Neurosurgeon. A Forty Year Experience. Springfield: Charles C Thomas, 1969. Struppler A: Principles of pain therapy. Verh Dtsch Ges Inn Med 86:1560-1562, 1980. Bishop GH: The relation between nerve fiber size and sensory modal¬ ity: Phylogenetic implication of the afferent innervation of cortex.

Beseitigung von Schmerzen. Berl Klin Wosenschr 50:1499, 1913. 17. Foerster O, Gagel O: Die Vorderseitenstrangdurchschneidung beim Menschen. Eine Klinische, pathophysiologisch, anatomische Studie.

References

2.

1990. Nathan PW, Smith MC: Clinico-anatomical correlation in anterolat¬

che Studien im Bereiche des Central-nervensystems. II. Uber die Forsetzung der hinteren Riickenmarkswurzeln zum Gehirn. AnatAnz

CONCLUSION

1.

1415

28.

1965. Nathan PW: The descending respiratory pathway in man. J Neurol Neurosurg Psychiatry 26:487^199, 1963. Rosomoff HL, Krieger AJ, Kuperman AS: Effects of percutaneous cervical cordotomy on pulmonary function. J Neurosurg 31:620-627, 1969. Lin PM, Gildenberg PL, Polakoff PP: An anterior approach to percu¬ taneous lower cervical cordotomy. J Neurosurg 25:553-560, 1966. Tenicela R, Rosomoff HL, Feist J, Safar P: Pulmonary function follow¬ ing percutaneous cervical cordotomy. Anesthesiology 29:7-16, 1968. Gildenberg PL, DeVaul RA: Management of chronic pain refractory to specific therapy, in Youmans JR (ed): Neurological Surgery, 2d ed. Philadelphia: Saunders, 1982, pp 3749-3768. Gildenberg PL: General and psychological assessment of the pain patient, in Tindall GT, Cooper PR, Barrow DL (eds): The Practice of Neurosurgery. Baltimore: Williams & Wilkins, 1996, pp

30.

2987-2996. Bonica JJ: Organization and function of a pain clinic, in Bonica JJ (eds): International Symposium on Pain. New York: Raven Press, 1974. Walker AE: History of Neurological Surgery. Baltimore: Williams &

31.

Wilkins, 1951. Armour D: Surgery of the spinal cord and its membranes. Lancet

29.

Wilkins, 1976. Willis WD: The Pain System. The Neural Basis of Nociceptive Transmission in the Mammalian Nervous System. Basel: Karger, 1985. Nathan PW, Smith MC: Some tracts of the anterior and lateral columns of the spinal cord, in Knighton RS, Dumke PR (eds): Pain.

32.

Boston: Little, Brown, 1966, pp 44—57. Lahuerta J, Bowsher D, Campbell J, Lipton S: Clinical and instru¬ mental evaluation of sensory function before and after percutaneous

34.

33.

1:691-697, 1927. Putnam TJ: Myelotomy of the commissure. A new method of treat¬ ment for pain of the upper extremities. Arch Neurol Psychiatry 32:1189-1192, 1934. Melzack R, Wall PD: Pain mechanisms: A new theory. Science 150:971-979, 1965. Melzack R, Casey KL: Sensory, motivational, and central control de¬ terminants of pain, in Kenshalo DR (ed): The Skin Senses. Springfield: Charles C Thomas, 1968, pp 423—439.

1416

Part 4/Functional Stereotaxis

35.

Long DM Erickson DE: Stimulation of the posterior columns of the spinal cord for relief of intractable pain. Surg Neurol 41:134-141, 1975.

36.

Gildenberg PL: The use of pacemakers (electrical stimulation) in

52. 53.

functional neurological disorders, in Rasmussen T, Marino R (eds): Functional Neurosurgery. New York: Raven Press, 1979, pp 59-74. 37.

Augustinsson LE, Sullivan L, Sullivan M: Physical, psychologic, and social function in chronic pain patients after epidural spinal electrical stimulation. Spine 11:111-119, 1986.

38.

Richardson DE. Akil H: Pain reduction by electrical brain stimulation in man. I: Acute administration in periaqueductal and periventricular sites. JNeurosurg 47:178-183, 1977.

54. 55.

39.

Foley KM: Opioids. Neurol Clin 11:503-522, 1993.

40.

Gybels J, Kupers R: Central and peripheral electrical stimulation of the nervous system in the treatment of chronic pain. Acta Neurochir Suppl (Wien) 38:64-75, 1987.

41.

Brazenor GA: Long term intrathecal administration of morphine: A comparison of bolus injection via reservoir with continuous infusion by implanted pump. Neurosurgery 21:484-491, 1987.

42.

Payne R: Role of epidural and intrathecal narcotics and peptides in the management of cancer pain. Med Clin North Am 71:313-327, 1987.

59.

43.

Onofrio BM, Yaksh TL: Long-term pain relief produced by intrathe¬ cal morphine infusion in 53 patients. J Neurosurg 72:200-209, 1990. Hitchcock ER: Stereotactic cervical myelotomy. J Neurol Neurosurg Psychiatry 33:224-230, 1970.

44.

Cowie RA, Hitchcock ER: The late results of antero-lateral cordo¬ tomy for pain relief. Acta Neurochir 64:39-50, 1982. Mansuy L, Sindou M, Fischer G, Brunon J: Spino-thalamic cordo¬ tomy in cancerous pain. Results of a series of 124 patients operated on by the direct posterior approach. Neurochirurgie 22:437-444, 1976. White JC, Sweet WH: Anterolateral cordotomy: Open versus closed comparison of end results. Adv Pain Res 3:911-919, 1979. Gildenberg PL, Zanes C, Flitter M, et al: Impedance measuring de¬ vice for detection of penetration of the spinal cord in anterior percuta¬ neous cervical cordotomy. Technical note. J Neurosurg 30:87-92 1969.

56.

Tasker RR: Percutaneous cordotomy—the lateral high cervical tech¬ nique, in Schmidek HH, Sweet WH (eds): Operative Neurosurgical Techniques: Indications, Methods and Results. New York: Grune & Stratton, 1982, pp 1137-1153.

57.

Levin AB, Cosman ER: Thermocouple-monitored cordotomy elec¬ trode. Technical note. J Neurosurg 53:266-268, 1980.

58.

Kneger AJ, Rosomoff HL: Sleep-induced apnea. I: A respiratory and autonomic dysfunction syndrome following bilateral percutaneous cervical cordotomy. J Neurosurg 40:168-180, 1974. Gildenberg PL, Lin PM, Polakoff PP, Flitter MA: Anterior percutaneous cervical cordotomy: Determination of target point and calculation of an¬ gle of insertion. Technical note. JNeurosurg 28:173-177, 1968.

60.

Gildenberg PL: Percutaneous cervical cordotomy. Clin Neurosurg 21:246-256, 1974.

45.

Schvarcz JR: Spinal cord stereotactic techniques re trigeminal neucleotomy and extralemniscal myelotomy. Appl Neurophysiol 41: 99-112, 1978.

61.

Grunert V, Kraus H, Sunder-Plassmann M, Gestring GF: Die kommissurale Myelotomie: Indikation und Ergebnis. Wien Klin Wochenschr 82:865-868, 1970.

46. 47.

Hitchcock ER: Stereotactic myelotomy. J Roy Soc Med 67:771, 1974. Cook AW: Commissural myelotomy. J Neurosurg 47:1, 1977.

62. 63.

48.

King RG: Anterior commissurotomy for intractable pain. J Neurosurg 47:7, 1977.

Sourek K: Commissural myelotomy. J Neurosurg 31:524-527, 1969. Wertheimer P. Lecuire J: La myelotomie commissurale posteriure. A propos de 107 observations. Acta Chir Belg 52:568. 1953.

M

49.

Gildenberg PL, Hirshberg RM: Limited myelotomy for the treatment of intractable cancer pain. J Neurol Neurosurg Psychiatry 47:94—96, 1984.

50.

Al-Chaer ED. Lawand NB, Westlund KN, Willis WD: Visceral nociceptive input into the ventral posterolateral nucleus of the thalamus:

65.

Gildenberg PL, DeVaul RA: The Chronic Pain Patient. Evaluation and Management. Basel: Karger, 1985.

A new function for the dorsal column pathway. J Neurophysiol 76:661-674, 1996.

66.

Bonica JJ, Loeser J: Management of Pain, 2d ed. Philadelphia: Lea & Febiger, 1990.

Nathan PW: Results of antero-lateral cordotomy for pain in cancer. J Neurol Neurosurg Psychiatry 26:353-362, 1963.

67.

Kanner R: Diagnosis and Management of Pain in Patients with Cancer. Basel: Karger, 1988.

51.

Gildenberg PL, DeVaul RA: Treatment of chronic pain refractory to specific therapy, in Youmans JR (ed): Neurological Surgery, 3d ed. Philadelphia: Saunders, 1989. pp 4144-4166.

CHAPTER

143

DESTRUCTIVE CENTRAL LESIONS FOR PERSISTENT PAIN

PART

I

AN OVERVIEW

John P. Gorecki

In a discussion about the treatment of intractable pain, the types of such pain are often arbitrarily divided into pain sec¬ ondary to cancer and pain of benign origin. The importance of this distinction lies in the fact that pain of benign origin is more frequently neuropathic or neuronal injury pain. Pain secondary to central nervous system injury, either injury to the brain itself, such as with a stroke, or injury to the spinal cord, is defined as central pain. Postherpetic neuralgia is often included in this category. Injury to the peripheral nervous system produces deafferentation pain. It is important, however, to realize that benign disease can also produce nociceptive pain—an example of this would be the pain secondary to chronic arthritis. Neurosurgeons rarely seem to be asked to deal with this type of benign nociceptive pain, based on a combination of referral patterns, patient expectations, and the general response to ex¬ isting medical management. The following is a paragraph taken from a review of tha¬ lamic pain by Davis and Stokes:3 Control of pain is one of man’s basic needs and has been solved over the centuries by both rational and superstitious means. The Egyptian culture attributed pain to demons, the gods, and various medicoreligious causes, but sensation was thought to be a function of the heart and vessels. The Chinese believed that pain was an excess of heat in the heart, while Plato taught that pain was the result of a violent disturbance of atoms in the body and a movement of these structures to the soul. Surgical intervention for benign pain is a major undertaking that should be considered only when conservative measures have failed or produce unacceptable side effects and the pain interferes enough with the patient’s quality of life to justify the risk associated with surgery. The level of the pain should be documented objectively.

EVALUATION OF THE PATIENT AND THE PAIN The most important step in formulating a management plan for chronic intractable pain is the determination of the underlying etiology of the pain disorder. The defined etiology should ac¬ curately and unambiguously explain the patient’s symptoms. Stereotactic treatment of vague, ambiguous pain syndromes is doomed to almost certain failure. The following is a good example of a patient in whom the pain was not adequately defined in the beginning. This 57-year-old white male was re¬ ferred for endoscopic thoracic sympathectomy with a diagno¬ sis of left upper extremity reflex sympathetic dystrophy. He had responded with transient pain relief to each of eight stel¬ late ganglion blocks. Earlier the same year he underwent an anterior cervical discectomy and fusion for a small central C5C6 disk. His pain did not improve. He then underwent an ulnar nerve transposition, based on abnormal nerve conduction stud¬ ies, and his pain was made worse. On examination when being evaluated for the sympathectomy, he was unable to sit up be¬ cause sitting made his pain intolerable. He had mild icterus and bilateral clubbing. There was wasting of all the muscula¬ ture in the left upper extremity, including biceps, triceps, as well as the intrinsic muscles of the hand. He had tender nodes in the left axilla. A chest radiograph and magnetic resonance imaging (MR1) confirmed a large apical mass which was found by biopsy to be non-small-cell carcinoma! He re¬ sponded to local radiation therapy, followed by percutaneous cordotomy (see Fig. 143-1-1). In addition to defining the etiology it is important to differ¬ entiate the character of the pain. Central pain is typically neu¬ ropathic and often spontaneous, steady and burning. Inter¬ mittent or shooting pain, as well as induced pain, often behaves more like nociceptive or cancer pain. It is important to consider

1417

Part 4/Functional Stereotaxis

Figure 143-1-1. A. Photograph of patient with apical lung cancer incorrectly referred with a diagnosis ol reflex sympathetic dystrophy. B. Chest radiograph showing a left apical lung lesion. C. CT scan through the upper chest showing left apical lung lesion compressing the brachial plexus. D. Coronal MR1 through the chest showing left apical lesion. E. Axial MRI through the upper chest showing left apical lesion impinging on the brachial plexus and the great vessels.

Chapter 143/Destructive Central Lesions for Persistent Pain: Part I

1419

gesics, nonsteroidal antiinflammatory drugs, steroids, antide¬ pressant agents, antiepileptic agents, and progressively more potent narcotic agonists. Consideration may also have been given to the use of chronic oral narcotic regimens such as maintenance methadone. In terms of defining the pain, history, especially prior inter¬ ventions, becomes an important component of the history tak¬ ing and examination. Prior denervating procedures such as cor¬ dotomy, rhizotomy, or trigeminal transection may, by definition, produce a deafferentation syndrome despite the original insult. Depending on the suspected problem, specific investigations are warranted. For instance, a patient who has residual radicular pain after lumbar disc surgery who is being considered for dorsal column stimulation deserves at least radi¬ ographs with flexion extension, a contrasted MRI, and suffi¬ cient laboratory studies to rule out a residual or recurrent disc fragment, instability, or subclinical infection. Prior to stereotactic or functional surgery for pain, patients normally undergo psychological evaluation. This serves sev¬ eral purposes. It can identify psychopathology or secondary gain issues which may amount to a contraindication for surgery D

E these distinctions when interpreting the outcome from pain procedures. For instance, ablative procedures seem to be suc¬ cessful at reducing intermittent, sharp, or nociceptive pain in patients with spinal cord injury, whereas the spontaneous, steady dysesthetic component tends to persist or even be made worse.10 It is therefore important to distinguish the type of pain as well as the severity. All patients should undergo a multidisciplinary manage¬ ment approach including the use of progressively more po¬ tent pharmacological agents in combination with physical therapy, reconditioning, psychotherapy when indicated, and biofeedback. Prior to surgical intervention, most patients have been treated with pharmacological agents that usually include anal¬

Figure 43-1-1. (continued) in the psychologist’s opinion. The evaluation may identify pathology that requires therapy either before or after surgery such as depression. The evaluation can help to define the pa¬ tient’s expectation for outcome and ensure that the patient un¬ derstands what the treating physician expects the procedure to accomplish, and the evaluation can help to confirm that the pa¬ tient understood the risks of the procedure. It has been traditional to detoxify patients from all narcotic medications prior to stereotactic procedures for pain. Although this is not always practical or possible, when treating benign pain it is advisable. It is essential, however, to formulate some plan for dealing with narcotic intake and clarifying this with the patient. The patient, as well as other health care providers, must clearly know where and when prescriptions will be obtained.

1420

Part 4/Functional Stereotaxis

and this should be from only one physician. It is our bias not to involve the surgeon in supplying maintenance medications.

the relief of acute pain such as that immediately following in¬ jury or for postoperative pain.

Remember, in general, the results of neuroablative proce¬ dures are not as good for benign or neuropathic pain when compared to the results of similar procedures performed for no¬ ciceptive pain. Pagni,8 in referring to stereotactic surgery, states: “I believe that it is only exceptionally indicated in cases of pain of non-malignant origin, and only after every other con¬ servative and surgical procedure has failed.”

It is this author’s belief that there is no specific nervous sys¬ tem pathway that is hard-wired for the experience of pain. This is supported by the fact that no “pain center” has been identified within the central nervous system in spite of the clear identifica¬ tion of eloquent motor cortex, speech cortex, and sensory cor¬ tex. It is believed that the experience of pain is the end result of conscious appreciation of the sum total of immediate sensory input in combination with the sum total of the level of activation or alertness and the emotional state of the central nervous sys¬ tem at any given time. This neuronal activity is probably com¬ bined in a network, rather than any given anatomical location. This would be consistent with the observation that psychologi¬ cal factors can modify pain as well as with the fact that changes

Trigeminal neuralgia (see Chaps. 170-175), which responds well to numerous lesioning procedures and microvascular decompression, as well as brachial plexus avulsion, which re¬ sponds well to DREZ lesioning (see Chap. 159), should be con¬ sidered exceptions to this general statement. Postherpetic neu¬ ralgia sometimes responds to nucleus caudalis DREZ when the pain involves the face and has occasionally responded to DREZ lesioning in the spinal cord. Therefore it is not clear how this benign disease fits into the general recommendations for surgical intervention for benign versus malignant pain. However, the present author would caution an inexperienced surgeon who is considering the use of DREZ coagulation for postherpetic neuralgia, particularly in the thoracic region, since the complication rate is high and the results are far from ideal.

SURGICAL TECHNIQUES FOR PAIN OF BENIGN ORIGIN The majority of surgical procedures for the treatment of pain can be classified as augmentative or neuroablative. The more tradi¬ tional procedures usually fall into the category of neuroablative surgery, which is often based on the simple concept that transec¬ tion of neural pathways that normally carry nociceptive input should eliminate that input and consequently eliminate pain. Anterolateral cordotomy, which transects the spinothalamic fibers, is an example of just such a procedure. Such procedures do not always succeed, otherwise pain management would be simple indeed. Surprisingly, sometimes temporary blockade of sensory input with local anaesthesia relieves pain while perma¬ nent transection of the same neural elements does not. In fact, in some circumstances, neural ablative procedures can produce pain or make pain worse, by producing, for example, anesthesia dolorosa, postcordotomy dysesthesia, or deafferentation pain. Augmentative procedures, however, rely on the ability of the central nervous system to manipulate or modify sensory in¬ put. Therapeutic use of this notion began following the intro¬ duction of the gate control theory of pain. This theory has never really been substantiated in spite of its value as an impetus for treatment. Examples of augmentative procedures include chronic stimulation of the dorsal columns (see Chaps. 154, 162), or deep brain structures (see Chaps. 155, 163), and intraspinal drug delivery (see Chap. 149). Sympathetic manipulation, although it is a form of ablative therapy, does not fall into this classification and will be dis¬ cussed separately (see Chap. 169). In general, we believe that nociceptive pain responds better to ablative procedures than does central or deafferentation pain. Augmentative therapy can be effective for both nociceptive and central or deafferentation pain, although chronic stimula¬ tion is not often used for pain secondary to malignancy. Augmentative therapies are often less effective for acute noci¬ ceptive pain and as such, have never gained an application for

in sensory input, including nonnociceptive sensory input, can modify even central pain despite the loss of traditional nocicep¬ tive pathways such as the spinothalamic tract. The observation that cerebral activation is identified in diverse locations such as the thalamus, sensory cortex, and cingulate gyrus on PET scans performed during the application of acute known painful stim¬ uli, is consistent with this hypothesis. Such a hypothesis would also support the notion that it may not be valid to assume that ablative procedures are never effective for the relief of central pain. It would be appropriate to seek the means to better define distinct painful states in specific patients, making it possible to apply direct therapy on a more logical and individualized basis.

AUGMENTATIVE SURGERY Spinal Cord Stimulation Spinal cord stimulation (see Chaps. 154, 162) has a proven track record in the treatment of deafferentation pain, particu¬ larly ischemic limb pain. This modality is useful for treating residual radicular pain following disk surgery that has been at least anatomically successful; the radicular component of post¬ laminectomy pain is presumably neuropathic in origin. Recent studies suggest that the results of this modality of treatment compare favorably with those of reoperation on the back. Spinal cord stimulation also deserves consideration in the syn¬ drome previously termed reflex sympathetic dystrophy, or chronic regional pain syndrome.

Deep Brain Stimulation (DBS) Deep brain stimulation (DBS) (see Chaps. 155, 163) involves the application of the same principles and technology that are employed in spinal cord stimulation to targets within the brain. Two general target choices appear to involve different physio¬ logical mechanisms. Stimulation of the sensory thalamus results in induced paraesthesia and may alter the central pro¬ cessing of sensory input. This is most effective for the relief of central and deafferentation pain. Stimulation of the peri¬ aqueductal and periventricular gray does not produce a recog¬ nized sensory experience and is more effective for nociceptive type pain. Stimulation of this target is believed to act via the endogenous opiate system or descending inhibitory pathways. The device employed for DBS is not currently approved for commerical distribution in the United States by the Food and Drug Administration. A multicenter trial was terminated in the

Chapter 143/Destructive Central Lesions for Persistent Pain: Part I

spring of 1995 without definitive results although there is on¬ going interest in the application of DBS for the relief of move¬ ment disorders. For this reason, and the fact that the results ob¬ served with this therapy have not been dramatic, the role of DBS in the treatment of pain is limited. The major advantage of DBS, particularly for central pain, is that it is nondestructive coupled with the fact that most abla¬ tive procedures, the alternative to DBS, are not successful in the long term for the relief of most central pain syndromes. There may well be renewed interest in DBS for the treatment of central and deafferentation pain when the device becomes commercially available for other indications.

Intraspinal Narcotic Analgesia Some forms of neural injury pain are clearly narcoticresponsive. For this reason intraspinal narcotic analgesia (see Chap. 149) can be effective for some forms of benign pain. This modality should be used with caution in patients who have a normal life expectancy, as the chronic effects of drug adminis¬ tration remain to be determined. Frequent minor interventions are required for equipment malfunction, catheter obstruction, migration, or fracture, and the patient becomes dependent upon a mechanical device for a very long time indeed. To date there has been a relatively small experience with the prolonged use of this modality. As expected there is a gradual decline in effec¬ tiveness over time, and drug tolerance develops in a large num¬ ber of patients. There is, however, a subset of patients who seem to maintain a prolonged acceptable level of pain relief using a stable drug infusion rate.2 Selection criteria to identify these pa¬ tients remain to be defined. At this institution we have initiated a prospective randomized controlled trial to evaluate the specific role of long-term intraspinal narcotic delivery in benign pain. The use of infusions of alternative pharmacological agents is being actively investigated. The agents include anesthetic agents, alpha agonists, serotonin reuptake blockers, GABA ag¬ onists, prostaglandin inhibitors, calcium channel blockers, Nmethyl-D-aspartate receptor antagonists, and somatostatin ana¬ logues. It may be that intraspinal narcotic analgesia will provide useful levels of analgesia long enough until alternative more ef¬ fective agents become available. It is recommended that the use of non-FDA-approved drugs, or drug combinations, be limited to clinical trial situations so that accurate data are collected as quickly as possible and risks to patients minimized.

SYMPATHECTOMY The mainstay of the treatment of pain that is sympathetically mediated or maintained is the use of serial temporary sympa¬ thetic blockade. This is successful only if accompanied by ag¬ gressive physical therapy and active exercise of the involved body part by the patient. This author is convinced that immobi¬ lization is counterproductive in the treatment of the entire syndrome of reflex sympathetic dystrophy or regional posttraumatic pain syndrome. If repeated blocks fail to result in increasingly longer periods of pain relief but the blocks do pro¬ duce at least transient pain relief, then it is reasonable to con¬ sider surgical sympathectomy. For the upper extremity the T2 and T3 sympathetic ganglia, and sometimes the lower part of the stellate ganglion, are removed. Improvement in endoscopic

1421

video equipment has made transthoracic endoscopic sympa¬ thectomy the approach of choice. This has a much lower post¬ operative morbidity and involves much less perioperative pain than the more traditional approaches that have employed thora¬ cotomy, a supraclavicular approach, or costotranversectomy. There is an extensive literature outlining the morbidity follow¬ ing endoscopic sympathectomy, mostly performed for the relief of hyperhydrosis.6 The LI and L2 ganglia are removed to re¬ lieve lower extremity pain. (See Chap. 169.)

ABLATIVE SURGERY It should be repeated that a number of authors are dubious about the role of ablative neurosurgical procedures in benign pain.

Cordotomy It is tempting to consider anterolateral cordotomy for the relief of focal benign pain syndrome (see Chaps. 141, 142, 151, 152). Simplistically, elimination of the neospinothalamic tract should effectively deal with the pain syndrome particularly if the pain is nociceptive in nature. Experience, however, has demon¬ strated a tendency toward pain recurrence. Tasker11 reports on 65 patients who underwent cordotomy for steady burning pain due to deafferentation and central pain. Complete pain relief was reported in 70.6 percent at the time of discharge from the hospital. By longest follow-up, only 33.3 percent had complete relief, and 50 percent reported significant relief, despite ade¬ quate levels of sensory loss. Those who benefited had incom¬ plete cord lesions or intermittent lancinating pain which appears to respond to ablative surgery much like cancer pain does. More important, cordotomy can result in a new, if not worse, pain syndrome, postcordotomy dysesthesia, particularly in a patient who survives for many years. The incidence of postcordotomy dysesthesia is poorly defined. Animal studies in our laboratory would suggest that neospinothalamic transection in the rat and monkey produces behavior suggestive of dysesthetic pain in a very high percentage of animals. We have in fact proposed that spinothalamic transection in the thoracic cord of the rat is a good model with which to study central pain of spinal cord origin. Cordotomy should be used cautiously, if at all, for benign pain, and this author would limit its use to pa¬ tients with a clearly shortened lifespan. I should add, however, that I have had the opportunity to examine a small number of patients who underwent cordotomy years ago for benign pain who have persisting analgesia and no new pain.

DREZ Spinal cord and nucleus caudalis DREZ coagulation (see Chap. 159) are discussed elsewhere in this book. DREZ coagulation in the spinal cord is indicated for pain secondary to brachial plexus avulsion or lumbosacral plexus avulsion. DREZ is also effective for the relief of nociceptive pain associated with spinal cord injury. Nashold refers to this type of pain more in terms of location, calling this “end zone” pain, and Tasker prefers to distinguish this responsive pain by its description: in¬ termittent, evoked or shooting, rather than dysesthetic. Nucleus caudalis DREZ coagulation is useful when other ablative procedures fail for the treatment of certain cases of tic

1422

Part 4/Functional Stereotaxis

douloureux, anesthesia dolorosa, atypical facial pain, and post¬ herpetic neuralgia. This procedure may be more effective for first-division or eye pain than for third-division pain, which is contrary to most procedures used for trigeminal neuralgia. According to Nashold,7 caudalis DREZ may also have a role in treating migraine or cluster headaches.

dicted patient. A carefully performed prospective outcome evaluation of the procedure is probably warranted to define whether it should be an option for the treatment of benign pain and, if so, when it should be considered.

Neurectomy and Rhizotomy Midbrain Tractotomy Midbrain tractotomy (see Chap. 168) is very effective for the relief of head, neck, and shoulder pain. Many authors suggest that the use of this modality should be limited to the treatment of pain secondary to malignancy. However, a small number of patients with pain secondary to benign etiologies have experi¬ enced excellent long-term pain relief. Proponents for the use of this modality in pain of benign origin, especially for central pain, include Nashold9 and Amano and colleagues.1 This proce¬ dure is also used when nucleus caudalis DREZ coagulation fails. The argument is put forward that, in order to achieve last¬ ing pain relief, the lesion must include the more medically lo¬ cated midbrain reticular formation which constitutes the termi¬ nation of up to three-quarters of the spinothalamic tract. Midbrain tractotomy carries a fairly high risk of complica¬ tions. Extraocular movement is most commonly affected. Of these, gaze palsy is relatively well tolerated, and diplopia can be managed with an eye patch. Midbrain tractotomy results in widespread analgesia and thermalgesia over half of the body and face.

Thalamotomy Medial thalamotomy (see Chap. 144) consists of creating le¬ sions stereotactically in the center median, parafascicular and intralaminar nuclei. These nuclei are believed to receive input from the nonspecific, or protopathic, portion of the spinotha¬ lamic system which reaches the thalamus after polysynaptic re¬ lay in the midbrain periaqueductal reticular formation. Some authors would suggest that lesions created in the pulvinar have a similar clinical effect to medial thalamic lesions. The present role of thalamotomy in the treatment of benign pain cannot be defined. Many alternative procedures are avail¬ able, some of which are not destructive. Good pain relief fol¬ lowing thalamotomy tends to be short-lived. A systematic eval¬ uation of this procedure in the setting of failure of alternative medical and surgical management is justified. Accumulated in¬ formation already suggests that midbrain tractotomy alleviates pain more frequently than medial thalamotomy but that the lat¬ ter can be performed with fewer complications.4 Medial thala¬ motomy does not produce any detectable sensory loss, thus giving it an advantage over both cordotomy and tractotomy that may also include avoidance of iatrogenic dysesthesia.

Transection of a sensory nerve is obviously the simplest form of ablative neurosurgery. With the exception of tic douloureux, it is rarely indicated or performed. Although it is sometimes worthwhile to resect a neuroma in the presence of very focal and triggered stump pain, it is almost never appropriate to re¬ peat this procedure when it is unsuccessful. Facet rhizotomy is incorrectly named; in fact, the term refers to ablation of the individual nerve branches that supply the synovial facet joint. This procedure can be performed percutaneously but is done quite infrequently. Proponents carry out temporary blocks of these same nerves prior to contemplat¬ ing the more permanent radiofrequency lesions. Some modest success for mechanical back pain has been recorded. Individual sensory root transection can be peformed either where the root exits the neural foramen or within the dural sac. It has been recommended that the dorsal root ganglion also be removed to interrupt sensory fibers traveling through the ven¬ tral root. Radiofrequency percutaneous rhizotomy is also possi¬ ble. Rhizotomy is performed infrequently, the most common indication being residual radicular pain following disc surgery. It is usually recommended that near complete pain relief be ob¬ tained during individual root blocks performed on more than one occasion prior to considering this type of ablative surgery. In addition, it is helpful to know that isolated blocks of the roots above and below the affected root do not produce pain re¬ lief. Note that, depending on individual anatomy, the L5 nerve root may be difficult to block percutaneously. The various treatments advocated for trigeminal neuralgia represent some form of neurectomy or rhizotomy, but this dis¬ ease is usually considered independently and usually not classi¬ fied under the rubric of benign chronic pain. Some skeptics might even consider that microvascular decompression of the trigeminal nerve produce some form of injury to the root in or¬ der to achieve pain relief. Alcohol ablation, surgical avulsion, glycerol injection, radiofrequency rhyzolysis, percutaneous compression, partial or complete root transection, and radio¬ surgery all use varying degrees of denervation to achieve relief of the lightning-like spontaneous and triggered pain of tic.

Midline Myelotomy It is possible to take advantage of the crossed nature of fibres entering the spinothalamic tract, and to transect these crossing fibers in the midline (see Chap. 142). I am not aware of this procedure being used to treat benign pain.

ClNGULOTOMY Some comment should be made about several interesting fea¬ tures of cingulotomy, a procedure reviewed elsewhere in the text (see Chap. 146). It is possible to perform cingulotomy “noninvasively” using the gamma knife. This procedure may have particular application in desperate situations where the pain is accompanied by a significant component of anxiety, suf¬ fering, or depression and it may have a special role in the ad¬

SUMMARY Hassler5 made the interesting suggestion years ago that the ideal solution to the chronic pain problem was general anesthe¬ sia, since it removed the conscious mind from the problem; however, in a more practical vein a few summary comments are possible. A number of specific syndromes respond favor¬ ably to specific surgical interventions (see Table 143-1-1).

Chapter 143/Destructive Central Lesions for Persistent Pain: Part I

TABLE 143-1-1. Management

1423

Suggested Surgical Therapies for Various Specific Benign Pain Syndromes That Have Failed Conservative

Surgical Therapy

Diagnosis

Alternative Surgical Therapy

RSD

Sympathectomy

SCS

Causalgia

1. Nerve repair, decompression 2. Sympathectomy INA

1. PNS 2. SCS

Postherpetic neuralgia, body Postherpetic neuraliga, face

Caudalis DREZ

Atypical facial

Caudal is DREZ

DBS

Anesthesia dolorosa

Caudalis DREZ

DBS

Stroke

DBS

Postlaminectomy syndrome; radicular pain

SCS

1. Medial thalamotomy 2. Midbrain tractotomy Repeat back surgery

Mechanical back pain

Repeat surgery

Fusion

Peripheral vascular disease Plexus avulsion

SCS

INA

Angina Pelvic pain

Angioplasty

CABG INA

Spinal cord injury, nociceptive

DREZ

INA

Spinal cord injury, central

DBS

INA

Cluster headache Postcordotomy

INA

DBS

Phantom pain Stump pain

INA SCS

Postthoracotomy pain

INA

DBS 1. DBS 2. INA Neurectomy

Trigeminal neuralgia

1. Microvascular decompression

DREZ

1. 2. 3. 4. 5.

Possible Therapy for Failures

Not Recommended

1. INA 2. Medial thalamotomy 3. DBS 1. Medial thalamotomy 2. Midbrain tractotomy 3. DBS DREZ 1. 2. 3. 1. 2.

DBS Trigeminal stimulation Midbrain tractotomy Midbrain tractotomy Medial thalamotomy

1. Midbrain tractotomy 2. Medial thalamotomy

1. INA 2. DBS 3. Medial thalamotomy

1. RF Tic 2. Microvascular decompression 1. RF Tic 2. Microvascular decompression

1. DREZ 2. Cordotomy

1. SCS 2. INA 3. Facet rhizotomy

1. Cordotomy 2. Midbrain tractotomy 3. Medial thalamotomy 4. DBS 5. INA SCS 1. SCS 2. DREZ 3. Rhizotomy 1. Medial thalamotomy 2. Cordotomy 3. Tractotomy 4. Cordectomy SCS (for incomplete) Caudalis DREZ 1. Midbrain tractotomy 2. Thalamotomy SCS 1. Midbrain tractotomy 2. Thalamotomy 1. Midbrain tractotomy 2. Cordotomy

Amputation

DREZ DREZ Repeated neurectomy

RFTic Glycerol Compression Avulsion Alcohol ablation

RSD = reflex sympathetic dystrophy; SCS = spinal cord stimulation; INA = intraspinal narcotic analgesia; DBS = deep brain stimulation; PNS = peripheral nerve stimulation; DREZ = dorsal root end zone coagulation; CABG = coronary artery bypass grafting; RF Tic = retrogasserian radiofrequency rhizolysis.

1424

Part 4/Functional Stereotaxis

Trigeminal neuralgia is effectively treated by microvascular decompression, and effective alternatives include radiofre¬ quency retrogasserian rhizolysis, gasserian glycerol injection, gasserian ganglion percutaneous compression, or even partial section of the trigeminal root. Nucleus caudalis DREZ lesioning warrants further evaluation as a possible intervention when these therapies fail. This procedure deserves further evaluation for atypical facial pain, but complication rates remain high. Other ablative therapies are not effective for atypical facial pain or anesthesia dolorosa. Nashold apparently has obtained excellent results with nucleus caudalis DREZ7 in 8 patients with migraine. The central pain due to brachial plexus and lumbosacral plexus avulsion respond to DREZ lesioning. The nociceptive component, or end zone pain seen following spinal cord injury, responds to DREZ, but the diffuse central pain in the deafferented part of the body usually does not. Sympathetically mediated pain responds to sympathectomy, which can now be done endoscopically. This same pain also re¬ sponds to spinal cord stimulation or peripheral nerve stimula¬ tion. Failed back surgery syndrome with mainly radicular pain responds well to spinal cord stimulation, as does ischemic pain of peripheral vascular disease. Back pain associated with post¬ laminectomy syndrome responds less well to stimulation; how¬ ever, the technical innovation of dual leads for dorsal column stimulation holds out some promise for improved relief of axial pain. In Europe spinal cord stimulation is used for angina. Postherpetic neuralgia remains very difficult to treat. At this time, this author will at least test intraspinal narcotics in the el¬ derly. We still use DREZ coagulation with caution. The role of midbrain tractotomy, medial thalamotomy, or cingulotomy are unclear. Thalamotomy has the advantage that it does not result in sensory loss. Phantom and stump pain are equally difficult to delineate. Reexploration for neuroma is probably not indicated more than once. We favor the augmentative modalities of stimulation and intrathecal narcotic administration. DREZ coagulation has given only limited benefit. Beyond those specific examples, some general principles apply. Ablative procedures are less effective in benign pain. Reversible or augmentative procedures are therefore consid¬ ered first. The use of spinal cord stimulation is the first con¬ sideration. This author believes there will be further study of

DBS in benign pain once the equipment becomes available as a result of its use for the treatment of Parkinson’s disease. Intraspinal narcotic analgesia is another therapy being consid¬ ered before ablative procedures for the relief of benign pain. We believe long-term controlled outcome studies of intraspinal narcotic analgesia will be very important. Midbrain tractotomy, medial thalamotomy, and cingulotomy remain therapies of last resort. Some authors suggest they should not be used in pa¬ tients with benign pain. It is this author’s bias that it is reason¬ able to continue to evaluate these procedures but that their use should be limited to settings in which outcome is being care¬ fully evaluated and followed, probably in a prospective, ran¬ domized fashion.

References 1.

2.

Amano K, Kawamura H, Tanikawa T, et al: Long-term follow-up study of rostral mesencephalic reticulotomy for pain relief: Report of 34 cases. Appl Neurophysiol 49:105-111, 1986. Bloomfield SM, Gross RT: Intrathecal morphine infusion for chronic intractable benign pain: Experience with 60 patients. Paper presented at the International Neuromodulation Society, Third International Congress, March 6-10, 1996.

3.

Davis RA, Stokes JW: Neurosurgical attempts to relieve thalamic pain. Surg Gynecol Obstet 123:371-384, 1966.

4.

Frank F, Fabrizi AP, Gaist G, et al: Stereotactic mesencephalotomy versus multiple thalamotomies in the treatment of chronic cancer pain syndromes. Appl Neurophysiol 50:314-318,1987. Hassler R: The division of pain conduction into systems of pain sen¬ sation and pain awareness, in Janzen R, Keidel WD, Flerz A, Steichele C (eds). Pain: Basic Principles—Pharmacology Therapy. Stuttgart: Georg Thieme, 1972, pp 98-112. Kheng HL, Hwang YK: Video endoscopic sympathectomy for palmar hyperhydrosis. J Neurosurg 84:484^486, 1996. Nashold Jr BS: Personal communication, unpublished data. Pagni CA: Place of stereotactic technique in surgery for pain. Adv Neurol 4:699-706, 1974. Shieff C, Nashold Jr BS: Stereotactic mesencephalic tractotomy for the relief of thalamic pain. Br J Neurosurg 1:305-310, 1987. Tasker RR. De Carvalho GTC, Dolan EJ: Intractable pain of spinal origin: Clinical features and implications for surgery. J Neurosurg 77:373-378, 1992.

5.

6. 7. 8. 9. 10.

11.

Tasker RR: Management of nociceptive, deafferentation and central pain by surgical intervention, in Fields HL (ed). Pain Syndromes in Neurology. London: Butterworth, 1990, vol 7, pp 143-199.

CHAPTER

143

DESTRUCTIVE CENTRAL LESIONS FOR PERSISTENT PAIN

PART II

OUTCOME

Keiichi Amano

THALAMOTOMY White and Sweet34 summarized the results of thalamotomies in nine patients who had pain not caused by malignant tumors. Etiologies of the pain were postherpetic neuralgia in two pa¬ tients, spine and spinal cord injuries in two patients, and one patient each with phantom pain, tabes dorsalis, thalamic syn¬ drome, multiple sclerosis, severely contused leg. The pain in these patients was considered to be of a deafferentation origin. Stereotactic electrode placement was made either in a single location—ventralis posterolateralis nucleus (VPL), ventralis posteromedialis nucleus (VPM), anterior nucleus (AN) or parafascicularis nucleus (Pf)—or in multiple loci [combina¬ tions of VPL, VPM, AN, Pf, and dorsomedian nucleus (DM)] within the thalamus. These thalamotomies were made unilaterally in five patients and bilaterally in four patients. Good relief of both pain and suffering was obtained in only one patient (11 percent) and good relief either of pain or of suffering was seen in two pa¬ tients (22 percent) during a follow-up period between 5 months and 4 years. The results were discouraging. The complications were psychological deterioration (contused leg), thalamic hem¬ orrhage with fatal hydrocephalus (spinal injury), and death by suicide (phantom pain). The morbidity directly due to thala¬ motomy was 22 percent. In one patient, pain recurred in 6 months after the procedure. Voris and Whisler32 treated 58 patients for chronic pain not due to malignancy with stereotactic lesions in the thalamus, cingulum, or mesencephalon. Although the etiology of pain in these patients was ascribed to various causes, it appears to be neuropathic. The target for thalamotomy was placed for 23 pa¬ tients in centromedian (CM) nucleus with supplementary lesions in the interlaminar nuclei (they used the term interlami¬ nar instead of intralaminar) in some of the patients, especially in centralis lateralis (CL) nucleus. Unilateral thalamotomy was done in 13 patients, bilateral in 10. After unilateral thala¬ motomy, there was no pain relief in 3 patients, pain relief for 1

to 12 months in 7 patients and 1 to 3 years in 2, and pain relief over 3 years in 1. Bilateral thalamotomy resulted in no pain re¬ lief in 1 patient, relief for 1 to 12 months in 5 patients, and pain relief over 3 years in 4. Voris and Whisler considered that no stereotactic operations should be considered worthwhile for intractable pain not due to malignant disease unless the period of pain relief exceeded 1 year and that only periods of pain re¬ lief of more than 3 years could be considered really satisfac¬ tory.32 According to these criteria, the effectiveness of unilat¬ eral thalamotomy was 23.1 percent (3 of 13 patients) of bilateral thalamotomy, 40 percent (4 of 10 patients), and 30 percent (7 of 23 patients) all told. They contrasted the difficulty in obtaining sufficient relief of chronic neuropathic pain not due to malignancy not only by thalamotomy but also by cingulotomy (valid pain relief in 2 of 11 patients, 18 percent) and by mesencephalotomy (valid pain relief in 5 of 13 patients, 38 per¬ cent) with the excellent results for cancer pain achieved by mesencephalotomy (pain relief until death in 19 of 23 patients, 82.6 percent) or by cingulotomy (pain relief until death in all cases), although thalamotomy failed to relieve cancer pain (see Chap. 144). The complications of thalamotomy observed in 4 percent of 54 thalamotomies included one patient each with hemiparesis and prolonged stupor. Thalamolaminotomy, proposed by Sano in 196623 and re¬ viewed by Amano in 1976,1 is essentially similar to CM-Pf thalamotomy and probably CL thalamotomy. The procedure was employed in 47 patients. The etiology included 14 cases of malignant neoplasm, 10 cases of thalamic pain, 14 cases of other types of central pain, 4 cases of trigeminal neuralgia, 4 cases of causalgia, and 1 case of tabes dorsalis. Evaluation of pain relief was made as follows: 4 + was complete pain relief, i.e., no pain; 3 + was almost complete pain relief, slight resid¬ ual pain but tolerable; 2+ was residual pain, but tolerable with medication; 1 + was some pain relief, but still intolerable; 0 was no pain relief. Effective pain relief was considered to be ei¬ ther 4+ or 3 + . The follow-up period was 1 to 24 months. In cases of cancer pain, pain relief at discharge from the hospital

1425

1426

Part 4/Functional Stereotaxis

was 4+ in 4 patients, 3+ in 2 patients, and 2+ in 8 patients (42.9 percent valid pain relief), but at follow-up, 4+ in 4 pa¬ tients and 2+ in 10 patients (28.6 percent valid pain relief). In cases of thalamic pain, pain relief at discharge was 4+ in 3 pa¬ tients, 3+ in 6 patients, and no pain relief in 1 patient (90 per¬ cent valid pain relief) but at follow-up, 4+ in 3 patients, 3+ in 4 patients, 2+ in 2 patients, and no pain relief in 1 patient (70 percent valid pain relief). In cases of other types of central pain, pain relief at discharge was 4+ in 2 patients, 3+ in 6 pa¬ tients, 2+ in 3 patients, 1+ in 1 patient, and no pain relief in 2 patients (57.1 percent valid pain relief), but at follow-up pain relief was 4+ in 2 patients, 3+ in 4 patients, 2+ in 3 patients, 1 + in 2 patients, and no pain relief in 2 patients (42.9 percent valid pain relief). Patients with both trigeminal neuralgia and causalgia enjoyed good pain relief (75 percent), although the period of follow-up was not long enough to evaluate. The pro¬ cedure was not effective for tabes dorsalis. In summary, CM-Pf thalamotomy was not effective for cancer pain but gave pain relief in some of the patients with neuropathic pain caused by benign disease through the interruption of discriminative rather than affective pain pathways.1 Ventralis intermedius (Vim) thalamotomy, which has been widely used for the treatment of Parkinsonism, was also per¬ formed for the amelioration of thalamic pain by Ohye.22 Based both on the clinical observation that Vim thalamotomy for tremor relieved muscle pain as well as tremor in Parkinsonian patients and on anatomical and physiological data showing that the spinothalamic tract terminates in part in Vim and CL nucleus in humans and in ventroposterior oral lateral (VPLo) and ventroposterior caudal lateral (VPLc) and CL nucleus in monkeys, although the main terminals were found in VPL or ventrocaudal nucleus (VC), he performed Vim and/or CL thala¬ motomy in 9 patients with thalamic pain secondary to cere¬ brovascular disease. Although satisfactory pain relief was obtained in 4 of his patients, the procedure was effective only for deep pain and not for the superficial nor the dysesthetic component of thalamic pain. The complications of Vim thala¬ motomy for pain relief are not mentioned in the report. Gildenberg16 summarized the use of thalamotomy for pain relief into 4 groups: (1) thalamotomy of the ventral posterior nuclei (VPL, VPM) interrupting the lemniscal projections; (2) basal thalamotomy interrupting the extralemniscal fibers before they enter into the intralaminar nuclei, CM nucleus, and Pf; (3) medial thalamotomy interrupting the extralemniscal projections at the level of the intralaminar nuclei and CM nu¬ cleus; (4) DM thalamotomy interrupting the projections to the frontal lobe. Since the combination of basal and medial thala¬ motomy for pain of benign origin had only a 30 to 35 percent long-term success rate,16 28-29 it should be reserved only for pain due to malignancy, in which early pain relief is generally re¬ ported in 80 to 90 percent of the patients. Poor relief of central neuropathic pain by VP (equivalent to VC according to Hassler’s classification) thalamotomy is obvious from a num¬ ber of reports even with the lesion involving the parvocellular ventrocaudal nucleus (VCpc), a nociceptive relay in the VC group. DM thalamotomy24 should not be employed unless pain is due to cancer, because the procedure may elicit profound changes in personality and depression.16 A recent review of thalamotomy for pain by Tasker31 gives extensive information on what has been done in this field of stereotaxis in the past. In

patients with central and deafferentation pain, VC thalamot¬ omy gave a success rate of 20 to 50 percent (average of 36 per¬ cent) with complications in 42 to 70 percent (average of 34 per¬ cent). Medial thalamotomy for central and deafferentation pain gave a success rate of 25 to 83 percent (average 29 percent), with a complication rate as high as 54.2 percent for transient cognitive disturbances after unilateral lesions and 75 percent after bilateral lesions. Tasker’s review found an overall compli¬ cation rate of 4 to 21 percent. In spite of the low success rate and high incidence of com¬ plications, there may be a place for ablative lesions made in the medial thalamus for the treatment of central and deafferenta¬ tion pain, particularly for allodynia and hyperpathia when chronic electrical stimulation of VC nucleus fails.31

MESENCEPHALIC TRACTOTOMY Stereotactic mesencephalotomy was performed by Spiegel2730 and Wycis.35 But the fundamental concept of the procedure in those days was to aim at the classical lateral spinothalamic tract believing that that tract was the major pain pathway at the mid¬ brain level. They achieved, over all, complete or partial relief of pain in 31 percent, one of the patients operated upon in 1947 for iatrogenic facial dysesthesia enjoying pain relief for 18 years; however, the mesencephalic lesion was combined with a lesion in DM and probably in the intralaminar nuclei of the thalamus.32 Nashold renewed interest in stereotactic mesencephalotomy based on his observations on direct electrical stimulation in the rostral midbrain.19-20 His concept of mesencephalotomy was new in the sense that structures (extralemniscal) lying more medially than the classical lateral spinothalamic tract were recognized to be related to pain sensation. But his stereotactic procedure for pain relief in the midbrain was not confined, in the beginning, to the medial structures alone but included a relatively large area, a target zone rather than a target point, extending from the medial (extralemniscal) to the far lateral (lemniscal) structures of the rostral midbrain. Nashold has reported that 50 percent of a group of 15 patients that had mesencephalotomy for central dysesthesia or phantom pain continued to have pain relief 5 years after oper¬ ation and that unilateral mesencephalotomy was sufficient to relieve bilateral pain in most cases, implicating the important neurophysiological evidence that the medial mesencephalic reticular formation receives bilaterally ascending multisynaptic projections of nociceptive impulses. Parinaud’s sign was no¬ ticed as one of the complications in all his mesencephalotomies, but it was not really disabling to the patients who might not be aware of it until it was called to their attention. Diplopia due to paresis of ocular movement occurred postoperatively in some cases (1 to 5 percent) but was transient.21 Central dyses¬ thesia varied in severity in the early mesencephalotomies. Walker33 reported postoperative dysesthesia in as many as 70 percent of cases secondary to open mesencephalotomy. This was a natural consequence of the concept that it was necessary to cut both the medial lemniscus and the spinothalamic tract resulting in deafferentation hypersensitivity. With much smaller and more controlled stereotactic lesions in the ex¬ tralemniscal fine-fibered projections, dysesthesia secondary to mesencephalotomies affects fewer than 5 percent.1-20

Chapter 143/Destructive Central Lesions for Persistent Pain: Part II

Rostral mesencephalic reticulotomy (RMR) for pain relief, proposed by Amano,1 was performed in 34 patients with in¬ tractable pain, 25 with thalamic pain due to cerebrovascular disease, 1 patient with thalamic pain due to oligodendroglioma of the thalamus, 1 patient with tabes dorsalis, 1 patient with postcordotomy dysesthesia, and 6 patients with cancer. In spite of the fact that the ascending projections of nociceptive im¬ pulse to the medial mesencephalic reticular formation are bi¬ lateral, RMR was performed unilaterally contralateral to the side of the pain in all cases to avoid complications due to bi¬ lateral mirror lesions. Unilateral mesencephalic lesions are known to relieve bilateral pain in some cases as reported by Nashold19'20 and Voris.32 This procedure is based on the ana¬ tomical investigations7'14,18 and the neurophysiological evi¬ dence,18-9-10'15 with microelectrode recordings in the medial mes¬ encephalic reticular formation in humans2 indicating that the major part of the central conduction of nociceptive impulses in the brainstem in humans is not mediated by the classical lateral spinothalamic tract but by the paleospinoreticular projections and, in particular, by the medial portion of the reticular forma¬ tion. Since the target for RMS is 14 mm posterior to the mid¬ point of the AC-PC line, 5 mm below the AC-PC line, and 5 mm lateral to the center of the aqueduct, located at the border between the lateral edge of the periaqueductal gray matter and the most medial portion of the rostral mesencephalic reticular formation at the level of the superior colliculus, considerably medial to the classical lateral spinothalamic tract, RMR is totally different from the classical mesencephalic tractotomy based on the classical concept of the lateral spinothalamic tract being erroneously believed to be the major pathway for noci¬ ceptive conduction in the brainstem.4 The target of RMR ap¬ pears to be close to the one proposed by Nashold,19'20 but it differs in the sense that only the paleospinoreticular extralemniscal pathway is targeted. These 34 patients undergoing RMR were classified into two groups, those with denervation pain and those without such pain.5 Denervation pain must be accom¬ panied by clinical evidence of denervation characterized by the presence of hypesthesia or anesthesia in the painful region. Of 26 patients with thalamic pain, 1 with tabes dorsalis, and 1 with postcordotomy dysesthesia (cordotomy for pain due to spinal cord astrocytoma), all met the criteria of denervation pain. None of 6 patients with acute pain due to cancer showed clini¬ cal evidence of denervation; they were considered to be suffer¬ ing from nondenervation pain. For clinical evaluation of effectiveness of RMR, grading of pain relief was made in relation to the postoperative need for analgesics. A grade A result is complete relief of pain; grade B is almost complete pain relief of pain (the patients have slight pain but require no pain medication); grade C patients have persisting pain tolerable with mild nonnarcotic analgesics; grade D have persisting pain not tolerable even with narcotic analgesics. In 28 cases of denervation pain, 8 (28.6 percent) had grade A pain relief, 10 (35.7 percent) grade B, 9 (32.1 per¬ cent) grade C, and 1 (3.6 percent) grade D pain relief. In 6 pa¬ tients with nondenervation pain, 4 (66.7 percent) had grade A relief, (16.7 percent) grade B, 1 (16.7 percent) grade C. No pa¬ tient had grade D. Thus, clinically acceptable pain relief (grade A and grade B) was obtained in 64.3 percent of the denervation pain group and 83.3 percent of the nondenervation pain group. Follow-up for 28 patients with denervation pain was from 3 to

1427

70 months and for 5 of the 6 patients with nondenervation pain 1 to 5 months, and 10 months for the other patient. One of the patients who had complete relief of severe thalamic pain after RMR was followed for 11 years postoperatively without recur¬ rence of pain.6 He did not have Parinaud’s sign postoperatively and returned to his previous work in excellent condition. He had no complication except almost complete loss of thermal and pain sensation on the left side of the body including the face, and decreased tactile sensation on that same side—50 to 70 percent in the face, 40 percent in the upper extremity, and 10 to 30 percent in the trunk and lower extremity. He did not have postoperative dysesthesia but he had unilateral loss of his eye¬ brow contralateral to the side of the mesencephalotomy. He be¬ gan to notice all these neurological changes not immediately but 7 to 8 years after RMR. Parinaud’s sign was noticed in 9 of the 34 patients (26 percent) immediately after RMR but gradu¬ ally disappeared spontaneously within 3 weeks to 6 months in most cases. Permanent Parinaud’s sign was observed in 3 of the 34 patients (8.8 percent). There was a tendency toward somno¬ lence for 3 to 4 days after RMR in some patients, but no patient showed long-term or severe disturbance of consciousness. There was no postoperative motor weakness and no death due to RMR. Nashold reported postoperative Parinaud’s sign in all of his patients.20 In RMR, the trajectory to the rostral midbrain was improved by making the burr hole for the electrode inser¬ tion more frontally so as not to penetrate the tectal or pretectal area, thus decreasing the complications.3 One can ascribe the exceedingly good result of RMR, 64.3 percent pain relief for denervation pain and 83.3 percent pain relief for nondenerva¬ tion pain, with fewer complications compared to the other mesencephalotomies, to making a precise selective lesion in the most medial portion of the midbrain reticular formation using an electrode of much smaller diameter (1.6 mm) guided by sensory-evoked potential studies and microelectrode record¬ ing in the target area. Voris and Whisler32 also considered the direct recording of spontaneous electrical activity and/or evoked potentials to be essential in such a critical area as the mesencephalon. An extensive investigation of the results of mesencepha¬ lotomy was made by Voris and Whisler.32 They performed mes¬ encephalotomy, almost identically to Nashold,20 in 23 patients with cancer pain and 13 patients with chronic pain not due to malignancy. In the group of patients with cancer pain, there was a remarkable relief of pain after unilateral mesencepha¬ lotomy (21 patients) over 1 to 12 months in 19 patients and over 1 year in 1 patient; 1 patient had no pain relief. Seventeen of 21 patients were relieved until death. Bilateral mesencepha¬ lotomies were done in 2 patients resulting in pain relief until death. In another 2 patients, mesencephalotomy was com¬ bined with cingulotomy, which gave pain relief until death. Excluding the 2 cases combined with cingulotomy, 19 of 23 patients were relieved of pain until death (82.6 percent suc¬ cess). In the group of 13 patients who had chronic pain not due to malignancy, mesencephalotomies were done unilaterally in all cases with 1 to 12 months of pain relief in 8 patients (61.5 percent), 1 to 3 years in 2 (15.4 percent), over 3 years in 3 (23.1 percent); there were no failures. In spite of the good pain relief, the rate of complications in the 52 operations on 36 patients by Voris is, however, rather disappointing: hemiparesis (3 pa¬ tients), central dysesthesia (6), ocular palsies (9), and intracra-

1428

Part 4/Functional Stereotaxis

nial hemorrhage (1) affecting 37 percent of 52 mesencephalotomies, a much higher rate of complication than seen after thal¬ amotomies (4 percent) or cingulotomies (16 percent). Recent reviews on mesencephalotomy by Shieff and Nashold25-26 and by Gybels and Sweet17 show that mesen¬ cephalotomy was effective for pain in the head, neck, and up¬ per trunk due to malignancy in 270 patients in eight series, with successful short-term pain relief in 85 percent. Pain relief lasted for many months or until death and was accompanied by the additional benefit of ameliorated behavioral and psycholog¬ ical symptoms in the cancer patients, probably due to the inter¬ ruption of projections to the limbic system. Mesencephalotomy is also effective for central and deafferentation pain,17 although the rate of success is less than for cancer pain, 39 percent short-term, 44 percent long-term in 150 patients in eight series. Shieff and Nashold25 reported 78 per¬ cent pain relief at hospital discharge and 67 percent pain relief at follow-up (up to 5 years) in patients with thalamic pain. Combined investigations by Amano5 and Nashold25 showed 76 percent long-term pain relief in patients with central and deafferentation pain. The overall morbidity of mesencephalotomy is about 4 percent.26 Postoperative dysesthesia was seen in less than 15 percent on average. The incidence of motor weakness was less than 2 percent; transient disturbances of ocular motil¬ ity, including convergence defects, divergence paresis, skew deviation, and myosis, were observed in some of the patients but cleared in several days or in a few weeks. The incidence of Parinaud’s sign has been reduced from 83 to 16 percent in Nashold’s series25 and was 26 percent in the immediate postop¬ erative period and 8.8 percent at follow-up in the report by Amano.5 Stereotactic mesencephalotomy still has a place in the treatment of intolerable pain because of the high rate of pain re¬ lief, provided a careful stereotactic procedure is employed to make a small selective lesion at the rostral medial mesen¬ cephalon which minimizes the complications.626

patient at discharge from the hospital. Thus the rate of effective pain relief in cancer patients at discharge was 92.9 percent (13 out of 14 patients). Pain relief at follow-up in cancer patients was 4+ in 10 patients, 2+ in 2, and 1 + in 2; effective overall pain relief was 71.4 percent (10 of 14 patients). In spite of good pain relief in cancer pain, posteromedial hypothalamotomy gave poor results in cases of pain not due to malignancy. Out of two cases of causalgia, one had 4+ relief and the other 3+ at discharge, but at follow-up, both had either 2+ or 1 + relief. In four cases of neuralgia, pain relief at discharge was rated at 3+ in two and 2+ in two but at follow-up was 2 + and 1+. In one patient with thalamic pain, the pain relief was 2+ at discharge and 1+ at follow-up. Since effective pain re¬ lief was considered to be 4+ or 3 + , posteromedial hypothala¬ motomy was not effective at all for chronic neuropathic pain of nonmalignant disease. This procedure appeared to be indicated for intractable pain secondary to malignant disorders and for motivational pain but appeared to be contraindicated even in cancer patients who were in poor general condition (profound anemia, decubitus) or who had preexisting altered levels of consciousness or preexisting psychiatric manifestations or who were above 70. Postoperatively, there were no sensory deficits. Spontaneous pain disappeared but pain was still induced by pin-prick. This dissociation between spontaneous pain and induced pain after posteromedial hypothalamotomy was similar to that seen after CM-Pf thalamotomy. There was no postoperative change in be¬ havior. The mecolyl test before and after the operation showed A7 type in all cases. Posteromedial hypothalamotomy was effec¬ tive also for visceral pain due to malignancy. This may reflect the observation in experimental animals that the periventricular gray matter targeted in humans receives visceral sensory in¬ puts.11-12 There was no operative mortality.1

References

HYPOTHALAMOTOMY Relief of suffering in patients with intractable pain often can be obtained by interrupting the limbic system rather than the pain pathways.16 So-called posteromedial hypothalamotomy for pain relief was based on the observation that nociceptive neurons exist in the periventricular gray matter of the third ven¬ tricle which is the rostral extension of the midbrain periaque¬ ductal gray matter in humans124 as well as in experimental animals11-12 and that the area is a part of the limbic system af¬ fecting the attitude to pain perception.13 The procedure was termed posteromedial hypothalamotomy by Sano, but the target zone was not anatomically in the hypothalamus in humans but rather in the third ventricular gray matter. The procedure was employed to alleviate pain both in cancer patients and in those with benign disease.113-24 The report by Amano1 included 21 patients (12 males and 9 females, ages from 28 to 76 years) consisting of 14 patients with cancer pain, 4 with neuralgia, 2 with causalgia, and 1 with thalamic pain. The site of pain was in the head and neck in 12 patients, elsewhere in 9 patients. Posteromedial hypothalamotomy was done unilaterally in 15 patients and bilaterally in 6. The follow-up period was 1 to 17 months. The results in cancer patients, using the 4+ to 0 scale de¬ scribed above, were 4+ in 10 patients, 3+ in 3, and 2+ in 1

1.

Amano K, Kitamura K, Sano K, et al: Relief of intractable pain from neurosurgical point of view with reference to present limits and clini¬ cal indications: A review of 100 consecutive cases. Neurol Med Chir 16:141-153, 1976.

2.

Amano K, Tanikawa T, Iseki H, et al: Single neuron analysis of the human midbrain tegmentum: Rostral mesencephalic reticulotomy for pain relief. Appl Neurophysiol 41:66-78, 1978.

3.

Amano K, Iseki H, Notani M, et al: Rostral mesencephalic reticulotomy. Report of 15 cases. Acta Neumchir (Wien) 30(suppl):391-393, 1980. Amano K: Role of spinothalamic tract in relation to pain with special reference to percutaneous high cervical cordotomy and rostral mesen¬ cephalic reticulotomy (RMR), in Kikuchi H (ed). Neurosurgeons, vol 4. Proceedings of the 4th Annual Meeting of the Japanese Congress of Neurological Surgeons. Tokyo: The Japanese Congress of Neurological Surgeons, 1985, pp 13-21. Amano K. Kawamura H, Tanikawa T. et al: Long-term follow-up study of rostral mesencephalic reticulotomy for pain relief. Report of 34 cases. Appl Neurophysiol 49:105-111,1986. Amano K, Kawamura H, Tanikawa T. et al: Stereotactic mesen¬ cephalotomy for pain relief: A plea for stereotactic surgery. Stereotact Fund Neurosurg 59:25-32, 1992. Bowsher D: Diencephalic projections from the midbrain reticular for¬ mation. Brain Res 95:211-220, 1975.

4.

5.

6.

7. 8. 9.

Casey KL: Somatosensory responses of bulboreticular units in awake cat: Relation to escape-producing stimuli. Science 173:77-80, 1971. Collins WF, Randt CT: Evoked central nervous system activity relat¬ ing to peripheral unmyelinated or C fibers in cat. J Neurophysiol 21:345-352, 1958.

Chapter 143/Destructive Central Lesions for Persistent Pain: Part II

10. 11.

12. 13.

14. 15. 16.

17.

18.

19. 20.

Collins WF, Randt CT: Midbrain evoked responses relating to periph¬ eral unmyelinated or C fibers in cat. JNeurophysiol 23:47-53, 1960. Dafney N, Bental E, Feldman S: Effect of sensory stimuli on single unit activity in the posterior hypothalamus. Electroenceph Clin Neurophysiol 19:256-263, 1965. Dafney N, Feldman S: Unit responses and convergence of sensory stimuli in the hypothalamus. Brain Res 17:243-257, 1970. Fairman D: Hypothalamotomy as a new perspective for alleviation of intractable pain and regression of metastatic malignant tumors, in Fusek I, Kune Z (eds), Present Limits of Neurosurgery. Prague: Avicenum, 1972, pp 525-528. French JD, Verzeano M, Magoun HW: An extralemniscal sensory

23. 24. 25. 26.

system in the brain. Arch Neurol Psychiat 69:505-518, 1953. Fuller JH: Brain stem reticular units: Some properties of the course and origin of the ascending pathway. Brain Res 83:349-367, 1975. Gildenberg PL: Functional neurosurgery, in Schmidek HH, Sweet WH (eds), Operative Neurosurgical Techniques. Indications, Method and Results. New York: Grune and Stratton, 1983, vol 2, pp

27.

1001-1016. Gybels JM, Sweet WH: Stereotactic mesencephalotomy, in Gybels JM, Sweet WH (eds). Neurosurgical Treatment of Persistent Pain. Basel: Larger, 1989, pp 210-219. Mehler WR, Feferman ME, Nauta WJH: Ascending axon degenera¬ tion following anterolateral chordotomy: An experimental study in

29.

the monkey. Brain 83:718-750, 1960. Nashold Jr BS, Wilson WP, Slaughter DG: Sensation evoked by stim¬ ulation in the midbrain in man. J Neurosurg 30:14-24, 1969. Nashold Jr BS, Wilson WP, Slaughter DG: Stereotaxic midbrain lesions for central dysesthesia and phantom pain. J Neurosurg 30:

21.

116-126, 1969. Nashold Jr BS: Brainstem stereotaxic procedures, in Schaltenbrand G, Walker AE (eds), Stereotaxy of the Human Brain. New York:

22.

Thieme, 1982, pp 475-583. Ohye C: Vim thalamotomy for the treatment of central pain, in Kikuchi H (ed): Neurosurgeons, vol 4. Proceedings of the 4th

28.

30. 31.

32. 33. 34. 35.

1429

Annual Meeting of the Japanese Congress of Neurological Surgeons. Tokyo: The Japanese Congress of Neurological Surgeons, 1985, pp 39—45. Sano K, Yoshioka M, Ogashiwa M, et al: Thalamolaminotomy. A new operation for relief of intractable pain. Confin Neurol 27:63-66, 1966. Sano K, Sekino H, Amano K, et al: Posteromedial hypothalamotomy in the treatment of intractable pain. Confin Neurol 37:285-290, 1973. Shieff C, Nashold Jr BS: Mesencephalotomy for thalamic pain. Neurol Res 9:101-104, 1987. Shieff C, Nashold Jr BS: Stereotactic mesencephalotomy, in Friedman WA (ed), Neurosurgery Clinics of North America. Phila¬ delphia: Saunders, 1990, vol l,pp 825-840. Spiegel EA, Wycis HT: Mesencephalotomy in treatment of in¬ tractable facial pain. Arch Neurol Psychiat (Chicago) 69:1-13, 1953. Spiegel EA, Wycis HT, Szekely EG, et al: Combined dorsomedial, in¬ tralaminar and basal thalamotomy for relief of so-called intractable pain. J Int Coll Surg 42:160-168, 1964. Spiegel EA, Wycis HT, Szekely EG, et al: Medial and basal thalamot¬ omy in so-called intractable pain, in Knighton RS, Dunke PR (eds), Pain. Boston: Little Brown, 1966, pp 503-517. Spiegel EA, Wycis HT: Present status of stereoencephalotomies for pain relief. Confin Neurol 27:7-17, 1966. Tasker RR: Thalamotomy, in Friedman WA (ed), Neurosurgery Clinics of North America. Philadelphia: Saunders, 1990, vol 1, pp 854-864. Voris HC, Whisler WW: Results of stereotaxic surgery for intractable pain. Confin Neurol 37:86-96, 1975. Walker AE: Relief of pain by mesencephalic tractotomy. Arch Neurol Psychiatr 48:865-882, 1942. White JC, Sweet WH: Pain and the Neurosurgeon. A Forty-Year Experience. Springfield, IL: Thomas, 1969, p 854. Wycis EA, Spiegel EA: Long-range results in the treatment of intractable pain by stereotaxic midbrain surgery. J Neurosurg 19: 101-108, 1962.

CHAPTER

144

THALAMOTOMY FOR CANCER PAIN

PART

I

AN OVERVIEW

John P. Gorecki

does not allow extensive, broadly applicable conclusions to be drawn; drawing conclusions about multiple combined lesions

After the development of stereotactic techniques, the thalamus received interest as a target for destructive lesions in patients suffering from pain. Sensory tracts from both the dorsal col¬ umn medial lemniscal system and the spinothalamic tract sys¬ tem terminate in the thalamus, and there are numerous in¬ terneuronal connections within the thalamus. It is therefore reasonable to postulate that sensory input is manipulated, if not experienced, here, and there are numerous connections between the thalamus and widespread areas of the cerebral

is next to impossible at this time. Lesions made in the thalamus with the use of current tech¬ nology do not respect the specific physiological borders of the various nuclei. More than one nucleus may be damaged by the lesion, or the lesion may not involve the entire individual nu¬ cleus. It has been suggested that various lesions be reported more in terms of the localization employed to target the lesion, for instance, the coordinates relative to the midcommissural point and the volume of the lesion.3 This author believes there is value in attempting to segregate the types of thalamic lesions by anatomic nuclei, but it is essential to understand the specific localization used by individual surgical teams. Over the past two decades, there has been increasing inter¬ est in the use of deep brain stimulation (DBS) for the manage¬ ment of neuropathic pain conditions. This fact, combined with the failure of any single type of thalamotomy to produce out¬ standing long-term relief, has led to a substantial decline in the use of thalamotomy for neuropathic pain. In fact, Tasker4 saw

cortex. Before the development of stereotactic surgery, anterolat¬ eral lesions of the spinal cord involving the spinothalamic tract successfully produced analgesia and thermoanalgesia on the opposite side of the body.1 Such lesions were employed to treat many painful conditions with some consistency. It is only logi¬ cal that one of the earliest stereotactic procedures, carried out by Spiegel and Wycis, involved lesioning the dorsal medial thalamus and the spinothalamic tract in the mesencephalon.2 This review of thalamotomy begins with a brief discussion of thalamic anatomy. Interpretation of the literature on thala¬ motomy can be confusing because of the use of more than one system of nomenclature, primarily the Anglo-American termi¬ nology and that of Hassler. Evaluation of the literature is made difficult by the fact that many reports include patients who re¬ ceived lesions in more than one nucleus in the thalamus or le¬ sions both in the thalamus and in other locations in the brain. This results in a heterogeneous group of procedures that are de¬ scribed together. Individual reports often involve only small numbers of patients who received comparable therapy. Most reports are retrospective and uncontrolled, and follow-up peri¬ ods have been short, variable, or difficult to determine with confidence. For these reasons, this chapter concentrates on iso¬ lated lesions of the thalamus and single lesions within the thal¬ amus; this constitutes a body of literature that is already con¬ fusing enough. In the author’s opinion, the existing literature

little indication for destructive thalamic procedures. At the same time, the management of pain secondary to can¬ cer was modified by the development of long-acting systemic narcotic agents and more recently by the use of intraspinal nar¬ cotic analgesia delivery techniques. Currently, the electrodes used for DBS are relatively unavailable, at least in the United States, as a result of the termination of the multicenter trial to evaluate the equipment’s safety and efficacy for the Food and Drug Administration in May 1995. This may result in a re¬ newed interest in the use of destructive lesions in the brain, such as thalamotomy, for intractable pain syndromes. At the same time, a modest resurgence in the use of cingulotomy has occurred in the last 5 to 10 years.5 After reviewing the literature, Tasker6 was able to identify 175 patients with nociceptive pain and 47 patients with central

143

1432

Part 4/Functional Stereotaxis

and deafferentation pain who underwent medial thalamotomy. The review was limited to reports that categorized pain by type and provided adequate information to subclassify the proce¬ dures and outcomes. In 1975, Gildenberg7 reported the results of a survey sent to 1998 neurosurgeons in Canada and the United States. On the basis of 637 responses, the annual num¬ ber of cordotomies performed was estimated to be between 1824 and 2040; thalamotomies, between 129 and 149; mesencephalotomies, between 18 and 21; cingulotomies, between 32 and 44; and placement of DBS electrodes, 23 to 24. In this chapter, thalamic lesions are somewhat arbitrarily summarized under the following classifications; 1.

4.

Ventrocaudal nucleus (in Hassler’s terminology), referred to as the nucleus ventralis posterior (VPL and VPM in the Anglo-American classification) Parvicellular ventrocaudal nucleus (VCpc) Dorsal medial thalamus (centrum medianum, parafascicular nucleus, intralaminar nuclei, centrolateral nucleus, nu¬ cleus submedius) Pulvinar

5.

Anterior nucleus

2. 3.

The results obtained after various thalamic lesions in pa¬ tients with and without malignancy are reviewed together, while comments are made about the individual types of pain whenever possible. The surgical technique is reviewed last.

Figure 144-1-1. Drawing of the thalamus showing the internal medullary lamina dividing it into three major subdivisions. The nuclei are labeled in the Anglo-American nomenclature. (Used with permission of Frank H. Netter, Ciba Collection of Medical Illustrations, vol I, Nervous System. Case-Hoyt Corp., Rochester, NY, 1972.)

ANATOMY The dorsal thalamus makes up the largest portion of the dien¬ cephalon, flanking the third ventricle and extending posterior to it. The unqualified term thalamus often is used synonymously with the term dorsal thalamus and is used throughout this chap¬ ter. The total length of the thalamus is about 4 cm. The thalamus consists mainly of gray matter but is incompletely divided into major parts by the Y-shaped white internal medullary lamina. This results in anterior, medial, and lateral parts of the thalamus (Fig. 144-1-1). The lateral part of the thalamus is divided into dorsolateral and ventral medial regions. Therefore, there are five major subdivisions or parts. The anterior and medial parts of the thalamus are sometimes regarded as phylogenetically older and are designated the paleothalamus. The neothalamus reaches full development in anthropoid apes and humans. Each thalamic nucleus may connect with other thalamic nu¬ clei, adjacent subcortical nuclei, ascending tracts from the brain stem and spinal cord, and the cerebral cortex. Some thalamic nuclei receive a large proportion of discrete, often somatotopically ordered input and have discrete cortical projections. These nuclei are classified as relay nuclei, as opposed to asso¬ ciation nuclei, which have multiple subcortical connections.

Anterior Group of Thalamic Nuclei The anterior nuclei interconnect with both the medial and the lateral thalamic groups. There are numerous ipsilateral mamil¬ lothalamic tract connections, and the main thalamocortical fibers from these nuclei reach the cingulate gyrus. The anterior thalamic nuclei link the hippocampus and hypothalamus with other thalamic nuclei and other limbic cortical areas.

Medial Group of Thalamic Nuclei The medial thalamic nuclei include the nucleus medialis dor¬ salis (MD) and the nuclei parafascicularis, submedius, paracentralis, and centralis lateralis. The last four nuclei often are as¬ signed to the intralaminar group or the nuclei of the midline. The larger nucleus centromedianus is also one of the intralami¬ nar nuclei (Fig. 144-1-2). The MD has abundant connections with the prefrontal cor¬ tex and the amygdaloid complex. MD is therefore an integral part of the limbic-associated structures. A specific function has not been assigned to the medial thalamus; however, the effects of ablation in humans partially parallel the results of prefrontal lobotomy.

Lateral Group of Thalamic Nuclei Ventral medial group of thalamic nuclei This group of nuclei can be divided into three nuclei named se¬ quentially: ventralis anterior (VA), ventral intermedius (VI or VL), and ventral posterior (VP) in the Anglo-American termi¬ nology. Various authors use different names for these nuclei, and the VP nucleus is often referred to as the ventrocaudal nu¬ cleus of the thalamus or the ventrobasal nucleus. In addition, the ventral posterior nucleus typically is subdivided into the ventralis posterior lateralis (VPL) and the ventralis posterior medialis (VPM) (Fig. 144-1-2). The VP nucleus receives me¬ dial lemniscal and spinothalamic fibers, with somatotopy gen¬ erally preserved. Fibers from the body segments terminate lat¬ erally in VPL, while fibers from successively higher segments

Chapter 144/Thalamotomy for Cancer Pain: Part 1

1433

Figure 144-1-2. Coronal section through the thalamus showing the main nuclear aggregations at the level of the mammillary bodies 04) and at the level of the tuber cinereum (B). Note the nucleus ventralis posterior lateralis, nucleus medialis dorsalis, nucleus centromedianus, and nucleus parafascicularis. (Used with permission of Williams PL, Warwick R, Dyson M, Bannister LH (eds), in Gray’s Anatomy, Edinburgh: Churchill Livingstone, 1989, p 1000.)

end progressively more medially with trigeminothalamic fibers from the face and head terminating in VPM. Lemniscal fibers are crossed. Most spinothalamic fibers cross in the spinal cord, but some ascend to the ipsilateral thalamus. While most spinothalamic fibers end in VPL, fibers have been identified in a number of other locations in the thalamus. Local intemeurons are identified in VPL. The main thalamocortical radiations from VPL and VPM travel in the posterior limb of the internal capsule to areas 1 through 3 of the primary somatic sensory cortex. The cortical areas project back to the thalamic nuclei, and precise somatotopy is preserved. The VI nucleus receives input from the contralateral dentate nucleus and the ipsilateral red nucleus as well as the globus pallidus. The main projection from the VI nucleus is somatotopic through the internal capsule to motor and premotor cortex areas 4 and 6. The VI nucleus is often a target for stereotactic manipulation in Parkinson’s disease patients. The VA nucleus has many connections with other thalamic nuclei: nucleus centromedianus, intralaminar nuclei, midline nuclei, and reticular thalamic nucleus. There is input from the brain stem reticular formation, and there are connections from the globus pallidus. Dorsolateral group of thalamic nuclei This group of nuclei is divided into the nuclei lateralis dorsalis (LD), lateralis posterior (LP), and pulvinar. The pulvinar is phylogenetically more recent, and its functional significance is

poorly understood. The pulvinar has abundant connections with Wernicke’s speech area and has been implicated in the perception of chronic pain. There are few connections with pri¬ mary sensory areas.

NONSPECIFIC GROUPS OF THALAMIC NUCLEI It has been suggested that the brain stem reticular formation is connected to thalamic nuclei, and these nuclei have diffuse thalamocortical radiations. The assumption has been made that such connections are involved in maintaining cortical pre¬ paredness for the reception of rapid localized patterns from the larger specific relay nuclei. This remains to be substantiated. These nonspecific groups of thalamic nuclei include the reticu¬ lar thalamic nucleus, intralaminar nuclei, nuclei of the midline (which are not well developed in humans), and the nucleus centromedianus (well developed in primates and humans). The nucleus centromedianus is embedded in the internal medullary lamina. There is disagreement regarding the connections of the nucleus centromedianus, although most authors agree that it is not connected with the cortex.

SUMMARY There are prominent somatotopically organized connections between the medial lemniscus and the spinothalamic tract and

1434

Part 4/Functional Stereotaxis

VPL and VPM. These nuclei have somatotopically organized connections with the sensory cortex. It has been suggested that the spinothalamic tract selectively terminates in the parvocellular ventrocaudal nucleus (VCpc), which is located in the infe¬ rior margins of VPL and VPM (the ventrocaudal nucleus in Hassler’s classification). The ventralis intermedius and ventralis anterior are intimately involved in interactions of outflow from the corpus striatum and cerebellum with projections to motor and premotor cortices. The nucleus dorsalis medialis, along with other nonspecific thalamic nuclei, has many inter¬ connections with the frontal cortex and hypothalamus and of¬ ten has been regarded as being involved in the complex inte¬ gration of visceral and somatic functions. The anterior thalamic nuclei have complex connections through mammillothalamic tracts and connections with the hypothalamus and limbic struc¬ tures. The lateral spinothalamic tract is the major pathway car¬ rying information derived from noxious stimuli. It contains ap¬ proximately 150,000 fibers. This tract bifurcates in the brain stem, with the lateral branch directed to the nucleus ventralis posterior of the thalamus. About 1500 fibers reach the ventro¬ caudal thalamus. The medial portion projects to the reticular nuclei of the medulla and pons. Brain stem fibers may be in¬ volved in reflex control of vasomotor, cardiac, and respiratory changes. There are diffuse connections from the brain stem reticular nuclei that project to the nucleus parafascicularis, in¬ tralaminar nuclei, and nucleus centromedianus.

VENTROCAUDAL (VENTRALIS POSTERIOR) THALAMOTOMY The somatosensory afferent input, including the medial lemnis¬ cus and nociceptive spinothalamic tracts, terminates in the ven¬ tralis posterior (VP) or ventrocaudal nucleus of the thalamus. Similarly, somatosensory input from the face is carried by the trigeminal nerve, ganglion, and nucleus and eventually termi¬ nates in the medial portion of VPM. Accordingly, it is intuitive to assume that once stereotactic ablative techniques became available, lesions would be made in the VP nucleus of the thal¬ amus to treat pain. Pioneering work was performed by Hecaen and associates,8 who reported six patients, one with combined lesions; five patients were relieved for more than 2 months. Monnier and Fischer9 also reported early experience. Spiegel and Wycis10 reported 24 cases, including midbrain lesions, VPL lesions, and dorsomedial lesions. This early work was fol¬ lowed by the experience of Riechert,11 who in addition to pre¬ senting his experience also surveyed the neurosurgical commu¬ nity with questionnaires. Mark and colleagues carried out an extensive analysis of thalamic lesions, having chosen the ventral posterior thalamus as the initial target.3-12'16 Pathological evaluation was included in 11 cases. Twenty-eight patients were evaluated, with 18 obtaining good pain relief, 7 fair relief, and 3 poor relief. Importantly, they were able to define these syndromes after lesions in the thalamus: (1) VPL sensory nucleus syndrome, (2) intralaminar or parafascicular nucleus syndrome, and (3) anterior nucleus syndrome. The first syndrome was charac¬ terized by profound sensory loss and mediocre pain relief. The second produced little sensory loss but good pain relief, while the third produced profound change in affect, similar to the effect of frontal lesions. The recognition of improved pain

relief in the absence of sensory loss in the second syndrome was responsible for a shift in interest to lesioning the medial thalamus. Bettag and Yoshida17 described transient relief in four pa¬ tients with nociceptive pain, while one patient developed pare¬ sis. In the group of 31 patients with central or deafferentation pain, 6 patients experienced persisting relief and 11 developed paresis, and there were 2 deaths.7 Umatsu and coworkers18 de¬ scribed 7 patients with good relief among 13 patients with ma¬ lignancy. Orthner and von Roeder19 reported a patient with deafferentation pain who obtained good pain relief at the ex¬ pense of hemiparesis. Tasker, in a review of the literature,6 was able to identify 22 patients treated for nociceptive pain with ventrocaudal thalamotomy. Pain relief was identified in 82 per¬ cent of the patients at the expense, however, of complications in 32 percent. This review identified a 36 percent incidence of pain relief in patients with central or deafferentation pain. Once again, the complication rate was 34 percent. This study in¬ volved 56 patients. It is no surprise that the patients experi¬ enced at least transient loss of all contralateral sensory modali¬ ties immediately postoperatively, leaving them with varying degrees of permanent contralaterally reduced appreciation of pinprick, temperature, and touch and some loss of appreciation of position sense and vibration sense. The substantial sensory loss results in a pseudoparesis. In addition, the sensory loss is associated with some degree of dysesthesia, and this has lim¬ ited the usefulness of the procedure. Tasker’s personal experience with ventrocaudal thalamot¬ omy is limited to three patients with cancer pain. One patient underwent a simultaneous medial thalamotomy. All these pa¬ tients had failed previous midbrain tractotomy, and all experi¬ enced pain relief until death at the expense of dysesthesia.20 Richardson21 reported six patients receiving lesions in the thalamic sensory relay nuclei 13 to 18 mm from the midline. All these patients had malignancy; all the patients had good re¬ lief of pain but also had some disability from sensory apraxia. Ventrocaudal thalamotomy carries a high incidence of dysesthesia and a high incidence of loss of position sense. There have been few recent reports of ventrocaudal thalamo¬ tomy, although Kandel reported three children operated on for erythromelalgia in 1989.22 According to at least one author, ventrocaudal thalamotomy is probably of historical interest.23-24

PARVOCELLULAR VENTROCAUDAL THALAMOTOMY Hassler and Reichert25 identified a nociceptive relay at the infe¬ rior or caudal margin of the ventrocaudal nucleus that has been given the name parvocellular ventrocaudal nucleus (VCpc). There were seven patients with central and deafferentation pain treated by VCpc thalamotomy. All obtained short-term pain re¬ lief. Various authors26-29 have reported the induction of dissoci¬ ated sensory loss, with mild or no loss of lemniscal modalities, after lesions of this subdivision of the ventrocaudal or ventralis posterior nucleus. It has been hypothesized that this represents the termination of the spinothalamic tract fibers that do not end in the midbrain periaqueductal gray reticular formation. VCpc can be identified electrophysiologically by a dramatic shift in the response to stimulation over a distance of 1 to 2 mm

Chapter 144/Thalamotomy for Cancer Pain: Part I

occurring at the inferior margin of the ventral posterior nu¬ cleus. The usual ventrocaudal response to stimulation is somatotopically arranged paresthesia, and this experience suddenly changes to warm, cold, throbbing, burning, smarting, or painful sensations as VCpc is entered. In addition, there is usually a dramatic change in the somatotopic arrangement of the pro¬ jected field, for instance, a shift from hand to leg. Hassler and Reichert25 described somatotopographic organization in a me¬ dial to lateral direction in this separate relay. By contrast, Tasker20 described an orientation that was vertical, similar to that of the rat. Emmers30 demonstrated a separate relay for the spinothalamic tract in rats. Hitchcock and Teixeira31 reported an overall success rate of 82.4 percent in three patients with stroke, six with postherpetic neuralgia, five with postcordotomy dysesthesia, and three with multiple sclerosis. The complication rate was 48 percent with 18 percent of the patients experiencing permanent complica¬ tions. Siegfried and Krayenbiihl, in contradistinction, were dis¬ couraged by lesions of the parvicellular ventrocaudal nucleus, as pain relief was obtained in only one of nine patients.32 It is difficult to reconcile the wide variation in success re¬ ported when lesions are limited to this nucleus. This author sus¬ pects that it is technically difficult to limit lesions to this nucleus alone with the current technology. However, an evalua¬ tion of the patients who received such isolated lesions would be very interesting. Such a target represents third-order neurons, and the process of lesioning it therefore is different from that of cordotomy and midbrain tractotomy. Also, spinoreticulothalamic fibers and their third-order neurons are spared by such le¬ sions. If one accepts the suggestion, based on midbrain tractot¬ omy work, that it is essential to include the reticular structures in the lesion to obtain relief of chronic pain, one may postulate poor results. Our preliminary laboratory results from a rat model of central pain after neospinothalamic tract lesions in the spinal cord also suggest a high incidence of secondary central pain. For these reasons, this author believes that it would be very important to study the clinical results of lesions in the par¬ vicellular ventrocaudal nucleus over the long term in a suffi¬ ciently large population.

MEDIAL THALAMOTOMY There is no clear agreement about which nuclei are included in the lesion classified as a medial thalamotomy. It is apparent that stereotactically produced thalamic lesions are not limited strictly to one nucleus. Various authors812'2132-34 include the center median, parafasicular nucleus, centrolateral nucleus, in¬ ternal thalamic lamina, and nucleus submedius. Medial thalam¬ otomy was pioneered by the same workers who developed ven¬ trocaudal thalamotomy.3'8,9'13-15 The goal of this stereotactic procedure is interruption of the reticulothalamic tract at its ter¬ mination in the thalamus. The theoretical advantage of medial thalamotomy is the avoidance of the sensory loss produced with ventrocaudal thalamotomy.14 The spinothalamic nociceptive afferent pathway divides before reaching the thalamus. The somatotopographically organized portion is directed toward the ventral posterior nucleus (ventrocaudal nucleus in Hassler’s classification), and the nonspecific portion is directed toward the mesencephalic reticular formation, with polysynaptic relays terminating in

1435

the medial thalamic nuclei. Radiofrequency lesions in the me¬ dial thalamus produce no clinically detectable neurological change. The reported incidence of pain relief after medial thal¬ amotomy varies from 13 to 100 percent.16 The results may be better after bilateral procedures. The most serious and most common complication consists of confusion, which is more common after bilateral than unilateral lesions, affecting 7 to 29 percent of patients. Tasker6 reported personal experience with 21 patients with nociceptive pain who underwent medial thalamotomy, some¬ times with additional lesions. Some degree of pain relief was reported in 62 percent, and transient confusion in 67 percent. In addition, Tasker’s review of the literature20 identified 175 pa¬ tients who received medial thalamotomy for nociceptive pain, with an overall incidence of pain relief of 46 percent. An addi¬ tional 47 patients were identified as having central or deafferentation pain, with 29 percent experiencing pain relief after isolated medial thalamotomy or thalamotomy combined with additional lesions. The complication rate varied between 4 and 21 percent. Because of the greater popularity of and lower risk associ¬ ated with medial thalamotomy, there have been a larger number of publications concerned with this procedure than with ventro¬ caudal lesions or ventrocaudal parvicellular lesions. A few ex¬ amples follow. Urabe and Tsubokawa35 performed unilateral medial thala¬ motomy in seven patients with nociceptive pain, successfully in two cases. Bilateral medial thalamic lesions were successful in all seven patients; confusion occurred in three (21.4 per¬ cent), and dysesthesia in two (14.3 percent). Similarly, Sugita and associates26 reported 47 patients with cancer and pain, with 81 percent pain relief and a 15 percent incidence of confusion. In 1979, Sano36 reported 31 percent pain relief in patients with cancer who received internal thalamic lamina lesions and only a 20 percent rate of pain relief in patients receiving lesions in the center median and parafascicular nuclei. Siegfried and Krayenbuhl32 commented on the incidence of pain recurrence in 19 patients, which was 60 percent at 6 months, 70 percent at 1 year, and 75 percent after 3 years. Tsubokawa and Moriyasu37 also noted a significant recurrence of pain in 45 percent of 25 patients. In 1981, Hitchcock and Teixeira31 remained optimistic about the results of medial thalamotomy for pain in patients with cancer; all eight of their patients obtained relief. They made a comparison of center median lesions performed in 19 patients with basal thalamotomy performed in 23; basal thala¬ motomy corresponded to lesions in VCpc. The best results were obtained for pain in the upper body and with bilateral cen¬ ter median lesions. Center median (CM) thalamotomy was more effective than basal thalamotomy. Sixty-seven percent of these patients did not have a malignancy. The results of medial thalamotomy for central pain or deafferentation pain have not been as favorable. Voris and Whisler38 reported a 30.4 percent incidence of relief in 23 pa¬ tients with varying lesion sites. Sano36 compared a 50 percent relief rate after what he called thalamolaminotomy with 60 per¬ cent relief after center median-parafascicular lesions. In 1980, Niizuma and associates39 reported 56 percent transient im¬ provement after CM thalamotomy in 18 patients. Laitinen16 ex¬ pressed enthusiasm for CM thalamotomy in 1988, reporting sustained pain relief in 9 of 11 patients.

1436

Part 4/Functional Stereotaxis

In reporting the results of medial thalamotomy, Pagni33 was less enthusiastic, suggesting that unilateral lesions produced only a transient effect similar to that of leukotomy and that bi¬ lateral lesions only increased the risk of cognitive impairment associated with the surgery. Fairman and Llavallol40 briefly re¬ ported on 521 patients, indicating 70 percent relief with 10 per¬ cent morbidity. In contradistinction to the other thalamic lesioning proce¬ dures that have been reviewed, there are some current reports of the results of medial thalamic lesioning. In 1988, Laitinen16 experienced no complications and achieved long-term relief in five patients. In 1995, Young and associates41 reported 24 me¬ dial thalamic lesions performed in 19 patients. An average fol¬ low-up of 12 months (minimum, 3 months) was available in 15 patients. Four (27 percent) patients were pain-free, and five (33 percent) had greater than 50 percent pain relief. Jeanmonod and Schweiz42 reported 50 to 100 percent pain relief in 67 percent of 69 patients undergoing medial thalamotomy. In view of the limited but ongoing interest in the application of medial thalamotomy for pain control, there have been re¬ ports on the use of the gamma knife to produce anatomically targeted lesions in the medial thalamus. Leksell and asso¬ ciates43 treated 25 patients with center median-parafascicular complex lesions for pain caused by cancer. Forty percent ob¬ tained relief. Steiner and coauthors44 also reported a 46 percent incidence of relief for cancer-related pain. Forster and col¬ leagues43 reported 20 patients treated with gamma thalamot¬ omy, 13 unilaterally and 7 bilaterally. The responses were good in four, moderate in four, slight in seven, and none in five. There was a latency of 1 to 6 weeks before a response. Lesions were made 2.5 to 3.0 mm above the intercommissural line, 8 to 9 mm behind the midcommissural point, and 8 to 12 mm from the midline. In a recent review of stereotactic ablative procedures for pain relief, Young and Rinaldi46 suggested that 65 to 85 percent of patients with cancer should obtain lasting relief until death if they do not survive more than 1 year. For nonmalignant pain, these authors suggested 20 percent immediate surgical failure, pain relief for less than 1 year in 60 to 70 percent, and pain re¬ lief for more than 1 year in 50 to 60 percent. These authors fur¬ ther discussed the belief that it is important to completely ab¬ late hyperactive cells identified with microelectrode recording in the medialis dorsalis, centralis lateralis, intralaminar nuclei, centrum median, and nucleus parafascicularis. These hyperac¬ tive units are thought to be similar to those identified in the sen¬ sory thalamus of patients with chronic pain.47 Richardson48 reviewed his experience with thalamotomy. Initially, lesions were made in the ventrocaudal nucleus, with a resultant marked sensory loss. He then switched his attention to the center median, based on the work of Mark.312"16 Stimu¬ lation in the center median produced contralateral paraesthesia, but only at much higher thresholds than those used in the ven¬ trocaudal nucleus. Increasing the stimulation beyond threshold suddenly produced severe painful paresthesia. This group had limited experience with the dorsomedial nucleus and was not convinced that this area has a significant relationship to pain transmission. Stimulation produced anxiety and agitation. Richardson went on to comment that lesions in CM sometimes extend laterally to impinge on VPM, resulting in unpleasant numbness. To reduce this occurrence, the lesion target site was

gradually moved more posteriorly, resulting in the observation that lesions in the medial pulvinar also produce a reduction of painful phenomena without producing analgesia to acute painful stimuli. Voris and Whisler38 reviewed 90 patients treated over 10 years, 32 with cancer and 58 without cancer. Two of the cancer victims underwent thalamotomy, as did 23 of the other patients. In the entire group of patients without cancer, 20 percent had no pain relief at 1 month, over 50 percent had pain relief lasting less than 1 year, 28 percent had pain relief lasting more than 1 year, and only 20 percent had pain relief beyond 3 years. These authors concluded that CM lesions must be bilateral to be ef¬ fective and that such lesions carry less risk than does mesencephalotomy. To summarize, lesions in the medial thalamus concentrated around CM, the parafascicular nucleus, and intralaminar nuclei result in no detectable loss of sensory function. Stimulation at this location before lesioning does not produce a diagnostic sensory response, although at high thresholds, stimulation can produce paresthesia. Sometimes an unpleasant painful response is experienced by the patient. Hyperactive units have been identified in this location by microelectrode recording. The results in terms of pain relief after lesions in this loca¬ tion are superior to those in lesions produced in VPL or VCpc. The results are better for nociceptive pain than for central and deafferentation pain. It is possible to treat bilateral pain with unilateral lesions. Patients with cancer have better outcomes, and more of these patients remain pain-free until death. Upper body pain responds better than does lower body pain. It is not clear from the literature whether bilateral lesions are necessary to obtain relief. It is also not clear to what extent bilateral le¬ sioning increases the risk of complications. The results for uni¬ lateral nociceptive pain are better after midbrain tractotomy than after medial thalamotomy, although they are associated with greater risk. There is ongoing interest in the study of the medial thala¬ mus as a target for pain manipulation, particularly as a target for stereotactic radiosurgery using the gamma knife. The po¬ tential role of chronic stimulation has not been delineated. I will not comment about lesions combining the medial thalamus and pulvinar.

PULVINAR Relatively little is known about the physiology and function of the pulvinar. In Tasker’s review of thalamotomy in 1990,6 he commented that the results of pulvinar lesioning for central and deafferentation pain are difficult to evaluate. The comment was made that the procedure probably is still performed in some centers for nociceptive pain. As indicated in the section on medial thalamic lesions (see above), an attempt was made to reduce the sensory loss that sometimes accompanied CM-parafascicular (PF) lesions by progressively moving the target more posteriorly. This resulted in lesions being produced in the pulvinar with such targeting, while the outcomes remained similar to those for lesions of CM plus PF. It was believed that sensory loss occurred after CM plus PF lesions as a result of encroachment on VPM, which is located immediately laterally. When the target was moved into

Chapter 144/Thalamotomy for Cancer Pain: Part I

the pulvinar, the target was behind VPM and thus farther away from it. Richardson and Zorub49 also carried out a number of experiments in cats to show that evoked potentials recorded from the pulvinar could be abolished by lesions in the dorsal cord and anterolateral cord. Thus, it was suggested that the pul¬ vinar plays a role in pain perception. Twelve patients obtained pain relief that was comparable to that after CM thalamotomy, with no detectable sensory loss. Kudo and coworkers50 reported 17 patients who underwent pulvinar lesioning; 6 had stroke, 9 had cancer, and 2 had facial pain. Pain relief was complete in eight and remarkable in six, and slight pain remained in three. The same authors describe relief of pain and relief of numbness in three patients after stroke and in one with cancer.51 Richardson and Zorub49 considered the pulvinar an extension of the medial thalamic group and as such a reasonable target for the relief of cancer pain. Mayanagi and Bouchard52 were able to demonstrate better results when medial thalamic lesions also encroached on the pulvinar. Pain relief in patients with cancer increased from 60 percent to 89 percent; however, pain relief in patients with neural injury remained at 33 percent. Siegfried53 reported the results after pulvinar lesions in 14 patients with neural injury pain and 8 patients with cancer, ob¬ taining 77 percent early relief at the expense of a mortality of 9 percent. Among these 22 patients, lesions were made bilater¬ ally in 20. Three patients obtained no relief, and two died from disease early in the postoperative period. Pain relief was excel¬ lent in the remaining 17 but recurred in 3 days in 2 patients, 1 week in 1, 2 weeks in 1, 4 weeks in 1, 6 weeks in 1, and 1 year in 2. Five patients remained pain-free at 1 year, 1.5 years, 2.5 years, 3 years, and 3.5 years. Three patients were pain-free un¬ til death. This report included a literature review to date. Cooper and coworkers54 reported complete pain relief at 6month follow-up in three patients. Laitinen55 expressed moderate enthusiasm for pulvinar le¬ sions in patients with benign pain but concluded that the results were best with cancer pain and postherpetic neuralgia. In a re¬ view of 41 patients, 5 of whom had cancer, the complication rate was 15 percent and the relief tended to be transient. At im¬ mediate evaluation, 19 patients were pain-free, 12 had good re¬ lief, and 10 had no benefit. On postoperative follow-up at an average of 29 months, 12 patients (29 percent) remained painfree. Lesions were made 3 mm posterior to the posterior com¬ missure, 5 mm above the anterior commissure-posterior com¬ missure (AC-PC) line, and at sites 10 to 11 mm and 15 to 16 mm from the midline. Two patients received bilateral lesions. The tendency for pain recurrence is a theme throughout reports on the results of pulvinar lesions.3 55'56 In 1975, Fraioli and Guidetti56 reviewed 18 patients with dyskinetic movements and/or pain treated with pulvinar lesions or pulvinar and later¬ alis posterior lesions. Good early complete pain relief was re¬ ported, but there was a tendency for recurrence. In a similar re¬ port, Martin-Rodriguez and Obrador57 reported nine patients who were subjected to pulvinar manipulation for movement disorders. One patient with cancer obtained relief after a lesion until death 4 weeks later. One patient with a benign pathology responded to chronic stimulation with pain relief that outlasted stimulation by 30 h. Yoshi and associates58 probably published the largest num¬ ber of articles about pulvinotomy. In 1975, they reported their

1437

results in 26 patients, including 12 with cancer. Complete relief was obtained in 16 patients, including all 12 with cancer. This group then reported its experience with 52 patients and re¬ viewed the pathological findings in 7.59 They reported long¬ term follow-up of 42 patients in 1980.60 Nineteen patients were followed for more than 1 year, and the results were 6, excellent; 4, good; 5, fair; and 4, poor. The results at 1 month were 26 excellent, 11 good, and 5 fair. Nine patients died, leaving 33 to evaluate at less than 1 year: 16 excellent, 7 good, 8 fair, and 2 poor. Yoshii and associates61 also looked at the size of the lesion in 45 patients and concluded that the results were slightly better for bilateral lesions. Smaller lesions have better outcomes. In a review of the literature, Tasker20 identified 76 patients treated for nociceptive pain, with relief occurring in 81 percent and with a 21 percent complication rate. Once again, recur¬ rence of pain was noted and pain relief was less satisfactory for patients with neural injury pain, with only 22 percent experi¬ encing relief. In summary, lesions in the pulvinar seem to behave simi¬ larly to lesions in the medial thalamus. The current literature does not provide enough data to define specific guidelines for the use of such lesions. There is a tendency for pain recurrence, particularly in patients with benign pathology. Pulvinar lesions are still being performed, although not frequently. Whittle and Johnson62 reported two patients with cancer receiving lesions in the CM PF nucleus and the pulvinar. They were both re¬ lieved until death for 3 months and 6 weeks, respectively.

Anterior Thalamotomy The effects of stereotactic lesions in the anterior thalamus more closely mimic those of lesions performed in the cingulate gyrus or frontal lobe as a result of the limbic connections of the ante¬ rior thalamus.20 For this reason, further discussion of this pro¬ cedure is not included in this chapter.

SURGICAL TECHNIQUE Stereotactic localization is employed to perform the lesions de¬ scribed here (Fig. 144-1-3). The original technique involved positive-contrast ventriculography to identify structures in the diencephalon. Most of the targeting is based on reference points consisting of AC and PC, which can be identified easily indenting the third ventricle. With the development of com¬ puted tomography (CT), many neurosurgeons modified their technique to utilize CT stereotactic localization. It is our cur¬ rent practice to create stereotactic lesions with magnetic reso¬ nance imaging (MRI) localization. A number of surgeons have reservations about the use of MRI for stereotactic localization, believing that there are nonlinearity, distortion, and chemical shifts as well as some limitations of resolution based on slice thickness and pixel size. Though the pixel size with MRI re¬ mains larger than it is with CT, it is now possible to obtain 1-mm-thick slices with MRI using three-dimensional se¬ quences. A number of investigations have been carried out to evaluate the accuracy of MRI for stereotactic localization both for biopsy and for functional work. On the basis of previous experience with biopsy, this author has been satisfied with the

1438

Part 4/Functiona! Stereotaxis

sn:m;oT\< 11
1.5 times the sensory threshold to confirm that the lesion will be made at a safe distance from the anterior root. Postoperative discomfort is prominent in approximately 40 to 60 percent of patients who experience a neuritis-like reaction in the dermatome. This usually appears some days after the procedure and gradually disappears by 3 to 6 weeks. Complications of this procedure are extremely rare in the cervical area. We are aware of one patient with both sensory and motor dysfunction out of an estimated total of 20,000 to 30.000 procedures performed over the last 5 years in the Netherlands. In the lumbar region, we are aware of two complications of rhizotomies after failed back surgery. There was one motor complication after a partial rhizotomy at L5. and one patient developed anesthesia dolorosa after a partial rhizotomy at L4. I his might be due to local hemorrhage, or it might underline the necessity of knowing more about the spread of RF lesions under abnormal circumstances.

No complications have been described after this lesion. There may be postoperative discomfort, probably resulting from swelling in the vicinity of the segmental nerve. Central

RF

lesion in the

INTERVERTEBRAL DISK A central RF lesion in the intervertebral disk is a new RF pro¬ cedure for the treatment of spinal pain. It is based on the as¬ sumption that the intervertebral disk has several properties that favor the expansion of an RF lesion, allowing it to be used to heat the nerve fibers in the anulus fibrosus sufficiently to re¬ duce noxious input from that structure. First, the disk is avascu¬ lar, so that the heat is not carried away by circulation. Second, the bony end plates of the adjoining vertebrae act as insulators. Third, the disk is an area with very low electrical impedance. This probably reflects a high water content and accordingly allows an easy spread of heat throughout the disk. The lesion is characterized by a very high energy output of the lesion generator, as high as 15 W in the equilibrated phase of the lesion in the lumbar area and 4 W in the cervical region. Since the disk is avascular, this suggests global heating of the disk and a rapid washing away of heat outside the anulus fibro¬ sus. There is no proof, however, that the rise in temperature in the disk is uniform. Finch (personal communication) intro¬ duced a second electrode from the side opposite to that under treatment and could not confirm the expected rise in tempera¬ ture. This suggests a more localized effect of the lesion com¬ patible with the clinical finding that there may be some residual pain on the contralateral side. It also makes it less likely that pain originating in the anterior part of the lumbar disk can be treated effectively with this lesion. In the cervical region, how¬ ever, conditions are different, since the approach is anterolat¬ eral and the dimensions ol the cervical disk are considerably smaller. The avascularity of the disk is confirmed by the slow fall in tip temperature after completion of the lesion. The rate of fall is compatible with an RC time of the surrounding tissue of 70 to 80 s, compared with 5 to 20 s for RF lesions in other areas. The lesion is further characterized by two conspicuous fea¬ tures. First, it is completely painless, and the whole procedure can be performed without the use of a local anesthetic unless one insists on making a skin wheal. Second, the effect is usu¬ ally instantaneous. There has been no evidence of any damage to the disk on magnetic resonance imaging (MRI) scans, computed tomogra¬ phy (CT) scans, and conventional x-rays done up to 18 months after the lesion. We have so far decided against doing animal

Chapter 160/Radiofrequency Lesions in the Treatment of Pain of Spinal Origin

work since a knowledgeable anatomist suggested that the most modem MRI scanners were more sensitive than routine histo¬ logical methods (Drucker, personal communication). There is circumstantial evidence that the disk is unaffected. There is a slight but perceptible fall in impedance during the equilibrated phase of the lesion. This indicates a heat effect at a distance from the electrode that is not counteracted by coagulate forma¬ tion that would increase the impedance.

Technique Many of these procedures require a special technique to intro¬ duce the prognostic blocking needle or RF electrode. There are several problems. The liberal use of local anesthetic solution in performing a prognostic block is undesirable since it may ob¬ scure the effects of the block itself. When an RF lesion is made, the reliability of electrical stimulation before lesion making must not be compromised by anesthetic agents. However, the patient should not be subjected to discomfort, especially since the patient may have to undergo various prognostic and RF procedures before treatment is complete and a painful experi¬ ence may make the patient less confident on those occasions. It is therefore important to make the introduction of the nee¬ dle as painless as possible with minimal use of local anesthesia. It is helpful to know where the painful structures—that is, the nerves and the periosteum—are located and to get to the target with as few corrections of the direction of the needle as possible. Naturally, experience plays a role, but the use of a special radiological technique is equally important. In many proce¬ dures, the C-arm is directed in such a way that the x-rays run parallel to the intended path of the needle. If the needle is placed properly, it will be projected on the screen as a dot. Since it allows the use of a small diaphragm, this technique is called tunnel vision. The advantage is that the operator sees on the screen “what the needle sees.” When one is using this technique, a needle path can be se¬ lected that avoids painful structures, keeping corrections of the needle direction to a minimum; any corrections can be made while the needle is still in the superficial-layers, where there are no painful structures. As an example, this technique enables the operator to avoid contact with the periosteum during a lumbar sympathetic block. The operator has to be familiar with the radiological images when using these projections. This requires some training, but the result is a confident and cooperative patient and a doctor who enjoys doing the work. Another point to keep in mind is the choice of a C-arm image intensifier and a suitable operating table. There have been many improvements in quality and op¬ tional possibilities with image intensifiers over the last several years, but the main goal remains easy, effortless mobility of the C-arm and a suitable operating table free of interfering metal,

pain, and serious spinal pathology. The last category usually calls for treatment directed toward the cause and will not be considered here. Mechanical back pain originates from one of the compo¬ nents of the three-joint complex: the disk or the posterior joints. The role of the facet joints as a source of pain has been the subject of debate. Kuslich and associates43 studied the ef¬ fect of mechanical stimulation of various structures in patients who underwent a laminectomy for a prolapsed disk under local anesthesia. They found that the outer part of the anulus fibrosus and the posterior longitudinal ligament were invariably painful but that stimulation of the facet joints produced only mild pain in a minority of patients. Their findings may, however, have been influenced by their selection of patients; all these patients had radicular rather than mechanical pain. Several other authors regard the facet joint as a common source of pain.2,4,44-47 Facet joint pain may be referred to the buttock and thigh,21,48 there is often pain on hyperextension, and the pain may be provoked by sudden movements. Para¬ vertebral tenderness is common but is a nonpecific finding that is easily masked by tension of the overlying muscles. The cause of discogenic pain is not always clear. A bulging disk may be painful because of pressure on the posterior longi¬ tudinal ligament. Another cause of discogenic pain is an “empty disk,” in which the contrast material injected during diskography simply disappears into the epidural space and the disk does not fill. In these cases, disk material is thought to leak into the epidural space, causing an inflammatory reaction. The anterior part of the disk also may be a source of pain. Jaffray and O’Brien49 described an inflammatory reaction in tissue that was removed from the prevertebral region during spinal fusion. The question remains whether the degeneration of a disk is painful. Friedenberg and Miller36 did not find any correlation between disk pain and degeneration of the disk. Van Haranta and colleagues,50 in contrast, stated that especially in patients with disk deterioration, provocation diskography was positive. In our experience, a disk that appears to be normal on diskogra¬ phy occasionally may be a source of pain, but this is a rare ex¬ ception. In the vast majority of patients, a positive response to the prognostic block correlates with some degree of degenera¬ tion of the disk, varying from slight to severe. Disk pain is characterized by midline tenderness and aggra¬ vation of pain on flexion rather than extension. Many patients with disk pain find it painful to deflect and do so in a curious biphasic manner. If there is lateralization during this maneuver, this is called the corkscrew phenomenon. Nerve root pain is characterized by dermatomal spread, usu¬ ally well into the lower leg and often into the foot. In many pa¬ tients, there is loss of nerve function to a variable degree and there may be signs of sympathetic overactivity.

permitting easy handling of the C-arm.

BACK PAIN AND SCIATICA Diagnosis As was stated above, spinal pain has a complex mechanism with many interrelationships, defying compartmentalization into sophisticated, concise diagnoses. Waddell and colleagues divided back pain into mechanical low back pain, nerve root

1589

Protocol of Treatment The following protocol should be used: 1.

Prognostic block of the posterior primary ramus at relevant levels. We prefer this block over the facet joint block since in our hands the injection into the joint is not invariably technically successful. Marks and associates44 pointed out that these blocks are of equal value. If this block is posi¬ tive, a percutaneous facet denervation is performed.

1590

Part 4/Functional Stereotaxis

2.

Prognostic sympathetic block. This step is omitted if there is bilateral back pain without leg pain, because a bilateral RF sympathetic block has not been found to be helpful in that situation. If the block is positive, an RF sympathetic block is performed.

3.

Prognostic diskography at all relevant levels. If the prog¬ nostic block is selectively positive at one of these levels, a central RF disk lesion is performed.

4.

RF lesion of the communicating rami. This step is relevant only in patients with discogenic pain who have not bene¬ fited from an RF disk lesion. The lesion is performed cra¬ nial and caudal to the nociceptive disk.

5.

Prognostic injection of the relevant segmental nerves, fol¬ lowed by a percutaneous partial rhizotomy if the block is selectively positive at one level. This step is omitted if there is sensory loss in the relevant dermatome, since this is a contraindication for a partial rhizotomy. It is also omit¬ ted if the main problem is mechanical back pain, in which case a partial rhizotomy is unlikely to be successful. This limits the use of a partial rhizotomy in the lumbar area to patients with monoradicular pain without sensory loss in the relevant dermatome, in whom there is no possibility of treatment to correct the cause. This occurs only rarely. A

Techniques The following techniques can be used. Percutaneous facet denervation With the patient prone on the operating table, the C-arm is po¬ sitioned in a slightly (10- to 15-degree) oblique projection until the ridges between the superior articular and transverse processes are clearly visualized. Entry points are marked overlying the grooves at the L4, L5, and SI levels. In these grooves run the posterior primary rami of L3, L4, and L5. Another entry point is marked overlying the SI foramen. An SMK CIO cannula with a 5-mm bare tip is introduced at each entry point. The upper three electrodes are positioned un¬ der tunnel vision until the tip lies in the groove (Fig. 160-2A). The lowest electrode is introduced slightly upward until con¬ tact is made with bone just distal to the articular space. This electrode should lesion the communicating nerve that runs cranially from the SI foramen. The proper position of the electrodes should always be checked on the transverse projection (Fig. 160-25). This is es¬ sential to prevent damage to the segmental nerves. Stimulation at 50 Hz should give a response below 1 V when a 60-s 80°C lesion is made.

RF

SYMPATHETIC BLOCK

An RF sympathetic block usually is performed at the L4 level. With the patient prone on the operating table, the C-arm is po¬ sitioned in an oblique direction so that the spinous processes are projected over the facet joint column on the opposite side. An entry point is selected overlying the side of the vertebral body at the junction of the lower and middle thirds of the verte¬ bra. A 20-gauge SMK C15 cannula with a 10-mm bare tip is in¬ troduced under tunnel vision. It is carefully advanced, passing cranial to the segmental nerve and avoiding contact with the periosteum of the vertebral body.

B Figure 160-2. Electrode position during lumbar facet denervation. A. Slightly oblique projection. B. Transverse projection.

The position is then checked on the tranverse and antero¬ posterior (AP) projections. The tip should lie level with the an¬ terior margin of the vertebra and just medial to the middle of the facet column. This is important to avoid damage to the il¬ ioinguinal nerve. Injection of contrast should show typical spread; 2 ml of 2% lidocaine (Xylocaine) is then injected, and a 60-s 80°C lesion is made.

Chapter 160/Radiofrequency Lesions in the Treatment of Pain of Spinal Origin

RF DISK LESION With the patient prone on the operating table, the C-arm is ad¬ justed in an approximately 45-degree oblique projection. The position is further adjusted along the horizontal axis until there are no more double contours in the end plates. For L5-S1, this may result in considerable obliqueness in two planes. An entry point is marked overlying the middle of the disk just lateral to the facet joint. A 20-gauge SMK C15 cannula with a 10- or 15-mm bare tip is introduced using tunnel vision (Fig. 160-3A). It is important that the cannula be directed as far medially as possible, since this ensures passage medial to the exiting segmental nerve. The cannula should be advanced very slowly in the vicinity of this nerve. If the patient reports pares¬ thesias, the direction should be adjusted very slightly medially and caudally. Injection of local anesthetic solution at this stage is not recommended because it might cause mechanical dam¬ age to the exiting nerve that might go unnoticed. When the disk is entered, there is a characteristic loss of re¬ sistance. Continuous impedance monitoring confirms the cor¬ rect position by recording a marked fall in impedance at this stage. The projection is then checked in the tranverse and AP planes, and the cannula is advanced until the tip lies in the cen¬ ter of the disk (Figs. 160-3B and Cj. At the L5-S1 levels, this is not always possible if there is a high iliac crest. A compromise then has to be made, but the tip of the cannula should at least lie medial to the facet column. Stimulation at 2 Hz and 50 Hz should not give a response below 2 V. A 90-s 70°C lesion is then made. The tip tempera¬ ture is monitored for 30 s after the lesion is completed, during which time it usually falls to 50 to 52°C. The technique for prognostic disk injections is identical. A 22-gauge SMK C15 can be used to minimize discomfort. When the needle is in position, a mixture of 2 ml of 2% lidocaine and 1 ml of iohexol (Omnipaque 300) is injected. If there is over¬ flow of solution into the epidural space, the patient should rest

1591

electrode is carefully advanced to make contact with the junc¬ tion of the lower border of the tranverse process and the lam¬ ina. It then is manipulated slightly caudally and anteriorly until it slips into the craniodorsal part of the foramen. It is advanced until the tip is projected over the middle of the facet column. Next, the posterior position in the foramen is confirmed on the transverse projection. Stimulation and lesion parameters have been described under “Techniques,” above. For L5, the approach may be more difficult because of the position of the iliac crest. The utilization of tunnel vision is then preferable. The dorsal root ganglion of SI cannot be reached with a straight instrument. For a partial rhizotomy at this level, a small hole has to be drilled with a Kirschner wire into the dorsal aspect of the sacrum. The reader is referred to the original description of this technique.4

NECK PAIN, BRACHIALGIA, AND CERVICAL HEADACHE Diagnosis There is a higher incidence of posttraumatic pain syndromes in the cervical region than elsewhere, and the concomitant occur¬ rence of headache, migraine, and facial pain is specific to this region of the spine. Stenosis of the spinal canal may cause cer¬ vical myelopathy. Otherwise, the same general considerations apply that are used in the lumbar region and classification of the related pain syndromes is similar: neck pain, nerve root pain, and serious spinal pathology. Spinal pathology will not be discussed here, since RF treatment is usually not indicated

With the patient prone on the operating table, the C-arm is ad¬ justed as it is for a sympathetic block. An entry point is selected overlying the lateral part of the vertebral body just caudal to the transverse process. An SMK C15 cannula with a 2-mm bare tip is introduced under tunnel vision until it makes contact with bone at the described point (Fig. 160-4A). The position is checked in the lateral projection, which should show the tip of the electrode lying somewhat posterior to the middle of the ver¬

for it. The relationship between headache and cervical pain symp¬ toms is still controversial. Neurologists have long denied such a relationship. Sjaastad and associates51 hypothesized the exis¬ tence of cervicogenic headache, which they characterized as strictly unilateral attacks of headache that could be precipitated by neck movements or by pressure on tender spots in the neck. This was later confirmed by other authors,52-54 who reported a favorable effect of blocking the major occipital nerve with lo¬ cal anesthetic solution in treating this type of headache. In our opinion, these criteria are too stringent. Any patient with either unilateral or bilateral headache who has signs of pain originating from the cervical spine should be regarded with suspicion as suffering from cervicogenic headache. Cervical spinal pain of any type may simply cause an excess of nociceptive input, and this would fit well into the concept of Olesen55 that headache results from such an excess of

tebral body (Fig. 160-4B). Electrical stimulation at 50 Hz should elicit a sensation in the back at less than 1.5 V. There should be no motor response to 2-Hz stimulation at 2 V. If these conditions are not met, the electrode is carefully manipulated in the sagittal and transverse planes to find a better position. A 60-s 80°C lesion is then

input. This concept is in accordance with the lack of specificity in the level and type of cervical pain that is reported to cause headache. All segmental levels from C2 to C5 have been in¬ criminated, along with the uncovertebral joints C2-C353 and C4-C5.51 Michler and colleagues54 described relief of headache

in bed until the effects of the lidocaine have worn off.

RF LESION OF THE COMMUNICATING RAMUS

made. Percutaneous partial rhizotomy With the patient prone on the operating table, the C-arm is po¬ sitioned in the AP direction. An SMK CIO cannula with a 5mm bare tip is introduced at an entry point 8 cm from the mid¬ line and 4 cm caudal to the relevant transverse process. The

in a patient operated on for a C6-C7 prolapsed disk. This is in accordance with our experience. Headache of any type—both unilateral and bilateral and both the continuous type and the type characterized by attacks that resemble mi¬ graine—may be relieved by appropriate RF treatment of the neck if there are signs of cervical spinal involvement. There is no specificity in the type of lesion that is likely to provide a benefit.

1592

Part 4/Functional Stereotaxis

A

B

C figure 160-3. Central RF lesion of the lumbar disk. A. Introduction of the electrode under tunnel vision. B. Transverse projection. C. AP projection.

Mechanical neck pain, like back pain, originates from the posterior joints or the disk.56-58 Barnsley and coworkers38 performed provocation diskography and facet joint blocks in patients with neck pain and found that both structures played an equally important role, with 41 percent of patients having pain from both structures. On physical examination, rotation may be limited, usually to the unaffected side if the pain is

unilateral. There is tenderness over the affected facet joints, and if the disk is involved, there is usually discrete tender¬ ness in the midline, facilitating the search for the nociceptive level. Nerve root pain may be caused by a prolapsed disk or by de¬ generative narrowing of the intervertebral foramen. Prognostic segmental nerve blocks also may be effective in relieving pain

Chapter 160/Radiofrequency Lesions in the Treatment of Pain of Spinal Origin

1593

A

Figure 160-4. RF lesion of the communicating ramus. A. Introduction of the electrode under tunnel vision. B. Transverse projection.

that is supposedly due to functional abnormalities of the cervi¬ cal spine.59-60 This might be explained by the presence of irrita¬ tion of the segmental nerve in a hypermobile segment, but the effect could also be due to the blocking of normal input in a segment with a high input level from other sources. Whatever the cause, a partial rhizotomy at such a seemingly normal level may relieve pain effectively.39

On physical examination, one often finds circumscribed ten¬ derness at characteristic points that have a frequent but incon¬ stant relationship with segmental levels: C2: the major occipital nerve C3: the minor occipital nerve C4: a point just anterior to the trapezius border

1594

Part 4/Functional Stereotaxis

C5: a point over the trapezius border C6: a point just posterior to the trapezius border C7: a point approximately 3 cm posterior to the trapezius border61 Nerve function may be impaired if there is a prolapsed disk, in which case the patient often needs surgery. In nerve root pain caused by narrowing of the foramen, neurological signs are usually absent. Signs of secondary sympathetic hyperactivity may vary from very pronounced to absent.

Protocol of Treatment The following protocol should be used: 1.

Percutaneous facet denervation. This is the only RF proce¬ dure we perform without prior prognostic blocking. We do this because prognostic blocking of the joints is painful and, in our hands, not always successful. However, we find that tenderness over the joints is not a nonspecific sign, as it is in the lumbosacral area. Most patients with tender joints react favorably to facet denervation.

2.

Prognostic sympathetic block of either the stellate ganglion or the superior cervical ganglion, depending on the seg¬ mental level of the pain. This step is omitted if the patient has bilateral symmetrical or midline pain. If the block is positive, it is followed by an RF lesion.

3.

Prognostic block of the relevant segmental nerves, to be followed by a partial rhizotomy if the block is selectively positive at one level. Contrary to the situation in the lum¬ bosacral area, this procedure is effective in the cervical re¬ gion and there are few patients with a contraindication such as sensory loss in the dermatome.

4.

Prognostic diskography at the relevant levels, as indicated by the level of midline tenderness. If the prognostic block is selectively positive at one level, a central RF disk lesion is performed.

Figure 160-5. Electrode position during cervical facet denervation, oblique view. The upper electrode is placed on the lamina C2, where small rami of the major occipital nerve are on their way to the cranial aspect of the C2-C3 joint.

A 60-s 80°C lesion is made; when a TOP XE needle is used, 20 V is applied to the needle for 60 s. This should heat the needle tip to the same temperature, as can be verified by observing the fall in impedance during the lesion.

RF Techniques The following techniques can be used. Percutaneous facet denervation In the upper and middle cervical area, the patient is positioned supine on the operating table. The C-arm is positioned slightly obliquely so that the x-rays are parallel to the axis of the inter¬ vertebral foramen, which is upward and slightly caudal. In this position of the C-arm, the segmental nerves exit parallel to the x-rays. Since the electrodes are introduced posterolaterally, this projection makes it easy to monitor a safe distance between the electrode tip and the exiting segmental nerve. I he posterior primary ramus in this projection runs approxi¬ mately parallel to the joint space, which is clearly visible. Entry points are marked approximately 1 cm posterior to the poste¬ rior border of the facet column and in the extension of the line ol the joint spaces. An SMK C 5 cannula with a 4-mm bare tip or, alternatively, a TOP XE 6 needle is introduced and carefully advanced anteriorly and cranially until contact is made with the facet column. The position is adjusted until the tip lies in the facet joint line and a few millimeters posterior to the plane of the intervertebral foramen, making contact with bone (Fig. 160-5). Stimulation at 50 Hz should give a response at 38-50 The recent report on the analgesic activity of baclofen is in¬ teresting. This drug is a well-known GABA-B agonist, used for a long time for its antispastic activity.19 When delivered intrathecally in patients with spasms from spinal cord injury, its efficacy is impressive.35

References 1.

2.

Recently Herman reported reduction of pain in spinal cord injured patients, which he claims to be a truly antinociceptive activity of baclofen and not related to its antispastic action.20 Consequently Taira studied 5 patients with thalamic pain, in all but one of whom he reported good analgesia lasting more than 12 h after the injection of 50 mg of baclofen.45 We have tested the efficacy of both baclofen and/or morphine in 8 paraplegic patients in order to evaluate the possibility of treating their pain with intrathecal drugs. Of these patients, 5 received a bolus of 0.5 mg ol morphine; 2 were injected with 50 mg of baclofen, and 1 had both baclofen and morphine on different occasions. Morphine relieved the patients’ pain in 3 cases but had to be discontinued in 1 because of side effects (marked hypotonia and urinary retention even with low doses of 0.25 and 0.125 of the drug). The remaining 2 patients are reporting 50 percent pain relief after 12 months with a mean daily dose of 3 mg of morphine. In our experience with baclofen in SCI patients, we have seen good results only on spasm-related pain and no ef¬ fect on central dysesthetic pain (unpublished data). A very recent report by Reig claims pain relief with mor¬ phine infusion in 18 patients affected by central and neuro¬ pathic pain. According to Reig’s report, excellent pain relief was achieved in neuropathic but not in central pain.18 Destructive surgery is theoretically an option when dealing with nociceptive pain but not with deafferentation pain, with the important possible exception of the dorsal root entry zone(DREZ)-lesion. This operation was first proposed by Sindou et al. in 197443 for treating nociceptive pain. The rationale was to make the le¬ sion of the roots at the level of the entry zone where A-delta

3.

4. 5.

6.

Basbaum AL, Wall PD: Chronic changes in the response of cells in adult cat dorsal horn following partial deafferentation: Reappearance of responding cells in previously non-responsive regions. Brain Res 116:181-204,1976. Beric A: Altered sensation and pain in spinal cord injury, in Dimitrijevic MR, Wall PD, Lindblom ULF (eds): Recent Achieve¬ ments in Restorative Neurology, 3d ed. Basel: Karger, 1990, pp 27-36. Beric A, Dimitrijevic MR, Light JK: A clinical syndrome of rostral and caudal spinal injury: Neurological, neurophysiological and urodynamic evidence for occult sacral lesion. J Neurol Neurosurg Psychiatry 50:600-606, 1987. Beric A, Dimitrijevic MR, Lindblom U: Central dysesthesia syn¬ drome in spinal cord injury patients. Pain 34:109-116, 1988. Bonica JJ: Causalgia and other reflex sympathetic dystrophies, in Bonica JJ, Liebeskind JC, Albe-Fessard DG (eds): Advances in Pain Research and Therapy. New York: Raven Press, 1979, vol 3, 141-166.

Bonica JJ: Introduction: Semantic, epidemiologic, and educational is¬ sues, in Casey KL (ed): Pain and Central Nervous System Disease: The Central Pain Syndromes. New York: Raven Press, 1991, pp 13-30. 7. Burke DC, Woodward JM: Pain and phantom sensation in spinal paralysis, in Vinken PJ, Bruyn GW (eds): Handbook of Clincal Neurology. Amsterdam: North-Holland, 1976, vol 26, pp 489-499. 8. Cioni B, Meglio M, Penlimalli L, Visocchi M: Spinal cord stimula¬ tion (SCS) in the treatment of paraplegic pain. J Neurosurg 82:35-39, 1995. 9. Coombs DW, Saunders RL, Fratkin JD, et al: Continuous intrathecal hydromorphine and clonidine for intractable cancer pain. J Neurosurg 64:890-894, 1986. 10. Corkin S, Twitched T, Sullivan E: Safety and efficacy of cingulotomy for pain and psychiatric disorders, in Hitchcock E, Ballantine H, Meyerson B (eds): Modern Concepts in Psychiatric Surgery. Amsterdam: Elsevier, 1979, pp 253-272. 11. Devor M, Wall PD: Reorganization of spinal cord sensor map after peripheral nerve injury. Nature 275: 75-76, 1978. 12. Devor M: The pathophysiology of damaged peripheral nerve, in Wall PD. Melzack R (eds): Textbook of Pain. 3d ed. London: Churchill Livingston, 1994, pp 79— I (X). 13. Dimitrijevic MR, Faganel J, Lehmkuhl LD, Sherwood AM: Motor control in man after partial or complete spinal cord injury, in Desmedt JE (ed): Motor Control Mechanisms in Health and Disease. New York: Raven Press, 1983, pp 915-926.

Chapter 165/Evaluation and Management of Central and Peripheral Deafferentation Pain

14. 15.

16.

17.

18.

19. 20.

21.

Gammon GD, Starr I: Studies on the relief of pain by counterirrita¬ tion. J Clin Invest 20:13, 1941. Follett KA, Hitchon PW, Piper J, et al: Response of intractable pain to continuous intrathecal morphine: A retrospective study. Pain

32.

49:21-25, 1992. Glynn C, Dawson D, Sanders R: A double blind comparison between epidural morhpine and epidural clonidine in patients with chronic

33.

non-cancer pain. Pain 34:123-128, 1988. Hassenbusch SJ, Stanton-Hicks MD, Soukup J, et al: Sufentanil ci¬ trate and morphine-bupivacaine as alternative agents in chronic epidural infusion for intractable non-cancer pain. Neurosurgery 29:76-82, 1991. Hendler N: Drug therapy of chronic pain, in Wilkins RH, Rengachary SS (eds): Neurosurgery. New York: McGraw-Hill, 1985, vol 3, pp 2374-2381. Herman RM, D’Luzansky SC: Pharmacological management of spinal spasticity. J Neurol Rehabil 4: S15-S20, 1991. Herman RM, D’Luzansky SC, Ippolito R: Intrathecal baclofen sup¬ presses central pain in patients with spinal lesions. Clin J Pain 8:338-345, 1992. Hirayama T, Tsubokawa T, Katayama Y, et al: Chronic changes in activity of thalamic relay neurons following spinothalamic tracto¬ tomy in cat: Effects of motor cortex stimulation. Pain 5(suppl):273,

34. 35. 36. 37.

38.

39. 40. 41.

22.

1990. Hylden JLK, Nahin RL, Dubner R: Altered responses of nociceptive cat lamina I spinal dorsal horn neurons after chronic sciatic neuroma

43.

23.

formation. Brain Res 411:341 —350, 1987. Inbal R, Devor M, Tuchhendler O, Lieblich I: Autotomy following nerve injury: Genetic factors in the development of chronic pain. Pain 9:327, 1980. Kane K, Taub A: A history of local electrical analgesia. Pain 1:125,

44.

1975. Krames ES, Lanning RM: Intrathecal infusional analgesia for nonmalignant pain: Analgesic efficacy of intrathecal opioid with or without bupivacaine. J Pain Symptom Mgt 8:539-547, 1993. Liu CN, Chambers WW: Intraspinal sprouting of dorsal root axons. Arch Neurol Psychiatry 79:46-61, 1958. Meglio M, Cioni B, Prezioso A, Talamonti G: Spinal cord stimulation (SCS) in the treatment of postherpetic pain. Acta Neurochir Suppl

45.

46:65-66, 1989. Meglio M, Cioni B, Rossi GF: Spinal cord stimulation in the manage¬ ment of chronic pain. J Neurosurg 70:519-524, 1989. Melzack R, Wall PD: Pain mechanisms: A new theory. Science

48.

24. 25.

26. 27.

28. 29. 30.

31.

155:108, 1967. Mitchell-Heggs N, Kelly D, Richardson A, et al: Further experience in limbic leucotomy, in Hitchcock E, Ballantine H, Meyerson B (eds): Modern Concepts in Psychiatric Surgery. Amsterdam: Elsevier, 1979, pp 327-336. Murphy TM, Hinds S, Cherry D: Intraspinal narcotics: Nonmalignant pain. Acta Anesthesiol Scand 31 (suppl) 85:75-77, 1987.

42.

46.

47.

49. 50.

51.

1635

Nashold BS Jr, Urban B, Zorub DS: Phantom pain relief by focal de¬ struction of substantia gelatinosa of Rolando, in Bonica JJ, Albe Fessard D (eds): Advances in Pain Research and Therapy. New York: Raven Press, 1976, vol 1,959-963. Nashold BS Jr, Ostdahl RH: Dorsal root enlry zone lesions for pain relief. J Neurosurgery 51:59, 1979. Nashold BS Jr: Neurosurgical technique of the dorsal root entry zone operation. Appl Neurophysiol 51:136, 1985. Penn RD, Kroin JS: Long term intrathecal baclofen infusion for treat¬ ment of spasticity. J Neurosurg 66:181-185, 1987. Plotkin R: Results in 60 cases of deep brain stimulation for chronic intractable pain. Appl Neurophysiol 45:173-178, 1982. Procacci P, Maresca M: Reflex sympathetic dystrophies and algodistrophies: Historical and pathogenetic considerations. Pain 31:137, 1988. Reig E: Intrathecal morphine is useful in the treatment of intractable neuropathic pain. 6th International Congress: Pain Clinic, Atlanta, April 15/20, 1994. Roberts WJ: A hypothesis on the physiological basis for causalgia and related pains. Pain 4:297-311,1986. Schumacker HB: Causalgia: III. A general discussion. Surgery 24:485-504, 1948. Seltzer Z, Devor M: Ephaptic transmission in chronically damaged peripheral nerves. Neurology 29:1061-1064, 1979. Sherrington CS: The Integrative Action of the Nervous System. New York: Scribner, 1906. Sindou M, Fischer G, Goutelle A, Mansuy L: La radicellotomie postdrieure selective: Premiers resultats dans la chirurgie de la douleur. Neurochirurgie (Paris) 20:391-408, 1974. Sweet WH: Sympathectomy for pain, in Youmans JR (ed): Neuro¬ logical Surgery, 3d ed., Philadelphia: Saunders, 1987. Taira T, Tanikawa T, Kawamura H, et al: Spinal intrathecal baclofen suppresses central pain after a stroke../ Neurol Neurosurg Psychiatry 57:381-382, 1994. Tsubokawa T, Katayama Y, Yamamoto T, et al: Chronic motor cortex stimulation in patients with thalamic pain. J Neurosurg 78:393-401, 1993. Wall PD, Egger MD: Formation of new connections in adult rat brains after partial deafferentation. Nature 232:542-545, 1971. Wall PD, Devor M: Physiology of sensation after peripheral nerve in¬ jury, regeneration and neuroma formation, in Waxman SG (ed): Physiology and Pathobiology of Axons. New York: Raven Press, 1978. Wang JK, Nauss LA, Thomas JE: Pain relief by intrathecally applied morphine in man. Anesthesiology 50:149-151, 1979. Winkelmuller M, Winkelmuller W: Continuous opioid intrathecal in¬ fusion in patients with intractable nonmalignant pain. Schmerz 5:28-36, 1991. Yamamoto T, Katayama Y, Tsubokawa T, et al: Usefulness of the morphine/thiamylal test for the treatment of deafferentation pain. Pain Res 6:143-146, 1991.

-»

CHAPTER

166

NONSURGICAL CONSIDERATIONS IN NEUROPATHIC PAIN

C. Peter N. Watson

For the purposes of this discussion, neuropathic pain will be considered to include pain caused by injury or dysfunction in the peripheral or central nervous system. The term peripheral neuropathic pain will be used for peripheral (nerve or nerve root) generated pain and the term central pain will be applied to pain arising from the spinal cord or in more rostral areas in the central nervous system. Trigeminal neuralgia (tic doulou¬ reux) although clearly a neuropathic pain, is not discussed, as it is, in the author’s view, a rather unique type of neuropathic pain only occurring in the head and with specific and usually successful medical and surgical management to which a large literature is devoted. Reflex sympathetic dystrophy (sympathet¬ ically maintained and sympathetically independent) is also not discussed as it is a subject unto itself. Tables 166-1 and 166-2 list the broad range of conditions that may be encompassed under the rubrics of peripheral neu¬ ropathic pain and central pain respectively. Neuropathic pain is commonly seen by neurologists and neurosurgeons and is difficult to treat even in sophisticated hands. For many of these conditions there are no controlled tri¬ als, and to some extent a mythology persists that needs to be dispelled. For example, it is held that carbamazepine is a good agent for lancinating and other neuropathic pain outside the head, phenothiazines are useful adjuncts to antidepressants or as sole therapy, and opioids are ineffective and to be avoided because of the fear of physical and psychological dependency and tolerance. This presentation attempts to clarify what is re¬ ally effective, dispel misconceptions, and indicate how to use these approaches properly by focusing on two peripheral neu¬ ropathic pain conditions in which there are good clinical trials

TABLE 166-1.

Some Types of Peripheral Neuropathic Pain

Carpal tunnel syndrome Meralgia paresthetica Diabetic neuropathy Alcohol/nutritional neuropathy Acute/subacute radicular pain L5-S1 C6-C7 Trigeminal neuralgia Trigeminal neuropathy Atypical facial pain Anesthesia dolorosa Posttraumatic neuropathy Postherpetic neuralgia

Failed back syndrome Root sleeve fibrosis Arachnoiditis Brachial plexus neuropathies/ avulsion Incisional neuralgia Postmastectomy pain syndrome Postthoracotomy pain Causalgia Guillain Barre syndrome Phantom limb pain

(postherpetic neuralgia and diabetic neuropathy), and referring to 25 years of clinical experience with other peripheral neuro¬ pathic conditions and on the controlled trials relating to central pain. The issue of whether preemptive or early and aggressive treatment of acute pain may prevent the evolution into a chronic painful state is also raised.

POSTHERPETIC NEURALGIA Postherpetic neuralgia (PHN) is a common cause of chronic pain in the elderly population. The eruption of herpes zoster (HZ), the commonest neurological illness, is a harbinger of persistent neuropathic pain in at least 50 percent of those over 60 years of age. Although the natural history is one of slow im¬ provement in some, many patients suffer for years. With a judi¬ cious choice of agent and careful monitoring, it is possible to control approximately 70 percent of patients satisfactorily. About 30 percent remain unsatisfactorily relieved or are in¬ tractable, and it may be that prevention with vaccination of children and the elderly and early aggressive treatment of the acute zoster pain may be crucial with this group. Two types of pain may be found: one a steady burning or aching, the other a paroxysmal, lancinating pain. Both may oc¬ cur spontaneously and are often aggravated by tactile contact with the involved skin, such as friction from even the lightest clothing. Paradoxically, firm pressure may give some relief. Examination of the affected, scarred skin (Fig. 166-1) often reveals loss of sensation to pinprick, temperature, and touch over a wider area than the scars and paradoxically an even wider area of sensitive or painful skin. This sensitive skin may be of a much larger area than that occupied by the scarring but may paradoxically include the anesthetic areas, where it is elicited by a different type of stimulation (skin stroking or skin traction between thumb and forefinger). The latter stimuli pre¬ sumably causes a summation effect on hypersensitive, deafferented central neurons with expanded receptive fields. Postherpetic neuralgia is a particularly good model of neuro-

TABLE 166-2.

Central Pain Syndromes

Thalamic syndrome (stroke, tumor) Multiple sclerosis (tic douloureux, painful tonic seizures) Wallenberg’s (lateral medullary) syndrome Syringomyelia Posttraumatic central pain

1637

1638

Part 4/Functional Stereotaxis

pathic pain for drug trials because, if patients are chosen care¬ fully. the pain is fairly chronically stable over time and suffi¬ cient numbers of cases for trials can readily be obtained. Anti¬ depressant therapy, as opposed to many other putative therapies of this difficult problem, has come to have a sound scientific basis. Woodforde et al.1 were the first to recognize that amitriptyline could afford relief in truly chronic postherpetic pain problems. They thought that all 14 of their patients were depressed in this open-label trial, and that was their rationale for using the drug. They used an initial dose of 10 mg four times daily, gradually increasing to 25 mg four times daily, achieving good pain relief in 11 patients for from 1 to 11 months. Taub2 reported successfully treating 5 subjects with PHN of greater than 3 months’ duration with amitriptyline combined with a phenothiazine (fluphenazine, perphenazine, or thioridazine). In a later publication, Taub and Collins3 used amitriptyline 75 mg with fluphenazine 1 mg three times a day in 17 patients with pain of greater than 1 year’s duration. Patients had good relief in both studies, with some mild resid¬ ual pain at 3 to 6 years of follow-up. The authors commented on their belief in the lack of efficacy of amitriptyline alone, us¬ ing it mainly to combat the depressant action of the other drug. This regimen came into widespread use. Based on clinical ex¬ perience, we became convinced that amitriptyline by itself re¬ sulted in pain relief in PHN and also thought the phenothiazines alone were ineffective. We also observed that most patients did not seem very depressed except, in some cases, as a secondary response to pain. We therefore conducted a dou¬ ble-blind, placebo-controlled crossover trial of amitriptyline in 24 patients with this disorder.4 All patients had PHN of more than 3 months' duration, and good results were achieved in 16 of 24 (67 percent). Most patients were not depressed, and pain relief occurred without a change in depression ratings in most patients, indicating that the drug appeared to result in pain re¬ lief independently of its antidepressant effect. This analgesia occurred at lower doses than usually used to treat depression

(median 75 mg). Follow-up was a median 12 months, with good results maintained in 12 patients (55 percent) out of 22. By using small doses (10 to 25 mg) to start and small incre¬ ments in this study, significant side effects were few. A subse¬ quent trial has corroborated these results.5 Amitriptyline has se¬ vere limitations in the long term because of side effects and the fact that relief is rarely complete and occurs in only about twothirds of patients. This drug potentiates both serotonin and noradrenaline in the central nervous system. Subsequent research has explored whether selective serotonergic or nor¬ adrenergic agents might be more effective and have fewer un¬ toward effects. Experience with serotonergic agents (clo¬ mipramine, trazodone, nefasodone, fluoxetine, and zimelidine) in PHN has been disappointing.6-7 The evidence supporting the use of noradrenergic agents is more compelling. Although no controlled trial has been conducted with the predominantly noradrenergic drug nortriptyline, our clinical experience indi¬ cates that it is effective, and, interestingly, it is a metabolite of amitriptyline. I use it as the drug of first choice at present. Desipramine, a selective norepinephrine reuptake inhibitor, has been shown to be more effective than placebo in this disease, and pain relief with that drug as well was not medi¬ ated by mood elevation.8 Although desipramine is reported to have fewer side effects, we do not know how it compares to amitriptyline. A randomized, double-blind trial comparing maprotiline (noradrenergic) with amitriptyline attempted to de¬ termine whether such an agent possessed greater analgesia and effectiveness for PHN.9 Although we found amitriptyline to be more effective, 9 patients responded equally well to both drugs and 7 responded only to maprotiline. Thus, 16 of 32 patients (50 percent) completing the trial may have had predominantly noradrenergic pain-inhibiting systems, whereas 8 other respon¬ ders required an agent with an effect on serotonin and nor¬ adrenaline (amitriptyline). All three components of the pain of PHN responded to treatment—that is, steady pain, jabbing pain, and pain on tactile skin contact. We found side effects troublesome with both agents, therefore limiting effectiveness. Again, most patients were not depressed and pain relief oc¬ curred in most without change in depression rating scales. Based on this information, we believe the initial antidepressant of choice in PHN is amitriptyline or nortriptyline. If these fail, we would then try selective noradrenergic agents such as de¬ sipramine or maprotiline. There has been no good, practical placebo-controlled trial of a phenothiazine in PHN. although there is some informa¬ tion. 10,11 We believe that for the most part beneficial effects seen with the combination of an antidepressant and pheno¬ thiazine are due to the antidepressant, the efficacy of which has been proven by controlled trials. We have seen occasional pa¬ tients improve on different phenothiazines but have never been certain that the effect was due to the drug, a placebo effect, or a result of the natural history of pain resolution.

Figure 166-1. Findings on examining the skin of a case of postherpetic neuralgia: 1 = allodynia (pain on tactile stimulation); 2 = scarring; 3 = sensory loss.

Studies utilizing the anticonvulsants carbamazepine, phenytoin. and valproic acid for PHN have been either unimpressive or difficult to interpret because of the concomitant use of anti¬ depressants.12 15 Although carbamazepine is a popular agent for the paroxysmal lancinating pain that commonly occurs, there is no conclusive evidence to justify its use in this fashion and clinical experience, in my view, points to limited efficacy.

Chapter 166/Nonsurgical Considerations in Neuropathic Pain

For a long time there has been a bias against using opioids for nonmalignant pain. There is now increasing support for the view that they are helpful and justifiable in these condi¬ tions.16-18 Some of these reports were of neuropathic pain.19,20 Some reports suggest that opioids do not relieve neuropathic pain.21'22 However, one study did not include patients with PHN,21 and its conclusions have been challenged.19 Our experi¬ ence with PHN has indicated that opioids are useful for some patients with this condition.7 We were able to document that 25 of 90 patients with otherwise intractable pain achieved good to excellent results and 50 others had 25 to 50 percent relief. We continue to follow many postherpetic patients otherwise refrac¬ tory to all the usual approaches for whom we regularly renew prescriptions for opioids. We find that patients rarely develop problems with tolerance or dependency. There appears to be a ceiling effect with opioids in PHN; some relief occurs below this. Usually complete pain relief does not occur, and this is similar to the effect of antidepressant therapy. Short-acting opi¬ oid analgesics may take the extreme severity of the pain away for 2 to 4 h, but frequently they do not result in satisfactory im¬ provement. The relief is enough, however, that patients often choose to continue using the drug. Above this apparent ceiling, no further pain relief occurs, but side effects supervene to the point that they, with the lack of further analgesia, discourage further dose escalation. We have used a variety of opioids in¬ cluding morphine, sustained-release morphine, hydromorphone, anileridine, levorphanol, codeine, and oxycodone. The majority of our patients prefer acetaminophen with codeine preparations or oxycodone combined with acetaminophen or acetyl salicylic acid. This apparent preference could reflect our prescribing habit rather than a true effect. Topical application of local anesthetics, aspirin, and cap¬ saicin23 all have some published support, mostly by uncon¬ trolled trials. However, clinical experience indicates that the ef¬ fect is modest at best and that for most patients they are not helpful as sole therapy. I believe that for the 30 percent of pa¬ tients with truly intractable pain, prevention by vaccination of the elderly and early aggressive treatment of acute zoster with antivirals, opioids if necessary, nerve blocks, and even antide¬ pressants may limit inflammation and central neuron plasticity. This approach is entirely hypothetical at present.

PAINFUL DIABETIC NEUROPATHY Painful diabetic neuropathy is common and comprises a num¬ ber of diagnostic categories. The interested reader is referred elsewhere24 for a discussion of these as well as of their putative pathophysiology, which information unfortunately does not help guide therapy. Pharmacological approaches are based on a few clinical trials and upon clinical experience, which is not yet sufficient to allow tailoring of therapy to pain mechanism. The hope is that extrapolation from this limited experience will be useful in expanding our primitive state of knowledge of the therapy of most neuropathic pains. The role of diet and insulin and good diabetic control is felt to be important in the resolu¬ tion of the pain of diabetic neuropathy, although this suggestion is somewhat contentious and is not discussed here. As with postherpetic neuralgia, the most compelling infor¬ mation comes from controlled trials of antidepressants, which.

1639

presumably, previous clinical experience had shown to be most effective, particularly the older antidepressants. Some studies of antidepressants in painful diabetic neuropathy have been dif¬ ficult to interpret because of the concomitant use of phenothiazines.25,26 Turkington27 found amitriptyline and imipramine superior to diazepam in this painful condition in a double-blind trial and thought that relief accompanied amelioration of masked depression. Kvinesdal and colleagues28 found that imipramine was superior to placebo and commented that none of their patients were depressed, that pain relief was seen ear¬ lier, and with blood drug levels that were lower than usually seen with an antidepressant action. Max and colleagues29 found amitriptyline superior to active placebo in painful diabetic neu¬ ropathy. They observed that the drug produced relief of both the steady and the lancinating pain, that higher doses were as¬ sociated with greater relief, and that relief occurred both in de¬ pressed and nondepressed patients. Max and colleagues30 also reported that desipramine (noradrenergic) was more effective than active placebo in this painful state. Relief was greater in depressed patients but improvement in pain was also noted in nondepressed individuals. A further trial by Max and col¬ leagues31 found that desipramine provided relief similar to amitriptyline, both drugs being superior to placebo, but that flu¬ oxetine (serotonergic) was ineffective. From these studies in this neuropathic pain syndrome, it ap¬ pears that antidepressants with a mixed effect on serotonin and noradrenaline (amitriptyline and imipramine) or selective nor¬ adrenergic agents (desipramine) are effective analgesics, ami¬ triptyline having come to be the standard of therapy for this disorder. Serotonergic agents are not useful for most patients. The use of anticonvulsants may be regarded as a second therapeutic choice should amitriptyline fail. Carbamazepine has been reported to be effective in two double-blind placebocontrolled trials.32'33 A large placebo effect was present in both studies, and it is difficult to know how effective the drug was in producing satisfactory relief. An open-label trial of 54 patients indicated complete relief in 44.34 Clinical experience indicates to me that this drug is not as effective as amitriptyline; though it appears to help some patients, the response is rarely dra¬ matic. Two controlled trials of phenytoin have led to conflicting re¬ sults.35-36 One open-label trial found that 68 percent of 60 pa¬ tients had an excellent result.37 Uncontrolled observation sug¬ gested to one author that clonazepam was useful for some patients.38 There have been no studies of opioids in this condition. There are a number of studies of topical capsaicin in painful diabetic neuropathy.23 These have been very difficult to ap¬ praise because of a large placebo effect and the impossibility of blinding due to the burning induced by capsaicin.

OTHER PERIPHERAL NEUROPATHIC PAIN Good controlled trials do not exist in the variety of other pe¬ ripheral neuropathic pains listed in Table 166-1 (excluding trigeminal neuralgia). Topical capsaicin may be useful for some patients with the incisional neuralgia postmastectomy pain syndrome,23 but

1640

Part 4/Functional Stereotaxis

again the trials have been impossible to blind satisfactorily. Interestingly, Weir Mitchell recognized that opioids relieved causalgia at the time of the American Civil War; however, their abuse and overuse led to the opioid phobia that has been such a hindrance for such a long time.

CENTRAL PAIN Some central painful states are listed in Table 166-2. There is little specific therapeutic information about most of these ex¬ cept that which is based on clinical experience and uncon¬ trolled published observations. Carbamazepine appears partic¬ ularly effective for painful tonic seizures and for other central pain states due to multiple sclerosis.

ness, weight gain, and, in the older male, urinary retention. The drug may be given in a single dose at bedtime. Every 7 to 10 days the dose may be increased by 10 to 25 mg, and so on, un¬ til satisfactory pain relief occurs or unacceptable side effects supervene. Blood levels are of use, in my view, only as a guide to compliance and to substantiate the clinical impression gained, by noting a lack of a dry mouth, that a further increase is possible. The complaint of dry mouth may be a good indica¬ tion that a significant drug blood level is being achieved. There is no therapeutic range of blood levels for pain relief. If amitriptyline and nortriptyline fail, it is worth trying a more noradrenergic agent such as desipramine or maprotiline, using a similar dosing-escalation schedule. The aim with this therapy is to reduce the severity of the pain from moderate or severe to mild, complete relief being unusual. Side effects often have to be accepted if tolerable or manageable.

A three-phase placebo-controlled trial of amitriptyline and carbamazepine in central poststroke pain found a statistically significant reduction in pain with amitriptyline.39 Another trial found no effect of trazodone (a serotonin potentiating antide¬ pressant) in spinal cord injury pain.40 Desipramine trials have shown that this norepinephrine-potentiating antidepressant may relieve neurogenic pain.41 All of these three results are of interest because they parallel the research already discussed in connection with the peripheral neuropathic pain disorders of postherpetic neuralgia and painful diabetic neuropathy. No controlled trials exist of anticonvulsants or of opioids in central pain. There is a widespread belief that this type of pain is narcotic-resistant. This may, however, be generated in part by a fear of these agents and hence a hesitancy to use them to their full potential.

mazepine being considered as first-line treatment, particularly for lancinating pain with diabetic neuropathy and for the vari¬ ous pain syndromes of multiple sclerosis, including painful tonic seizures. Carbamazepine may be commenced in a dose of 100 mg two to three times a day. This can be increased in a week or two to 200 mg two to three times a day and further thereafter, using pain relief or drowsiness as an end point. Phenytoin may be used in an initial dose of 100 mg at bedtime in the elderly or 300 mg in a younger person. Drug levels may

PRACTICAL THERAPEUTIC GUIDELINES

be used to determine compliance and to guide dose escalation. Other anticonvulsants that may be tried are clonazepam and valproic acid, using guidelines available in any pharmacologi¬ cal reference source.

As can be seen from the preceding discussion of specific types of neuropathic pain, there is little guidance from scientific study. The following recommendations are therefore based on what scientific information there is as well as on clinical expe¬ rience. Since research with different types of neuropathic pain has yielded remarkably similar results, particularly supporting antidepressant therapy, it suggests general guidelines that may be applied in any neuropathic pain until we have more specific data on individual pain mechanisms and therapies.

Antidepressant Therapy It is my belief that the first-line therapy for most neuropathic pain should be amitriptyline or nortriptyline (one of its metabo¬ lites). 1 prefer the latter because I believe it has less side effects and better analgesic properties, but this is not scientifically proven by controlled clinical trials. Though the median dose that relieves neuropathic pain is 75 mg, effective dosages can be more or much less. Because of this and the risk of side ef¬ fects with these older agents, one should start with a low dose. In those less than 65 years of age, 25 mg, and in those older than 65, 10 mg. Prophylactic use of a stool softener such as do¬ cusate sodium and of a methylcellulose mouth spray to deal with constipation and dry mouth respectively are advised. Patients should be cautioned about the possibility of drowsi¬

Anticonvulsants Anticonvulsants may be useful if antidepressants fail, carba¬

Opioids The use of opioids for nonmalignant pain remains contentious but has growing support. Clinical experience indicates that when these drugs are used for pain, the risk of psychological dependency (addiction) is less than 0.5 percent, and major problems with physical dependency and tolerance do not occur in most patients. It is important to know this because opioids may be the only avenue of relief for some patients with severe neuropathic pain. Complete pain relief is unusual; the aim of opioid therapy being to make suffering more tolerable and to improve quality of life. It is advisable to follow certain guide¬ lines in the use of opioids which are good medical practice but also protect one in the face of the scrutiny of regulatory bodies: 1. 2.

A single prescriber A single pharmacy

3.

Regular visits with documentation of strength and number of pills prescribed and clinical status A copy of the prescription in the chart A flow sheet showing drug, strength, and number of pills prescribed

4. 5. 6. 7.

Avoidance in patients with a history of chemical depen¬ dency Cessation of therapy if drug-seeking behaviour occurs

Chapter 166/Nonsurgical Considerations in Neuropathic Pain

It is worth trying other narcotics (Table 166-3) if one agent fails because one may be more effective than another for an in¬ dividual patient or type of neuropathic pain. The dose may be slowly increased every few days, depending on response and side effects. It is reasonable to prescribe an antinauseant and stool softener as a matter of course in the opioid-naive patient. Once a response is achieved with a short-acting drug, a switch can be made to a sustained-action opioid such as MS Contin, which may be more convenient, have less side effects, and be more effective for chronic pain. Opioids may be combined with antidepressant therapy, but it is wise to start with one cat¬ egory (usually the antidepressant), increase to tolerance, and then add the second in a low dose followed by escalation in small increments. It is important, too, to use very small initial doses of any of these agents in the elderly. My patients often report that they obtain a certain amount of relief with increas¬ ing doses of opioid up to a ceiling effect beyond which only in¬ creasing side effects are encountered, negating escalation be¬

1641

or chloroform or Vaseline Intensive Care) and applied to the painful hyperesthetic skin as needed. Local anesthetics such as lidocaine or a eutectic mixture of local anesthet¬ ics (EMLA) may also be applied as needed. Topical ap¬ proaches are rarely useful as sole therapy except in occa¬ sional patients, but they may be a useful adjunct to antide¬ pressants or opioids.

Miscellaneous Treatments For desperate patients, there are a a variety of trial-and-error approaches, none of which is scientifically secure. These are possibly worth trying, however, because occasional individuals appear to respond.

Serotonin reuptake inhibitors This newest category of antidepressants does not appear to

yond that point.

have good pain-relieving properties. Some patients, however, say they feel better or cope better with the pain with the use of these drugs. Amongst them are fluoxetine, fluvoxamine, sertra¬

Topical Agents

line, and paroxetine. Doses of fluoxetine of 40 to 60 mg may be The topical agents most studied for the relief of neuropathic pain are capsaicin, nonsteroidal anti-inflammatory drugs (NSAIDs such as aspirin and indomethacin), and local anes¬ thetics. Use under an occlusive dressing may possibly provide greater efficacy. Capsaicin is the active ingredient in red peppers and other plants, which is thought to act by depleting substance P and other peptides in smaller primary afferents.23 It must be ap¬ plied repeatedly over 3 weeks, although a strong burning sen¬ sation induced by this compound during initial treatment may be intolerable. Guidelines for its use are given in Table 166-4. Capsaicin has been impossible to study in controlled trials because of the burning sensation.23 Aspirin is simply crushed (e.g., two tablets) and mixed in a vehicle (30 mL of ether TABLE 166-3.

more effective than 20 mg.

Mexiletine This orally active local anesthetic agent seems to help some pa¬ tients. Acetaminophen and nonsteroidal ANTI-INFLAMMATORY DRUGS These drugs are usually not useful but occasional patients ben¬ efit. Responses to NSAIDs may be idiosyncratic so that trials of different categories of agents may be warranted.

Relative Potencies of Some Opioids Used for Chronic Severe Pain Related to

Morphine Dose, mg Generic Morphine Heroin Hydromorphone Oxymorphone Codeine phosphate Oxycodone

Levorphanol Methadone Meperidine Anileridine

PO/PR 20-30 PO" 7.5 PO PR 5 PR 200 PO 30 PO 30 PR PO 4 PO 20 PO 300 PO 50 PO

Parenteral

Duration, h

10 4 1.5

4-5 3-4 4-5

1 120

4-5 4—6 PO 3-4 IM 4-5

10-15

2 10 75 25

4-5 3-5 2-3 2-3

“Parenteral-to-oral potency ratio for single doses of morphine in acute pain (1:6) and for repeated doses in chronic pain (1:2-3), reflecting the palliative care experience.

1642

Part 4/Functional Stereotaxis

TABLE 166-4. 1. 2. 3. 4. 5.

6.

Guidelines for the Use of Topical Capsaicin

The frequency of application should be four to five times a day, as less frequent use may be less effective. Treatment should persist for 4 to 5 weeks even if relief is not achieved in the first 2 or 3 weeks, as the onset and best response may be delayed until that time. Patients should be instructed to wash their hands after each application in case of inadvertent involvement of the eye by contact. Weekly or bimonthly visits are important to encourage compliance and to deal with postcapsaicin burning if it occurs. If severe postcapsaicin pain occurs, it may become more bearable after the first week or two and may be tolerated by pretreatment with 5% lidocaine ointment by covering smaller skin areas initially and by using an oral analgesic regularly in the first few days. At the end of 4 or 5 weeks, treatment may be withdrawn and reinstituted if there is recurrence of pain. The duration of treatment for most patients has not been established and could be prolonged.

Transcutaneous electrical nerve STIMULATION, ACUPUNCTURE, RELAXATION

of neuropathic pain, while in desperate patients, unproven ther¬ apy that does not expose the patient to undue risk is warranted.

THERAPY, AND OTHERS. There are many nonpharmacological approaches to neuro¬ pathic pain. In the author’s view, anything that is safe and rea¬ sonably economical is worth a trial in some of these truly des¬ perate patients. I believe that referral of these patients for behavior modification therapy in the presence of a clear history and signs of neuropathic pain is naive and callous.

References 1. 2. 3. 4.

THE PREVENTION OF NEUROPATHIC PAIN There is evidence that acute severe pain (the severing of a nerve during surgery under general anesthesia or acute herpes zoster) may create a state of hyperexcitability in central neu¬ rons which may provide the substrate for persistent pain. It is possible that this might be prevented during surgery by preemptive local anesthetic blockade proximally and perioper¬ ative opioids. Preemptive treatment is, of course, not possible for nonsurgical acute pain like herpes zoster, but here early ag¬ gressive relief of the acute pain may prevent the transition to postherpetic neuralgia. Examples of this would be nerve blocks lor acute zoster pain, antiviral agents, early antidepressant ther¬ apy, and adequate analgesia early with opioids if required. Such therapy is unproven at this time but appears reasonable and safe. Varicella vaccination applied to both children and the elderly may prevent herpes zoster and hence postherpetic pain. Better diabetic control may contribute to a reduction in long¬ term complications such as painful neuropathies. Careful pro¬ tection of nerves at operations such as thoracotomy may mini¬ mize nerve trauma and reduce the incidence and severity of postthoracotomy pain.

5.

6. 7. 8. 9.

10. 11. 12.

13.

14. 15. 16.

CONCLUSION Many strategies have been proposed for the treatment of neuro¬ pathic pain, few supported by scientific study. In our present in¬ complete understanding of the problem, those that have been established should be applied regardless of the particular type

17. 18.

19.

Woodforde JM, Dwyer B. McEwen BW, et al: The treatment of post¬ herpetic neuralgia. MedJAust 2:869-872, 1965. Taub A: Relief of postherpetic neuralgia with psychotropic drugs. J Neurosurg 39:235-239, 1973. Taub A, Collins WF: Observations on the treatment of denervation dysesthesia with psychotropic drugs. Adv Neurol 4:309-315,1974. Watson CPN, Evans RJ, Reed K, et al: Amitriptyline versus placebo in postherpetic neuralgia. Neurology 32:671-673, 1982. Max MB, Schafer SC, Culnane M. et al: Amitriptyline but not lorazepam relieves postherpetic neuralgia. Neurology 38:1427-1432, 1988. Watson CPN, Evans RJ: A comparative trial of amitriptyline and zimelidine in postherpetic neuralgia. Pain 23:387-394. 1985. Watson CPN, Evans RJ, Watt VR, Birkett N: Postherpetic neuralgia: 208 cases. Pain 35:289-298, 1988. Kishore-Kumar R. Max MB. Schafer SC, et al: Desipramine relieves postherpetic neuralgia. Clin Pharmacol Ther 47: 305-312, 1990. Watson CPN, Chipman M, Reed K, et al: Amitriptyline versus maprotiline in postherpetic neuralgia: A randomized double-blind crossover trial. Pain 48:29-36, 1992. Farber GA. Burks JW: Chlorprothixene therapy for herpes zoster neu¬ ralgia. South Med J 67:808-812, 1974. Nathan PW: Chloroprothixene (Taractan) in postherpetic neuralgia and other severe chronic pains. Pain 5:367-371, 1989. Gerson GR, Jones RB, Luscombe DK: Studies on the concomitant use of carbamazepine and clomipramine for the relief of postherpetic neuralgia. Postgrad Med J 54( suppl4): 104-109, 1977. Hatangdi VS, Boad RA, Richards EG: Postherpetic neuralgia: Management with anti-epileptic tricyclic drugs, in Bonica JJ and Albe-Fessard D (eds): Advances in Pain Research and Therapy. New York: Raven Press, 1976, pp 583-587. Killian JM, Fromm GH: Carbamazepine in the treatment of neuralgia. A rch Neurol 19:129-136. 1968. Raftery H: The management of postherpetic pain using sodium val¬ proate and amitriptyline. Irish Med J 72:399-401. 1979. France RD, Urban JB. Keefe FJ: Long-term use of narcotic analgesics in chronic pain. Soc Sci Med 19:1379-1382, 1984. Portcnoy RK: Chronic opioid therapy in nonmalignant pain. J Pam Sympt Mgl 5:46-62, 1990. Wan Lu C, Urban B. France RD: Long-term narcotic therapy in chronic pain. A paper presented at the Canadian Pain Society and American Pain Society Joint Meeting. Toronto, Canada, 1988:10-13. Fields HL: Can opiates relieve neuropathic pain? Pain 35:365. 1988.

Chapter 166/Nonsurgical Considerations in Neuropathic Pain

20.

21. 22.

23. 24.

Urban BJ, France RD, Steinberger DL, et al: Long-term use of nar¬ cotic/antidepressant .medication in the management of phantom limb pain. Pain 24:191-197, 1986. Arner A, Myerson BA: Lack of analgesic effect of opioids on neuro¬ pathic and idiopathic forms of pain. Pain 33:11-24, 1988. Max MB, Schafer SC, Culnane M, et al: Association of pain relief with drug side effects in postherpetic neuralgia: A single-dose study of clonidine, codeine, ibuprofen and placebo. Clin Pharmacol Ther 43:363-371, 1988. Watson CPN: Topical capsaicin as an adjuvant analgesic. J Pain Sympt Mgt 9:425^133, 1994. Dyck PJ, Karnes J, O’Brien PC: Diagnosis, staging, and classification of diabetic neuropathy and associations with other complications, in Dyck PJ, Thomas PK, Asbury AK, et al (eds): Diabetic Neuropathy.

31.

32.

33.

Max MB, Lynch SA, Muir J, et al: Effects of desipramine, amitripty¬ line, and fluoxetine on pain in diabetic neuropathy. N Engl J Med 326:1250-1256, 1992. Rull JA, Quibrera R, Gonzalez-Millan H, Castaneda OL: Sympto¬ matic treatment of peripheral diabetic neuropathy with carbamazepine (Tegretol): Double-blind crossover trial. Diabetologia 5:215, 1969. Wilton TD: Tegretol in the treatment of diabetic neuropathy. S Afr

34.

Med J 48:869, 1974. Chakrabartl AK, Samantary SK: Diabetic peripheral neuropathy: Nerve conduction studies before, during and after carbamazepine

35.

therapy. Aust NZ Med J 6:565, 1976. Chadda VS, Mathur MS: Double blind study of the effects of diphenylhydantoin sodium on diabetic neuropathy. J Assoc Phys India 26:403, 1978. Saudek CD, Werns S, Reidenberg MM: Phenytoin in the treatment of diabetic symmetrical polyneuropathy. Clin Pharm Ther 22:196,

25.

Philadelphia: Saunders, 1987, pp 36^14. Davis JL, Lewis SB, Erich JE, et al: Peripheral diabetic neuropathy treated with amitriptyline and fluphenazine. JAMA 238:2291-2292,

36.

26.

1977. Gomex-Perez FJ, Rull JA, Dies H, et al: Nortriptyline and fluphenazine in the symptomatic treatment of diabetic neuropathy: A

37. 38.

27.

double-blind study. Pain 23:395^100, 1985. Turkington RW: Depression masquerading as diabetic neuropathy. JAMA 243:1147, 1980. Kvinesdal B, Molin J, Froland A, Gram LF: Imipramine treatment of

39.

28.

40.

29.

painful diabetic neuropathy. JAMA 251:1727, 1984. Max MB, Culnane M, Schafer SC, et al: Amitriptyline relieves dia¬ betic neuropathy pain in patients with normal or depressed mood.

30.

Neurology 37:589, 1987. Max MB, Kishore-Kumar R, Schafer SC, et al: Efficacy of desipramine in painful diabetic neuropathy: A placebo-controlled trial. Pain 45:3-9, 1991.

1643

41.

1977. Ellenberg M: Treatment of diabetic neuropathy with diphenylhydan¬ toin. NY State Med J 68:2653, 1968. Swerdlow M, Cundill JG: Anticonvulsant drugs used in the treatment of lancinating pain: A comparison. Anaesthesia 36:1129, 1981. Leijon O, Boivie J: Central post-stroke pain—A controlled trial of amitriptyline and carbamazepine. Pain 36:27-36, 1989. Davidoff G, Guarricini M, Roth E, et al: Trazodone hydrochloride in the treatment of dysesthetic pain in traumatic myelopathy: A ran¬ domized, double-blind, placebo-controlled study. Pain 29:151-161, 1987. Leijon G, Boivie J: Pharmacological treatment of central pain, in Casey KL (ed): Pain and Central Nervous System Disease. New York: Raven Press, 1991, PP 257-266.

CHAPTER

167

PERIPHERAL NERVE STIMULATION FOR NEUROPATHIC PAIN

Andrew G. Shetter

The gate control theory of pain,1 which was proposed in 1965, predicted that the activation of large-diameter afferent fibers would have an inhibitory effect on small-diameter afferent fibers at the spinal cord level and would reduce the central transmission of pain messages. Shortly afterward, Wall and Sweet2 tested this hypothesis clinically by electrically stimulat¬ ing peripheral nerves and nerve roots with surface or subcuta¬ neous electrodes in a group of eight patients with chronic pain syndromes. There were three patients with posttraumatic neu¬ ralgias, and all the patients had their pain temporarily allevi¬ ated by stimulation. Wall and Sweet noted that pain relief could outlast the pe¬ riod of stimulation by many minutes and that paresthesias had to cover the area of pain to be effective. They also cautioned that the “clinical implications [of this technique] are at present equivocal because two of the first group of patients, who were stimulated many times per day, reported a decreased effect on their pain after several months.”2 These initial observations, made 30 years ago in a small group of patients, have been con¬ firmed by subsequent investigators and have proved to be re¬

cating that spinal cord neuronal circuitry must in part be re¬ sponsible. Inhibition was segmentally organized, since stimula¬ tion of a nerve innervating the receptive field of the spinotha¬ lamic neuron that was tested had the most potent effect. However, stimulation of the nerves innervating a limb other than the one on which the receptive field was found also pro¬

markably accurate. On the basis of this favorable experience, White and Sweet3 implanted a permanent peripheral nerve- stimulating system in a patient with pain after a prior median nerve injury. This repre¬ sents the first use of neuroaugmentative surgery for pain con¬ trol. Peripheral nerve stimulation (PNS) has since become es¬ tablished as an effective technique for treating carefully selected patients with chronic pain secondary to nerve injury.

spinal preparations. As opposed to the central mechanisms for PNS analgesia proposed by those authors, other investigators have demon¬ strated effects that are peripherally mediated. Ignelzi and Nyquist7 stimulated cat superficial radial nerves for 5- to 20-min intervals using stimulus parameters comparable to those em¬ ployed for clinical PNS. They then recorded from single nerve fibers proximal to the site where the conditioning stimulus was applied. The majority of the fibers tested demonstrated ex¬ citability changes after repetitive stimulation; this was charac¬ terized by a transient slowing of conduction velocity, an increase in electrical threshold, and/or a decrease in response

MECHANISM OF ACTION Although the exact mechanism by which PNS reduces chronic pain is not known, experimental evidence suggests that it may have both a central effect and a peripheral effect on acute pain perception. Chung and colleagues4-5 recorded from spinothalamic cells in the lumbosacral spinal cord of anesthetized monkeys. They found that the response of those neurons to both noxious ther¬ mal and electrical stimuli could be markedly inhibited by ap¬ plying a repetitive conditioning stimulus to the common pe¬ roneal nerve or the tibial nerve. The inhibition often outlasted the period of conditioning stimulation by 20 to 30 min. This ef¬ fect was observed in both spinalized and intact animals, indi¬

duced a degree of inhibition. Woolf and associates6 suggested that alpha fiber stimula¬ tion may activate descending inhibitory pathways from the brain stem in addition to its effect on dorsal horn inhibitory currents. They applied nonnoxious electrical stimulation to the base of the tail in rats and measured the flexor withdrawal re¬ sponse after immersion of the tail in hot water. Electrical stim¬ ulation in the intact animals produced a marked prolongation in the withdrawal reaction time. An antinociceptive effect also was seen in rats with a complete cord transection at T 10-Tll, but it was less pronounced. Both the spinal and the supraspinal inhibitory mechanisms could be blocked by naloxone. Pre¬ treatment depletion of 5-hydroxytryptamine attenuated the ef¬ fect of electrical stimulation in the intact animals but not in the

probability. Wall and Gutnick8 studied the physiological properties of sciatic nerve neuromas created in rats. Recordings from dorsal root filaments originating from a neuroma disclosed the pres¬ ence of axons that were continuously active in the absence of a peripheral stimulus. This degree of spontaneous activity was never seen in normal nerves. Tetanic stimulation of nerve fibers proximal to a neuroma produced a marked suppression in the rate of spontaneous firing that lasted up to I h. Similar changes in excitability were not observed in nerve fibers that had intact sensory endings. Those authors8 suggested that the clinical pain relief observed after PNS might be due in part to antidromic in-

1645

1646

Part 4/Functional Stereotaxis

vasion of damaged nerve fibers, which inhibits ongoing neu¬ ronal activity of the type observed in their animal model. Experimental studies such as these indicate that PNS may produce pain relief by acting at multiple sites and through vari¬ ous mechanisms. The likelihood that part of its effect may oc¬ cur peripherally has practical consequences, since it implies that PNS may produce results different from those of spinal cord stimulation in treating certain pain syndromes.

RESULTS After the initial application of PNS in 1965, a number of clini¬ cal series were reported in the literature over the next 10 to 15 years.9*15 The experience was generally favorable, but the use of PNS declined in the 1980s as surgeons active in neuroaugmentative procedures for pain control turned their attention to spinal cord and deep brain stimulation. In recent years, there has been renewed interest in this technique.16*19 Evaluation of the literature to determine the true efficacy of PNS is difficult for several reasons. There are no uniform crite¬ ria for the definition of success, and patient selection criteria vary considerably. Reported follow-up intervals are often less than 1 to 2 years despite the known tendency for surgical re¬ sults to decline with time. There is also considerable confusion and lack of standardization regarding the use of diagnostic cat¬ egories such as reflex sympathetic dystrophy, causalgia, and posttraumatic neuralgia. Finally, no randomized series exists comparing the results of PNS with the best medical care or with alternative surgical options such as spinal cord stimulation and peripheral nerve neurolysis. With these reservations in mind, some tentative conclusions can be drawn. The majority of patients treated with PNS have had pain af¬ ter trauma to a single peripheral nerve. Their symptoms may be accompanied by physical signs of sympathetic nervous system hyperactivity or trophic tissue changes, but this is not invari¬ ably the case. For pain of this type, the literature indicates that 50 to 60 percent of patients experience worthwhile relief after the implantation of a peripheral nerve-stimulating system. There is a wide variation among various series, however, and meaningful comparisons are impossible for the reasons out¬ lined above. Some surgeons have observed that success is more likely with purely sensory nerves (e.g., superficial radial nerve) than with mixed nerves14 and that upper extremity pain is more likely to respond than is pain in the lower extremities.912 The results with sciatic nerve stimulation have tended to be disap¬ pointing, in part because of the difficulty of activating sensory fibers without producing excess motor drive in this large, func¬ tionally important nerve. Initial experience using PNS to treat cancer pain,9 sciatica, pain after low back surgery, and nerve root injury and idio¬ pathic pain was generally unfavorable. Although there have been isolated instances of success in all these categories, suc¬ cess rates seem to be substantially less than 50 percent. One of the best early reports on PNS was that of Nashold and associates.12 It is distinguished by its long follow-up inter¬ val (4 to 9 years) and unusually stringent criteria for success. Patients so designated had subjective pain relief greater than 90 percent, were off all analgesic medications, and continued to use the stimulator regularly. Thirty-five patients were im¬ planted over an 8-year interval (1970-1977). The long-term

success rate for patients with upper extremity pain secondary to peripheral nerve injury was 53 percent (9 of 17 patients). Their results with sciatic nerve implantation were less favorable (31 percent success rate) because of the technical difficulty of stimulating this nerve effectively and the inclusion of some pa¬ tients whose pain was secondary to lumbar spine pathology. If the latter group is eliminated, their long-term success rate in¬ creases to 38 percent (5 of 13 patients). The authors felt that their results had improved over the course of the study period and that future advances in equipment technology and patient selection criteria would lead to better results in the future. By far the largest experience with PNS is that of Racz and colleagues. Much of their information is unpublished, but a re¬ cent communication19 described their results with 125 nerve implants performed in 117 patients. Two-thirds of the patients had pain in an upper extremity. Some had poorly localized pain [“whole-body reflex sympathetic dystrophy (RSD)”] that was felt to have been triggered by an initial injury to a peripheral nerve. Stimulation of the affected nerve was observed to help with pain outside the sensory distribution of the nerve itself. There were 66 patients available for follow-up at postoperative intervals of 1 to 53 months. Thirty-six (55 percent) were de¬ scribed as having “substantial relief’ of their symptoms.

COMPLICATIONS Although the efficacy of PNS is difficult to state with certainty from a review of the literature, the complication rate is well known. The most frequently encountered problem is the need for surgical revision to repair lead wire breakage or reposition electrodes that are not producing satisfactory paresthesias. This was required in up to 50 percent of patients in earlier series.10 The incidence of technical malfunction probably has declined in recent years as a result of improvements in the stimulating equipment. Multicontact electrode systems that permit the physician to change electrode combinations and polarities ex¬ ternally without the need for surgical exploration have been particularly helpful in this regard. The infection rate in a review of eight series9-1012-1416'18 that included 299 patients was 4.6 percent. A proportion of these in¬ fections were superficial in nature and did not require removal of the implanted material. Most of the earlier experience with PNS involved the use of electrodes mounted in a Silastic cuff that was wrapped cir¬ cumferentially around the implanted nerve. If the cuff was too tight or if excess scarring occurred in response to the foreign body, nerve damage could result. In an attempt to avoid this problem, more recent investigators16-18 have advocated the use of a longitudinally oriented electrode that does not encircle the nerve. However, the likelihood of nerve injury with a circum¬ ferential electrode is low. A review of six series9-10-12'15 involv¬ ing 247 patients who were implanted with cuff electrodes dis¬ closed five instances of nerve injury, for an incidence rate of 2.0 percent. Adverse occurrences other than technical malfunction, in¬ fection, and nerve injury occur infrequently and include essen¬ tially those which might be experienced after any peripheral nerve exploration under general anesthesia. It is apparent that the risk of damage by PNS is low, and that the complications are rarely serious.

Chapter 167/Peripheral Nerve Stimulation for Neuropathic Pain

SURGICAL TECHNIQUES The operative technique for implanting a peripheral nervestimulating system is straightforward but requires knowledge of peripheral nerve surgical anatomy. There are three compo¬ nents to an implant: a multicontact electrode, a radiofrequency receiver or battery-powered pulse generator, and a length of lead wire joining the electrode to the power source. Avery Laboratories and Medtronics currently manufacture equipment that is suitable for this purpose. The Avery electrode consists of four platinum contact points arranged in a radial fashion in a Silastic cuff. There are four different cuff sizes to accommodate nerves with different diameters. The electrode has a lead wire with four male connector pins at the opposite end. The lead pins are connected to a female receptacle plug joined to a radiofrequency receiver. Depending on the way in which the pins are placed in the receptacle, different electrode contact combinations can be selected. Postoperatively, the pa¬ tient is provided with an external battery-powered radiofre¬ quency transmitter and a loop antenna. Stimulation is per¬ formed by taping the antenna to the skin over the receive site and turning on the radiofrequency transmitter. Pulse amplitude, pulse rate, and pulse width can be adjusted externally. The hardwired electrode contact combinations, however, cannot be changed without resorting to surgical revision. The appropriate combinations must be set at the time of the initial operation by testing the patient under local anesthesia. An alternative ap¬ proach is to implant the electrode and the radiofrequency re¬ ceiver under general anesthesia and then reexpose the connec¬ tor site 1 to 2 days later under local anesthesia for testing. Stimulation is performed using each of the 21 possible elec¬ trode contact configurations. An electrode selector switch is provided by the manufacturers to assist in this process. Since mixed peripheral nerves contain multiple motor and sensory fascicles that weave in an unpredictable fashion throughout the epineural sheath, different geometric configurations of contact points may result in significantly different responses to thresh¬ old stimulation. The patient is asked to identify an electrode combination that produces paresthesias covering the area of pain without resulting in excess motor drive. The Medtronic equipment for PNS is identical to that used for spinal cord stimulation. The electrode consists of a rectan¬ gular Silastic plate with four oval contact points aligned longi¬ tudinally. The opposite end of the electrode is attached to a multicontact connector plug and a length of lead cable. This in turn mates with an implantable internal pulse generator pow¬ ered by a lithium battery. The pulse generator can be turned on or off when the patient uses a small hand-held magnet, and it is not necessary to tape an antenna to the skin while the device is in use. The patient also can be provided with a somewhat larger external programming wand that enables him or her to alter stimulus intensity, frequency, and pulse width. A more complex physician-controlled programmer permits a change of elec¬ trode contact combinations or polarities externally without the need for surgical exploration. This is a significant advantage over the Avery system, since scarring about the electrode some¬ times can produce changes in the pattern of electrode current densities and cause paresthesias to shift from their original lo¬ cation. The physician programmer also can set the internal pulse generator to cycle on and off automatically if this proves to be advantageous. The presence of an internal rather than ex¬

1647

ternal power source, however, means that the pulse generator must be surgically replaced at 2- to 5-year intervals as the lithium battery expires. A Medtronic radiofrequency transmit¬ ter-receiver device is available but has been used infrequently for PNS, since patients prefer the convenience of a totally im¬ plantable system. The Medtronic electrode stimulates one side of a nerve rather than achieving the circumferential stimulation provided by a cuff electrode. This could theoretically result in difficulty obtaining technically satisfactory paresthesias if, for example, a major motor fascicle were immediately adjacent to the contact points and a major sensory fascicle were on the opposite side. Problems of this type have not been reported by investigators using the longitudinal electrode.16’1719 The Medtronic electrode has a percutaneous lead extension that can be brought out through the skin for a test trial of stimulation be¬ fore a permanent implant is accomplished. The specific surgical dissection required for PNS is depen¬ dent on the nerve to be implanted. This information is available in standard textbooks on peripheral nerve anatomy. There are, however, several general principles to keep in mind. The stimu¬ lating electrode should be placed proximal to the presumed site of injury. In patients who have had prior peripheral nerve ex¬ plorations, this may require a new incision to visualize a more normal portion of the nerve. The exposure also should be planned so that the lead cable joining the electrode to the pulse generator or the radiofrequency receiver does not cross more than one joint space. This lessens the likelihood of lead break¬ age resulting from repetitive flexion and extension. Both the pulse generator and the radiofrequency receiver are relatively bulky and must be implanted subcutaneously in the infraclavicular region, the lower abdomen, or the lateral thigh to minimize incisional discomfort. The most commonly implanted nerves in the upper extrem¬ ity are the median and ulnar nerves. These nerves usually are exposed at a midhumeral level with the pulse generator or receiver placed in a subcutaneous pocket approximately 1 in. inferior to the clavicle. The most frequently implanted lower extremity nerves are the posterior tibial and common peroneal nerves. In most instances, these structures are best exposed above the medial malleolus and the tibial head, respectively, and the power source is buried subcutaneously in the anterolat¬ eral thigh. It is not necessary to dissect the nerve over a greater dis¬ tance than will be required to position the electrode. Care should be taken to keep as much adventitial tissue intact around the nerve as possible. If a circumferential electrode is utilized, a size should be selected that will not constrict the nerve when the tags of the cuff are sutured together. If a longitudinal elec¬ trode is employed, a bed is created adjacent to the nerve and the electrode plate is sutured to soft tissues. There must be sat¬ isfactory apposition of the nerve surface to the electrode con¬ tact points, and pressure on the nerve by the existing lead cable must be avoided. Racz and colleagues18 and Racz and Lewis20 have advocated suturing a piece of fascia to the face of the plate electrode so that the electrode does not come into direct contact with the nerve. Since a fibrous envelope rapidly sur¬ rounds Silastic material implanted in the body, it is not clear that the addition of a fascial barrier provides a further protec¬ tive effect. The lead cable joining the electrode to the pulse generator or radiofrequency receiver should be tunneled subcutaneously

1648

Part 4/Functional Stereotaxis

between the two incisions before final electrode positioning so that the electrode is not inadvertently dislodged. It is some¬ times necessary to make a third incision midway between the first two to assist in subcutaneous passage of the cable. Some surgeons prefer to bring temporary external lead wires through the skin for a trial period of stimulation before implanting a permanent system. In this case, the sequence described above is performed in two stages. Patients generally can be discharged 1 to 2 days after the fi¬ nal implant. They are instructed in the use of stimulating equip¬ ment and encouraged to try different stimulus parameters em¬ pirically. Most patients select a stimulus intensity and a pulse width that produce barely perceptible sensory paresthesias without activation of motor fibers. However, some patients re¬ port that brief periods of very high intensity stimulation are more effective. Similarly, some individuals prefer a pulse rate of 100 Hz or higher, which gives a “buzzing” or tingling sensa¬ tion, while others elect a lower stimulus rate. The amount of time required for stimulation also varies considerably from per¬ son to person, and no set guidelines can be given. Many pa¬ tients can stimulate for relatively brief intervals and obtain pain relief for hours afterward. Others note that their pain returns to baseline levels within minutes after the cessation of stimula¬ tion, and those patients tend to use their units continuously dur¬ ing waking hours.

PATIENT SELECTION CRITERIA Patients with intolerable pain after peripheral nerve trauma are the best candidates for PNS. They may or may not have signs of sympathetic nervous system overactivity or underactivity. Common clinical examples of this type of problem include pain after penetrating injury of the peroneal nerve or median nerve, pain after excision of a Morton’s neuroma, and persis¬ tent pain after ulnar nerve transposition. Ideally, the pain is confined to the sensory distribution of a single nerve. Some authors believe that PNS can be used to treat pain that began with a discrete nerve injury but later evolved into reflex sympathetic dystrophy encompassing an entire limb.19 This indication for PNS should be considered questionable pending further documentation. There also have been reports of implants involving two separate nerves19 or ele¬ ments of the brachial plexus.10 This may be warranted in un¬ usual instances, but most surgeons favor spinal cord stimula¬ tion as a better alternative if the pain is diffuse rather than focal. Pain associated with sciatica, prior low back surgery, can¬ cer, and nerve root injury did not consistently benefit from PNS in earlier trials, and these syndromes should no longer be con¬ sidered indications for this technique. There is no adequate documentation regarding the use of PNS for painful metabolic neuropathies or postherpetic neuralgia. Several tactics have been suggested to further refine the se¬ lection criteria for PNS. Sweet,14 Nashold and colleagues,12 and others strongly advocate the routine preoperative use of nerve blocks. If pain is not stopped or markedly reduced on a tempo¬ rary basis by local anesthetic blockade of the nerve that will be implanted, they feel that the patient should be excluded as a surgical candidate. Unfortunately, a favorable response to a nerve block does not guarantee success with PNS.

Picazza and associates13 analyzed the predictive value of transcutaneous neurostimulation for PNS. Patients who experi¬ enced pain reduction with a transcutaneous stimulator were more likely to benefit from the later implantation of a periph¬ eral nerve electrode than were those who had no response. However, a substantial number of patients with a negative trial of transcutaneous stimulation were later helped by PNS. In recent years, several investigators16'18 have described the use of an externalized lead wire for a temporary trial of PNS before permanent implantation. The lead extension from the electrode is tunneled away from the incision through a separate stab wound and is connected to an external battery-powered pulse generator. Stimulation is carried out over a 2- to 5-day in¬ terval, and the patient is asked to make a subjective estimate of the degree of pain relief. Those with little or no improvement have the electrode removed, while the remainder go on to per¬ manent implantation. We believe that all three screening methods have merit. Patients who do not have marked pain reduction after local anesthetic blockade of a single peripheral nerve are not good candidates for electrode implantation. Individuals whose pain is lessened by transcutaneous neurostimulation tend to have a higher likelihood of success with PNS, but a negative response should not be used to exclude patients who are otherwise ap¬ propriate candidates for this technique. Patients who do not ex¬ perience significant pain relief after a temporary trial of PNS should not have a permanent system implanted.

SUMMARY PNS has a good long-term success rate in treating carefully se¬ lected patients with pain in the distribution of a single trauma¬ tized peripheral nerve. More diffuse pain symptoms character¬ istic of reflex sympathetic dystrophy may be helped by this technique, but the documentation for this indication is less clear-cut. Serious operative complications are rare. Improved equipment has decreased the incidence of technical malfunc¬ tion. PNS should be considered the surgical procedure of choice for posttraumatic neuralgias that do not respond to sim¬ pler measures.

References 1.

Melzack R. Wall PD: Pain mechanisms: A new theory. Science 150:971-978, 1965.

2.

Wall PD, Sweet WH: Temporary abolition of pain in man. Science 155:108-109, 1967.

3.

White JC, Sweet WH: Pain and the neurosurgeon: A forty-year expe¬ rience. Springfield. IL: Charles C Thomas, 1969, pp 895-896. Chung JM. Fang ZR. Hori Y. et al: Prolonged inhibitor of primate spinothalamic tract cells by peripheral nerve stimulation. Pain 19: 259-275, 1984.

4.

5.

6.

7.

Chung JM, Lee KH. Hori Y, et al: Factors influencing peripheral nerve stimulation produced inhibition of primate spinothalamic tract cells. Pain 19:277-293, 1984. Woolf CJ, Mitchell D, Barrett GD: Antinociceptive effect of periph¬ eral segmental electrical stimulation in the rat. Pain 8:237-252, 1980. Ignelzi RJ. Nyquist JK; Excitability changes in peripheral nerve fibers after repetitive electrical stimulation: Implications in pain mod¬ ulation. J Neurosurg 51:824-833, 1979.

Chapter 167/Peripheral Nerve Stimulation for Neuropathic Pain

8. 9. 10.

11.

12.

Wall PD, Gutnick M: Properties of afferent nerve impulses originat-

15.

ing from a neuroma. Nature 248: 740-743, 1974. Campbell JN, Long DM: Peripheral nerve stimulation in the treat¬ ment of intractable pain. J Neurosurg 45:692-699, 1976. Law JD, Swett J, Kirsch WM: Retrospective analysis of 22 patients with chronic pain treated by peripheral nerve stimulation. J Neuro¬

16.

surg 52:482^185, 1980. Long DM, Erickson DL, Campbell JN, North RB: Electrical stim¬ ulation of the spinal cord and peripheral nerves for pain control: A 10-year experience. Appl Neurophysiol 44:207-217, 1981. Nashold BS, GoldnerJL, Mullen JB, Bright DS: Long-term pain con-

17.

18.

trol by direct peripheral nerve stimulation. J Bone Joint Surg 64A: 13.

1-10, 1982. Picaza JA, Hunter SE, Cannon BW: Pain suppression by peripheral

19.

14.

nerve stimulation. Appl Neurophysiol 40:223-234, 1977/78. Sweet WH: Control of pain by direct electrical stimulation of periph-

20.

eral nerves. Clin Neurosurg 23: 103-111, 1976.

1649

Waisbrod H, Panhams CH, Hansen D, Gerbershagen HU: Direct nerve stimulation for painful peripheral neuropathies. J Bone Joint Surg 67B:470-471, 1985. Cooney WP: Chronic pain treatment with direct electrical nerve stim¬ ulation, in Gelberean RH (ed): Operative Nerve Repair and Recon¬ struction. Philadelphia: Lippincott, 1991, 1551-1561. Hassenbusch SJ, Stanton-Hicks M, Walsh J, et al: Effects of chronic peripheral nerve stimulation in a Stage III reflex sympathetic dystro¬ phy (RSD). Presented at the Congress of Neurological Surgeons, 42d Annual Meeting, Washington, DC, Nov. 4, 1992. Racz GB, Lewis R Jr, Heavner JE, Scott J: Peripheral nerve stimulation implant for treatment of causalgia, in Stanton-Hicks M (ed): Pain and the Sympathetic Nervous System. Boston: Kluwer, 1990, pp 225-239. Shetter AG, Lewis R, Moss W, et al: Peripheral nerve stimulation, in Neurosurgical Management of Chronic Pain. New York: Springer-Verlag. Racz G, Lewis R Jr: Peripheral Nerve Stimulation (surgical technique notebook). Medtronic, 1992.

.

CHAPTER

168

STEREOTACTIC MIDBRAIN TRACTOTOMY

John P. Gorecki

The spinothalamic tract begins with second order neurons in the dorsal horn of the gray matter of the spinal cord. Many of these neuronal cell bodies are located in the second and fifth lamina of Rexed. The axonal fibers cross and ascend together in the anterolateral spinothalamic tract, a compact tract that is arranged in a somatotopic pattern. Advantage can be taken of this fact as witnessed by the surgical procedures to alleviate pain—cordotomy and midbrain tractotomy. In the brain stem the majority of these axons leave the spinothalamic tract and terminate with synapses in the reticular activating system and the periaqueductal gray. There are polysynaptic connections from the midbrain to the thalamus. The remaining axons con¬ tinue and terminate on third-order neurons in the thalamus. These synapses occur in the parvocellular ventrocaudal nucleus (Vcpc), in the ventralis posterolateralis (VPL), and in the ventralis posteromedialis (VPM) (see Fig. 168-1). The original tractotomy was performed by Walker as an open procedure.39 Transecting the spinothalamic tract consis¬ tently results in contralateral analgesia and loss of temperature appreciation with preservation of light touch and position senses. This successfully reduces or eliminates nociceptive pain. The original open procedure was difficult to perform and the risk of complications was significant. In addition the inci¬ dence of posttractotomy dysesthesia has made this procedure less attractive for patients with a normal life expectancy. The effectiveness of tractotomy for the reduction of neural injury

Figure 168-1. Diagrammatic representation of spinothalamic tract anatomy. [From Richardson DE: Recent advances in the

pain remains controversial. Today, better imaging techniques have made stereotactic midbrain tractotomy a much easier pro¬ cedure. For this reason, this type of surgery should be consid¬ ered appropriate for patients with malignant disease, with pain in the head, neck, and/or arm, who have not achieved satisfac¬ tory relief with pharmacological management. The use of intraspinal narcotic analgesia (INA) to relieve pain should also be considered as well as midbrain tractotomy, however; head and shoulder pain is more difficult to relieve with INA. It is also difficult to eliminate shoulder pain, or pain above the C5 dermatone, with percutaneous cordotomy. The occurrence of posttractotomy dysesthesia after mid¬ brain tractotomy makes the technique a perfect model with which to investigate central pain. It has been postulated that the occurrence of dysesthesia depends on the extent of inclusion or exclusion of the paleospinothalamic tract and periaqueductal

neurosurgical control of pain. South Med J 60(10): 1082-1086, 1967. Used with permission.]

HISTORICAL PERSPECTIVE Dogliotti first suggested, and carried out, section of the spinothalamic tract in the brain stem in 1938.'“ In 1942 Walker39 added three cases of open mesencephalic tractotomy to his pre¬ viously described two. Descriptions of the pathological speci¬ mens were included, showing the location of the lesion (see Fig. 168-2), and he detailed the resulting hemianalgesia and hemithermanesthesia on the side of the body opposite the le¬ sion as well as a peculiar feeling of “numbness or deadness.’ Proprioceptive sensibilities and coordination were not im¬ paired, and there was slight weakness of the contralateral leg.

gray in the putative lesion.

1651

1652

Part 4/Functional Stereotaxis

A

Walker's mesencephalotomy

Figure 168-2. A. Pathological specimen from Walker's original open midbrain tractotomy. (Used with permission from reference 39.) B. Drawing demonstrating

Walker’s midbrain tractotomy incision. (From Zapletal.45 Used with permission.)

Walker also described transient homonymous visual field ab¬ normalities secondary to intraoperative retraction on the infe¬ rior occipital lobe. The discussion accompanying Walker’s paper is particularly interesting;39 Paul C. Bucy points out that mesencephalic trac¬ totomy demonstrates that loss of sensation of organic origin may be strictly in the midline, refuting the common teaching that sensory loss from real organic lesions is not strictly in the midline and that such loss is indicative of hysteria. Both Walker and Peet agreed that unpleasant paresthesia following the operation will negate the value of tractotomy in the man¬ agement of pain. Walker goes on to postulate that tractotomy at the level of the mesencephalon might relieve central pain based on a reduction of afferent peripheral impulses, since patients with central pain commonly experience more distress when

they are receiving any type of impulses from peripheral parts of the nervous system. Drake and McKenzie13 abandoned open mesencephalic tractotomy after experience with 6 patients because of the ac¬ companying unpleasant posttractotomy dysesthesia. Spiegel and Wycis carried out the first stereotactic lesions in the midbrain in 1947.34,43 They report the long-term results of this procedure, performed in 54 patients, in 1962 in a descriptive article.44 The lesions in question included the spinothalamic and quintothalamic tracts and the adjoining areas of the tegmentum dorsal to the red nucleus. In a number of cases le¬ sions were also made in the dorsomedial thalamus. Patients were included with atypical facial pain (7), postherpetic pain (7). tabes dorsalis (2), spinal cord trauma (6), tumors (12), central pain (18), and stump or phantom pain (2). In this varied

Chapter 168/Stereotactic Midbrain Tractotomy

group of patients, 72.2 percent obtained immediate relief and 31 percent maintained long-term relief. Patients with tumors in general fared well. It is important to note that a small number of patients with facial pain, postherpetic pain, cord injury, central pain, and pain after amputation, obtained long-term relief. There were four deaths (7.4 percent), and dysesthesia occurred in 8 patients (14.8 percent), one transiently. The authors describe making the lesion more rostrally, away from the superior colliculus, reducing the incidence of auditory complications. In one case there was permanent hemiparesis and in one, transient hemiparesis. There were a number of ocular disturbances: difficulty with convergence (1), partial oculomotor paresis (3), Parinaud’s syndrome (3), and Horner’s syndrome (1). Voris and Whistler reported their experience with 118 stereotactic procedures for pain in 90 patients.38 The best re¬ sults were observed in 32 patients with malignancy, with only 1 patient not obtaining relief and 85 percent reporting relief until death. Twenty-seven of these patients underwent mesencephalotomy. Mesencephalotomy was deemed to be satisfac¬ tory for pain in the head, neck, and upper trunk. Fifty-eight pa¬ tients had pain that was not due to malignancy, and 13 of these patients were treated with mesencephalotomy. Three patients obtained more than 3 years of relief with mesencephalotomy, and none obtained no relief. For the whole group, 11 patients obtained more than 3 years of relief. Complications occurred in 19 out of 52 mesencephalotomies: hemiparesis (3), dysesthesia (6), ocular palsies (9), and hemorrhage (1). Zapletal authored an extensive review of mesencephalic tractotomy and thalamotomy, emphasizing the author’s experi¬ ence with 51 patients, operated upon via an open technique, over a 10-year period.45 Eighteen patients underwent a total of 24 open mesencephalotomies by way of a suboccipital, supracerebellar approach. The patients had a wide mix of pain etiol¬ ogies including both malignancy and central pain syndrome. In the immediate postoperative period, 9 patients (47.3 percent) reported nearly complete pain relief, 3 patients pain relief of up to 50 percent, 5 no benefit, and 1 patient was worse. Sustained long-term pain elimination was reported in 4 patients, 3 main¬ tained 50 percent pain relief, 6 were no better, and 4 were worse. One patient with causalgia had enjoyed 9 years of com¬ plete pain relief at the time of that publication. There was one death 5 days following surgery, 2 patients had transient oculo¬ motor paresis, tinnitus occurred in 7 patients; hyperpathia was described by 9 patients and was severe in 4. The author could not define any correlation between the extent of the incision in the brain stem and the appearance of hyperpathia. A further 14 patients underwent open mesencephalothalamotomy, with destruction of the spinothalamic tract where it is concentrated just before entry into the nucleus ventrocaudalis parvicellularis. A total of 8 patients experienced immediate dis¬ appearance of pain, and a permanent result was recorded in 4 patients. More important, hyperpathia occurred in only one case, there was no mortality, and tinnitus did not complicate any of these cases. The open mesencephalotomy originally described by Walker never did gain popularity for three main reasons. The surgical exposure was difficult and, in the words of White and Sweet,42 carried an excessive morbidity and mortality. Second, the lesion includes the acoustic pathway between the inferior

1653

colliculus and the medial geniculate, resulting in auditory com¬ plications. This problem can be resolved by shifting the lesion more rostrally. The most serious criticism of the procedure was the frequent occurrence of postoperative hypeipathia. This com¬ plication is relatively rare following spinal cordotomy, 4.3 per¬ cent,42 more common after medullary tractotomy, 8.5 percent,11 and quite common after mesencephalotomy, depending on the author. Walker39 described hyperpathia in 10 percent, Drake13 in 50 percent, and Zapletal45 in 47.3 percent. Tasker reviewed his experience with stereotactic midbrain tractotomy and thalamotomy for the management of pain sec¬ ondary to head and neck cancer in 1975.37 Thirty-three patients underwent 39 procedures with two deaths (5 percent) being re¬ ported. Initial pain relief was obtained in 90 percent and was maintained until death in 74 percent. Dysesthesia only occurred after lesions of the specific pain pathway, including the primary relay nuclei of the thalamus, and was usually minor. Whisler and Voris41 reviewed their experience with 40 stereotactic mesencephalotomies performed on 38 patients with cancer. Bilateral procedures were performed in two pa¬ tients. Thirty-five patients (92 percent) were pain-free until death. Of the remaining 3, one patient experienced pain recur¬ rence after 9 months, 2 obtained no relief, and 1 of these 2 was helped by a later cingulotomy. One patient was still alive and pain-free after 3 years. Beauvillain de Montreuil and coworkers5 report their expe¬ rience with stereotactic midbrain tractotomy in 11 patients with cervicofacial cancer, confirming excellent early pain relief in 10 patients. They report some pain recurrence after 3 months. Blond and colleagues6 further confirm the utility of mesen¬ cephalic tractotomy for the relief of unilateral pain secondary to head and neck cancer and recommend reserving intraventric¬ ular narcotic administration for diffuse and bilateral pain. In a very interesting report Colombo10 reviews sensoryevoked potentials, before, during and after mesencephalic trac¬ totomy in 8 patients, concluding that postoperative loss of sensory-evoked potentials corresponds to the lesion including medial lemniscal fibers. This finding appears to correlate with the induction of dysesthesia, may shed some light on this iatro¬ genic complication, and may be important in our further under¬ standing of central pain in general. Colombo refers to the pos¬ sibility of successful pain relief, with dense analgesia, with preservation of normal sensory-evoked potentials following cordotomy in the spinal cord. Hitchcock describes a technique for stereotactic lesioning of the spinothalamic tract in the pons,1718 describing a total of 15 patients in detail. Deep analgesia was successfully obtained, although survival was short in a number of the patients. Hitchcock mentions that this technique avoids the risk of ocu¬ lomotor disorders inherent with midbrain lesioning. Based on the literature, it is difficult to make objective state¬ ments about the results of midbrain tractotomy for pain sec¬ ondary to benign disease. Most reports contain a wide mix of patients and are presented as retrospective reviews. In general the procedure seems to be most clearly indicated for pain in¬ volving the head, neck, and/or shoulder or upper extremity sec¬ ondary to cancer. Bosch7 offers an interesting review of 40 cases and compares results between cancer pain and deafferentation pain of 33 patients with cancer; 57 percent obtained long-term pain relief. Seven patients had deafferentation pain

1654

Part 4/Functional Stereotaxis

of whom 4 described early pain relief; none obtained long-term relief. It should be pointed out that the surgical technique was performed under general anesthesia employing ventriculogra¬ phy for localization. The author concludes that mesencephalic tractotomy should be limited to pain secondary to cancer. Amano and coworkers3 also address the question of mesen¬ cephalic tractotomy for pain of benign origin in 34 patients, re¬ porting 83 percent pain relief for nondenervation pain and 64 percent pain relief for denervation pain. One patient was fol¬ lowed 11 years without return of pain. There was no mortality, no dysesthesia, and a 26 percent incidence of oculomotor dis¬ turbance. The author suggests that the lower incidence of ocu¬ lar complications is related to his choice of a more dorsal tar¬ get.4 In addition, the author emphasizes that it is important to use a small lesion that selectively destroys the extralemniscal paleospinothalamic system, as identified by the production of a painful sensation contralateral to the side of stimulation of the medial reticular formation. The target is limited to a range of 2 to 3 mm. From the historical perspective reviewed above, it is appar¬ ent that midbrain tractotomy has been used to treat benign pain as well as the pain secondary to cancer. Nashold25 continues to advocate the use of midbrain tractotomy for central pain. In a review of 27 patients treated for central pain secondary to stroke, lesions produced at the level of the superior colliculus were compared with those at the inferior colliculus.31 Moving the lesion more caudally toward the inferior colliculus reduced the incidence of oculomotor complications. Twenty-four pa¬ tients were available for follow-up with 16 (66.7 percent) ob¬ taining long-term relief. Lesions were performed at the supe¬ rior colliculus in 14 patients, and 12 of those were available for follow-up. Nine (75 percent) of these 12 patients demonstrated significant relief. Lesions were made at the inferior colliculus in 13 patients with lasting relief evident in 7 (58.3 percent) out of the 12 patients available for follow-up. The mortality rate was 7.4 percent; four patients were made somnolent. Ocular movement abnormalities were present in 83.3 percent of the patients treated with superior colliculus lesions, but this per¬ centage fell to 20 percent following inferior colliculus lesions. Abnormalities of binocular vision fell from 50 percent with su¬ perior collicular lesions to zero with inferior collicular lesions. In a 1990 review, Shieff and associates33 combined the long¬ term results reported by Amano and coworkers4 and Shieff and Nashold31-32 and reported 76 percent relief in a total of 46 pa¬ tients treated for benign pain. The importance of the report by Frank and colleagues14 rests in the large number of patients treated for pain due to cancer: 109 patients were operated upon with 83.5 percent remaining pain-free for 2 to 7 months. The mortality was 1.8 percent, anesthesia dolorosa occurred in 3 patients, and gaze palsies were reported in 10.1 percent. This experience was compared with that with thalamotomy performed in 52 patients, yielding pain relief in 51.9 percent and no mortality. This follows an earlier report with 14 patients16 and another with 40 patients undergoing mesencephalic tractotomy, with 85 percent main¬ taining pain relief for 6 months to 2 years and 15 percent com¬ plaining of dysesthesia.15 In 5 patients, bilateral lesions were performed and well tolerated. Ocular movement disorders were observed in 20 percent, most resolving after 2 week, being per¬ manent in only 3 patients. Parinaud’s syndrome was seen in 5, bilateral ptosis in 1. and Foville's syndrome in 2. The authors

conclude that for pain in the head, neck, shoulder, and arm re¬ gion due to cancer, midbrain tractotomy is the neuroablative procedure of choice when more conservative therapy fails or intraspinal narcotic infusion is not indicated. Liberson and coworkers23 report experience with recording evoked potentials from the stereotactically placed electrode dur¬ ing mesencephalic tractotomy in six patients with benign pain. All patients experienced pain relief, although the duration of this relief is not revealed. The authors suggest that the recorded potentials reflect impulses carried in the medial lemniscus and that the proper lesion location is between the medial lemniscus and the spinothalamic tract. Refinement of this type of tech¬ nique may allow others to better define the spinothalamic tract or the paleospinothalamic tract. Specific lesions in either or both of these tracts may allow better pain relief, elimination of dyses¬ thesia, and improved understanding of central pain.

ANATOMY The mesencephalon runs approximately 15 to 20 mm in length between the pons below and the diencephalon above and can be divided into three general parts. The cerebral peduncles lie ventrally, and the most important structure within them is the pyramidal tract located in the middle three-fifths. The area sur¬ rounding the aqueduct of Sylvius is referred to as the tegmen¬ tum, and the dorsal part is the tectum. Seen from the dorsal sur¬ face, the tectum is made up of the quadrigeminal plate. The brachium from the inferior colliculus runs to the medial genic¬ ulate body, the functional relay station of the acoustic pathway. The brachium of the superior colliculus carries optic reflex fibers to the lateral geniculate body. At the level of the inferior colliculus, the tegmentum con¬ tains decussating fibers of the brachium conjunctivum from the superior cerebellar peducle. The substantia nigra, an important dopaminergic nucleus of the extrapyramidal system, separates the cerebral peduncles from the tegmentum. The nucleus of the fourth cranial nerve is located in the ventral portion of the gray matter surrounding the aqueduct, and the medial longitudinal fasciculus lies ventral to this nucleus. On a cross section made at the level of the superior collicu¬ lus, the red nucleus is easily identified within the tegmentum, dorsal to the substantia nigra, a structure easily identified on MRI. The nuclear complex of the third cranial nerve is located in the ventral part of the central gray matter. The pretectal area is located at the junction between the mesencephalon and the thalamus, with the posterior commis¬ sure located at the junction between the third ventricle and the aqueduct within it. The medial lemniscus which carries sensory fibers predomi¬ nantly from the dorsal column is initially located dorsal to the substantia nigra and parallel to it. As the medial lemniscus trav¬ els more rostrally, however, it shifts to take on a more ventral dorsal direction, with the most medial portion remaining ventral. The spinothalamic tract contains the secondary fibers for pain and temperature. At the caudal extent of the mesen¬ cephalon this tract lies slightly dorsal and dorsolateral to the medial lemniscus. Painful sensations from the face are carried in the secondary bulbothalamic tract or quintothalamic tract which originates in the nucleus caudalis of the trigeminal

Chapter 168/Stereotactic Midbrain Tractotomy

nucleus, and traverses the mesencephalon medially, somewhat ventral to the spinothalamic tract, between this tract and the pe¬ riaqueductal gray. Upon entering the brain stem, the spinothal¬ amic tract contains approximately 150,000 fibers, but at the level of the superior colliculus only about 1500 axons remain, one-third with diameters of 4 to 6 microns and two-thirds with diameters of 2 to 4 microns. Many axons synapse with neurons located in the periaqueductal gray and reticular formation of the brain stem. This is believed to constitute the paleospinothalamic system (see Fig. 168-3).

SURGICAL TECHNIQUE The group at Duke uses a modification of the technique de¬ scribed by Nashold on numerous previous occasions. MRI has been very useful in improving localization due to the ability to visualize structures in the brain stem such as the aqueduct, the red nucleus, the superior and inferior colliculi, and the poste¬ rior commissure. Although the author is well aware of the con¬ cerns surrounding the exclusive use of MRI for stereotactic lo¬ calization, in our experience with biopsy, thalamotomy, pallidotomy, and midbrain tractotomy we have been satisfied with MRI localization and have confirmed the accuracy of our target selection with postoperative imaging.1'2-8-9'20-21-22’24’28’29-35-40 In addition, MRI localization is frequently supplemented with CT localization to confirm the selected target. So far there has only been one case of target mismatch between CT and MRI techniques caused by frame slippage and requiring reapplica¬ tion of the stereotactic frame. It is more difficult to choose the target with CT extrapolation from the positions of the anterior (AC) and posterior (PC) commissures being necessary. The au¬ thor uses a computer program36 developed at the University of Toronto to generate a patient-specific map of the thalamus and brain stem in the sagittal plane37 based on the original Schaltenbrand and Bailey atlas.30 It is not possible to choose

Figure 168-3. Anatomy of the midbrain. (From Heimer L: The Human Brain and Spinal Cord— Functional Neuroanatomy and Dissection Guide. New York: Springer-Verlag, 1983. Used with permission.)

1655

the spinothalamic tract or reticular formation directly from MR images; however, one can visualize landmarks that are very close to the proposed lesion site in addition to the traditional AC and PC. Nashold’s target is traditionally described as 5 mm behind PC, 5 mm below it, and 5 to 10 mm lateral to the mid¬ line based on ventriculography. These specific measurements may vary depending on the angle of the AC-PC line relative to the stereotactic frame or imaging plane and to individual pa¬ tient anatomy. With MRI it is convenient to describe the target as being in line with, or anterior to, the aqueduct in an anteriorposterior direction as seen on axial images. The target remains 5 to 10 mm lateral from the midline. The target is roughly in line with the lower border of the superior colliculus. A target that is too far ventral (toward the cerebral peduncles) and more rostral places extraocular movements at greater risk. However, a lesion that is more caudal can place auditory function at risk. It is this author’s belief that the unpleasant dysesthesias that may complicate this procedure are related to lesioning the me¬ dial lemniscal fibers. For this reason, confirming the target with electrophysiology is vital. Experience in performing this proce¬ dure is important, since stimulation of the lemniscal fibers will also produce “sensation,” or paresthesia, in the contralateral body that may be confused with the effect of stimulating the spinothalamic tract. The accurate use of MRI localization depends on the stereo¬ tactic frame system employed as well as the MRI magnet being used. Accurate use depends on not on the actual MRI magnet be¬ ing used but also on the specific installation and requires an on¬ going maintenance and calibration program. The only advan¬ tage that the author can see for using ventriculography for localization is that it allows the operator to visualize the probe in the operating room. But this technique is far inferior, as it provides only the most rudimentary anatomical detail and al¬ lows only indirect visualization of a remote landmark. Cur¬ rently we are investigating the use of a frameless stereotactic system (Radionics Optical Tracking system) which allows

Medial longitudinal fasciculus

Oculomotor nucleus fill)

Central gray Reticular formation

EdmgerAVVstpbat nucleus (III

Spinotectal tract Spinothalamic tract Brachium of inferior colliculus Medial geniculate body Medial lemniscus

Red nucleus

Parieto*. occipito- and temporopontine tracts Oculomotor nerve (III)

Substantia nigra

frontopontine tract

Corticospinal and corticobulbar tracts

1656

Part 4/Functional Stereotaxis

intraoperative, updated computer CT or MR images. For those who find it useful to have images with the electrode in place, this technique allows intraoperative virtual images that mimic those previously available with ventriculography. Intra¬ operative CT is already available at some institutions, and CT fluoroscopy will eventually generate better images. Intra¬ operative MRI will possibly provide another step in improving localization. The Leksell stereotactic frame is applied using local anes¬ thesia. Marcaine, or a mixture of lidocaine and marcaine is use¬ ful, since lidocaine is faster acting while the long-acting mar¬ caine should remain effective throughout the procedure even if there are delays. An MR scan is then obtained on a GE 1.5 Tesla scanner. One-millimeter slices are taken in the axial plane through the brain stem and thalamus. A midline sagittal image is helpful to show the aqueduct, red nucleus, superior and infe¬ rior colliculi. A coronal image is not always obtained, but it al¬ lows visualization of the lateral extent of the mesencephalon, and viewing the slices sequentially can sometimes provide more spatial information for the surgeon. Lesioning is performed in the operating room. General anesthesia is not used, but the patient may receive some seda¬ tion, usually propafol and narcotic analgesia, usually fentanyl, particularly during drilling the skull. The frame is connected to a Mayfield adapter, and the patient is positioned semireclining. A twist drill is sufficient to penetrate the skull and the entry point is made at the coronal suture roughly 15 mm from the midline. This trajectory usually results in the electrode passing along the longitudinal axis of the spinothalamic tract. The final site chosen for the lesion is based on electrophysiologic stimulation. Stimulation at a frequency of 100 Hz in the spinothalamic tract produces at a very low threshold (0.1 to 0.2 V) a contralateral sensation most commonly of burning, with some patients describing electrical shocks, cold, or pain. There is some difference in the literature in terms of reporting the

Lffl Anolqesio - Pm Prick - Porn Relief Conlrolof Body Loss-Up Goze No Reduction of Suffering Pom ond Suffering Relief Foce Oculor Chonges

sensation of pain, with some authors suggesting pain is only re¬ ported from reticulothalamic stimulation or in cases of deafferentation pain, whereas others believe this to be a response to neospinothalamic stimulation. Sensation is produced in the face more medially and in the leg more laterally. Stimulation closer to the aqueduct in the periaqueductal gray produces a more dif¬ fuse response, often with the description of pain, burning, cold, or vibration. There is usually an emotional reaction which seems to be difficult for patients to describe, that seems to be unpleasant, and some patients call it fear. There is an alerting re¬ sponse with the eyes often opening widely, and the patient sometimes appearing aroused or agitated. One patient could not explain the feeling but insisted on the stimulation being contin¬ ued and at a stronger intensity. Auditory responses are obtained if the electrode is near the lateral lemniscus and can be con¬ firmed by turning the stimulation on and off or by the patient recognizing changes in the frequency of the auditory hallucina¬ tion. Ocular responses in our hands have most commonly been forced version of the eyes away from the electrode, loss of up¬ ward gaze, loss of version toward the electrode, ocular oscilla¬ tion, and partial lid closure. The patient often recognizes this, and of course the examiner can see the response. It is usually possible to eliminate the ocular response by advancing the elec¬ trode or by moving it more dorsal or more lateral. We do not make a lesion if an ocular response occurs with a threshold of less than 1.0 V (see Fig. 168-4). The lesion electrode has a 3-mm exposed tip 1.2 mm in di¬ ameter. The electrode is monopolar, and the lesion is made using a Radionics radiofrequency generator, with thermister temperature control. A temporary test lesion can be made to 50°C, but the permanent lesion is made to 80° for 30 s. Ocular movement is tested during lesion generation as well as motor functioning of the contralateral arm, hand, and leg. Usually two lesions are made, the second after withdrawing the electrode 3 mm, and sometimes an additional lesion is made medially to

ELECTRICAL STIMULATION

Oiffuse Pom .Vibration,Cold Center Of Body oro-fociol chest .obdomen pelvis Blushing-Fociol-Nuchol Piioerection-Conlroiai Oculor Movements Strong Emotionol Reoction Feor Localized Pom Burning, Numbness Cold Controlot Foce,Arm,Chest,Leg Contralot Piloereclion Sweating Moderote Emotional Reaction

Figure 168-4. Response to stimulation within the midbrain at a site in the spinothalamic tract A, or in the periaqueductal gray (PAG) B. (From Shieff and Nashold.33 Used with permission.)

Chapter 168/Stereotactic Midbrain Tractotomy

affect the reticulothalamic tract and periaqueductal gray. A sin¬ gle stitch closes the entry point. The patient is observed in the neurosurgical intensive care or step-down unit overnight, and most patients stay in the hospital

2 or 3 days following surgery. During this time narcotics can be tapered. If diplopia results, an eye patch is very helpful, and the patient usually benefits from some physical therapy particularly to help with ambulation (see Figs. 168-5, 168-6, 168-7).

C Figure 168-5.

1657

MRI localization.

1658

Part 4/Functional Stereotaxis

C Figure 168-6. Postoperative MRI of lesion.

SUMMARY AND CONCLUSIONS This author has experience with eight midbrain tractotomies performed in seven patients over the past three years using MRI stereotactic localization as described. Four patients suf¬ fered from pain as a result of neoplasm. One patient had phan¬ tom pain secondary to a traumatic upper extremity amputation

which failed to respond to DREZ coagulation performed twice, deep brain stimulation, and intrathecal narcotic infusion. Midbrain tractotomy was performed twice, 1 year apart, with delayed pain recurrence occurring both times. Prior to the sec¬ ond procedure there was intermittent induced shooting pain with residual evidence of preserved patchy appreciation of pin¬ prick over the shoulder. On MRI the midbrain lesion was small

Chapter 168/Stereotactic Midbrain Tractotomy

1659

this modality when other more conventional therapies fail, es¬ pecially if it is being done as part of a clinical trial. It will be important to better define the indications for this stereotactic operation.

References 1.

2.

83:271-276, 1995. Alterman RL, Kali BA, Cohen H, Kelly PJ: Stereotactic ventrolateral thalamotomy: Is ventriculography necessary? Neurosurgery 37:

3.

712-721, 1995. Amano K, Kawamura H, Tanikawa T, et al: Stereotactic mesen¬ cephalotomy for pain relief. Stereotact Funct Neurosurg 59:16-19,

4.

1991. Amano K, Kawamura H, Tanikawa T, et al: Long-term follow-up study of rostral mesencephalic reticulotomy for pain relief: Report of

7.

34 cases. Appl Neurophysiol 49:105-111, 1986. Beauvillain de Montreuil C, Lajat Y, Resche F, et al: Use of stereotac¬ tic neurosurgery in the treatment of pain in cervicofacial cancers. Ann Oto-Laryngologie Chir Cervico-Faciale 100:181-186, 1983. Blond S, Assaker R, Meynadier J, Merienne L: La tractotomie pedonculaire stereotaxique: Sa place dans le traitement des algies cervico-faciales neoplastiques. Agressologie 29:77-80, 1988. Bosch DA: Stereotactic rostral mesencephalotomy in cancer pain and

8.

deafferentation pain. J Neurosurg 75:747-751, 1991. Burchiel KJ: Image-based functional neurosurgery. Clin Neurosurg

5.

Figure 168-7. Pathological specimen of a stereotactic lesion. (From Helfant MH, Leksell L, Strang RR: Experience with intractable pain treated by stereotaxic mesencephalotomy. Acta Chir Scand 129:573-580, 1995. Used with permission.)

and located a little lateral and dorsal to what was considered ideal. All the treated patients experienced at least early com¬ plete pain relief associated with dense dissociated analgesia. Recurrence has been identified only in the one patient after two procedures. There were no complaints of dysesthesia, all patients demonstrated immediate postoperative diplopia al¬ though, surprisingly, half did not volunteer this symptom until attention was brought directly to it on physical examination. One elderly patient with postherpetic neuralgia was made per¬ manently very drowsy and required placement in a nursing home. Nevertheless he could be roused to voice, was oriented, had no focal deficit other than analgesia, and denied pain. For pain in the head, neck, and shoulder secondary to malig¬ nancy that cannot be controlled with pharmacologic means, stereotactic midbrain tractotomy is very effective and should produce satisfactory pain relief that lasts until death in the ma¬ jority of patients. Specific conclusions regarding the use of this procedure for pain in this location due to benign pathology, or of a central and deafferentation nature, cannot be drawn. Some authors suggest that ablative procedures should be limited to patients with cancer, and others3-4,19-25,26,27,31,32,33 support the use of midbrain tractotomy for pain due to a more diverse group of etiologies. Certainly, from the historical review, it should be apparent to the reader that more than a few patients with central pain have obtained lasting relief following midbrain tracto¬ tomy. It will be important to establish if the likelihood of such long-term relief depends on the specific nuclei or tracts in¬ cluded in the therapeutic lesion or the specific preservation of certain anatomic structures. This author believes that midbrain tractotomy is less effec¬ tive for the treatment of central or deafferentation pain than for nociceptive pain. It is, however, reasonable to continue to use

Alexander III EA, Kooy HM, van Herk M, et al: Magnetic resonance image-directed stereotactic neurosurgery: Use of image fusion with computerized tomograpy to enhance spatial accuracy. J Neurosurg

6.

9.

39:314-330, 1992. Cohen DS, Lustgarten JH, Miller E, et al: Effects of coregistration of MR to CT images on MR stereotactic accuracy. J Neurosurg 82:

10.

772-779, 1995. Colombo F: Somatosensory-evoked potentials after mesencephalic tractotomy for pain syndromes. Neuroradiologic and clinical correla¬

11. 12.

13. 14.

tions. Surg Neurol 21:453—458, 1984. Crawford AS: Medullary tractotomy for relief of intractable pain in upper levels. Arch Surg 55:523-529, 1947. Dogliotti M: First surgical sections, in man, of the lemniscus lateralis (pain-temperature path) at the brain stem, for the treatment of diffuse rebellious pain. Anesth Analg 17:143-145, 1938. Drake CG, McKenzie KG: Mesencephalic tractotomy for pain. Experience with six cases. J Neurosurg 10:457^462, 1953. Frank F, Fabrizi AP, Gaist G, et al: Stereotactic mesencephalotomy versus multiple thalamotomies in the treatment of chronic cancer pain

15.

syndromes. Appl Neurophysiol 50:314—318, 1987. Frank F, Frank G, Gaist G, et al: Rostral stereotactic mesencephalo¬ tomy in treatment of cancer pain; a survey of 40 treated patients. Acta

16.

Neurochir Suppl 33:437^443, 1984. Frank F, Tognetti F, Gaist G, et al: Stereotaxic rostral mesencephalo¬ tomy in treatment of malignant faciothoracobrachial pain syndromes.

17.

A survey of 14 treated patients. J Neurosurg 56:807-811, 1982. Hitchcock ER, Sotelo MG, Kim MCh: Analgesic levels and technical methods in stereotactic pontine spinothalamic tractotomy. Acta

18. 19.

20.

21.

Neurochir 39:746-752, 1973. Hitchcock ER: Stereotaxic pontine spinothalamic tractotomy. J Neurosurg 39:746-752, 1973. Iacono RP, Nashold BS Jr: Mental and behavioral effects of brain stem and hypothalamic stimulation in man. Human Neurobiol 1:273-279, 1982. Kawashima Y, Chen HJ, Takehashi A, et al: Application of magnetic resonance imaging in functional stereotactic thalamotomy for the evaluation of individual variations of the thalamus. Stereotact Funct Neurosurg 58:33-38. 1992. Kondziolka D, Dempsey PK, Lunsford LD, et al: A comparison be¬ tween magnetic resonance imaging and computed tomography for stereotactic coordinate determination. Neurosurgery 30:402^406, dis¬ cussion 406-^407, 1992.

1660

22.

23.

24.

25.

26.

27. 28.

Part 4/Functional Stereotaxis

Lehman RM, Mezrich T, Sage J, Goldbe L: Peri- and postoperative

33.

magnetic resonance imaging localization of pallidotomy. Stereotact Funct Neurosurg 62:61-70, 1994.

Shieff C, Nashold BS Jr: Stereotactic mesencephalotomy. Neurosurg Clin North Am 1:825-839, 1990.

34. 35.

Spiegel EA, Wycis HT: Mesencephalotomy in treatment of “intractable” facial pain. Arch Neurol Psychiatry (Chicago) 69:1-13, 1953. Tasker RR, Dostrovsky JO, Dolan EJ: Computerized tomography

36.

(CT) is just as accurate as ventriculography for functional stereotactic thalamotomy. Stereotact Funct Neurosurg 57:157-166, 1991. Tasker RR, Hawrylyshyn P, Rowe IH, Organ LW: Computerized

Liberson WT, Voris HC, Uematsu S: Recording of somatosensory evoked potentials during mesencephalotomy for intractable pain. Confin Neurolog 32:185-194, 1970. Lunsford LD: Magnetic resonance imaging stereotactic thalamotomy: Report of a case with comparison to computed tomography. Neurosurgery 23:363-367, 1988. Nashold BS Jr: Brain stem stereotaxic procedures, in Schaltenbrand G, Walker AE (eds): Stereotaxy of the Human Brain. New York: Thieme, 1982, pp 475-483. Nashold BS Jr. Wilson WP: Central pain: Observations in man with chronic implanted electrodes in midbrain tegmentum. Confin Neurolog 27:30-44, 1966. Nashold BS Jr, Wilson WP, Slaughter DG: Sensations evoked by stimulation in the midbrain of man. J Neurosurg 30:14-24, 1969. Page RD, Miles JB: Validation of CT targeting for functional stereotaxis with postoperative magnetic resonance imaging. Comment in: Br J Neurosurg 9(2) 239, 1955. Br J Neurosurg 8: 461-467, 1994.

29.

Ruzicky E, Sramka M: Mathematical methods using CT and MR im¬ ages for stereotactic neurosurgery. Mo! Chem Neuropathol 25: 247-254, 1995.

30.

Schaltenbrand G, Bailey P: Introduction to Stereotaxis with an Atlas of the Human Brain. Stuttgart: Thieme, 1959. Shieff C, Nashold BS Jr: Stereotactic mesencephalic tractotomy for thalamic pain. Neurolog Res 9:101-104, 1987. Shieff C, Nashold BS Jr: Stereotactic mesencephalic tractotomy for the relief of thalamic pain. Br J Neurosurg 1:305-310, 1987.

31. 32.

37.

graphic display of results of subcortical stimulation during stereotac¬ tic surgery. Acta Neurochir (suppl 24):85-98, 1977. Tasker RR: Neurological concepts of pain management in head and neck cancer. Can J Otolaryngol 4:480-484, 1975.

38.

Voris HC, Whistler WW: Results of stereotaxic surgery for intractable pain. Confin Neurolog 37:86-96, 1975.

39.

Walker AE: Relief of pain by mesencephalic tractotomy. Arch Neurol Psychiatry 48:865-883, 1942.

40.

Walton L, Hampshire A, Forster DM, Kemeny AA: Stereotactic local¬ ization using magnetic resonance imaging. Stereotact Funct Neuro¬ surg 64 (suppl 1): 155—163, 1995.

41.

Whisler WW, Voris HC: Mesencephalotomy for intractable pain due to malignant disease. Appl Neurophysiol 41:52-56, 1978. White JC, Sweet WH: Pain: Its mechanisms and neurosurgical con¬ trol. Springfield, IL: Charles C Thomas, 1955. Wycis HT. Soloff L, Spiegel EA: Facial pain, persisting after retrogasserian rhizotomy, relieved by mesencephalothalamotomy. Surgery 27:115-121, 1950.

42. 43.

44. 45.

Wycis HT, Spiegel EA: Long-range results in the treatment of intractable pain by stereotaxic midbrain surgery. J Neurosurg 101-107, 1962. Zapletal B: Open mesencephalotomy and thalamotomy for intractable pain. Acta Neurochir (suppl 18): 1-119, 1969.

CHAPTER

169

SYMPATHECTOMY FOR PAIN AND HYPERHIDROSIS

Harold A. Wilkinson

BACKGROUND Surgery on the sympathetic nervous system was introduced in the 1890s, before the functional role of the autonomic nervous system had been fully elucidated and widely understood. Early sympathectomies were carried out for the treatment of epilepsy, exophthalmic goiter, spasticity, and angina pectoris, and it was not until the 1930s that the beneficial effects of lumbar and tho¬ racic sympathectomy were demonstrated for angina pectoris, vascular ischemic disorders, trophic ulcers, hypertension, hyperhidrosis, and pain.1 The advent of potent antihypertensive medications has largely eliminated the need for sympathec¬ tomy for blood pressure control, but each of the other latter conditions continues to provide indications for sympathectomy. Angina pectoris is now treated most commonly with medica¬ tions, but the variant form of Prinzmetal’s angina has been shown to be refractory to most medications and to surgical coronary vasodilatation but to be quite responsive to sympa¬ thectomy. The nomenclature regarding the clinical functional abnor¬ malities of the sympathetic nervous system, or sympathetic dysautonomias, is confusing and complicates the diagnosis of individual cases and the analysis of published reports. A lengthly list of terms has been used, and published definitions are often in conflict even for the more commonly used terms such as causalgia (major or minor), reflex sympathetic dystro¬ phy, and Raynaud’s syndrome. Some of the confusion results from the wide and often overlapping spectrum of symptoms at¬ tributable to sympathetically mediated disorders and to the varying anatomic sites of those symptoms. The principal mani¬ festations are vasospastic (often painful), causalgic (in the sense of sympathetically mediated pain without tissue destruc¬ tion or ischemia), dystrophic (usually affecting joints and skin more than other tissues), coronary vasospastic (Prinzmetal’s angina), or hyperhidrosis (congenital varieties and those ac¬ quired following trauma or stroke and including gustatory, plantar, palmar, and diffuse varieties). Sudek’s atrophy (in which dystrophy predominates over pain), reflex sympathetic dystrophy, and major causalgia (both combining severe pain with dystrophic features) are usually predominantly unilateral but frequently have at least some bilateral component. Raynaud’s syndrome (of peripheral vasospasticity) and hyper¬

ily, through sympathetic interruption.2-6 The pain may be ac¬ companied by or may be caused by dystrophic changes or im¬ paired circulation, but it can occur without these physical con¬ comitants. Sympathetically mediated pain most commonly affects the extremities or causes a specific type of cardiac pain. Diagnostic sympathetic blocks are important not only because they can determine when pain is sympathetically mediated but also because one or more sympathetic blocks may provide per¬ manent pain relief. Unfortunately, relief of the sympathetically mediated pain by sympathectomy may be temporary, and the sympathectomy may fail to reverse the associated vascular or dystrophic changes. Sympathetically mediated pain states are not uncommon but are frequently difficult to diagnose or to di¬ agnose with certainty. Their management frequently challenges the skill and perseverance of the clinician. The clinical syndromes of sympathetically mediated pain can be quite varied but do fall into identifiable patterns. The ex¬ treme limb pain that follows a documented acute major arterial occlusion (and which may persist following reestablishment of adequate blood flow), angina pectoris (which persists despite coronary vasodilators or angioplasty), the cold, blue and painful hand that develops after exposure to cold, and the clas¬ sic presentation of major causalgia should be readily identifi¬ able as most likely being associated with sympathetically me¬ diated pain. Greater diagnostic difficulty is encountered in those patients who complain of diffuse extremity pain (espe¬ cially if dystrophic changes are of limited severity) or who pre¬ sent with obstructive small vessel disease in one or more ex¬ tremities or with relatively painless atrophy and dystrophy of a limb periphery.7 Any of these syndromes can present in a wide array of variations, so the clinician is often challenged in mak¬ ing the diagnosis on a purely clinical basis. Psychological factors also are prominent in many patients with such painful conditions.4 Whether the psychopathology preceded the painful condition or developed as a result of chronic pain, disability, and loss of control, strong psychologi¬ cal factors clearly distort the patient’s response to pain, confuse the diagnosis of the painful condition, and can maintain “pain behavior” even after the sympathetically mediated component has been relieved. Interruption of the sympathetic supply to the affected area (lumbar, splanchnic, or thoracic sympathetic chains or stellate ganglia) can confirm whether at least a portion of the pain is sympathetically mediated, but even this evaluation can be con¬ founded by “placebo” reactions.4 Especially in those patients with obstructive vascular disease or significant dystrophic limb

hidrosis are predominantly bilateral. Sympathetically mediated or sympathetically dependent pain encompasses a spectrum of conditions that have in com¬ mon the factor that the pain can be relieved, at least temporar¬

1661

1662

Part 4/Functional Stereotaxis

changes, much of the pain is likely to be transmitted through somatic pathways and not to be under sympathetic mediation. Furthermore, most of the painful and dystrophic syndromes oc¬ cur following injury to a limb and especially following injury to a peripheral nerve, so that pain and disability secondary to the initiating injury likewise remain after elimination of the sympathetically mediated pain component. Visceral pain afferents from the pancreas travel bilaterally through the splanchnic chain and through the lower thoracic sympathetic ganglia. The biliary tract is supplied by the right splanchnic nerves, and each kidney is supplied unilaterally through the splanchnic nerves of the same side. Pain from these viscera is often also transmitted through somatic nerves, fre¬ quently with a referred pattern of radicular pain. That compo¬ nent of visceral pain which can be relieved by diagnostic sym¬ pathetic blocks can often be relieved in a lasting fashion by chemical or surgical splanchnic nerve and lower thoracic sym¬ pathetic ganglion resection.3,5.6,8-11 Splanchnicectomy has its greatest application in patients with pancreatic carcinoma but is occasionally useful in patients with chronic pancreatitis, severe biliary disease, or some types of kidney pain.

TREATMENT OF SYMPATHETICALLY MEDIATED PAIN: NONSURGICAL Nonsurgical treatment for syndromes with sympathetically me¬ diated pain includes physical therapy, pharmacological therapy, psychotherapy, and various anesthetic sympathetic blocks. Additional therapy is usually needed for treatment of both the initiating injury and the associated disability, including that as¬ sociated with dystrophic or ischemic changes in arms or legs. Physical therapy relies principally on topical modalities of heat, cold, and ultrasound and on exercise programs. Physical modalities become especially important in rehabilitating an ex¬ tremity after the sympathetically mediated pain has been re¬ lieved, but a residue of dystrophy, stiffness, and disuse atrophy persists. Pharmacotherapy relies principally on calcium channel block¬ ing agents, beta- or alpha-adrenergic blocking agents, non¬ steroidal or anti-inflammatory drugs, and antineuralgia drugs. Terazosin is a specific alpha^adrenergic blocking agent that is a peripheral vasodilator and may have a selective effect in blocking peripheral sympathetic augmentation of hyperpathic pain. These compounds can occasionally provide at least useful relief of pain or ischemia, though they rarely suffice to provide complete relief or relief of major causalgia. Nonsteroidal anti-inflammatory drugs and adrenal corticosteroids tend to be particularly helpful in those patients with dystrophic abnormalities and joints that are stiff and painful. Antineuralgia drug therapy tends to be most beneficial for somatic neuralgic pain but at times can be helpful in patients with extremely distressing syndromes of sympathetically mediated pain. As is true for the treatment of trigeminal and other forms of neuralgia, the most useful med¬ ications include carbamazepine, diphenylhydantoin, baclofen, clonazepam, and bedtime amitriptyline or desipramine. For pa¬ tients with strong primary or secondary psychiatric compo¬ nents of their pain, general-purpose anxiolytic, antidepressant, or psychotropic medications may be helpful as ancillary or even primary therapy. Psychotherapy has usually not been es¬

pecially helpful in these syndromes, even though many patients notice that emotional tension clearly aggravates their pain, and many patients clearly become distressfully anxious or de¬ pressed as a result of their pain.2-3,5 Anesthetic sympathetic blocks confirm sympathetic media¬ tion of a patient’s pain but can also provide long-duration or even permanent pain relief. Sympathetic fibers can be blocked along with peripheral nerves or at the level of lumbar or brachial plexus, but the resultant associated somatosensory blockade does not permit a conclusion regarding possible sym¬ pathetic mediation of the pain. The commonest anesthetic blocks confined to the sympathetic system are stellate ganglion or lumbar paravertebral blocks. The student of anatomy will recognize that the stellate ganglion supplies sympathetic inner¬ vation to the head and neck and that the sympathetic supply to the arm is derived principally from T2 and T3 ganglia, not from the stellate ganglion. The reason that stellate blocks are effec¬ tive in producing interruption of sympathetic supply to the arm is readily apparent if the stellate injection is done with anes¬ thetics mixed with radiographic contrast medium. Injections of greater than a few milliliters spread rapidly and widely in the paravertebral space and usually readily reach the second and third sympathetic ganglia—unless prevented from doing so by local scar (which prevents interruption of sympathetic innerva¬ tion of the arm). Anesthetic injections given early in a patient’s clinical course have a much greater chance of producing longlasting or even permanent pain relief. Some lasting success is encountered even in chronically persistent states of sympathet¬ ically mediated pain, so that an anesthetic sympathetic injec¬ tion that produces useful relief of sympathetically mediated pain should routinely be repeated at least once, and numerous times if the pain relief that results is of prolonged and increas¬ ing duration.

TREATMENT OF SYMPATHETICALLY MEDIATED PAIN: SYMPATHECTOMY Permanent or semipermanent interruption of sympathetic activ¬ ity can be produced by interrupting the paravertebral sympa¬ thetic ganglion chain, either through surgical dissection and re¬ section or through chemical, diathermy, or radiofrequency destruction. The human body is admirably capable of regener¬ ating the sympathetic system, and published reports document regeneration even after resection of portions of the sympathetic chain.12-15 Most reported surgical series do not include careful long-term follow-up studies but all document some percentage of recurrence. After following 35 patients who had undergone thoracic sympathectomy for Raynaud’s disease over a 3-year period, Haxton12,13 reported that over 63 percent had relapsed and that “severe relapse is rarely seen in the absence of demon¬ strable sympathetic activity.” One well-documented follow-up study reported recurrent sympathetic activity in 9.7 percent of 42 patients followed from 3 to 8 years after open thoracic sym¬ pathectomy for hyperhidrosis.14 The most popular surgical approaches to the thoracic sym¬ pathetic chain are interscapular, transaxillary, or supraclavicu¬ lar. The lumbar chain is usually resected through a lateral retroperitoneal approach and the splanchnic plexus through the bed of the eleventh rib.

Chapter 169/Sympathectomy for Pain and Hyperhidrosis

The interscapular approach to the upper thoracic sympa¬ thetic chain seems to be the most popular approach used by neurosurgeons.3'5'6,8'14"17 This approach involves resecting the head of one rib on each side to be sympathectomized and per¬ mits resection of T2 and T3 ganglia bilaterally through a single skin incision. A midline incision is made centered over T2 and T3 for bilateral sympathectomy, but a paramedian straight or curved incision simplifies dissection if only a unilateral proce¬ dure is planned. Paraspinal muscles are left in place and re¬ flected medially. Using radiographic marking preoperatively or intraoperatively, the proximal portion of the third rib is resected on the side or sides to be sympathectomized. Complete resec¬ tion of the head of the rib increases the operative complexity and postoperative pain and is not essential, though it does im¬ prove visualization of the sympathetic chain. The second and third sympathetic ganglia are found in paravertebral fat rostral and caudal, respectively, to the deep portion of the rib head. The chain should be cut as far as possible above and below the gan¬ glion to ensure resection of all ganglion cells, and the rami communicantes should be sectioned to permit removal of the two ganglia segments of the chain. Placing metallic clips on the cut ends of the chain that are left in the patient may impede regener¬ ation and prolong the benefit obtained. If the parietal pleura has been tom, this can usually be repaired by simple suturing, posi¬ tive pressure insufflation of the lung, and reinforcement of the suture line with gelatin foam. A chest tube will be needed if the lung itself has been torn. Incisional rib pain may be consider¬ able, and transient intercostal neuralgia is common. The transaxillary, transcostal approach to the upper thoracic chains seems to be preferred by thoracic and vascular surgeons, and bilateral procedures are usually staged days to weeks apart.18 This approach involves an intercostal opening of the chest and temporary collapse of the lung. Access to the T2 gan¬ glion is sometimes difficult, especially in obese patients, but T3, T4, and T5 ganglia can be removed if desired. A rib-spread¬ ing incision is made low in the axilla, usually between third and fourth ribs. The lung apex is partially compressed with a retractor to permit visualization of the thoracic chain as it lies beneath the pleura alongside the vertebrae near the apex of the pleural cavity. The second sympathetic ganglion not uncom¬ monly lies above the pleural reflection away from the vertebrae, and some dissection may be necessitated. In obese patients, the ganglia may not be readily apparent in the paravertebral ex¬ trapleural fat, but palpating the space between the ventral rib heads usually gives an accurate landmark. Care must be taken not to tear the azygous veins or thoracic duct. If the lung has not been tom, as can be tested by filling the cavity with saline, it is not absolutely necessary to leave a chest tube as long as the lung has been fully expanded under positive pressure at the time pleural closure is completed. Intercostal or mammary pain is re¬ ported to occur not infrequently following this exposure, and persistent pneumothorax, pleurisy, or empyema can be major complications. The third surgical alternative approach to the upper thoracic chain involves supraclavicular dissection.1'’ Bilateral incisions are required for bilateral sympathectomy, but both sides can be operated upon relatively easily in a single sitting. Dissection must be carried out near the great vessels, but there is usually little incisional pain. The subclavian artery is identified and the lower stellate and upper thoracic sympathetic ganglia can be

1663

found in the fatty tissues deep and medial to this artery, usually behind the carotid and vertebral arteries but ventral to the prox¬ imal portion of the brachial plexus. Care must be taken not to tear any of the major arteries or veins or to stretch or contuse the brachial plexus, recurrent laryngeal nerve, or phrenic nerve. Especially in a large or obese patient, reaching the third tho¬ racic ganglion may be difficult. Intraoperative radiography with a metallic marker may help to confirm that indeed the sec¬ ond and third ganglia have been exposed for resection. The apex of the parietal pleura lies nearby. A chest tube is usually not needed unless a tear in the lung is documented intraopera¬ tively or by progressive postoperative pneumothorax. Great vessel injury, hoarseness, and arm pain or weakness are among the major complications. A transthoracic endoscopic approach to the upper thoracic sympathetic chain was described by Kux in 1954,19 then redis¬ covered by four separate surgeons a quarter of a century later.20-33 The original technique involved a thoracoscope placed through the ribs, deflation of the lung, and electrolytic destruction of the sympathetic ganglia. Bilateral procedures are necessary for bilateral sympathetic interruption. The initial lim¬ ited popularity of the technique apparently was related to the difficulty in identifying and completely destroying the sympa¬ thetic ganglia, in reaching the T2 ganglia, and in obtaining long-lasting results. Nonetheless, thoracic sympathectomy is currently being reintroduced using modern endoscopic instru¬ ments and techniques to ablate the sympathetic chain with laser or diathermy or to resect and remove it using a two-portal tech¬ nique. Using diathermy, Byrne and coworkers have reported only three severe and four partial recurrences (14.9 percent) in 47 patients followed for more than 3 years.24 The author in 1979 devised a technique for stereotactic per¬ cutaneous radiofrequency upper thoracic sympathectomy.2526 In the ensuing 14 years, two major modifications have been made in the technique, each with improvement in initial out¬ come and long-term follow-up results. In its present tonn, the procedure is done on an outpatient or day-surgery basis under local anesthesia plus neuroleptanalgesia. Two 18-gauge ra¬ diofrequency needle electrodes are used simultaneously to re¬ duce fluoroscopy time and minimize periods of deep anesthe¬ sia. Electrodes are most commonly directed toward the T2 and T3 paravertebral ganglia to denervate the upper limb, and bilat¬ eral procedures are commonly performed in a single session. A series of lesions in a rostrocaudal direction to destroy the en¬ tire fusiform ganglia are important to reduce the frequency of late recurrence, though it is recognized that some late recur¬ rences are inevitable even following open surgical resection. Complications have been relatively few in a series of 227 limbs sympathectomized and have included 8 cases of symptomatic pneumothorax and 11 of transient intercostal neuralgia. In ad¬ dition to not requiring general anesthesia, other advantages of the procedure include the fact that it can be tailored intraopera¬ tively to the patient’s needs, based on monitoring of plethys¬ mography and skin temperature, and that the procedure can easily be repeated with good results. The approach to lumbar sympathectomy is quite different. The lumbar sympathetic chain is usually approached surgically through a flank incision on each side to be sympathec¬ tomized.3'5'811 A muscle-splitting approach through the abdomi¬ nal wall is used to reach the retroperitoneal space along the

1664

Part 4/Functional Stereotaxis

psoas muscle. The ureter is carefully elevated off the vertebral column, and the vena cava or abdominal aorta are carefully preserved at the extreme limits of the dissection. The sympa¬ thetic chain is identified alongside the lumbar vertebrae, and sympathetic chain, ganglia and rami communicantes are segmentally resected. The L2 through L4 ganglia can usually be accessed readily, but there has been considerable debate regarding which sympa¬ thetic ganglia should be included in the resection to assure sympathetic denervation of the leg. The sympathetic pregan¬ glionic fibers arise from the lower thoracic cord and run down¬ ward to the lumbar ganglia. Many of the sympathetic efferents seem to originate in the second or third lumbar ganglia and then pass further caudally through the chain, to exit with the postganglionic rami of L4 or even L5. Although short-term sympathectomy results are good with ablation of the L2 and L3 ganglia only, it has been advocated that long-term results can be improved by including L4 or even L5. Occasional cases have been reported of recurrent sympathetic activity following L2 and L3 ganglion resection, which was then abolished by resect¬ ing L4 or even by adding L5 resection to a prior resection of L2 through L4. Lumbar injections for chemical sympathectomy are made through paravertebral needle placement at the second or third lumbar vertebral body and appropriate placement is gauged by injection of x-ray contrast medium.910 The chemicals injected are usually 7% aqueous phenol, 50% alcohol, or absolute alco¬ hol. The volumes injected have varied from author to author and depending on the result desired, but volumes have gener¬ ally varied from 3 to 8 mL. Splanchnicectomy can be carried out by open surgical re¬ section or chemically, using a technique quite similar to that employed for lumbar chemical sympathectomy except that the needles are centered at L2.10 For open surgery, the patient is po¬ sitioned prone and an oblique incision is made centered over the 11th rib, 5 or 6 cm to the right of midline.5,8,11 Four to six centimeters of the rib are resected, beginning just lateral to the transverse vertebral process, and the pleura is dissected down¬ ward. Intercostal veins are ligated or clipped and the lateral as¬ pects of the 10th through 12th vertebral bodies explored. The sympathetic ganglia are identified ventral to the intercostal nerves and then the splanchnic nerves are identified ventral to them. The splanchnic nerves may be adherent to the pleura, are usually three in number, but are quite variable in their anatomy. An attempt is made to identify the 9th through 12th sympa¬ thetic ganglia. These are then isolated by clipping and cutting the sympathetic chain rostrally and caudally and dividing the rami communicantes. The splanchnic nerves are stripped as far as possible before being clipped and cut, then the whole sym¬ pathetic complex is removed. If the pleura is torn but not the lung, a rubber catheter can be left inside the pleura until the deep thoracic wall layers have been sutured. Suction is then ap¬ plied to the catheter and it is removed while positive pressure is applied by the anesthetist. A chest tube will be necessary if the lung itself has been torn. If splanchnicectomy is being carried out for pancreatic pain, a bilateral procedure must be done, but this can usually be done at a single sitting through right and left lateral incisions. Pernak:7 has best described the technique of radiofrequency stereotactic ablation for lumbar sympathectomy. While others

have advocated multiple lesions and extensive radiofrequency sympathectomy in the lumbar area, she has reported consider¬ able success from a technique in which only single lesions are made, usually at the L3 sympathetic ganglia, monitoring out¬ come acutely in terms of improved limb perfusion and in¬ creased temperature. While undoubtedly a single lesion in the sympathetic chain is unlikely to produce permanent sympa¬ thectomy, she achieves overall excellent results by integrating the sympathectomy rapidly into an aggressive restorative pro¬ gram for patients with low back problems. Others have ques¬ tioned the value of Dr. Pernak’s technique of lumbar sympa¬ thectomy28 or the value of sympathectomy generically for patients with persistent pain following lumbar disk surgery. Percutaneous alcohol or phenol injection for thoracic, splanchnic, or lumbar sympathectomy offers the advantage of technical simplicity but carries significant potential risk.9'10 Thoracic alcohol sympathectomy is uncommonly performed, ever since Leriche published a case of inadvertent tracking of alcohol through a nerve root sheath into the subarachnoid space, causing paraplegia, but lumbar and splanchnic chemical sympathectomy currently seem to be preferred by many clini¬ cians to open surgical sympathectomy. Since the sympathetic ganglia are connected by rather short rami communicantes to the segmental nerves, especially in the thoracic region, and since the genitofemoral nerve courses in the retroperitoneal space near the lumbar sympathetics, somatic nerve injury with severe neuralgia is a potential complication. In the lumbar area, damage to adjacent arteries, ureter, or veins and in the thoracic region damage to the pleura pose significant risks. Ogawa,9 who still performs thoracic as well as lumbar alcohol sympa¬ thectomy, advocates preceding injection of sclerosing solutions with injection of radiographic contrast medium to check for ad¬ equacy of contact with the planned sympathetic ganglia and re¬ assurance that the sclerosing agent will be less likely to reach and damage adjacent structures.

OUTCOME OF SYMPATHECTOMY Since pain and disability not uncommonly persist despite suc¬ cessful sympathectomy and since the sympathetic system has a tenacious propensity to regenerate, as discussed previously, it is important in evaluating patients with persistent symptoms to determine whether or not they are or remain completely sympathectomized. A simple and fairly accurate bedside test is the starch iodine test. The part of the patient’s body to be tested is painted with an iodine solution, which is allowed to dry thor¬ oughly. Powered cornstarch is then dusted lightly over the en¬ tire area, and the patient is placed in a hot room or beneath hot lights and given hot liquids to drink. Light exercise can also help to precipitate perspiration. The moisture produced allows the iodine and starch to interact, turning the white powder to black and thus delineating areas of retained sweating due to preserved or recurrent sympathetic innervation. Bilateral mea¬ surement of skin temperature by thermography or thermistors and measurement of limb perfusion by plethysmography can quantitate differences in sympathetically mediated functions between limbs. However, temperature measurements are sub¬ ject to considerable variation and cannot confirm whether sym¬ pathectomy is complete, especially when bilateral sympathec-

Chapter 169/Sympathectomy for Pain and Hyperhidrosis

tomy has been carried out. Variables include the extent of dys¬ trophic and vascular changes in the limb, ambient and body temperatures, and whether or not the patient has taken vasodi¬ lating medications. Diagnostic sympathetic blocks are the most reliable way of testing for completeness of sympathectomy and should be carried out with solutions containing radiographic contrast medium, which can be visualized under the fluoroscope and on permanent radiographs. Testing the completeness of sympathectomy usually begins with anesthetic injections into the area of presumed sympathectomy, followed later by anesthetization of adjacent sympathetic ganglia. The outcome of these diagnostic injections must be measured not merely in terms of improved circulation and limb temperature but also in terms of reduction in pain. Patients who continue to experience severe pain despite a sympathectomy that is already extensive rarely will obtain useful lasting pain relief by further enlarge¬ ment or extension of the sympathectomy, since sympathectomy seems to be effective in relieving sympathetically maintained pain states chiefly through interruption of the efferent, not af¬ ferent fibers. The results of sympathectomy for sympathetically mediated pain vary greatly according to the precise condition being treated. Sympathectomy for vascular spasm secondary to acute atrial occlusion provides nearly 100 percent long-term relief of the vasospastic component of the disorder. Sympathectomy for Raynaud’s syndrome initially provides almost 100 percent re¬ lief of painful ischemic symptoms. Unfortunately, nearly 15 percent of these patients later develop a collagen vasculopathy, and ischemic symptoms are found to recur in a large number of these patients despite sustained sympathectomy.22,30-31 Because of the known propensity for the sympathetic system to regrow, the percentage of patients who later develop recurrent ischemic symptoms is even higher. Haxton12,13 reported that 63 percent of his 35 patients had relapsed after a 36-month follow-up, se¬ vere relapse being “rarely seen in the absence of demonstrable sympathetic activity.” Patients with ischemic obliterative vas¬ cular disorders usually obtain transient relief of pain and im¬ proved healing of necrotic and ulcerated extremities,31 but the disorder usually progresses and ischemic symptoms that are no longer under sympathetic mediation eventually develop. Sympathectomy for Prinzmetal’s angina has been carried out only in a relatively limited number of patients, but results in these patients have generally been quite good.5,32,33 Sympathectomies carried out for sympathetically mediated disorders characterized principally by pain, with or without dystrophic features, characteristically have yielded only lim¬ ited success. Most authors report sustained pain relief in only two-thirds to three-fourths of patients with any of the surgical techniques.2,4,5,8,11 Dystrophic features may improve steadily but usually require extensive secondary therapy. Since most of these disorders were initiated by some form of painful process, often a peripheral nerve injury, further therapy is usu¬ ally necessary to restore the patient to a fully functional status, to obtain relief from persistent somatic pain, and to rehabili¬ tate the often chronically disabled patient to a usefully func¬ tioning status. The time and extent of sympathectomy are important in de¬ termining outcome. It was mentioned earlier that anesthetic sympathetic interruptions shortly after the beginning of sympa¬ thetically mediated pain states not uncommonly can provide long term relief. Similarly, sympathectomy seems to provide a

1665

better chance of success in those patients with syndromes char¬ acterized principally by pain when the surgery is performed earlier in that patient’s course rather than later.3-6 The extent of sympathectomy necessary to control sympathetically mediated pain likewise is not clear from published data. In the lumbar area, sympathectomy has ranged from single- level destruction at L2 or L3 to destruction carried from L2 through L4. In the thoracic region, destruction most commonly has been carried out at T2 and T3, but recommendations have ranged as broadly as T2 through T5.

References 1.

Greenwood B: The origins of sympathectomy. Med Hist 11:166-169,

2.

1967. Dawson DM, Katz M: Reflex sympathetic dystrophy. Neurol Chron

3. 4. 5. 6. 7. 8.

9.

10. 11.

8:1-6, 1993. Gybels JM, Sweet WH: Sympathectomy for pain, in Neurosurgical Treatment of Persistent Pain. New York: Karger, 1984, pp 257-282. Schwartzman RJ, McLellan TL; Reflex sympathetic dystrophy: A re¬ view. Arch Neurol 44:555-561, 1987. Sweet WH: Sympathectomy for pain, in Youmans JR (Ed): Neurolog¬ ical Surgery, 3d ed. Philadelphia: Saunders, 1990, pp 4086-4107. White JC, Sweet WH: Pain: Its Mechanisms and Neurosurgical Control. Springfield, IL: Charles C Thomas, 1955. Ascheri R, Blumel G: Zum Krankheitsbild der Sudek’schen Dystrophie. Fortrschr Med 99:712-720, 1980. Hardy RW: Surgery of the sympathetic nervous system, in Schmidek HH, Sweet WH (eds): Operative Neurosurgical Techniques: Indica¬ tions, Methods and Results. New York: Grune & Stratton, 1982, vol 2, pp 1045-1061. Ogawa S; Sympathectomy with neurolysis, in Hyodo M, Oyama T, Swerdlow M (eds): The Pain Clinic, IV. Utrecht. The Netherlands: VSP Publishers, 1992, pp 138-146. Reid W, Watt JK, Gray TG: Phenol injection of the sympathetic chain. BrJSurg 57:45-50, 1970. Sadar ES, Cooperman MA: Bilateral thoracic sympathectomysplanchnicectomy in the treatment of intractable pain due to pancre¬

12.

atic carcinoma. Cleve Clin Q 41:185-188, 1974. Haxton HA: The technique and results of upper limb sympathectomy.

13.

J Cardiovasc Surg 11:27-34, 1970. Haxton HA: Upper limb sympathectomy. Br J Surg 57:106-108,

14.

1970. Howng S-L, Loh J-K: Long-term follow-up of upper dorsal sympa¬ thetic ganglionectomy for palmar hyperhidrosis—A scale of evalua¬

15.

tion. Kaohsiung J Med Sci 3:704-707, 1987. Mattassi T, Miele F, D’Angelo F: Thoracic sympathectomy: Review of indications, results and surgical techniques. J Cardiovasc Surg

16.

22:336-339, 1981. Dohn DF, Sava GM: Sympathectomy for vascular syndromes and hy¬ perhidrosis of the upper extremities. Clin Neurosurg 25:637-650,

17. 18.

1978. Shih CJ, Wang YC: Thoracic sympathectomy for palmar hyperhidro¬ sis: Report of 457 cases. Surg Neurol 10:291-296, 1978. Berguer R, Smit R: Transaxillary sympathectomy (T2 to T4) for relief of vasospastic/sympathetic pain of upper extremities. Surgery

19.

89:764-769, 1981. Kux E: Thorakoskopische Eingriffe am Nervensystem. Stuttgart:

20.

Thieme, 1954. Kux M: Thoracic endoscopic sympathectomy by transthoracic elec¬

21.

trocoagulation. Br J Surg 67:71, 1980. Malone PS, Dingnan JP, Hederman WP: Transthoracic electrocoagu¬ lation (TTEC)—A new and simple approach to upper limb sympa¬

22.

thectomy. Irish Med J 75:20-21, 1982. Rosner K, Goldberg S: Der Stellewert der thorakoskopischen Sympathectomie bei der Behandlung des Raynaud-Syndrome. Z Gesamte Inn Med 34:127-128, 1979.

1666

23. 24.

25. 26.

27.

28.

Part 4/Functional Stereotaxis

Weale FE: Upper thoracic sympathectomy for transthoracic electro¬ coagulation. Br J Surg 67:71-72, 1980. Byrne J, Walsh TN, Hederman WP: Endoscopic transthoracic sympa¬ thectomy of the sympathetic chain for palmar hyperhidrosis. Hr J Surg 77:1046-1049, 1990. Wilkinson HA: Percutaneous radiofrequency upper thoracic sympa¬ thectomy: A new technique. Neurosurgery 15:811-814, 1984. Wilkinson HA: Radiofrequency percutaneous upper thoracic sympa¬ thectomy: Technique and review of indications. N Engl J Med 311:34-36, 1984. Pernak JM, Erdmann W: Radiofrequency lumbar sympathectomy, in Kepplinger B. Pernak JM. Ray AL, Schmid H (eds): Pain—Clinical Aspects and Therapeutic Issues, Part II. Linz, Austria: Edition Selva Verlag, 1993, pp 59-64. Kepplinger B. Papst H, Schmid H, Dominkus M: Plantar skin temper¬ ature change after percutaneous radiofrequency lumbar sympathec¬

tomy and local anesthetic blockade of the sympathetic chain, in Kepplinger B, Pernak JM, Ray AL, Schmid H (eds): Pain-Clinical Aspects and Therapeutic Issues, Part II. Linz, Austria: Edition Selva Verlag, 1994, pp 75-78. 29. 30.

Wilkinson HA: Sympathectomy for pain, in JR Youmans (ed): Neurological Surgery, 4th ed. Philadephia: Saunders, 1994. Montorsi W, Ghringelli C, Amoni F: Indications and results of the surgical treatment of Raynaud’s phenomenon. J Cardiovasc Surg 21:203-219, 1980.

31. 32. 33.

Shionoya S, Barr I, Nakata Y, et al: Surgical treatment of Buerger’s disease. J Cardiovasc Surg 21:774-784, 1980. Bailie Y, Siwalt M, Waillant A. Resultats h distance de la chirurgie de l’angor de Prinzmetal. Ann Chir 36: 613-614, 1982. Henrard L, Pierard L, Limet R: Traitement par sympathectomie thoracique de l’angor de Prinzmetal it coronaires saines. Arch Mai Coeur 75:1317-1319, 1982

CHAPTER

170

THE PATHOPHYSIOLOGY OF TRIGEMINAL NEURALGIA

William H. Sweet

TRIGEMINAL NEURALGIA Definitions This disorder is characterized by the paroxysmal occurrence, in abrupt attacks, of pain limited to the trigeminal domain on one side and provoked by minimal local stimuli, in the absence of any sensory loss or continuing pain of duller character. There is, I think, general agreement that these defining features of trigeminal neuralgia (TN) are correctly stated by the Sub¬ committee on Taxonomy of the International Association for the Study of Pain (IASP).94 Some patients meet all of these cri¬ teria except for long periods of much milder trigeminal pain as an unprovoked background on which the major paroxysms are superimposed; this latter group may be classified as atypical TN. The more pronounced and lasting any steady pain compo¬ nent is, the less likely are the standard treatments used for the typical disorder to stop this aspect of the pain. When my own series had reached 790 patients, I had placed 185 (23 percent) of them in the atypical category; 86 percent of those with some steady component were relieved of all aspects of the pain if the main paroxysms were eliminated.35 Pain typical of TN may also occur in the presence of patho¬ logically unequivocal lesions, also defined in the IASP taxon¬ omy under the term secondary trigeminal neuralgia. It may re¬ sult from lesions of the central nervous system or from those affecting peripheral branches, trigeminal ganglion, or rootlets

myelin of the nerves. In all 11 cases there was strikingly grotesque hypermyelination, demyelination, and axonal hyper¬ trophy with extreme tortuosity, as shown in Figs. 170-1 and 170-2. Beaver pointed out that “these are probably the same changes as those described almost 40 years ago by Lignac and Van der Bruggen. . . . Without an electron microscope it would be impossible to differentiate these alterations from those seen in autolysis and in non-specific focal degeneration due to age or to occult disease.”64 However, of the 11 gasserian ganglia those earliest pioneers studied, only 2 specimens were from pa¬ tients with no previous invasive procedure. In all specimens, there were many abnormalities in ganglion cells and fibers, with proliferation of endothelial, capsule, and Schwann cells and infiltration by lymphocytes, plasma cells, and eosinophils. The axons as described by Beaver usually but not always lost their investment by Schwann cells only after considerable de¬ generation of myelin had occurred. He also identified in the Nissl substance of neurons in the gasserian ganglion a peculiar vacuolization (Fig. 170-3). These vacuoles tended to enlarge to form irregular lacunae (Fig. 170-4). Neither severe mitochon¬ drial swelling as in autolysis, dilatation of the Golgi apparatus, nor any other cytoplasmic or nuclear change was identified.

or, very rarely, from facial trauma.

LESIONS IN THE TRIGEMINAL PATHWAYS Site of Anatomic Lesion I shall first present the evidence connecting the bursts of pain with a specific anatomic lesion in the trigeminal pathways. Beaver and coworkers8'9 Beaver,7 and Moses72 did the first in¬ tensive studies with the electron microscope on the trigeminal ganglion of normal animals and humans, and Beaver studied biopsies of the gasserian ganglion in 11 patients with classic TN who had been symptomatic for an average of 4'A years. The specimen was taken and thereafter handled with a minimum of trauma because of the special vulnerability of the axons and

Figure 170-1. The single myelinated nerve fiber shows severe fragmentation and disruption of the myelin but is still surrounded by an attenuated Schwann cell and basement membrane. The eccentrically lying axon is not in direct contact with the extracellular space. (X4400.) (From Beaver,7 with permission.)

1667

1668

Part 4/Functional Stereotaxis

Figure 170-2. Tortuous hypertrophic axon appearing like a “plexiform microneuroma/’ Degenerating Schwann cell cytoplasm visible between folds of axon. Myelin absent on upper surface of axon and almost gone inferiorly. Myelin remaining is almost all at one end. (X6750.) Intermediate stage of degeneration, not included here, shows loss of Schwann cell investment and a moderately enlarged axon in direct contact with the extracellular collagen. (From Beaver,7 with permission.)

Figure 170-3. Cytoplasm of gasserian ganglion cell. In right middle third of illustration, a clump of vacuolated Nissl substance, from which vacuoles seem to arise by dilatation of ergastoplasmic lamellae. (X93(X).) (From Beaver.7 with permission.)

Kerr and Miller53 and Kerr51,52 did even more extensive studies by both light and electron microscopy on specimens of trigeminal ganglion and adjoining rootlets obtained at middle fossa operation in 19 patients with TN. They were divided into two groups: the first consisted of 10 patients with completely typical TN and no previous invasive procedures, and the sec¬ ond was made up of 9 patients who had had either mildly or moderately atypical symptoms or a previous invasive proce¬ dure on peripheral trigeminal divisions. Both sets of investiga¬ tors studied normal controls of gasserian ganglion and neigh¬ boring rootlets from guinea pigs, rabbits, and monkeys; in addition, Kerr had human specimens taken 1 to 4 h postmortem in patients who had died acutely without prior facial pain at ages 42 to 77 years. Kerr’s electron micrographs are essentially identical to those of Beaver in 18 of the 19 patients, with no ap¬ preciable difference in the abnormal myelin between his own two groups. He noted that the major abnormalities in the myelin were gross enough to be seen readily in light mi¬ croscopy. Indeed, in these latter slides, the extent of the in¬ volvement of myelinated fibers of both the ganglion and rootlets was more readily appreciated because of the much larger field of view. Kerr agrees that the myelin abnormalities may look similar in some presumably normal trigeminal nerves, but the myelin disintegration is far more pronounced in TN. In particular, rupture of Schwann cells with scattering of amorphous clumps of degenerating myelin were seen only in TN. Some masses of myelin had no axons. Complete filling of an axon with swollen mitochondria that had lost their typical internal structure was occasionally seen and in fact occurred in Kerr’s 19th patient without abnormal myelin. He and Beaver find these myelin changes to be unlike any reported in other diseases. He also agrees with Beaver in being uncertain as to the significance of the vacuolization of the cytoplasm or any other feature in the ganglion cells. They conclude that these might be merely a general age-related change.

Figure 170-4. Gasserian ganglion cell with nucleus at upper left; as compared with Fig. 170-3, a later stage of vacuolar degeneration to large, irregular lacunae; normal-looking mitochondria. (X7440.) (From Beaver,7 with permission.)

Chapter 170/The Pathophysiology of Trigeminal Neuralgia

We owe to Kune and his colleagues in Prague a description of biopsies taken incidental to trigeminal tractotomy from 9 pa¬ tients with TN.58 The precise boundaries of the descending spinal trigeminal tract at the upper end of nucleus caudalis were identified by electrical stimulation of the relevant surface of the medulla oblongata in the awake cooperating patient. The bulbar tissue removal was for the full dorsoventral extent of the tract and 2- to 4-mm long rostrocaudally at a level about 16 mm rostral to the highest C2 posterior rootlet, i.e., at the up¬ permost level of nucleus caudalis. Maximal care was taken to minimize trauma. No neurons in the nucleus of the descending tract were included. Postoperative sensory testing in 8 of the patients revealed complete analgesia in 6 of them in the do¬ mains of cranial nerves V, IX, and X; analgesia was nearly as complete in the other 2. The published illustrations support the author’s statement that they are almost identical or very similar to those of Beaver and Kerr with respect to grossly abnormal demyelination, hypermyelination, and tortuous hypertrophied axons. The authors agree that no other disorder is accompanied by such microscopic pathology. Biopsies were taken of peripheral relevant nerve branches in two patients with sharply localized third division TN—in one in the mental nerve and in the other the lingual.57 The first patient, 19 years old, had had her pain only 1 week before oper¬ ation. The second patient, aged 68 years, had been in pain for 5 months before operation. In both cases abnormally large nerve fibers with hyperplastic myelin sheaths and segmental demyeli¬ nation were scattered throughout the nerve. The author notes the similarity to the illustrations of Beaver and Kent If a lesion in the root entry zone is capable of initiating the typical pain, it is puzzling that an early prepainful lesion appears to cause the myelin changes in the ganglion itself7 and in the peripheral branches.57

TRIGEMINAL NEURALGIA AND MULTIPLE SCLEROSIS Of 11,120 patients with TN reported in 17 publications, 194 (2 percent) also had multiple sclerosis. Conversely, of 5723 pa¬ tients with multiple sclerosis, 60 (1 percent) also had TN.49108 However, these figures have been obtained mainly from large series having many patients with milder, medically managed disease. In my own surgical series, by the time I had treated 702 patients by invasive procedures, 44 (16 percent) of them had multiple sclerosis; 16 of the 44 (36 percent) were atypical for TN in one or more respects. Adequate relief was provided in all but one case with an extremely atypical clinical picture. In this patient, in addition to “short electric shocks’’ in the tem¬ ple, there were 15-min to 2-h bouts of steady pain of agonizing severity at the same site. Later in such an attack, either steady pain or “electric shocks” would occur in the ipsilateral radial forearm or in the ipsilateral shoulder and arm to the elbow. In two of the most severe attacks, there was wild involuntary flail¬ ing of the opposite arm. The patient lay on the arm to try to control the movements, which stopped when the attack of pain ended. There was not the slightest tendency for a local stimulus to provoke pain anywhere. Toxic doses of carbamazepine (Tegretol) controlled the pain, but three radiofrequency (RF) root lesions yielding complete trigeminal analgesia of skin and mucosa on the painful side were still followed by bouts of in-

1669

Figure 170-5. From the gasserian ganglion of a 22-year-old woman just after death in an acute attack of multiple sclerosis. Three months before she had had a transitory period of unilateral facial numbness. There is degenerative hypermyelination in three nerve fibers with axonal hypertrophy and tortuosity in the fiber on the left. (From Beaver,7 with permission.)

tense pain in the analgesic face as well as in the upper limb. It is, I think, reasonable to conclude that quintothalamic or other more rostral fibers for facial sensation were active in this man. The following neurosurgeons report TN in patients with multiple sclerosis: Broggi et al., 14 cases;13 Brandt and Wittkamp, II cases;10 Brisman, 16 cases;12 Rovit, 18 cases;83 Siegfried. 20 cases;88 and Brett et al., 8 cases." Only 1 of these 87 patients failed to get adequate relief from an RF lesion in the middle fossa (she refused reoperation after the initial inade¬ quate lesion). It is crystal clear that appropriate analgesia in the trigeminal primary afferent neuron stops the pains typical or moderately atypical of TN, whether associated with multiple sclerosis or not. One unusual patient relevant to our thinking here was studied by Beaver.8 A 22-year-old woman with multiple sclerosis had a transient attack of unilateral facial numbness without pain 3 months before she was admitted to hospital moribund with an acute attack of this disorder. No more history was obtainable. However, by electron microscopy (Figs. 170-5 and 170-6), Beaver found in the gasserian ganglion on the affected side the same abnormalities in myelin and axons as those seen in pure TN.

FUNCTIONAL SIGNIFICANCE OF SITE OF LESION The site of the lesion in the neural trigeminal pathways that is best correlated with each of the clinical features of TN has not been established. A number of the reports are extremely sketchy. However, there was a substantial typical plaque* of the disease at autopsy in the root entry zone into the upper pons *The French word plaque has a more general meaning than the same word in English: namely, any identifying device or object, where as in English it usually connotes some firm often elevated structure such as an arterioscle¬ rotic plaque. The English meaning of the word plaque makes it a poor sub¬ stitute for the previously used French word, since the lesions are not neces¬ sarily firm or raised.

1670

Part 4/Functional Stereotaxis

all pain was replaced by disagreeable constant paresthesia.28 Autopsy revealed, in addition to the root entry zone plaque, two more large, right bulbopontine plaques including the de¬ scending trigeminal tract—one at the cervicobulbar junction, the other extending from the emergence of the glossopharyn¬ geal rootlets all the way up the tract to the motor nucleus of

Figure 170-6. From same patient as in Fig. 170-5; enormous hypertrophy of a tortuous, demyelinated axon, remarkably like our Fig. 170-2. (X7200.) (From Beaver,7 with permission.)

of the trigeminal nerve in the single cases of Carrillo et al.,14 Daum et al.,22 Garcin et al.,28 Gurevich,34 Lazar and Kirk¬ patrick,59 Marburg,67 Olafson et al.,74 Oppenheim,77 Parker,79 and case 1 of Tyndel et al.102 The last of these had the only pa¬ tient in whom bilateral TN was associated with plaques in the trigeminal root entry zone on each side. We thus have this clinicopathological correlation on 11 sides of 10 patients. Only in the 64-year-old female patient of Daum et al. were the pains grossly atypical in that they began abruptly with con¬ tinuous pain in the entire right face and oral cavity with the ex¬ ception of the forehead, temple, and tongue.22 On this pain were superimposed extremely severe paroxysms two to four times per day. There were, however, no trigger zones, although for one 15-day period all mastication was precluded by the se¬ vere pain it provoked. The continuous pain gradually disap¬ peared. In addition to the oldest plaque at the right root entry zone, there were two others probably related to the patient’s right facial pain. One was at the junction of the tegmentum and basal part of the left upper pons in the vicinity of the quintothalamic tract and in the same transverse microscopic section as the oldest lesion. The second, more recent plaque was in the right descending trigeminal tract at midbulbar level (Fig. 170-7). One can hypothesize that the latter two lesions gave rise to the atypical features. Likewise the pain of Car¬ rillo’s patient had a number of atypical features, including on¬ set with continuous pain and later numbness and sensory loss.14 These lesions, in addition to one at the root entry zone, were also in the motor and main sensory nuclei, the tract leading thereto, and the bulbar portion of the descending trigeminal tract. It seems plausible that the later sensory loss may be ex¬ plicable on the basis of the main sensory and/or descending tract lesions. The right-sided pain of Garcin’s patient was typical for 6 years; then continuous pain was added, and finally, 1 year later.

cranial nerve V. Again one may hypothesize that the extensive destruction of the descending tract of V greatly decreased and finally stopped the pain related to the root entry zone lesion. This lesion in Lazar’s patient was seen at operative exploration in the cerebellopontine angle, was central within the V rootlet bundle and had the appearance of the lesions demonstrated by Beaver and Kerr.59 The rootlets all around the periphery of the bundle were normal, accounting for the almost normal facial touch sensation. The importance of a plaque in the root entry zone is also supported by Olafson’s well-studied patient, whose painful side had that lesion plus a small one in the motor nu¬ cleus, whereas on the nonpainful side the large plaque involved only the mesencephalic root, the upper end of the descending tract, the quintothalamic tract, and the fibers leading to these areas.74 All of the preceding cases can be understood if a lesion in the root entry zone is the prime starter of the trigeminal pain. The following data do not fit this hypothesis. Of Friedman’s two patients with typical TN, one had, in the trigeminal path¬ ways, only small discolored areas near the nucleus of the trigeminal descending tract, and the other had a large highcervical plaque involving that tract and its nucleus.25 There was some facial numbness in the first case, none in the second. Jensen’s patient with typical but mild right V2 and later VI pain had large plaques on each side including the motor and main sensory nucleus and extending down into the descending tract of V with no root entry zone lesion on either side.49 The two cases of TN of van Gehuchten and Brucher are not readily explicable; one with 13 years of left typical neuralgia had a sin¬ gle trigeminal lesion confined to the motor nucleus.103 The

Figure 170-7. Transverse section of the pons at level of root entry zone; (short arrow) plaque at that zone on right; two (long arrows) plaques at far lateral inferior comer of tegmentum in region of quintothalamic tract. See text. Illustration reverses patient's sides. (Myelin stain.) (From Daum et al.,22 with permission.)

Chapter 170/The Pathophysiology of Trigeminal Neuralgia

other patient, with 6 years of left facial hypesthesia but never any left-sided pain, had a plaque in the left root entry zone plus two large symmetrical plaques engulfing the main motor and sensory nuclei on both sides (Figs. 170-8 and 170-9). Amezua’s patient likewise had never had any right-sided pain despite a major right root entry zone plaque.3 All of the pain had been on the left, on which side a massive plaque included the motor and main sensory nuclei and the root fibers leading to them; but there was only a tiny plaque at the actual site of entry of the root. To summarize: on one side of each of four patients there

%

1671

was no root entry zone lesion on the painful side; contrariwise, on one side of each of two patients there was a root entry zone lesion but no pain on that side.

OTHER CENTRAL CAUSES OF TRIGEMINAL NEURALGIA Syringobulbia There is a well-studied patient with syringobulbia at whose au¬ topsy two small cavities, one on each side, occupied almost symmetrical areas within the nuclei of the descending trigemi¬ nal tracts.23 The pain in the right face was worse than that on the left and the lesion on the right was larger. The pain on the right was a severe continuous burning with superimposed typi¬ cal paroxysms provoked by a current of air or by light brushing of the patient’s mustache. There were no other lesions in the brain stem and no objective sensory loss, so that, at least in sy¬ ringobulbia, a lesion in the nucleus of the descending tract can evoke paroxysmal provocable facial pain.

Neurinoma Invading Lateral Aspect Cl-2 Cord Segment A single case of neurinoma invading the descending trigeminal tract at the Cl-2 level has been accompanied by severe parox¬ ysmal provocable facial pain, which stopped after removal of the tumor.17 Figure 170-8. Transverse section of pons at level of motor and main sensory nuclei and root entry zones. Two large, symmetrical plaques include these nuclei. A third plaque on the left (right side of photograph) lies at the root entry zone. Hypesthesia of the entire left trigeminal area persisted unchanged until death 6 years later. There was never any trigeminal pain or paresthesia on either side. (Spielmeyer stain.) (From Van Gehuchten and BrucherJ03 with permission.)

Figure 170-9. Same patient as in Fig. 170-8 and same pontine level. Dense fibrillary gliosis in the three plaques of demyelination. (Holzer stain.) (From Van Gehuchten and Brucher,'03 with permission.)

Adhesions Binding the Posterior Inferior Cerebellar Artery to the Closed Medulla at the Site of the Descending Tract Pressure by a loop of the posterior inferior cerebellar artery (PICA) against the closed medulla and including the descend¬ ing trigeminal tract was deemed significant in the causation of typical TN in two patients by Sunder-Plassmann et al.95 They were impressed that, upon lysis of adhesions binding the artery against the medulla, a groove in that structure remained. In one of the cases a firm band of scar—3 mm wide, 1 mm thick, and 10 mm long—seemed so likely to be causative of the pain that the planned bulbar tractotomy was not done. However, com¬ plete relief of pain lasted only 6 weeks; tractotomy then yielded relief for the short follow-up of 6 months. The second patient had a tractotomy at once. These 2 patients were part of a series of 42 bulbar tractotomies for TN, among which were 8 others with delicate adhesions holding the PICA against the medulla but not indenting it. These experiences suggest that the primary afferent trigeminal fibers in the lower medulla are not as sensi¬ tive to local mechanical pressure and manipulation as the rootlets at and near their entry into the pons. However, Weber has reported two patients in whom parox¬ ysmal provocable facial pains were unequivocally related to le¬ sions on the lateral aspect of the medulla.IM In both cases dense arachnoidal adhesions bound the PICA firmly against and in¬ denting the side of the medulla. The first patient was described as having typical left second division TN except that she could

1672

Part 4/Functional Stereotaxis

stop the pain by rubbing her left cheek with a wool cloth for about half a minute. She had done this so much that she had at¬ rophy and pigmentation of the left cheek. In both patients the arteries were found during cutting of the dense adhesions. In the first patient, a 54-year-old woman, there was a period of re¬ lief from pain; recurrence was then studied by pneumoen¬ cephalography, which was followed by 2 pain-free years. Thereafter, the pain reappeared on both sides. Adhesions were now found on both sides; pain was again relieved solely by di¬ viding these, again without cutting rootlets or the trigeminal tract. In the second case, a 41-year-old woman, the atypical feature was the presence, also, of left unilateral head pain on turning the head. Provocation of pain by talking and especially by eating led to a 65-lb weight loss. Cutting of the adhesions around the PICA was followed by pain relief, enabling the pa¬ tient to regain the weight rapidly. These two patients support the concept that a lesion of the nucleus caudalis may suffice to provoke typical TN.

DEFICIENCIES IN OUR ANATOMIC INFORMATION Attempts to interpret the significance of the demyelinating plaques suffer from gross inadequacy of the data on two scores. The clinical description of the pain is minimal in the cases of Gurevich,34 Marburg,67 Oppenheim,77 and Tyndel.102 An even more significant deficiency is the absence in nearly all of the publications of detailed accounts of the lesions. The illustra¬ tions are usually confined to myelin stains showing the lesion as a featureless white hole. There is rarely a demonstration of impaired axonal anatomy, lymphocytes, macrophages, blood vessels, and pigments (Figs. 170-10 and 170-11) or of fibrillary gliosis (Fig. 170-9). Lazar’s micrographs indicate how much better a chance we might have to determine whether a lesion was early or late, impulse-conducting or not, and whether or not the quintothalamic tract was involved.59 The nearly com-

Figure 170-11. Multiple sclerosis. Coarsely swollen, frayed, and broken axons in a plaque. (Bielschowsky stain, X 178.5.) (From Zimmerman and Netsky,114 with permission.)

plete absence of electron micrographs has prevented us from appreciating the status of the major lesions characteristic of TN—i.e., the grotesquely disordered hypermyelination, demyelination, and tortuously hypertrophied axons. In addition, especially in patients with markedly atypical pain features, a search for lesions in sensory thalamic, pre- and postcentral gyri, and superior lip of the sylvian fissure might prove rewarding. Very few of the pathological specimens in multiple sclerosis have been assessed with regard to the preservation of axons in the demyelinated zones and the correlation of this loss with type and degree of sensory loss. However, long ago, Adams and Kubik described intactness of most of the axis cylinders in Cajal silver stains, even in lesions so old that both the myelin sheaths and the subacute cellular reaction to their degeneration was gone.2 Only a nearly acellular fibrous glia remained be¬ tween the axons. Zimmerman’s studies showed abnormality of the axons with no data on their behavior.114 However, Lazar’s description of a completely normal ring of nerve root fibers around the central lesion could account for sufficiently normal conduction to yield a normal clinical sensory examination.59 Although the studies of Beaver and Kerr revealed essentially normal neurons in the gasserian ganglion, I have not found de¬ scriptions of trigeminal neurons in their brain-stem nuclei in any form of TN.7-9-51'53

NEURAL AREAS MEDIATING PAROXYSMAL PROVOCABLE PAIN Cranial Nerves V, IX, and X ANI) NERVUS INTERMEDIUS Figure 170-10. Normal axons in longitudinal section. (Bielschowsky stain, X 178.5.) (From Zimmerman and Netsky,114 with permission.)

The brief paroxysms of intense facial pain provoked by mini¬ mal stimulation of touch fibers innervating the face represent a feature almost unique to the trigeminal sensory system. The

Chapter 170/The Pathophysiology of Trigeminal Neuralgia

deeper cephalic somatosensory system involving the nervus intermedius and the cephalic glossopharyngeal and vagal path¬ ways are similarly but much less typically and much less fre¬ quently affected. Moreover, differences from the trigeminal prototype occur in at least five different categories in the deeper nervus intermedius, and cranial nerves IX and X sys¬ tem: (1) variability in type of pain and extreme variability in its duration; (2) variability in location of the pain with much more frequent radiation well beyond the aural and oropharyngeal zones; (3) local tenderness; (4) striking ancillary manifesta¬ tions apart from pain related to activity of the carotid sinus; and (5) preoperative sensory loss in the zones of cranial nerves IX and X. However, as first described by Ramon y Cajal, some of the rootlets of IX and X entering the medulla oblongata at the level of the restiform body promptly join the descending tract of the trigeminal nerve, which in the fetal cat lies superficially at that level (Fig. 170-12).82 The precise destinations of the en¬ tire sensory components of the nervus intermedius and cranial nerves IX and X remain to be worked out. The fashion in which these sensory terminations differ from those in the sensory trigeminal group may possibly be correlated with the differ¬ ences in the associated syndromes of pain. The fibers continue on down to terminate in the nucleus caudalis. That this entire bundle is devoted principally to mediation of pain and temperature was first established in humans by Sjoqvist.91 His analysis of the often complicated neurological

1673

deficits in patients with the Wallenberg syndrome of the lateral fossa of the medulla oblongata (pages 87 to 92 of Ref. 91) led him to conclude that the bulbospinal trigeminal tract was re¬ sponsible for the sensations of heat, cold, and pain in the entire face on the side of that tract. Hun’s patient was the first one to show from the beginning a complete loss of sensation for these modalities with perfect preservation of tactile sense.44 Sjoqvist’s first human tractotomy on a patient with normal sensa¬ tion in the face preoperatively (Sjoqvist’s case IV) showed, early on after operation, the same ipsilateral trigeminal sensory findings as had been reported by Hun and later seen in many other patients with bulbar arterial strokes.

PROVOCATION OF TRIGEMINAL NEURALGIA AND LESS TYPICAL FACIAL NEURALGIA BY SPACE¬ TAKING DISORDERS Lesions distal to the gasserian ganglion elicit the syndrome with extreme rarity. In 1969, White and Sweet were able to find reports of only six such cases; an osteoma, a sublingual aneurysm, and four nodules of malignant tumor.108 Pain as a feature of benign tumors pressing on or invading the gasserian ganglion or rootlets in the middle fossa or rootlets in the poste¬ rior fossa is not uncommon. However, these pains are totally characteristic of TN in only a small percentage of patients. The more slowly the mass evolves, the more likely it is that the ac¬ companying pain will mimic TN. Thus cerebellopontine angle epidermoid tumors and the more slowly evolving arteriovenous malformations and ectatic tortuous basilar-vertebral arteries are more likely to cause typical TN than are meningiomas or acoustic neuromas. The trunk arterial lesions were found in 3 percent of Sindou’s 420 cerebellopontine (c-p) angle opera¬ tions.90 Olivecrona states: “It is the small tumors that cause tic ... . between the size of a pea and a hazelnut. 75 However, even in the epidermoid tumors, Lepoire and Pertuiset pointed out that only 2 of their 20 patients had isolated TN without ob¬ jective trigeminal signs.62 Each of the following disorders has, in a few instances, been clearly associated with pain similar to TN and was the probable cause of such pain: arachnoidal cysts,68 arachnoidal adhesions binding the rootlets together or against the side of the brain stem,19 basilar impression of the congenital origin or that asso¬ ciated with Paget’s disease,16 persistent primitive trigeminal artery,45 99 and “cystic angioma” too small to be seen on angiog¬ raphy (7 cases in 1257 explorations).100 Since basilar impres¬ sion tends to be symmetrical, it is not surprising that it may cause bilateral TN.26 Ample documentation to support all of these statements had already been published by 1968 and was summarized by White and Sweet.108 More recent articles are in the same vein, e.g., Nguyen et al. found pain characteristic of TN in 7 of 44 pa¬ tients with c-p angle meningiomas.77 Sindou and Mertens, re¬ porting on 24 c-p angle tumors and malformations, found that in one-third of them the TN was typical, with no sensory

Figure 170-12. Bulb of fetus of cat. Golgi method. Note: A = restiform body; B= descending root of trigeminal nerve; C = fasciculus solitarius; D = nucleus of vestibular nerve; E = glossopharyngeal and vagal fibers joining trigeminal bundle, e = motor fibers of IX and X supplying nucleus ambiguus. (From Ramon y Cajal,82 with permission.)

deficits.90 Perhaps the least common well-documented cases are those due to single acute trauma to one side of the face. The full ac¬ counts of Harris of four patients,41 and of Chakravorty of one patient15 have been followed by a few other accounts.

1674

Part 4/Functional Stereotaxis

That changes in focal intracranial pressure can result in the development of facial pain contralateral to the side of a c-p angle tumor had been reported in 20 cases collected by Paillas et al.78 However, very few had typical TN. A recent report of Michelucci et al. describes two such patients who did have typ¬ ical TN.7i In one of them, the basilar artery had been pushed by the meningioma against the opposite trigeminal nerve. The TN pains gradually disappeared in the first postoperative year. Michelucci et al. found reports of 30 other cases with contralat¬ eral pain, in only 4 of whom it was characteristic of TN. There are a few other recorded cases where paroxysmal fa¬ cial pains were caused by increased pressure by such lesions as suprasellar craniopharyngiomas or a pituitary tumor not in di¬ rect contact with the trigeminal pathway. White and Sweet re¬ fer to 7 such patients recorded in the literature in whom correc¬ tion of the lesion, which was not near the trigeminal nerve, stopped the pain.108 One of these had hydrocephalus from aqueductal stenosis. Tucker et al. had two more such cases, both relieved by appropriate shunts.101 In one other patient TN asso¬ ciated with communicating hydrocephalus and without aqueductal stenosis was relieved by shunt.69 Patients in all of the foregoing groups demonstrate that ex¬ trinsic pressure against trigeminal rootlets can bring on TN. However, the obvious lesions just cited actually do so in a small minority of the cases, whereas a clear majority of the few recorded plaques of multiple sclerosis in the root entry zone are associated with ipsilateral TN. Hence the time I have devoted to analyzing these cases.

BULBAR AND/OR PONTINE VASCULAR OCCLUSIVE DISEASE When these lesions involve trigeminal tracts or nuclei, they may cause severe shooting pains, but these are not provoked by light touching or movements of the face. The major difference in the microscopic pathology between infarcts and the plaques ot multiple sclerosis is the relative preservation of the axons and neurons in the plaques, especially in the earlier stages of the lesions. On the other hand, strokes afflict with greater avid¬ ity the highly vascular clusters of neurons. Early in the course of an arterial occlusion, all components of involved tracts de¬ generate as well. Contrariwise, with the plaques, the far greater preservation of specific sensory modalities and the transmis¬ sion of the high-voltage touch impulses traversing the normal or hypertrophied axon to the area of its demyelination probably permit jumping to many lightly myelinated pain fibers.

ROLE OF NEURAL CROSS¬ COMPRESSION BY ARTERIES AND/OR VEINS OF TRIGEMINAL ROOTLETS IN THE POSTERIOR FOSSA Dandy, the first to conclude that some extrinsic lesion of the sensory root is usually the cause ot TN, saw such lesions in 129 of his 215 posterior fossa operations.19 In 66 cases, the superior cerebellar artery “in some way affected the rootlets”; in 3 cases, a branch of the petrosal vein “crossed the sensory root or

passed through it.” Ten other pathological disorders made up the other 33 positive findings. In the remaining 87 patients, there were “no gross findings of any kind.” The profession was slow in heeding these observations, the next papers being by Olivecrona75 in 1941 and by Lazorthes et al. in 1949.61 Out of 25 autopsies on TN patients, the French group found “a loop or some portion of the superior cerebellar artery” in contact with the trigeminal rootlets in 19 cases, 14 times on the right and 4 on the left. When Gardner and Miklos31 and Gardner30 found, in 6 of 18 patients with TN, an arterial loop compressing the nerve, they separated the two structures and placed a gelatin sponge between them—the first purely microvascular decom¬ pression. When Jannetta, using a binocular dissecting microscope, saw mild to severe compression of the trigeminal root by one or more small tortuous arteries, he and Rand planned to offer a future series of patients “this possibly definitive procedure, namely release of the artery without nerve section.”48 Jannetta, and many other neurosurgeons following his example, have been increasingly more convinced that TN is caused by smaller and smaller arteries and veins as well cross-compressing the trigeminal rootlets at or near their entry zone into the upper pons. By 1981, Jannetta had found neurovascular compression of the root entry zone in 395 (96 percent) of 411 patients ex¬ plored.47 The compression was arterial in 242, venous in 57, and mixed arterial-venous in 96. Jannetta has implicated, as clinically significant, cross-compression of rootlets by a 50 mu arteriole. In lower facial TN, the compression was most often caused by a loop of the superior cerebellar artery on the anterosuperior aspect of the root entry zone, whereas in first-division TN. a normal horizontal loop of the superior cerebellar artery compressed the inferolateral side of the trigeminal root entry zone. The reverse anatomic disposition is described by Gudmundsson et al.33 In the largest series of trigeminal poste¬ rior fossa operations for microvascular decompression (MVD), neural compression was diagnosed in all but 54 (3.3 percent) of 1620 patients, with a 10-year cure rate of 97 percent.27 In April 1994, Jannetta reported on 1186 patients with typical TN who had not undergone previous MVD elsewhere.6 Kaplan-Meier analysis revealed that, at 10 years postoperatively, 69.4 percent could be expected to be pain-free and off all medication; 4.3 percent would have such minor pain that it required no medica¬ tion. Such data have led Hughes to conclude “There is now lit¬ tle doubt that TN is usually caused by compression of the trigeminal sensory root by arterial loops.”43 Skipping several dozen clinical publications on trigeminal MVD, I shall summarize the especially careful study of Hamlyn and King.19 They found vasculoneural contact or grooving in 37 (90 percent) of their 41 patients. In 4 with arter¬ ial compression and 4 with no compression, partial section of portio major was done. Of the 33 whose vascular compression was "decompressed,” 23 (70 percent) were pain-free for fol¬ low-ups of 1 to 814 years. Only 4 recurrences (17 percent) en¬ sued in the 24 with arterial contacts, whereas 75 percent of the 4 cases with purely venous contacts had major recurrences and 60 percent of the 5 with mixed arterial and venous contacts had major or minor recurrences. This correlation between type of contact and clinical result was first made by Wilkins.80 When an artery distorted a root or was wedged between the root and the pons (37 cases). MVD yielded a cure rate of 83 percent. This dropped to 62 percent in 31 cases in whom the nerve

Chapter 170/The Pathophysiology of Trigeminal Neuralgia

merely made contact with the artery. When the vessel was a vein that either distorted or contacted the nerve, or when no vascular contact was present (30 percent), the success rate fell to 42 percent. In 5 patients in whom a vein grossly distorted the root, MVD was followed by recurrences in 3. In his latest pa¬ per, Wilkins logically makes a judgment as to whether a vascu¬ lar contact is significant; he decided in 102 of 254 TN patients either that the contact was not significant or that it would be un¬ safe to separate the nerve from the vessels."3 The last of a series of especially informative articles by Sindou and associates was published in 1994.89 He operated at the c-p angle in 350 patients with TN, finding an extrinsic mass lesion in 28, a neurovascular “conflit” in 312 (96.9 percent), and no extrinsic lesion at all in 10 (3 percent). The total number of neurovascular relations that he classified as conflicts came to 138.3 percent of the case total—i.e., many patients had two or even three “offending” vessels. This is the highest percentage of such contacts reported to date. At the other end of the scale of the incidence of significant lesions are the data of Adams, who noted indentation or distortion of the root in 6 (10 percent) of his 57 patients.1 Mere vascular contact was not accepted by him as significant.

POSTMORTEM STUDIES OF NEUROVASCULAR RELATIONSHIPS IN THOSE FREE OF FACIAL PAIN The incidence of neurovascular contacts in individuals who never had facial pain has been studied at autopsy by four groups, of which three are cited in Table 170-1.36 40 70 In each case, all central nervous system (CNS) structures were re¬ moved rostral to a midcollicular section. The in situ c-p angle relationships were studied before fixation, which was most carefully done by Hardy, who injected latex into the arteries.40 The descriptions and numerous photographs of Hardy are espe¬ cially convincing, and his dissections were carried out at a magnification up to X20. The problem of deciding the precise nature of vasculoneural relationships is illustrated by the discrepancy in two reports from the same group. In 1967, Jannetta said "It is of interest that in none of the 56 fresh cadavers that we studied did we see any evidence of trigeminal nerve compression by blood vessels at or near the pons.”46 In 1980, Haines, Jannetta, and Zorub re¬ ported seeing vasculoneural contacts in 35 percent of normal cadavers!36 This statement seems to me to strike a telling blow against the concept that such contact usually has major patho¬ logical import. Hamlyn and King went to the trouble of doing

TABLE 170-1.

prompt postmortem studies with arterial and venous perfusions at respectively 50 to 110 mmHg, and 0 to 15 mmHg, with final perfusions for 5 min at much higher levels, up to 200 mmHg. Even at these high pressures, there were the amazingly few instances—only two veins and one artery (superior cerebellar)— which were in contact with the nerve. Perhaps also astonishing are the somewhat disappointing results of the operations, inas¬ much as they say, “there was marked distortion of all 33 nerves and a groove remained following mobilization of the vessel.”

PUZZLING PROTRACTED RELIEF FROM MODEST MANIPULATION AT THE TRIGEMINAL STRUCTURES IN THE MIDDLE CRANIAL FOSSA From the standpoint of pathophysiology, there is agreement that at least some vessels crossing trigeminal rootlets may evoke pain typical of TN. The problem of deciding the thresh¬ old criteria for such an event is not going to be easy to solve, because the minimal trauma of compression of the ganglion and middle fossa rootlets for 1 min by an inflated balloon has an excellent chance of producing long-lasting relief of TN. The 10-year follow-up by the original proponents of that procedure, Lichtor and Mullan, revealed no recurrence in 80 percent at 5 years and an estimated 70 percent of protracted remissions at 10 years.63 The sequence of events that led to Mullan s success began 40 years ago, when the notion that the branches of the nerve were compressed at the foramen rotundum or ovale led Pudenz and Shelden to “decompress” these branches.81 Similarly, Taarnhpj proposed that the compression was at the dural fibrous roof of the porus trigemini.96 Ten “decompres¬ sions” by each group at their favored site were equally and amazingly successful. In another five patients in whom Taarnhpj suspected a c-p angle tumor as the cause of pain, his posterior fossa exposure revealed no mass.9 He then passed a hook forward through the porus trigemini in different direc¬ tions to “enlarge” Meckel’s cave but carried out “no real de¬ compression.” All five of these patients were also rendered pain-free with preserved normal sensation. With a view to stopping an “abnormal vascular reflex, Stender modified the first Taarnhpj operation by not cutting the superior petrosal sinus and emphasizing a maximally atrau¬ matic removal of the dural roof over the ganglion and rootlets in the middle fossa.92 All 16 typical TN patients were still painfree at up to a maximum of 18 months. Only 2 had any sensory loss—a moderate hypesthesia.

Autopsy Studies of Vasculoneural Relationship in Patients Never Afflicted

with Facial Pain

Hardy, Rhoton40 Haines et al.36 Mehta70

1675

Number of Sides

Arterial Contact, %

Venous Contact, %

Arterial Compression, %

50 40 60

52 25 13

23

“often” 10 0

1676

Part 4/Functional Stereotaxis

Malis sought to improve the open decompression procedure by carefully dividing a band of dural fibers he found constantly crossing above the posterior root at the petrous apex.66 He used maximal care to avoid pressure on the rootlet bundle by exert¬ ing sharp dissecting pressure upward toward the temporal dura and away from the dura propria of the V rootlets. All 43 pa¬ tients thus operated upon had complete relief of pain, with 4- or 5-day delay in 8 of them. They were similar in this respect to some patients after MVD. There were three recurrences of TN in the 32 patients followed more than 18 months. Of the pa¬ tients who had had no prior blocks at the foramen ovale, only one had a decrease in sensation postoperatively. Although the decompressive operations in the middle fossa have been discontinued, I think this was due to skepticism that the nerve was actually compressed in the middle fossa and that the operations perhaps gave less well maintained relief than de¬ liberate compression. One notes that compression of the root in the middle fossa and decompression in the posterior fossa are being recommended. Shelden concluded that the common denominator of the procedures he and Taarnhpj had used was moderate trauma to the nerve.87 He changed the objective of the procedure from de¬ compression to compression, which was administered by vig¬ orous downward pressure on the ganglion and adjoining nerve fibers at open operation. By 1969, White and Sweet could sum¬ marize reports of 1790 patients whose surgeons attested to a useful degree of pain control by such surgery, with recurrence requiring further surgery varying from 8 to 28 percent in all ex¬ cept one series of 35 cases with 54 percent recurrences.108 With up to 10-year follow-ups Shelden recorded minimal loss of sensation and 25 percent recurrences severe enough to require reoperation.86 This was encouraging enough to lead Mullan in 1978 to astutely begin his development of a percutaneous bal¬ loon inflation procedure to achieve the compression more safely.63 Still another minor insult to trigeminal rootlets in the middle fossa, injection of about 0.2 to 0.4 nrL of glycerol into the cerebrospinal fluid of Meckel’s cave has produced com¬ plete pain relief in 65 percent over a 1- to 6-year follow-up of the first 100 cases of TN in whom it was tried by Hakanson.37,38 Pain thresholds to calibrated points “were found to be slightly elevated in only a few cases.” These procedures have similar outcomes to those of MVD in the posterior fossa. It seems to me impossible that a 1-min balloon inflation confined to Meckel’s cave, or any of the other above five types ot nondestructive middle fossa open operations, has any signif¬ icant likelihood of causing long-lasting separation of an artery, a vein, or any other structure away from the nerve at or near its entrance into the pons. However, that is what the successful middle fossa procedures would have to accomplish if vascular compression of the nerve at the root entry zone is the usual cause of TN, as is now so widely accepted. I think the results of middle fossa compression render totally, unequivocally, and absolutely untenable the concept that compression by vessels of the nerve rootlets near the pons is the commonest cause of TN and that this requires maintained separation of the struc¬ tures if TN is to be relieved. There is some unknown factor that we do not understand decreasing neural excitability. The quantitative assessment of most types of chronic pain is a difficult task—not so with TN. One attractive feature about which none of us is in doubt is the cheerful fact that, after most invasive procedures, TN pain stops completely for a long time.

MORE PUZZLING PROTRACTED RELIEF FROM MORE DISTANT PROCEDURES There are a number of examples of even less localized success¬ ful paratrigeminal maneuvers. In one of my patients, the minor manipulation of passing a plastic cuff containing two platinum electrodes around the second trigeminal division just behind the foramen rotundum was done with a view to stimulating the nerve to treat TN in that division.73 This procedure produced (without stimulation) no sensory loss but stopped the pain for 8 years. Another man had had pain for 6 years, which spread to involve the first division. With the hope of relieving him by MVD without producing corneal sensory loss, I carried out an unusually easy exposure with almost no retraction. It revealed the two superior cerebellar arterial branches well anterior to the rootlets. No instrument came within 1 cm of the rootlets. I closed the wound, since I thought I could make a more pre¬ cisely controlled first-division lesion by RF heating. Despite the absence of any identified decompression, the aborted MVD stopped the pain for 8.5 years until the patient died of a heart attack. In a third patient, I inadvertently punctured the internal carotid artery below the base of the skull with my RF needle electrode before producing any third-division sensation. It has been my practice to stop the procedure at once on entering the artery; in one patient who had had TN for 7 years, this proce¬ dure was followed by complete relief until her death 14 years later. In 6 of my 10 other patients with suberanial arterial punc¬ ture, the TN was arrested for periods of from 1 month to over 10 years. Even more distant, invasive procedures, such as ligature of the ipsilateral common carotid artery over a century ago, stopped TN for more than 3 years in 4 patients, 1 to 3 years in 3, 1 year in 4, and gave partial relief in 1, none in 2. One patient died and 2 were noted “cured,” duration unknown.24 Stephen Tatter's calculation, using Fisher’s exact test, the most appro¬ priate statistical test in this situation, gives the chance of im¬ proving TN as 73 percent, with a 95 percent confidence interval of 39 to 93 percent.98 This analysis gives some support even to this therapy of TN, as devoid of rationale as it is. The extraordi¬ narily minor, seemingly unrelated gestures, which may be fol¬ lowed by cessation of the pain in TN, are obviously not under¬ stood.

SPECIAL FEATURES OF THE ROOT ENTRY ZONE The root entry zone region, extending about 3 mm out from the pons, is the junctional area in which central trigeminal myelin within oligodendroglia merges with peripheral myelin sur¬ rounded normally by Schwann cells. It has been hypothesized that this is an area especially vulnerable to cross-compression. The electron microscopic studies also place it as a vulnerable trigeminal site for ephaptic impulse transmission. Dandy’s pio¬ neering article included 7 patients in whom adhesions at the root entry zone bound the nerve to the side of the pons.19 The evidence is clear that a number of other sites are also somewhat vulnerable. Thus Hamlyn and King found that the vasculoneural contact was at the root entry zone in 22 patients and peripheral to it in 11.,9 They found no relationship between site

Chapter 170/The Pathophysiology of Trigeminal Neuralgia

of contact and recurrence rate. Similarly, Sindou et al. describe the site of the “conflit” to be the root entry zone in 78 percent, the middle third of the root in 40 percent, and the third closest to the porus trigemini in 12 percent.89 See also the lesions in multiple sclerosis described earlier. Apfelbaum has said con¬ cerning the area of affliction of the nerve root, “It must be em¬ phasized that the site of the pathologic condition is at the brain stem.”4 This formulation would seen to overstate the specificity of the region in the pathogenesis of TN.

HYPOTHESES REGARDING PATHOPHYSIOLOGIC MECHANISMS OF THE PAIN Several possible etiologic mechanisms are merely mentioned here because they have not gained general acceptance. We owe to Olivecrona the concept of modest elevation of the medial portion of the petrous pyramid (which probably explains TN in major basilar impression) and/or a deepening of the posterior fossa stretching the trigeminal nerve.75 Hughes’s description of obliteration of gasserian ganglionic arteries by hypertrophy of their muscularis, similar to that of Raynaud’s disease, has not been confirmed.42 Impaired arterial supply to the ganglion was also suggested later by Weber.107 Kerr proposed that age-related decreasing density of the fibrous roof over the lacuna in the anteromedial end of the intrapetrous carotid canal exposed the overlying gasserian ganglion unduly to the pulsation of the artery.50 Wolff hypothesized that attacks of tic douloureux are due to episodes of ischemia of “trigemi¬ nal structures,” especially when the vascular bed is also nar¬ rowed by occlusive disease.109,110 Schaltenbrand supported this view.84 After a substantial analysis of the evidence. List and Wilkins concluded that such vascular factors play no etiologic role in TN.65

HYPOTHESES REGARDING FOCI OF ABRUPT PAROXYSMS— EPHAPTIC EXCITATION Gardner confirmed the good results of Taarnhpj in relieving as¬ sumed compression of the trigeminal rootlets by dividing the dural roof of the porus trigemini.29 This led him to propose that the compression there induced demyelination. He noted that this is also the principal pathological change in multiple sclero¬ sis, and he was the first to suggest that the nervous impulse jumps to small fibers at the site of myelin loss and induces the paroxysm of pain. Lazorthes and Lacomme are among the many who have agreed.60 Olafson et al.74 concluded wrongly that the demyelinated zones in multiple sclerosis always involved the root entry zone, and Selby states that “paroxysmal tic-like pain has never been reported ... in syringobulbia or tumors of the brain stem that invaded the descending trigeminal tract and nucleus.”85 As al¬ ready cited in this chapter,17,23 there are not only case reports that controvert these statements but also four patients in whom descending trigeminal tract fibers may have been activated by external pressure against them by PICA trunks held against the medulla by adhesions.95,106

1677

Kerr agreed that a short-circuiting of the neural impulse was the crucial event initiating the paroxysm and might occur be¬ tween demyelinated surfaces of two adjacent axons or from a hypertrophied demyelinated fiber to an intact unmyelinated fiber that had lost its Schwann cell envelope.52 This suggestion was made in the light of the findings he and Beaver had gleaned from their electron micrographs in multiple sclerosis.52 Indeed, I suspect that some of the action potentials in huge naked axons might well be high enough to penetrate the mini¬ mal myelination of a group of neighboring normal pain fibers. Darian-Smith criticizes this concept of ephaptic transmission of the neural impulse of a single fiber, stating that there is “nor¬ mally a long latent period of 5 to 30 seconds between the trig¬ ger stimulus (touch) and the onset of pain.”20 This statement in¬ completely quotes Kugelberg and Lindblom,56 who state “in a few patients a single touch of the trigger zone elicited a stab of pain with a very short latency.” They also quote Arvanutaki5 and Granit and Skoglund,32 at whose artificial synapses the de¬ lay was exceedingly short. Indeed, a paroxysm initiated by a single touch is the dramatic hallmark of typical TN.

DETAILED ANALYSIS OF THE PAROXYSMS OF PAIN Kugelberg and Lindblom have reported the most intensive analysis of the surface stimuli and the ensuing paroxysms in 50 patients, 48 of whom had typical TN (of cryptogenic type).56 One had platybasia and the other an arterial aneurysm with pressure against trigeminal rootlets respectively by bone and aneurysm. Since these are the firmest pathophysiological data we have in humans, they are given in detail. The commonest sites for trigger zones were the nasolabial fold, upper lip, lat¬ eral part of the lower lip, and alveolar gingiva, but they could be anywhere and were sometimes widespread. One patient of Crue et al. placed her trigger zone in the ipsilateral axilla; in another it was in the big toe.18 Kugelberg and Lindblom con¬ firmed that the adequate stimulus to set off an attack is touch, vibration, or other stimuli increasing proprioceptive inflow, such as talking or mastication.56 However, even a severe pinch of trigger-zone skin with a forceps, slowly applied firm pres¬ sure, a warm rod, or an ice cube were all ineffective. Sudden application or release of pressure and a vibratory stimulus causing rapid distortion of skin usually caused an attack. In two patients with upper-lip trigger zones, a needle-electrode in the infraorbital foramen giving repetitive weak shocks provoked vibratory sensation typical of tactile stimulation but no pain. Increasing stimulus strength to the threshold of the largei pain fibers still failed to provoke a paroxysm. Carried out in this way, electrical stimulation did not inhibit an attack triggered from the upper lip during that stimulation. However, the same type of stimulation carried out by Wall and Sweet on them¬ selves produced cutaneous second-division hypalgesia. This we interpreted as an inhibitory effect by large-fiber activation on nociceptor mechanisms. This observation has led to the widespread efforts to control pain by appropriately sited elec¬ trical stimulation. Darian-Smith suggests that the lesion in TN may selectively block the inhibitory effect of myelinated fibers on nociception, thereby sensitizing these pathways and con¬ verting a tactile stimulus into a painful one/1

1678

Part 4/Functional Stereotaxis

The observations of Kugelberg and Lindblom have been valuable in demonstrating that a central rather than a purely pe¬ ripheral mechanism is active in TN.56 Both spatial and temporal summation of stimuli occur, i.e., spatial summation of impulses from a large area triggers the burst of pain at a lower stimulus strength and at a shorter latency than it a small area is stimu¬ lated. Concerning temporal summation, although in one case a single vibrating pulse elicited a stab of pain and a facial twitch in 57 ms, use of weak vibratory stimuli at 7 Hz did not evoke an attack until applied for 15 s, whereas at 30 Hz this summa¬ tion time was only 1.5 s. Another indication of the central character of the pain de¬ scribed by Kugelberg and Lindblom was the refractory phase after an attack during which the threshold was raised. Excitability returned gradually to the baseline level, often in 1 to 3 min after the end of a severe attack. Also, attacks occurring during the partially refractory period tended to be less severe, shorter, and with less tendency to spread. Responses in the re¬ fractory phase are dependent chiefly on the attack of pain that preceded it and not on the subsequent stimuli applied—i.e., on

trally placed abnormal area has been demonstrated, although the four patients with arteries bound to the medulla also sug¬ gest this location.95'106 Both phenytoin and lidocaine have central and peripheral effects, so that raising the trigger threshold by their use does not help in deciding the site of the pathophysiology of the dis¬ ease. Kugelberg and Lindblom have recorded data attesting to the extreme variability of the susceptibility to attacks of TN in the same patient, ranging from a situation where attacks occur spontaneously with no ascertainable provocative factor to such a degree of inhibition of pain that repeated stimulation of the worst trigger zone elicits no discomfort—all on the same day.56 These rapid fluctuations and instability of the neurophysiologi¬ cal abnormality responsible for TN have been observed by many clinicians. Conceivably a tiny zone innervated by a few demyelinated and hypertrophied axons might fire only in spe¬ cific states of metabolic excitability. The capacity to repair tiny lesions may well account for the long remissions that may oc¬ cur, especially in the earlier years during which the patient suf¬ fers from the disorder.

the state of central excitability persisting in the relevant parts of the brain. Although the pain usually starts near the trigger zone, it may begin in an area supplied by a different trigeminal division. It is my experience that it is the area of the trigger zone that must be rendered analgesic. Production of analgesia and even of highgrade hypesthesia in the division in which the pain occurs yields no relief at all. The transfer of the signal from the center for response to touch in one division to the center for pain in an adjoining division probably involves some central area, al¬ though it is conceivable that a group of demyelinated large ax¬ ons in the trigeminal root could develop a high-voltage signal capable of jumping to an adjoining group of pain fibers from a different nearby trigeminal division. This phenomenon has re¬ cently occurred in a patient of mine in such fashion as to demonstrate that both the site of the production of the trigger zone to touch and the different site responsible for the pain were both in the nucleus caudalis. The patient’s third-division TN pain was triggered at first from the second and third divi¬ sions. She was treated by six radiofrequency heat lesions over 4 years and ended up with analgesia in all of V2. V3, and part of VI. Then, agonizing pains developed in the temple, cheek, and ramus of the mandible provocable only by swallowing. They were completely and immediately controlled by cocaine or lidocaine applied to the oral pharynx. Increasing duration of relief from such applications occurred for about 1 month. In the 10 months since then, relief has been complete with formerly ineffective medication. The only place in the nervous system where innervations of cranial nerves IX. X, and V are in close proximity is the trigeminal nucleus caudalis. The impulses aris¬ ing from the triggering stimulus reaching nucleus caudalis via touch fibers in the cranial nerves IX and/or X were close enough to trigeminal pain fibers to activate them. The nucleus caudalis is the only peripheral or central site in which this could occur, as tar as we know. The patient also demonstrates that the afferent fibers for touch are the abnormally behaving fibers, since the primary afferent trigeminal pain fibers had been rendered inactive by the previous lesions. Furthermore, the abnormal connection between the touch and pain fibers must be in the nucleus caudalis—at least in this patient. This is the only patient I know of in whom the precise locus of the cen¬

TRIGEMINAL ANATOMY IN THE BRAIN STEM We can at least say for certain that we see such a marked differ¬ ence between the brain-stem anatomy of the cephalic sensory system and that of the rest of the body that it is not surprising that we see remarkably different phenomena in the two sys¬ tems. The cell bodies of the various components of the afferent pathways of the trigeminal nerve extend downward from the mesencephalic nucleus in the midbrain through the main sen¬ sory nucleus in the upper pons on down through the pons and medulla as the descending or trigeminal tract to at least the sec¬ ond cervical segment. In these upper cervical segments, Kerr has demonstrated individual second-order neurons with both a trigeminal and cervical input.54 The various second-order neu¬ rons on which this fiber tract terminates lie medial to the tract.76 They form a complex lower portion, the nucleus caudalis, with a thin subnucleus zonalis next to the tract, then a thicker subnu¬ cleus gelatinosus densely packed with neurons of various sizes, and finally, most medially and most extensive, the subnucleus magnocellularis. At about the level of the obex, the neuronal pattern changes drastically to form the nucleus interpolaris, which contains two types of cells, many small and a few large. I hen, at about the level of the oral third of the inferior olive, the neuronal pattern changes again to that of the nucleus oralis, containing a single type of small- to medium-sized cell. This continues up to the junction with the main sensory nucleus at the level of the rostral end of the long hypoglossal nucleus. The cytoarchitecture of the three subnuclei in the nucleus caudalis corresponds to that in the posterior horn of the cord. Respectively, the subnucleus zonalis matches the cord's posteromarginal cells, the subnucleus gelatinosus pairs with the substantia gelatinosa of Rolando, and the subnucleus magno¬ cellularis is associated with the nucleus proprius of the poste¬ rior horn. However, the nuclei interpolaris and oralis are not obviously represented in the cord, nor are we clear as to exactly what they do normally. The problem is increased by the tremendous number of secondary afferent neurons, with which collaterals from most entering fibers make complex arboriza-

Chapter 170/The Pathophysiology of Trigeminal Neuralgia

tions in the whole descending tract. Descriptions of these go back to Kolliker and Cajal.55-82 The latter showed that these collaterals do not constitute a single diffuse plexus; on the con¬ trary, they permit each fiber to have independent cellular connections. This might account for the remarkable specificity of trigger zones. The merging of the trigeminal with the upper cervical inputs at the Cl-2 level may also explain the unusual occurrence of trigger zones in the cervical skin.18

ANIMAL STUDIES ON TRIGEMINAL PATHWAYS Massive efforts have been devoted to the intriguing, peculiar trigeminal anatomophysiology. I have elected not to include a review of these because of my uncertainty as to their relevance to TN. Thus Stewart and King have demonstrated an ascending trigeminal intranuclear fiber pathway arising in nucleus caudalis and distributing preterminal fibers to all of the other more rostrally lying trigeminal nuclei in the medulla and pons as well as to the other adjacent brain-stem nuclei.93 On the basis of the selective loss of pain sensation after nucleus caudalis tractotomy, they suggest that these pathways are concerned with interpreting noxious stimuli. Exactly how remains to be determined. However, the nucleus caudalis is not the only com¬ ponent of the bulbar trigeminal complex directly concerned with pain. This I learned in the early 1940s. Having found that deep cephalic pain pathways entered the descending trigeminal tract, so that tractotomy rendered analgesic the oral pharynx and ear canal, I sought to treat cancer pain of the throat and face by bulbar tractotomy at the obex. Pain usually persisted, especially in the oral cavity. Young and Perryman have shown, in macaque monkeys, that primary afferent fibers for dental pain perception travel in the trigeminal nerve but relay only in all three rostral trigeminal nuclei—principalis, oralis, and interpolaris.112 The problem of translating data from animals to humans has been illustrated by Wall and Taub.105 They found no cells in the nucleus caudalis in animals that responded to heavy pressure on the skin, correctly describing this as paradoxical, because deafferenting this nucleus in humans causes analgesia to pin¬ prick and minimal loss of touch sensation. The groups of investigators who have contributed notably to the electrophysiological studies of the trigeminal system have not added to their publications in the last 5 years. This suggests that some new approach is needed to supplement the data al¬ ready gathered by some twenty groups of investigators.

RANGE OF CLINICAL SEVERITY OF PAIN CORRELATED WITH TREATMENT REQUIRED An effort to come up with some valid generalization leads me to suggest that there is a continuum of degrees of severity of the disorder. The pain in most patients in the completely typical group is controlled without producing a sustained, unequivocal sensory loss. This is the most puzzling group, in whom the only known common denominator for achieving relief by a local maneuver seems to be almost any manipulation at some zone at or near the ganglion or nerve root. The advocates of compres¬

1679

sion in the middle fossa describe results similar to the results of those who decompress in the posterior fossa. The lesions of multiple sclerosis usually require sustained dense analgesia to the trigger zones. For a much smaller group, some 20 to 30 per¬ cent, a major degree of hypalgesia or analgesia seems to be necessary. This may be achieved either by open rhizotomy as described by Wilkins113 or by percutaneous RF heating to the point of trigger zone analgesia, as we do. A few patients may need destruction of all fibers in all por¬ tions of the root, lest, for example, some pain fibers be lurking in the usually purely motor root. Thus a patient of mine, after each of five RF lesions in a 4-year period, had recurrence of pain as soon as postoperative analgesia faded to hypalgesia in the trigger zone. Finally, after the sixth RF lesion, he had anal¬ gesia to single pin jab and anesthesia to finger touch throughout the trigeminally innervated skin, mucosa, and cornea. By 2 years later, he had recovered pinprick sensation only intermittently and only at the right comer of the mouth. He could now local¬ ize finger touch only on the right nose, upper lip, lower lip skin, and chin. However he was having mild to severe pain attacks in the nostril and lower jaw triggered from touch to the upper lip and chin and from talking or eating. Exploration of the poste¬ rior fossa disclosed a spectacular degree of pressure against all trigeminal root fibers from in front by two branches of the su¬ perior cerebellar artery. The vessels shone through the greatly widened, ultrathin layer of nerve fibers. After presumed tran¬ section of all trigeminal fibers, the patient finally maintained relief for the 17 years until his death. By 6 years after opera¬ tion, he had recovered pinprick sensation only in the initially analgesic front and back walls of the ear canal and sensation of touch only to the eyebrow and temple. These results suggest that the patient had afferent pain fibers traveling in the motor root, as concluded by Young,111 whose electron microscopy revealed that up to 20 percent of the nerve fibers in human trigeminal motor roots are unmyelinated. Although visceral efferent fibers are unmyelinated, these are thought to be absent from the trigeminal root, leaving pain as the most likely function for these unmyelinated fibers.

SUMMARY AND CONCLUSIONS Nearly all of our knowledge of the anatomic lesions in typical TN is based on the biopsies of gasserian ganglion and adjoin¬ ing rootlets taken in 30 patients by Beaver and Kerr, on 9 biop¬ sies of the descending trigeminal tract at the level of the rostral nucleus caudalis by Kune, and in biopsies of third-division pe¬ ripheral branches in two patients by Kumagami. All four groups agree that the extreme hypermyelination, demyelination, and tortuous hypertrophied axons they saw are not present in any other disease. Despite the substantial occurrence of mul¬ tiple sclerosis in patients with severe TN, there are only 17 pa¬ tients in whom we have histology of the brain or trigeminal nerve—all but 2 of these having been studied only at autopsy. Only Fazar’s patient was biopsied at the root entry zone, show¬ ing on electron microscopy lesions similar to those seen in the fibers in and near the gasserian ganglion. There were clear-cut areas of demyelination at the root entry zone on the side of the pain in 11 sides of 10 patients. There was no root entry zone le¬ sion on the painful side in 4 patients; conversely, there was a root entry zone lesion in 2 patients but no pain on that side.

1680

Part 4/Functional Stereotaxis

Tentative correlations between the features of clinical progres¬ sion of the trigeminal symptoms and the brain lesions of multi¬ ple sclerosis were probably tenable in several patients. The many other types of obvious lesions often associated with trigeminal pain are described. None of them inflicts as high an incidence of pain typical of TN as multiple sclerosis. The remarkable and mysterious high percentage of longsustained pain relief following a variety of procedures in the middle and posterior fossae defies rational explanation, at least for some of us. There are six types of “decompressive” and two types of compressive operations in the middle fossa followed by minor, if any, sensory loss and a 70 to 80 percent incidence of fairly long-term good results. Around 2500 of these were of the compressive type, whereas several thousand “decompres¬ sive” operations in the posterior fossa enjoyed a similar out¬ come. A crucial advantage of the posterior fossa decompres¬ sion, in the view of its advocates, is that it deals with the cause of TN—a cross-compression of nerve rootlets by one or more arteries or veins. By repositioning the arteries and dividing the coagulated veins, they eliminate the cause. To make this con¬ cept tenable, one has to explain how all the middle fossa proce¬ dures that produce relief with little or no sustained sensory loss accomplish repositioning of the arteries and occlusion of the veins at or near the root entry zone. This explanation seems to me to be an impossible hurdle for the vascular decompressors to surmount. Explanation for the complexities of the paroxysmal pain may well be sought in an understanding of the special, extraor¬ dinary, extended pontobulbar trigeminal second-order neuronal groups. Although massive efforts have been devoted to linking animal studies of the trigeminal system with TN, much more effort is needed. This review in the allotted space cannot do justice to the yeoman efforts already expended.

ACKNOWLEDGMENT The author wishes to express his appreciation to the NeuroResearch Foundation for its support during the preparation of this manuscript and to Deborah Wallace for her intelligent assistance.

7.

Beaver DL: Electron microscopy of the gasserian ganglion in trigeminal neuralgia. J Neurosurg 26:138-150, 1967.

8.

Beaver DL, Moses HL, Ganote CE: Electron microscopy of the trigeminal ganglion: II. Autopsy study of human ganglia. Arch Pathol 79:557-570, 1965.

9.

Beaver DL, Moses HL, Ganote CE: Electron microscopy of the trigeminal ganglion: III. Trigeminal neuralgia. Arch Pathol 79: 571-582, 1965.

10.

11.

Brett DC, Ferguson GC, Ebers GC, et al: Percutaneous trigeminal rhizotomy: Treatment of trigeminal neuralgia secondary to multiple sclerosis. Arch Neurol 39:219-221, 1982.

12. 13.

14.

Brisman R: Trigeminal neuralgia and multiple sclerosis. Arch Neurol 44:379-381, 1987. Broggi G, Franzini A, Giorgi C, et al: Radiofrequency percutaneous trigeminal rhizotomy: Considerations in 1,000 consecutive cases of essential trigeminal neuralgia. J Neurosurg Sci 29:165, 1985. Carrillo R, Chichilnisky S: Neuralgia del trigemino y esclerosis en placas. Semin Med 2.T 12-126, 1938.

15.

Chakravorty B: Trigeminal neuralgia. J Indian Med Assoc 41: 503-507, 1963.

16.

Clarke CRA. Harrison MJG: Neurological manifestations of Paget’s disease. J Neurol Sci 38:171-178, 1978.

17.

Conrad B, Mergner T: High cervical neurinoma (C1/C2) diagnosed falsely as multiple sclerosis because of trigeminal neuralgia. Arch Psychiatr Nervenkr 227:33-37, 1979.

18.

Crue BL, Shelden CH, Pudenz RH, et al: Observations on the pain and trigger mechanism of trigeminal neuralgia. Neurology 6: 196-207, 1956.

19.

Dandy WE: Concerning cause of trigeminal neuralgia. Am J Surg 24:447-455, 1934.

20.

Darian-Smith I: Peripheral versus central factors in trigeminal neu¬ ralgia, discussion by Kerr FWL, in Hassler R, Walker AE (eds): Trigeminal Neuralgia: Pathogenesis and Pathophysiology. Philadelphia: Saunders, 1970, pp 187-188.

21.

Darian-Smith I, Mutton P, Proctor R: Functional organization of tac¬ tile cutaneous afferents within the semilunar ganglion and trigemi¬ nal spinal tract of the cat. J Neurophysiol 28:682-694, 1965. Daum S, Vogein-Rappaport, Gruner J, et al: Sclerose en plaques rev61ee a Page de 64 ans par une n6vralgie trigdminale: 6tude anatomo-clinique. Rev Neurol 102:500-503, 1960. Foix, Thevenard, Nicolesco: Algie faciale d’origine bulbotrigeminale au cours de la syringontyelie: Troubles sympathiques. Rev Neurol 38:990-998, 1922.

22.

23.

24. 25.

References

Brandt F, and Wittkamp P: Stiitresultate der Thermokoagulation in Ganglion gasseri beim tic douloureux. Neumchirurgia 26:133-135 1983.

26.

Fowler GR: The operative treatment of facial neuralgia—A compar¬ ison of methods and results. Ann Surg 3:269-320. 1886. Friedman AP, Carton CA, Hirano A: Cyclical head and face pain: Its diagnosis and treatment. Arch Neurol 2:1-11, 1960. Fukuda S, Shimizu S, Toya S, et al: A case of bilateral trigeminal neuralgia with basilar impression. Brain Nerve 16:153-157, 1965. Fukushima T: Microvascular decompression for hemifacial spasm and trigeminal neuralgia: Results in 4000 cases. J Neurol Neurosurg Psychiatry 53:811, 1990.

1.

Adams CB1 Kaye AH. Teddy PJ: The treatment of trigeminal neu¬ ralgia by posterior fossa microsurgery. J Neurol Neurosurg Psychiatry 45:1020-1026, 1982.

27.

2.

Adams RD. Kubik CS: The morbid anatomy of the demyelinative diseases. Am J Med 12:510-546, 1952.

28.

3.

Amezua L: Esclerosis en placas y neuralgia del trigemino: A proposito de dos observaciones neuroquirgicas. Arch Neurocirug 9: 385^134, 1952.

Garcin R, Godlewski S, Lapresle J: Ndvralgie du trijumeau et scldrose en plaques. (A propos d’une observation anatomo-clinique.) Rev Neurol 102:441-451, 1960.

29.

Gardner WJ: The mechanism of tic douloureux. Trans Am Neurol Assoc 87:168-173, 1953.

30.

Gardner WJ: Concerning the mechanism of trigeminal neuralgia and hemifacial spasm. J Neurosurg 19:947-958, 1962. Gardner WJ. Miklos MV: Response of trigeminal neuralgia to "de¬ compression” of sensory root. JAMA 170:1773-1776. 1959. Granit R, Skoglund C'R: Facilitation, inhibition and depression at the "artificial synapse" formed by the cut end of a mammalian nerve. J Physiol 103:435-448, 1945.

4.

Apfclbaum RI: Surgical management of disorders of the lower cra¬ nial nerves, in Schmidek HH, Sweet WH (eds): Operative Neuro¬ surgical Techniques, 2d ed. New York: Grune & Stratton, 1988, pp 1097-1109.

31.

5.

Arvanitaki A: Effects evoked in an axon by the activity of a contigu¬ ous one. J Neurophysiol 5:89-108, 1942.

32.

6.

Barker FG, Jannetta PJ. Jho HD, et al: Microvascular decompres¬ sion for typical trigeminal neuralgia: A 20-year experience. Paper #736 in Scientific Program, 62nd Annual Meeting of the American Association of Neurological Surgeons, April 9-14, 1994:145.

33.

Gudmundsson K. Rhoton AL. Rushlon JG: Detailed anatomy of the intracranial portion of the trigeminal nerve. J Neurosurg 35: 592-600, 1971.

Chapter 170/The Pathophysiology of Trigeminal Neuralgia

34.

Gurevich D: Sistema del nervio trigemino. Thesis, University of

35.

Buenos Aires, 1945. Gybels J, Sweet WH: Neurosurgical Treatment of Persistent Pain.

36.

Basel: Karger, 1989. Haines SJ, Jannetta PJ, Zorub DS: Microvascular relations of the trigeminal nerve: An anatomical study with clinical correlation.

61.

62.

1681

Lazorthes G, Soujeole AC, Espagno J: Note sur les vaisseaux de 1’angle ponto-cerebelleux: Variations et rapports avec la racine du trijumeau. Compte Rendues de l’Association des Anatomistes, 36e reunion, Lyon, 1949, p 437-438. Lepoire J, Pertuiset B: Les kystes epidermoides cranio-enceph-

63.

aliques. Paris: Masson & Cie, 1957. Lichtor T, Mullan JF: A 10-year follow-up review of percutaneous microcompression of the trigeminal ganglion. J Neurosurg 72: 49-54, 1990. Lignac GOE, van der Bruggen J: Uber mikroskopische Veranderungen des Ganglion gasseri in 22 Fallen von Trigeminus-

37.

J Neurosurg 52:381-386, 1980. Hakanson S: Trigeminal neuralgia treated by injection of glycerol

38.

into the trigeminal cistern. Neurosurgery 9:638-646, 1981. Hakanson S: Retrogasserian glycerol injection as a treatment of tic

64.

douloureux. Adv Pain Res Ther 5:927-933, 1983. Hamlyn PJ, King TT: Neurovascular compression in trigeminal neu¬ ralgia: A clinical and anatomical study. J Neurosurg 76:948-954,

65.

neuralgie. Krankheitsforschung 5:419—425, 1928. List CF, Williams JR: Pathogenesis of trigeminal neuralgia. Arch

66.

Neurol Psychiatry 11:36-43, 1957. Malis LI: Petrous ridge compression and its surgical correction.

39.

40.

41. 42. 43.

44.

45.

1992. Hardy DG, Rhoton AL: Microsurgical relationships of the superior cerebellar artery and the trigeminal nerve. J Neurosurg 49:669-678, 1978. Harris W: Neuritis and Neuralgia. London: Oxford University Press, 1926, pp 167-170. Hughes B: The radical treatment of trigeminal neuralgia as exhibited in seventeen consecutive cases. BMJ 1:823-824, 1926. Hughes RAC: Diseases of the fifth cranial nerve, in Dyck PJ, Thomas PK, Griffin JW, et al (eds): Peripheral Neuropathy. Philadelphia: Saunders, 1993, pp 801-817. Hun H: Analgesia, thermic anaesthesia and ataxia, resulting from foci of softening in the medulla oblongata and cerebellum due to oc¬ clusion of the left inferior posterior cerebellar artery: A study of the course of the sensory and co-ordinating tracts in the medulla oblon¬ gata. NY J Med 65:513-519; 613-620, 1897. Jackson U, Garza-Mercado R: Persistent carotid-basilar artery anas¬ tomosis: Occasionally a possible cause of tic douloureux. Angiology

46.

11:103-112, 1960. Jannetta PJ: Arterial compression of the trigeminal nerve at the pons in patients with trigeminal neuralgia. J Neurosurg 26:159-162,

47.

1967. Jannetta PJ: Vascular compression in trigeminal neuralgia, in Samii M, Jannetta P (eds): The Cranial Nerves. Berlin: Springer-Verlag,

48.

49.

50. 51.

52. 53. 54.

55.

56. 57. 58. 59.

60.

1981, pp 331-340. Jannetta PJ, Rand RW: Transtentorial subtemporal retrogasserian neurectomy in trigeminal neuralgia by microsurgical technique. Bull LA Neurol Soc 31:93-99, 1966. Jensen TS, Rasmussen P, Riske-Nielsen E: Association of trigeminal neuralgia with multiple sclerosis: Clinical and pathological features. Acta Neurol Scand 65:182-189, 1982. Kerr FWL: The divisional organization of afferent fibers of the trigeminal nerve. Brain 86:721-732, 1963. Kerr FWL: Correlated light and electron microscopic observations on the normal trigeminal ganglion and sensory root in man. J Neurosurg 26:132-137, 1967. Kerr FWL: Pathology of trigeminal neuralgia: Light and electron microscopic observations. J Neurosurg 26:151-156, 1967. Kerr FWL, Miller RH: The pathology of trigeminal neuralgia. Electron microscopic studies. Arch Neurol 15:308-319, 1966. Kerr FWL, Olafson RA: Trigeminal and cervical volleys: Convergence on single units in spinal gray at C-l and C-2. Arch Neurol 54:161-178, 1961. Kolliker A: Handbuch der Gewebelehre des Menschen: Nervensystern des Menschen und der Thier. Leipzig: Englemann, 1986, vol 2. Kugelberg E, Lindblom U: The mechanism of the pain in trigeminal neuralgia. J Neurol Neurosurg Psychiatry 22:36-43, 1959. Kumagami H: Neuropathological findings of hemifacial spasm and trigeminal neuralgia. Arch Otolaryngol 99:160-164, 1974. Kune Z, Fuchsova M, Novak M: Excision of the spinal trigeminal tract. Acta Neurochir 41:233-241, 1978. Lazar ML, Kirkpatrick JB: Trigeminal neuralgia and multiple scle¬ rosis: Demonstration of the plaque in an operative case. Neuro¬ surgery 5:711-717', 1979. Lazorthes G, Lacomme Y: L’etiologie de la nevralgie faciale dite essentielle. Presse Med 72:1637-1640, 1964.

67.

68. 69.

70. 71.

72. 73.

74.

J Neurosurg 26:163-167, 1967. Marburg O: Neue Beitrage zur Frage der multiplen Sklerose nebst Untersuchungen fiber den Bauchdeckenreflex bei Derselben. Wien Med Wochenschr 59:2147-2153, 1909. Martuza RL, Ojemann RG, Shillito J: Facial pain associated with a middle fossa arachnoid cyst. Neurosurgery 8:712-716, 1981. Maurice-Williams RS, Pilling J: Trigeminal sensory symptoms asso¬ ciated with hydrocephalus. J Neurol Neurosurg Psychiatry 40: 641-644, 1977. Mehta L, Fatani J, Rao G: Superior cerebellar artery in the pontine zone. Saudi Med J 2:213-216, 1981. Michelucci R, Tassinari C, Plasmati R, et al: Trigeminal neuralgia associated with contralateral intracranial tumour: A false localising sign caused by vascular compression? Report of 2 cases. J Neurol Neurosurg Psychiatry 52:1202-1203, 1989. Moses HL: Comparative fine structure of the trigeminal ganglia, in¬ cluding human autopsy studies. J Neurosurg 26:112-126, 1967. Nguyen M, Maciewicz R, Bouckoms A, et al: Facial pain symptoms in patients with cerebellopontine angle tumors: A report of 44 cases of cerebellopontine angle meningioma and a review of the literature. Clin J Pain 2:3-9, 1986. Olafson RA, Rushton JG, Sayre GP: Trigeminal neuralgia in a pa¬ tient with multiple sclerosis: An autopsy report. J Neurosurg 24:

75.

755-759, 1966. Olivecrona H: Die Trigeminusneuralgie und ihre Behandlung.

76.

Nervenarzt 14:49-57, 1941. Olszewski J: On the anatomical and functional organization of the

77.

spinal trigeminal nucelus. J Comp Neurol 92:401-413, 1950. Oppenheim H: Text-book of Nervous Diseases for Physicians and

78.

79. 80.

81.

Students, 5th ed. New York: Stechert, 1911. Paillas JE, Pellet W, Janny P, et al: L'atteinte controlaterale des nerfs craniens au cours des tumeurs de la fosse posterieure. Rev Neurol 121:452-464, 1969. Parker HL: Trigeminal neuralgic pain associated with multiple scle¬ rosis. Brain 51:46-62, 1928. Piatt JH, Wilkins RH: Treatment of tic douloureux and hemifacial spasm by posterior fossa exploration: Therapeutic implications of various neurovascular relationships. Neurosurgery 14:462-471, 1983. Pudenz RH, Shelden CH: Experiences with foraminal decompres¬ sion in the surgical treatment of tic douloureux. Presented at the American Academy of Neurological Surgery, New York, October 1,

82.

1952. Ramon y Cajal S: Histologic du systtme nerveux de I’homme et des

83. 84.

vertebres. Paris: Maloine, 1909. Rovit R: Personal communication, 1985. Schaltenbrand G: liber den anatomischen Befund bei Trigeminus¬

85.

86.

neuralgie. Dtsch Z Nervenheilk 170:95—105, 1953. Selby G: Diseases of the fifth cranial nerve, in Dyck PJ. Thomas PK, Lambert EH, et al (eds): Peripheral Neuropathy. Philadelphia: Saunders, 1984, pp 1253-1265. Shelden CH: Compression procedure for trigeminal neuralgia: Review and clinical appraisal of ten years’ experience. Presented at the 26th Annual Meeting of the American Academy of Neurological Surgery, Key Biscayne, FL, 1964.

1682

87.

Part 4/Functional Stereotaxis

Shelden CH, Pudenz RH, Freshwater DB, et al: Compression rather

100.

than decompression for trigeminal neuralgia. J Neurosurg 12: 123-126, 1955. 88. 89.

90.

Siegfried J: 500 percutaneous thermocoagulations of the gasserian ganglion for trigeminal pain. Surg Neurol 8:126-131, 1977. Sindou M, Chiha M, Mertens P: Anatomical findings in microsurgical vascular decompression (MVD) for trigeminal neuralgia (TN) and cor¬ relations between topography of pain and the site of the conflict around the root (abstr). Presented at the European Society for Stereotactic and Functional Neurosurgery, Antalya, Turkey, September 1994. Sindou M, Mertens P: Microsurgical vascular decompression

Tsubaki S, Fukushima T, Tamagawa T, et al: Parapontine trigeminal cryptic angiomas presenting as trigeminal neuralgia. J Neurosurg 71:368-374,1989.

101.

Tucker WS, Fleming R, Taylor FA, et al: Trigeminal neuralgia in aqueduct stenosis. Can J Neurol Sci 5:331-333, 1978.

102.

Tyndel FJ, Bilbao JM, Tucker WS: Unsuspected lesions in patients with bilateral tic douloureux. Lancet 1:1418, 1984.

103.

Van Gehuchten P, Brucher JM: Sclerose en plaques et nevralgie du trijumeau. Rev Neurol 106:257-265, 1962.

104.

Wall PD, Sweet WH: Temporary abolition of pain in man. Science 155:108-109, 1967.

(MVD) in trigeminal and glosso-vago-pharyngeal neuralgias. A twenty-year experience. Acta Neurochir (Suppl) 58:168-170, 1993. Sjoqvist O: Studies on pain conduction in the trigeminal nerve: A contribution to the surgical treatment of facial pain. Acta Psychiatr Scand Suppl 17:1-139, 1938.

105.

Wall PD, Taub A: Four aspects of trigeminal nucleus and a paradox. J Neurophysiol 25:110-126, 1962.

106.

Weber E: Die Form der Schadelbasis in ihrer Beziehung zum

92.

Stender A: “Gangliolysis” for the surgical treatment of trigeminal neuralgia. J Neurosurg 11:333-336, 1954.

107.

Weber E: Problematik der Trigeminus Neuralgie. Nervenarzt 31: 88-91, 1960.

93.

Stewart WA, King RB: Fiber projection from the nucleus caudalis of the spinal trigeminal nucleus. J Comp Neurol 121:271-286, 1963. Subcommittee on Taxonomy. Classification of chronic pain. Pain (Suppl) 3:S1-S226, 1986.

108.

White JC, Sweet WH: Pain and the Neurosurgeon: A Forty-Year Experience. Springfield, IL: Charles C Thomas, 1969.

109.

Wolff HG: Headache and Other Head Pain. New York: Oxford University Press, 1948.

110.

Wolff HG: Headache and Other Head Pain. 2d ed. New York: Oxford University Press, 1960.

111.

Young RF: Unmyelinated fibers in the trigeminal motor root: Possible relationship to the results of trigeminal rhizotomy. J Neurosurg 49:538-543, 1978.

112.

Young RF, Perryman KM: Pathways for orofacial pain sensation in the trigeminal brain-stem nuclear complex of the macaque monkey. J Neurosurg 61:563-568, 1984. Young JN, Wilkins RH: Partial sensory trigeminal rhizotomy at the pons for trigeminal neuralgia. J Neurosurg 79:680-687, 1993. Zimmerman HM. Netsky MG: The pathology of multiple sclerosis. Assoc Res Nerv Mental Dis 28:271-312, 1950.

91.

94. 95.

96.

97.

Sunder-Plassmann M, Grunert V, Bock F: Zur Frage vascularen Kompresion des Tractus spinalis Nervi trigemini als mogliche Ursache der Trigeminusneuralgie. Nervenarzt 42:323-325, 1971. Taamhoj P: Decompression of the trigeminal root and the posterior part of the ganglion as a treatment in trigeminal neuralgia: Preliminary communication. J Neurosurg 9:288-290, 1952. Taarnhqj P: Decompression of the trigeminal root. J Neurosurg 11:299-305,1954.

Gesichtsschmerz, spezielle zur Trigeminusneuralgie. Acta Neuro¬ chir (Suppl) 3:72-78, 1955.

98.

Tatter S: Personal communication, May 2, 1994.

113.

99.

Tibbs PA, Walsh JW, Minix MB: Persistent primitive trigeminal artery and ipsilateral acquired blepharoptosis. Arch Neurol 38: 323-324, 1981.

114.

CHAPTER

171

OVERVIEW OF THE TREATMENT OF CRANIAL NEURALGIAS

Ian M. Turnbull

Any consideration of the treatment of cranial neuralgias must begin with trigeminal neuralgia, a worldwide problem that af¬ flicts all populations in which large numbers live long enough to reach the average age of onset, the early 50s. The pains that occur reach such severity at times that what must have been re¬ garded as extremely hazardous operations were undertaken al¬ most as soon as the relationship between the pains and the trigeminal nerve was recognized. Unless cited in the references, historical facts in this sec¬ tion have been taken from the scholarly chapter written by Penman.1 He took great pains to try to establish priority for first discovery among the many physicians and surgeons who di¬ rected their attention to the problem of the treatment of trigem¬ inal neuralgia. Except for phenytoin, which continues to be effective in some patients, no drug introduced before carbamazepine be¬ came available in the 1960s has withstood the test of time. The numerous enthusiastic reports of nonsurgical treatments that have been published in the past can be attributed both to a widespread acceptance of uncontrolled therapeutic trials and to the natural history of the disease itself. Trigeminal neuralgia, like many chronic disorders, may ap¬ pear to respond to medical treatment when it is merely entering a period of spontaneous remission. Indeed, from one week to the next, the pain invariably improves or gets worse. Deterioration is characterized by more intense pains of longer duration that occur more frequently. When the condition sub¬ sides, it may reach the point of complete remission or be pre¬ sent as slight twinges, occurring occasionally with eating. A pa¬ tient observed, “It’s almost gone, but I can feel it lurking there.” When severe, the pain surpasses in intensity any pain in the patient’s experience. I remarked to a relative that I thought the pain could be compared with that caused by having a tooth drilled without anesthesia, but I was corrected. "No,” said the patient, “I never have anesthesia for dental care. This pain is worse.” Frazier2 noted that the cumulative experience of the pain breaks down patients’ morale and exhausts their en¬ durance, so that pain at first tolerated with a certain amount of composure later seems unbearable. He also concluded that these people were “troubled in their souls as much by appre¬ hension as by the actual exhibition of pain.’ Carbamazepine has proved to be a most helpful drug, induc¬ ing a remission in a majority. Its usefulness may be vitiated by

allergic or toxic reactions or by the side effects that are in¬ evitable when a maximum tolerated dose is exceeded. Above a given dose level (which varies among individuals), ataxia, gas¬ trointestinal upset, and mental confusion begin to appear. A tol¬ erable dose may, after months or years, no longer continue to keep the pains from breaking out with intensity. This is com¬ monly the indication that surgical treatment is needed. If pa¬ tients on carbamazepine are experiencing no pain at all, it is likely they have entered a spontaneous remission and the drug can be discontinued for a while. Isolated descriptions of individuals with the characteristic pains of trigeminal neuralgia were published before the report by Andre in 1756, in which he described 8 to 10 cases and coined the term tic douloureux. In 1773, Fothergill described 14 patients with intermittent facial pains who experienced what clearly is now regarded as classic trigeminal neuralgia. Surgical treatment followed the demonstration by Mayo, in 1822, that the trigeminal nerve conveyed sensation from the face. Until the 1890s, surgical treatment was directed entirely to¬ ward peripheral branches of the nerve. Neurectomy ot those branches of the nerve accessible to the surgeon has remained a useful palliative treatment, as has alcohol neurolysis of these same branches, which was introduced in the early twentieth century. Regeneration of the nerves ensues, so the pain will usually recur within months or a year. The procedure depends for its success on the pain being confined to the distribution of that particular peripheral branch, which often is not the case. The dense numbness created may be bothersome but is usually accepted by the patient as a good trade-off for pain relief. Despite repetition of the procedure on the involved nerve and other peripheral branches, trigeminal neuralgia often returns in full fury. The modem era in the surgical treatment of trigeminal neu¬ ralgia began in the 1890s with the introduction of ablative op¬ erations on the gasserian ganglion or sensory root of the nerve. These procedures became the mainstay of treatment until the past twenty or thirty years. Nowadays, open transection of the root or chemical destruction of the ganglion is seldom under¬ taken unless all other treatments have failed. Interestingly enough, of the two principal methods of reaching the root, the one that was initially the least popular, the posterior fossa ap¬ proach championed by Dandy,3 is used today. The technique

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Part 4/Functional Stereotaxis

for gaining access to the ganglion and root by a subtemporal extradural pathway has been largely forgotten. The process of discovery of surgical treatment can be re¬ garded as having a series of steps. First comes the idea. It is easier to advocate excision of the gasserian ganglion than to do it. The second stage is undertaken by those working out meth¬ ods. The third and perhaps most important stage occurs when technically skilled surgeons learn how to apply the method reli¬ ably and safely. Next, the students of these leaders make the operations available to the community at large. With continu¬ ing experience and improvements in operating equipment and anesthetic techniques, the point is reached where the incidence of complications may appear to be further irreducible, or to be inherent in the nature of the procedure. At this time, new ideas are transformed into new procedures, and the process begins again. In what may be noted as one of the earliest examples of skull base surgery, Rose, between 1890 and 1892, excised the gasserian ganglion after enlarging the foramen ovale in six pa¬ tients. The approach to the sphenoid bone, a difficult exercise, was followed by heavy bleeding as the ganglion was uncov¬ ered. In 1890 Horsley performed a squamous temporal bone craniotomy, opened the dura and then Meckel’s cave, and avulsed the nerve root. Unfortunately, when the nerve was avulsed from the pons, the patient had a brief respiratory arrest and succumbed later that day. Hartley and Krause are credited with developing the ex¬ tradural subtemporal approach to the ganglion. Hartley, in 1892, used the exposure to section the mandibular and maxil¬ lary nerves at the foramen ovale and rotundum. Penman inter¬ prets his description of the procedure to indicate that he also excised part of the ganglion. In 1893, Krause, having worked out the exposure on cadavers, operated and removed the gan¬ glion. Cushing, in 1900, after remarking on the inadequacy of medical treatment for trigeminal neuralgia, stated that surgical removal of the ganglion was generally regarded as hazardous and uncertain in its permanent effects.4 The ill repute accorded the operation he attributed to a mortality rate ordinarily placed at 20 percent and to recurrences of pain due to incomplete op¬ erations. Surgeons commonly got no further than cutting the mandibular and maxillary nerves before being forced to back out because of severe hemorrhage. He felt that a permanent cure would depend on complete excision of the ganglion, be¬ lieving that the nerve could regenerate if only the sensory root was transected. He favored the extradural Hartley-Krause ap¬ proach with retraction of the middle meningeal artery with the dura, while taking care not to injure the vessel where it enters the skull at the foramen spinosum. He describes his technique, which he had used on four patients, all with pain that had re¬ curred after peripheral branch surgery. All developed complete trigeminal anaesthesia and loss of motor function with atrophy of the temporal region. All had transient abducens nerve palsies. He protected the eye with a sheet of rubber following the procedure. Cushing’s assumption that permanent cure of trigeminal neuralgia depended upon complete removal of the ganglion seemed self-evident at the time. The operation was technically difficult, due in part to bleeding from the cavernous sinus. Now that we know that compression of the ganglion often provides

long-term pain relief, we can wonder what those surgeons must have thought, having backed out after tamponading bleeding veins over the ganglion and then finding that their patients were pain-free. The world was not ready to recognize that such an operation might be effective. Spiller believed that transection of the root would likely not be followed by nerve regeneration, an opinion he supported by studying the pathological effects of rhizotomy in dogs. On his advice, Frazier performed a rhizotomy in 1901, which led to long-lasting pain relief. Although other physicians and sur¬ geons contributed to the dialogue at the time and reported their surgical experiences, the Philadelphia school of Spiller and Frazier kept at it and took the procedure from a surgical adven¬ ture to the standard operation for trigeminal neuralgia for the next fifty years. Frazier lowered the mortality rate, so that in 1928 he reported only one death among his last 269 cases. He selectively divided that portion of the root concerned with the site of the pain, commonly the lateral two-thirds in patients with second- and third-division pain, and he learned to spare the motor root.2 Reporting on 250 patients with trigeminal neuralgia oper¬ ated on by way of the posterior fossa, Dandy recorded in 1932 that he had experienced no operative deaths and no postopera¬ tive complications in his last 150 cases.3 Having demonstrated a degree of safety comparable with the Spiller-Frazier subtem¬ poral operation, Dandy claimed a number of advantages for the cerebellar approach, including the observation that division of the posterior half of the sensory root will cure the pain in any branch of the nerve with practically no loss of sensation. Because such a partial rhizotomy posed the possibility of pain recurrence, he divided the nerve totally in patients of advanced age. Neurosurgeons in the two decades following Dandy’s report of 1932 largely shared the opinion expressed by Olivecrona in 1947.5 His experience with two deaths in 445 subtemporal op¬ erations and five in 158 cerebellar approaches convinced him that the Frazier operation was safer. Furthermore, he noted a lower recurrence rate. He had conducted a medullary trac¬ totomy as described by Sjoqvist6 in 101 patients with two fatal¬ ities, but he felt that the morbidity hazard and the high recur¬ rence rate limited the value of this procedure. Subtemporal rhizotomy became a widely applied practi¬ cal treatment for trigeminal neuralgia. One of the main prob¬ lems was anesthesia dolorosa, an intense, steady, burning facial pain that replaces the neuralgia in 5 to 10 percent of cases. Olivecrona noted that this complication could be closely re¬ lated to the extent of denervation achieved. The hazard of ker¬ atitis was ever present if first division rootlets were transected. Traction on the superficial petrosal nerve at times led to de¬ layed but usually transient facial palsy. These complications and operative deaths, the rates of which are inevitably elevated when a procedure developed by surgical masters is widely adopted, can be recognized as the motivation for developing other treatments. Alternatives to open operation in order to section the gasse¬ rian ganglion and posterior root began in the first decade of the twentieth century, when needles became available that were strong enough for the purpose. By 1910, Taptas had injected al¬ cohol into Meckel’s cave. Hartel, one of the first to use the technique, later advocated the use of radiography for guidance.

Chapter 171/Overview of the Treatment of Cranial Neuralgias

1685

While being a minor procedure as compared to craniotomy, in¬ jection of a neurolytic substance poses the risk of injury to nearby nerves, and the degree of sensory loss achieved is un¬ controllable as to the portion of the nerve involved. Sensory

The development of percutaneous techniques to partially in¬ jure the root and ganglion thermally, mechanically, or chemi¬ cally changed the equation. With the risks of craniotomy set aside, a repeat procedure at a later date becomes more an in¬

loss is usually total. Kirschner, in 1932, described a percutaneous way to coagu¬

convenience than a danger to one’s life. In 1983, Mullan and Lichtor described a technique for com¬ pressing the ganglion percutaneously by introducing a balloon catheter by way of a needle under general anesthesia and then inflating the balloon. In 1990, Mullan reported a follow-up of 100 patients and demonstrated the safety of the technique.11 There had been a 20 percent recurrence rate in those followed for at least 5 years. Mullan found that in the group subjected to no more than 1 min of compression, the incidence of disagree¬ able dysesthesia was very low, being noted in only 1 of his last

late the gasserian ganglion electrically using a Bovie unit, which was effective but caused many complications, resulting mainly from the unpredictable extent of the denervation achieved. Thiry reduced the intensity of the electrocoagulation while attempting to preserve some touch sensation.7 In 1934, Dandy reviewed his operative notes written after 215 cases in which he divided the sensory root by the cerebel¬ lar route.8 He recognized compression of the root as a cause of the pain but did not recommend decompression as a treatment. In addition to tumors, a widened basilar artery, and cavernous angiomas as causes of the pain, he observed the nerve root to be compressed by an artery, commonly a branch of the superior cerebellar artery, which in many cases had been hardened by age. He also observed branches of the petrosal vein crossing over and through the root. While he did not identify any gross compression of the nerve in about 40 percent of the cases, he cautioned the reader to remember that the entire sensory root was not visible with his operative exposure. In 1951, Taamhoj operated on a young man with trigeminal neuralgia and found the root compressed by an epidermoid tu¬ mor, which he removed.9 Unlike his predecessors, Dandy and Olivecrona, he did not simultaneously treat the pain by cutting the root. His patient recovered pain-free and without loss of sensation. This led him to speculate that the cause of “genuine trigeminal neuralgia could perhaps also be sought in a com¬ pression of the trigeminal root.” He felt that the likely site of compression might be in the channel formed by the dura be¬ tween the ganglion and the upper sharp margin of the petrous bone. Small changes, perhaps of vascular origin, could narrow the channel. This led him to undertake an operation to divide the dura over the root in 10 patients, with good pain relief over a short postoperative period of observation. Sheldon and his associates in 1955 reported on 10 patients treated successfully between 1951 and 1953 by enlarging the foramen ovale and foramen rotundum with a dental drill and incising the nerve sheaths, thereby decompressing these nerves distal to the ganglion.10 Noting that the only feature common to this procedure and Taarnhoj’s decompression of the root was operative trauma, they operated, exposed the root, and gently compressed it in 29 patients. All became pain-free without fa¬ cial anesthesia; most became aware of a minimal difference in facial sensation when compared to the other side. The idea that partial injury to the fibers of the root may give long-term pain relief with little sensory loss can be attributed to Dandy, who transected the posterior part of the root, and to Sheldon and his colleagues. Whether Taamhoj should be cred¬ ited with pioneering decompression or included in the trigemi¬ nal compression vanguard can be debated. Since compression of the root is associated with a higher rate of recurrence than rhizotomy, the surgeon faced a dilemma as long as an open operation was required. Was it best to go for the long-term cure, with its associated dense anesthesia, or to accept an increased recurrence rate with only mild side effects?

60 patients. Hakanson injected glycerol into Meckel’s cave as a vehicle for a radioopaque marker but found that his planned prelimi¬ nary step for radiotherapy resulted in long-term pain relief.12 He has reported good results in patients with trigeminal neural¬ gia so treated with little sensory loss. Others have expressed concern about the technique’s failure to give pain relief at times, a significant recurrence rate, and the occasional occur¬ rence of dysesthesia. It is agreed, however, that the procedure is safe and can be recommended for patients who are medically unfit or otherwise do not wish to undergo a craniotomy. The widely used procedure of thermal coagulation of the gasserian ganglion and sensory root was developed by Sweet and Wepsic.13 A percutaneous route was developed to achieve two ends. The first was to limit the lesion to the portion of the nerve concerned with the pain, an adaptation of Frazier s subtotal rhizotomy. The second was to limit the extent of the denervation to causing analgesia but not anesthesia, a lineal de¬ scendant of Dandy’s subtotal rhizotomy. Intermittent general anesthesia with short-acting intravenous agents permitted the use of stimulation to localize the electrode to the portion of the nerve conveying sensation from the part of the face where the pain is felt and stepwise creation of the lesion to achieve an appropriate degree of sensory loss. While recurrences and dysesthesia may occur, the safety and ease with which the pro¬ cedure may be repeated has led to its widespread adoption as a satisfactory surgical treatment. Microvascular decompression, a surgical technique for in¬ terposing a synthetic material between the trigeminal root and a blood vessel in contact with it, as described and developed by Jannetta, has become a widely undertaken operation on the ba¬ sis that it can stop the pain without causing sensory loss and that it directly addresses the cause of the pain.14 While Jannetta and others have undeniably achieved consistently good results with few complications, controversy surrounds the procedure on two planes. The first relates to the efficacy of the operation when performed by neurosurgeons who are relatively unfamil¬ iar with subtle abnormalities in the disposition of blood vessels around the root—a knowledge that can only be obtained with extensive experience. Jannetta himself identifies this prob¬ lem.15 The second controversy relates to the possibility that by manipulating the root, one is in fact performing a compressiontype operation, or by placing something in contact with the root, one is providing long-term compression.16 After analyzing literature related to surgical complications and reflecting on his own knowledge of long-term pain relief

1686

Part 4/Functional Stereotaxis

ensuing from all kinds of disparate interventions. Sweet con¬ cluded that not enough is known about the cause of trigeminal neuralgia to allow an ideal treatment to be identified.17 Transection of the glossopharyngeal nerve under the base of the skull, where it can be found deep to the styloglossal muscle, was described by Sicard and Robineau in 1920 for the treat¬ ment of glossopharyngeal neuralgia.18 Recurrences following this operation and difficulties separating the nerve from the va¬ gus led to the intracranial approach being developed by Adson19 and Dandy.20 It was soon recognized that the upper one or two filaments of the vagus nerve should also be sectioned. Microvascular decompression has been advocated, but since rhizotomy is highly successful, with little morbidity related to the actual denervation, it is usually felt that having exposed the nerves intracranially, the surgeon should do the procedure most certain to provide a long-term cure. Percutaneous neurolysis of the glossopharyngeal nerve at the jugular foramen was described by Tew.21 The problem this procedure poses is that with damage to the adjacent vagus nerve, the patient may develop dysphagia related to loss of the ipsilateral gag reflex and hoarseness with denervation of the vocal cord. These risks may well be justified for the treatment of severe pain in a patient not medically fit for craniotomy. Geniculate neuralgia, while rare and difficult to diagnose, can be treated by intracranial section of the nervus intermedius at the porus acousticus.22 Experience with attempts to alleviate postherpetic neuralgia by ablative surgery to the sensory pathway has convinced most neurosurgeons that this pain, being the result of denervation, cannot be stopped by increased denervation. Attempts to con¬ trol the pain by stimulation of the thalamus or gasserian gan¬ glion with implanted electrodes have had limited success.23 Occipital neuralgia, usually a pain secondary to muscle spasms in the suboccipital muscles induced by a wide variety of conditions arising either spontaneously or as a result of trauma, has in the past been considered as somewhat akin to trigeminal neuralgia—that is, a specific disorder that may be treated by transection of the occipital nerve. Unfortunately, al¬ though local anaesthetic blocks may be therapeutic, they can¬ not reliably predict long-term pain relief or even the persis¬ tence of pain and the new onset of troublesome numbness. Few chronic pain syndromes anywhere in the body, particularly if posttraumatic, can be relieved by denervation. Most neurosur¬ geons would see occipital neuralgia in this light.

3.

Dandy WE: The treatment of trigeminal neuralgia by the cerebellar route. Ann Surg 96:787-893, 1932.

4.

Cushing HW: A method of total extirpation of the gasserian ganglion for trigeminal neuralgia by a route through the temporal fossa and be¬ neath the middle meningeal artery. JAMA 34:1035-1044, 1900.

5.

Olivecrona H: The surgery of pain. Acta Psychiatry 46(suppl 2) 268-280, 1947.

6.

Sjoqvist O: Trigeminal neuralgia: A review of its surgical treatment and some aspects of its aetiology. Acta Chir Scand 82:201-217 1939.

7.

8. 9.

Thiry S, Hotermans JM: Traitment de la nervrolgie essentielle du trijumeau par stereotaxie du ganglion de Gasser: Experience partout sur 365 cas traite entre 1950 et 1970. Neurochirurgie 20:55-60, 1974. Dandy WE: Concerning the cause of trigeminal neuralgia. Am J Surg 24:447^155, 1934. Taarnhoj P: Decompression of the trigeminal root and the posterior part of the ganglion as treatment in trigeminal neuralgia: Preliminary complications. J Neurosurg 9:288-290, 1952.

10.

Sheldon CH, Pudenz RH, Freshwater DB, Crae BL: Compression rather than decompression for trigeminal neuralgia. J Neurosurg 12:123-126, 1955.

11.

Mullan S: Percutaneous microcompression of the trigeminal gan¬ glion, in Rovit RL, Murali R, Jannetta PJ (eds): Trigeminal

12.

Neuralgia. Baltimore: Williams & Wilkins, 1990, pp 137-144. Hdkanson S: Trigeminal neuralgia treated by the injection of glycerol into the trigeminal cistern. Neurosurgery 9:638-646, 1981.

13.

Sweet WH, Wepsic JG: Controlled thermocoagulation of trigeminal ganglion and results for differential destruction of pain fibers: Part 1. Trigeminal neuralgia. J Neurosurg 40:143-156, 1974.

14. 15.

Jannetta PJ: Arterial compression of the trigeminal nerve in patients with trigeminal neuralgia. J Neurosurg 26(suppl): 159— 162, 1967. Jannetta PJ: Microvascular decompression of the trigeminal nerve root entry zone: Theoretical considerations, operative anatomy, surgi¬ cal technique, and results, in Rovit RL, Murali R, Jannetta PJ (eds): Trigeminal Neuralgia. Baltimore: Williams & Wilkins, 1990, pp 201-222.

16.

Adams CBT: Microvascular compression—An alternative view and hypothesis. J Neurosurg 70:1-12, 1989.

17.

Sweet WH: Complications of treating trigeminal neuralgia: An analy¬ sis of the literature and response to questionnaire, in Rovit RL, Murali R, Jannetta PJ (eds): Trigeminal Neuralgia. Baltimore: Williams & Wilkins, 1990, pp 251-279.

18.

Sicard JA, Robineau V: Algie vSIopharyngee essentiaile: Traitment chirurgical. Rev Neurol 36:256-277, 1920.

19.

Adson AW: Surgical treatment of glossopharyngeal neuralgia. Arch Neurol Psychiatry 12:487-506, 1924.

20.

Dandy WE: Glossopharyngeal neuralgia (tic doloureux). Arch Surg 15:198-214, 1927.

21.

Tew JM Jr: Percutaneous rhizotomy in the treatment of intractable fa¬ cial pain (trigeminal, glossopharyngeal and vagal nerves), in Schmidek HH, Sweet WH (eds): Current Techniques in Operative Neurosurgery. New York: Grune & Stratton, 1977, pp 409-426.

References 1.

Penman J: Trigeminal neuralgia in Vinken PJ. Bruyn GW (eds): Handbook of Clinical Neurology. Amsterdam: North Holland, 1968, vol 5, pp 296-322.

2.

22.

Frazier CH: Operation for the radical cure of trigeminal neuralgia: Analysis of five hundred cases. Ann Surg 88:534-547, 1928.

White JC, Sweet WH: Intermedius vagoglossopharyngeal and upper cervical neuralgias, in White JC, Sweet WH (eds): Pain and the Neurosurgeon: A Forty-Year Experience. Springfield, 1L: Charles C Thomas, 1969, pp 257-305.

23.

Young RF, Kroening R. Fulton W. et al: Electrical stimulation of the brain in the treatment of chronic pain: Experience of 5 years. J Neurosurg 62:389-396. 1985.

CHAPTER

172

RADIOFREQUENCY RHIZOTOMY FOR TRIGEMINAL AND OTHER CRANIAL NEURALGIAS

Jamal M. Taha and John M. Tew, Jr.

Cranial neuralgias can be successfully treated with percuta¬ neous radiofrequency rhizotomy. In this chapter, the technique and results of percutaneous radiofrequency rhizotomy are dis¬ cussed in the treatment of trigeminal neuralgia, vagoglossopha¬ ryngeal neuralgia, and chronic migrainous neuralgia (cluster headache).

TRIGEMINAL NEURALGIA

Clinical Features and Diagnosis Trigeminal neuralgia, a painful condition of the face, is charac¬ terized by these stereotypic symptoms and signs that usually al¬ low its clinical diagnosis: episodes of brief lancinating pain distributed in one or more divisions of the trigeminal nerve; presence of pain trigger zones; absence of neurological deficits; and a clinical course characterized by remissions and relapses of pain. Patients under 60 years of age, those with atypical pain, and those with neurological deficits should be evaluated further to exclude tumor, vascular abnormalities, or multiple sclerosis. In the authors’ experience, 1 percent of patients suffering from multiple sclerosis develop trigeminal neuralgia and 3 per¬ cent of patients suffering from trigeminal neuralgia have multi¬ ple sclerosis. Compared with the patients without multiple sclerosis, those with trigeminal neuralgia associated with mul¬ tiple sclerosis are usually younger and have a greater incidence (18 percent) of bilateral facial pain.

Patients are informed about the sensory deficit to be ex¬ pected after percutaneous radiofrequency rhizotomy and are encouraged to consult other patients who have had the proce¬ dure to better understand this sensory loss. Patients are also en¬ couraged to indicate their expectations; if they are concerned about sensory deficit, the surgeon should avoid a lesion that produces a dense sensory loss. Microvascular decompression is offered to patients who desire to avoid sensory deficit, to healthy individuals with pain in the first trigeminal division or in all three divisions, and to patients with a symptomatic lesion such as a tumor or vascular malformation. Preoperative preparation Percutaneous radiofrequency rhizotomy is performed on an outpatient basis in the radiographic suite (Fig. 172-1). The pa¬ tient’s oral intake of tic medication is restricted 6 h prior to the procedure. Atropine (0.4 mg intramuscularly) is administered preoperatively to reduce oral secretions and to prevent brady¬ cardia during sedation; prophylactic antibiotics are not usually administered. The patient’s blood pressure and pulse are closely monitored. The patient lies supine with the head in the neutral position. Three anatomic landmarks are placed on the face: a point 3 cm anterior to the external auditory meatus; another beneath the me¬ dial aspect of the pupil; and a third 2.5 cm lateral to the oral com¬ missure (Fig. 172-2A). A 21-gauge spinal needle, placed subcu¬ taneously in the deltoid muscle, acts as a reference electrode. Technique of percutaneous

Surgical Treatment

RADIOFREQUENCY RHIZOTOMY

Radiofrequency rhizotomy for trigeminal neuralgia is based on electrophysiological and clinical observations concerning tem¬ perature-dependent selective destruction of nociceptive A-delta and C fibers.' Initially, patients with trigeminal neuralgia should be treated medically, surgical candidates being those who do not enjoy long-term relief with drug therapy, either be¬ cause pain recurs or because toxic side effects develop. The au¬ thors recommend percutaneous radiofrequency rhizotomy for most patients undergoing their first surgical treatment for typi¬ cal trigeminal neuralgia and in those with trigeminal neuralgia and multiple sclerosis, in whom microvascular decompression usually fails.2

The procedure for percutaneous radiofrequency rhizotomy is the same for all patients with trigeminal neuralgia with or with¬ out multiple sclerosis.

Needle Placement Retrogasserian needle placement is achieved by freehand ma¬ nipulation using Hartel’s anterior approach to the foramen ovale and guided by lateral fluoroscopy5 (Fig. 172-2). Stereotactic frames and computed tomography-guided techniques have been developed to cannulate the foramen ovale;4-5 however, in the authors’ experience, they are not helpful.

1687

1688

Part 4/Functional Stereotaxis

Figure 172-1. Percutaneous radiofrequency rhizotomy is accomplished under lateral image intensification. (From the Department of Medical Communications of the Mayfield Clinic, with permission.)

Figure 172-2. A. Anatomic landmarks for electrode placement: (1) 3 cm anterior to the external auditory meatus; (2) medial aspect ot the pupil; and (3) site of needle penetration 2.5 cm lateral to oral commissure. B. Free-hand needle placement according to Hartel’s technique. C. The guiding finger of the right hand touches the lateral pterygoid wing. (From Tew,M with permission.)

Chapter 172/Radiofrequency Rhizotomy for Trigeminal and Other Cranial Neuralgias

The patient is anesthetized with an intravenous injection of 30 to 50 mg methohexital (Brevital; Eli Lilly & Co., Indianapolis, Indiana). An oral airway is placed between the patient’s jaws to prevent involuntary biting of the surgeon’s in¬ dex finger, which is placed just inferior to the lateral pterygoid wing. A standard 100-mm-length 20-gauge cannula with a stylet penetrates the skin 2.5 cm from the oral commissure. The surgeon’s finger prevents the cannula from penetrating the oral mucosa and also guides the cannula into the foramen ovale. The cannula is directed into the medial portion of the foramen ovale by aiming it toward the intersection of the coronal plane 3 cm anterior to the tragus, with the sagittal plane through the medial aspect of the pupil. Using cineradiographic control in the lateral plane, the cannula is directed 5 to 10 mm below the floor of the sella turcica along the clivus (Figs. 172-3A and B). Entrance of the cannula into the foramen ovale is signaled by a

1689

brief contraction of the masseter muscles, indicating contact with the mandibular fibers. Proper positioning of the cannula within the trigeminal cis¬ tern is usually accompanied by free flow of cerebrospinal fluid, the exception being in patients who have had previous percuta¬ neous radiofrequency rhizotomy or chemical injection. Egress of cerebrospinal fluid does not ensure that the needle is in the proper (retrogasserian) position, however, because cere¬ brospinal fluid can also be obtained from the infratemporal subarachnoid space if the needle has been advanced too far or from the region distal to the gasserian ganglion if the dural sub¬ arachnoid sleeve extends beyond the rootlets. Attention to the trajectory of the cannula is important to avoid vascular and neural complications. The carotid artery can be injured at three sites: the foramen lacerum when the cannula is inclined posteromedially; Meckel’s cave when the cannula is inclined posterolaterally (the carotid artery in the petrous bone lacks a bony covering); and the cavernous sinus when the can¬ nula is inclined cephalad, anteriorly, and medially. If the carotid artery is penetrated, the needle should be withdrawn and manual pressure should be applied over the posterior pha¬ ryngeal space. The procedure is then discontinued and the pa¬ tient allowed to recuperate for 48 h. Ischemic complications such as hemiparesis and carotid-cavernous fistula from punc¬ ture of the internal carotid artery have been reported after at¬ tempts to place a needle in Meckel’s cave.3 Fluoroscopy eliminates inadvertent cannulation of the supe¬ rior orbital fissure, which lies anterosuperiorly of the jugular foramen which lies posteroinferior to the forament ovale. The abducens nerve can be injured when the needle is advanced to project more than 7 mm past the profile of the clivus; trochlear and oculomotor palsy can occur when the needle is located too far cephalad in the cavernous sinus.

Electrode Localization

Figure 172-3. Illustration of the relationship of the electrode to the floor of the sella turcica and the profile of the clivus. A. The

needle is inserted 5 to 10 mm below the intersection of a line drawn from the floor of the sella turcica to the clival line. (From Tew,34 with permission.) B. The relationship of the electrode tip to the clival line for stimulation of trigeminal rootlets. (From Tew and Taha,35 with permission.)

The curved electrode tip carries a thermocouple, stimulator, and lesion-generating probe. When the electrode is inserted into the cannula as far as it will go, the curved tip protrudes 5 mm and projects 3 mm perpendicular to the axis of the elec¬ trode. Because the cannula is insulated, only the extruding por¬ tion of the electrode is conductive. The electrode can be rotated 360° for stimulation and lesion production in different direc¬ tions around the cannula. Electrode placement is guided by anatomic location with lateral fluoroscopy: for V3 pain, the electrode tip lies 5 mm proximal to the profile of the clivus and is directed caudally; for V2 pain, the electrode tip lies at the profile of the clivus; and for VI pain, the electrode tip lies 5 mm distal to the profile of the clivus and is directed cephalad (Fig. 172-3B). Final placement of the electrode tip is determined by the re¬ sponse to electrical stimulation. Proper placement is confirmed by the production of paresthesias or ticlike pain in the involved part of the nerve by a square-wave current of 0.2 to 0.3 V at 50 to 75 Hz and 1 ms duration. Stimulation at a higher voltage (0.5 to 1 V) may be required for patients who have previously undergone an intracranial rhizotomy or alcohol injection. Different rootlets can be stimulated by rotating the curved elec¬ trode about its axis and varying the depth or the angle of trajec¬ tory of the cannula (Fig. 172-4). The ophthalmic division is ac¬ cessed by rotating the electrode medially or by redirecting the

1690

Part 4/Functional Stereotaxis

Dural Sac

Figure 172-4. Illustration of the trigeminal rootlets and the Tew curved electrode. The curved electrode is capable of producing lesions in any of the three divisions from one position. (From Tew and van Loveren,36 with permission.)

cannula anteriorly. The mandibular fibers are accessed by rotat¬ ing the electrode laterally. If the masseter muscle contracts dur¬ ing stimulation, the electrode is rotated laterally to avoid trigeminal motor palsy. Eye movement during stimulation indi¬ cates that the cannula is too deep in the cavernous sinus or that it is near the brain stem; stimulus-evoked facial contractions in¬ dicate that the electrode is too deep, inclined too low on the clivus, or that the level of stimulation is too high.

Lesion Production The electrode tip is 0.5 mm in diameter and produces lesions measuring 5 by 5 by 4 mm. The geometry of the lesion varies with the medium but is usually oriented toward the curve of the electrode. The thermocouple sensor, located at the tip of the electrode, provides a calibration accuracy of ± 2°C at 30 to 100°C. Alter intravenous anesthetic is administered, a preliminary lesion is produced at 60°C for 60 s. The patient’s facial flush helps to localize the nerve rootlet undergoing thermal destruc¬ tion.'’ Constant sensory testing allows fine control of denerva¬ tion. Additional enlargement of the lesion can usually be made without further sedation in 5°C increments until the desired ef¬ fect is achieved. The goal is usually dense hypalgesia in the painful trigger zone with preserved touch sensation. Alter sensory loss is achieved, the patient is observed for 15 min to determine it a fixed lesion has been produced. The elec¬ trode and the cannula are then withdrawn and manual pressure is applied to the posterior pharyngeal space for 3 min.

Postoperative care Postoperatively, the patient is instructed in eye care and the avoidance of jaw strain. If corneal sensation is diminished, the patient should plaee artificial tears on the cornea every 2 to 4 h and watch for and report any ocular abnormalities. Diet is restrieted to soft food for 1 week and jaw exercises should be

practiced for 2 weeks. The patient should avoid biting the lips, tongue, or buccal mucosa. Anticonvulsant medications are ta¬ pered off and discontinued.

Results Tables 172-1 to 172-4 summarize the authors’ results in treat¬ ing 1200 patients with trigeminal neuralgia by percutaneous ra¬ diofrequency rhizotomy. Table 172-5 summarizes major series of the operation reported in the recent literature,7-12 revealing effective pain control with minimal morbidity and low rates of pain recurrence. In the authors’ series, side effects were re¬ duced by selective lesioning using the curved electrode and by limiting the depth of sensory deficit. Although the incidence of

TABLE 172-1. Characteristics of 1200 Patients Selected for Percutaneous Radiofrequency Rhizotomy" Characteristic

Sex Female Male Side of coagulation Right Bilateral Division of trigeminal nerve involved VI V2 V3 VI and V2 V2and V3 VI, V2,and V3

Percent

63 37 60 5 1 16 16 15 39 13

■Average age, 65 years; patients with multiple sclerosis excluded. source: From Tew and Tatra,’ with permission.

1691

Chapter 172/Radiofrequency Rhizotomy for Trigeminal and Other Cranial Neuralgias

TABLE 172-2.

Follow-up Results of Percutaneous Radiofrequency Rhizotomy in 1200

Patients'1

Excellent Good Fair Poor Failure

Percent

Description

Result

72 21 4 1 2

No tic pain, dysesthesia, or troublesome paresthesia No tic pain, minor dysesthesia or paresthesia No tic pain, moderate dysesthesia or paresthesia No tic pain, major dysesthesia or paresthesia Immediate

"Average follow-up, 9 years. Includes patients undergoing multiple percutaneous stereotactic rhizotomies; subjective rating determined by the patient. Patients with multiple sclerosis are excluded. Twenty percent of patients experienced pain recurrence: pain was minor in 5 percent and did not require additional treatment, pain was controlled with medication in 5 percent, and pain required another surgery in 10 percent. source:

From Tew and Taha,3 with permission.

TABLE 172-3. Complications in 1200 Percutaneous Radiofrequency Rhizotomy"

Patients

after

TABLE 172-4. Complications of Percutaneous Radio¬ frequency Rhizotomy (Curved Electrode versus Straight Electrode)

Complication

Percent Patients, %

Masseter weakness* Pterygoid weakness Dysesthesia or paresthesia (minor) Dysesthesia or paresthesia (major) Anesthesia dolorosa Absent corneal relfex with V1 pain with V2 pain with V3 pain Keratitis Diplopia Oculomotor Trochlear Abducens Meningitis Carotid-cavernous fistula Intracranial hemorrhage Death

16 7 17 3 1 6 15 5 1 2 1.2 0.1 0.5 0.6 0.2 0.1 0 0

“Includes patients undergoing multiple percutaneous rhizotomies. ‘Nearly all nerve palsies (motor root and extraocular) represented axonotmesis and resolved within 6 months. source: From Tew and Taha,3 with permission.

pain recurrence may be greater with limited sensory loss, the authors believe that the ease of repeating the procedure justifies its use. The lesion should be tailored to suit the patient’s needs. Temporary relief associated with mild sensory deprivation may provide a trial period for the patient who is concerned about her or his ability to tolerate numbness. Most patients do not ex¬ press concern about repetition of the procedure when it be¬ comes necessary to control pain recurrence.

Discussion Among the percutaneous techniques, the authors favor ra¬ diofrequency rhizotomy using a curved electrode and selective lesioning because this provides the most controllable lesion, produces side effects no more severe than those of other percu¬

Complication

Curved electrode, n = 500

Straight electrode, n = 700

Dysesthesia Minor Major Anesthesia dolorosa Absent comeal reflex VI pain V2 pain V3 pain Keratitis Diplopia Masseter weakness

11 9 2 0.2 3 8 2 0.3 0.6 0.5 7

27 22 5 1.6 8 20 8 2 4 2 24

source: From Tew and Taha,3 with permission.

taneous techniques, and has the lowest pain recurrence rate.3 The authors prefer to create milder lesions to avoid side effects from sensory deprivation. Compared with posterior fossa ex¬ ploration, percutaneous radiofrequency rhizotomy has a lower incidence of permanent cranial nerve palsy, intracranial hemor¬ rhage or infarct, and perioperative morbidity and mortality while the recurrence rates of the two procedures are similar.3 The advantage of posterior fossa exploration with microvascular decompression is the possibility of long-term pain relief without facial sensory loss;3 the surgeon should offer the most appropriate procedure for each patient guided by personal ex¬ perience as well as patient preference.

VAGOGLOSSOPHARYNGEAL NEURALGIA Clinical Features and Diagnosis Vagoglossopharyngeal neuralgia is characterized by paroxys¬ mal lancinating pain in the somatosensory distribution of the glossopharyngeal and/or the vagus nerve (i.e., throat, ear, ton-

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Chapter 172/Radiofrequency Rhizotomy for Trigeminal and Other Cranial Neuralgias

1693

sillar fossa, larynx, pharynx, base of the tongue). Pain is usu¬ ally triggered by swallowing, while periods of exacerbation and remission occur in most patients. Ten percent of patients develop vagoglossopharyngeal syncope.13 Vagoglossopha¬ ryngeal pain from a mass lesion in the oropharynx or cerebello¬ pontine angle is usually more constant and associated with neu¬ rological deficits; it frequently involves other cranial and upper cervical nerve fibers.14 The diagnosis of vagoglossopharyngeal neuralgia is con¬ firmed by applying 10% cocaine solution to the tonsillar fossa for temporary relief during a pain attack.14 When this procedure fails in patients with classic symptoms, cocaine application in the piri¬ form fossa of the larynx or tetracaine hydrochloride blockade at the jugular foramen help to identify patients with pain conducted primarily by the vagus nerve.15 A tumor in the oropharynx or cerebellopontine angle should be excluded in all patients.

Surgical Treatment The initial treatment for vagoglossopharyngeal neuralgia is medical (i.e., carbamazepine, diphenylhydantoin, lioresal).16 Although these medications are usually initially successful, most patients have pain recurrence or develop side effects.14 When surgery is necessary, the authors usually recommend in¬ tracranial glossopharyngeal and upper vagal rhizotomy. Elderly patients in poor health and patients with pain from a tumor in the oropharynx are offered percutaneous radiofrequency rhizo¬ tomy of the glossopharyngeal nerve at the jugular foramen. Percutaneous radiofrequency rhizotomy for vagoglossopha¬ ryngeal neuralgia is performed by a freehand technique guided by lateral fluoroscopy, similar to that described for trigeminal neuralgia. The cannula is placed in the anteromedial compart¬ ment (pars nervosa) of the jugular foramen, which contains the glossopharyngeal nerve. An anterior fibrous or bony band sepa¬ rates this compartment from the larger posterolateral compart¬ ment (pars venosa), which contains the jugular bulb and the tenth and eleventh cranial nerves17 (Fig. 112-5A). To cannulate the pars nervosa, the needle is aimed 14° caudally to and in the same sagittal projection as the foramen ovale. On lateral fluo¬ roscopy, the jugular foramen is situated posterior to the tem¬ poromandibular joint and anterior to the occipital condyle, 27 to 33 mm below the floor of the sella turcica (Fig. 172-55). A lateral percutaneous approach, stereotactic frames, and com¬ puted tomography (CT)-guided percutaneous cannulation of the jugular foramen have also been described.1118 Physiological localization and lesion making are similar to that described for trigeminal neuralgia. The needle should be readjusted if stimulation or lesioning produce cough, stern¬ ocleidomastoid contraction, or vagal autonomic changes. The goal is to produce analgesia of the tonsillar pharynx and to pre¬ vent triggering. Because patients can develop dangerous hyper¬ tension, hypotension, bradycardia, syncope, or even cardiac ar¬ rest during stimulation or lesioning,14 hemodynamic changes should be closely monitored.

Results Percutaneous radiofrequency rhizotomy of the glossopharyn¬ geal nerve achieves pain relief in more than 90 percent of pa¬ tients who have idiopathic vagoglossopharyngeal neuralgia (Table 172-6). Although there are no large series reporting

B Figure 172-5. A. Needle penetrates the neural portion of the jugular foramen. The bony spur divides the neural from the vascular portion. (From Tew,34 with permission.) B. Schematic diagram of a lateral projection of the head. The needle is inserted 27 to 33 mm below the floor of the sella turcica and lies posterior to the temporomandibular joint and anterior to the occipital condyle. (From Taha and Tew,33 with permission.

1694

Part 4/Functional Stereotaxis

TABLE 172-6. Results of Percutaneous Radiofrequency Rhizotomy in the Treatment of Idiopathic Vagoglossopharyngeal Neuralgia

Author

No. of patients

Lazorthes and Verdie27

1

Pain-free 2.5 years

Temporary hoarseness, dysphagia, vocal cord paralysis

Tew and van Loveren26

2

Pain-free

Vocal cord paralysis

Isamat et al.23

3

Pain-free 5-32 months

No permanent deficits

Giorgi and Broggi28

5

3 pain-free 3-5 years, 2 failed

Hoarseness, dysphagia

Arias22

2

Pain-free 1-2 years

No deficits

Salar et al.18

3

Pain-free 7 months

No permanent deficits

Gybels and Sweet25

4

3 pain-free 1-8 years, 1 failed

No permanent deficits

Arbit and Krol4

1

Pain-free dysphagia

Temporary hoarseness.

source:

Results

Comments

From Taha and Tew,33 with permission.

long-term results, a low rate of pain recurrence is expected be¬ cause the lesion is usually preganglionic and the lesion current involves the vagus nerve, which can contribute to the pain. In patients with vagoglossopharyngeal neuralgia from cervicofa¬ cial tumors, 70 percent are pain-free or significantly improved after this procedure (Table 172-7). Injury to the vagus nerve during the procedure resulted in paralysis of the ipsilateral vocal cord, hoarseness, and dyspha¬ gia in several series (Tables 172-5 and 172-6). Complications are minimized by accurate localization of the needle, produc¬ tion of a carefully graded lesion with small temperature incre¬ ments, and frequent neurological examinations.

Discussion Percutaneous radiofrequency thermal rhizotomy is a controver¬ sial surgical treatment for patients with vagoglossopharyngeal neuralgia. The authors believe that the high incidence of post¬ operative hoarseness, vocal cord paralysis, and dysphagia re¬ ported limits the use of this procedure to neuralgia of neoplas¬ tic origin and to idiopathic neuralgia in elderly patients who cannot tolerate other surgery.2021 Based on favorable experi¬ ence with this procedure, other clinicians have recommended percutaneous radiofrequency rhizotomy for most patients with vagoglossopharyngeal neuralgia.22'23

TABLE 172-7. Results of Percutaneous Radiofrequency Rhizotomy in the Treatment of Vagoglossopharyngeal-mediated Pain of Orofacial Neoplastic Origin

Author

No. of patients

Lazorthes and Verdie27

Results

Comments

11

6 good/excellent relief 4-25 months, 5 mild/no relief

3 had temporary hoarseness or dysphagia

Broggi et al.7

2

Pain-free 1 year

1 had temporary dysphagia

Pagura et al.29

15

11 pain-free, 4 some relief

All had worsening dysphagia

Giorgi and Broggi28

5

3 pain-free until death, 2 improved

1 dysphagia

Salar et al.18

5

Improved 7 months

Gybels and Sweet25

2

Poor

Tew and van Loveren26

9

5 pain-free 4-18 months, 4 no relief

source:

From Taha and Tew,33 with permission.

Chapter 172/Radiofrequency Rhizotomy for Trigeminal and Other Cranial Neuralgias

have cluster headache are more likely to develop anesthesia do¬ lorosa than patients who have trigeminal neuralgia, tolerance to sensory deprivation is important to document.25 Over 30 per¬ cent of patients who responded to lidocaine blockade reported that the analgesia was intolerable and were therefore ineligible for percutaneous radiofrequency rhizotomy. The technique of percutaneous radiofrequency rhizotomy for chronic cluster headache is similar to that described for trigeminal neuralgia. Analgesia in the VI and V2 divisions of the trigeminal nerve should be achieved to avoid pain recur¬ rence.25

CHRONIC MIGRAINOUS NEURALGIA (CLUSTER HEADACHE) Clinical Features and Diagnosis Cluster headache is characterized by the sudden onset of excru¬ ciating unilateral pain that starts around the eye, temple, or cheek associated with parasympathetic overactivity (e.g., ipsilateral lacrimation, conjunctival injection, nasal stuffiness, rhinorrhea). Attacks may last several hours and usually occur at regular intervals. Sympathetic paresis resulting in miosis and ptosis occurs in 60 to 70 percent of patients during the attack.24 Characteristically, the attacks occur once or twice a year for periods or clusters of 6 to 12 weeks; remissions average 2 years. In 10 percent of patients, the chronic cluster headaches (also termed chronic migrainous neuralgia) may last more than 1 year without remission.

Results Some 50 to 70 percent of patients with cluster headache achieve immediate pain relief and 10 to 30 percent improve af¬ ter percutaneous radiofrequency rhizotomy (Table 172-8). Better results were reported in patients who responded to retrogasserian lidocaine blockade.25 Longer pain relief was achieved in those patients with greater levels of analgesia. Although there is frequently a link between manifestations of autonomic activity and pain, pain may persist despite abolition of auto¬ nomic signs after surgical treatment and autonomic signs may persist despite cessation of pain.25

Surgical Treatment The pain of cluster headache is usually controlled with medical treatment, less than 4 percent of patients requiring surgical therapy. Percutaneous trigeminal radiofrequency rhizotomy for the treatment of chronic cluster headache produces thermal le¬ sions that reduce nociceptive afferent input and the release of substance P and other vasoactive polypeptides involved in pain transmission.24 25 Some surgeons recommend preoperative retrogasserian injection of 0.3 to 0.5 mL of 1% lidocaine to ascer¬ tain if analgesic block of trigeminal rootlets stops the pain.25 Favorable responses indicate that the major pain pathway is through the trigeminal system and that surgery directed to the trigeminal system may be beneficial. Because patients who

TABLE 172-8.

CONCLUSION Percutaneous radiofrequency rhizotomy remains an effective and safe procedure for the treatment of many painful condi¬ tions of the face. Meticulous attention to the technique mini¬ mizes the side effects. When patients are properly selected, per¬ cutaneous radiofrequency rhizotomy achieves excellent results.

Results of Percutaneous Radiofrequency Rhizotomy in the Treatment of “Cluster Headache” No. of patients

Results

Sweet12

20 (28 procedures)

12 pain-free 1-20 years 2 pain recurrence at 3 and 10 years 6 poor 1 anesthesia dolorosa

Watson et al.30

13 (27 procedures)

10 pain-free 10-36 months 3 poor 1 anesthesia dolorosa

Onofrio and Campbell31

21 (23 procedures)

Author

Tew and van Loveren26 Maxwell32 source:

1695

12 pain-free 10-32 months 4 pain recurrence 1 -6 months 7 poor 1 comeal abrasion 1 hyperacusis 2 had prickly eyes

8

6 good results 2 failed

8

5 pain-free 7-59 months 3 pain recurrence

From Taha and Tew,33 with permission.

Comments

All had analgesia 14/15 who were pain-free after lidocaine hydrochloride blockade were pain-free after percutaneous rhizotomy 5/14 with VI analgesia had some corneal sensation 7/10 analgesics had pain relief 3/17 hypalgesics had pain relief 11/12 analgesics had pain relief 1/11 hypalgesics had pain relief 2/12 VI analgesics had some comeal sensation

2/2 analgesics had pain relief 3/6 hypalgesics had pain relief

16%

Part 4/Functional Stereotaxis

ACKNOWLEDGMENT

17.

Rhoton A, Buza R: Microsurgical anatomy of the jugular foramen. J Neurosurg 42:541-550, 1975.

The authors thank Kathy Fogle and Mary Kemper of the Department of Neurosurgery Editorial Office for their editorial assistance.

18.

Salar G, Ori C, Barratto V, et al: Selective percutaneous thermolesion of the ninth cranial nerve by lateral cervical approach: Report of 8 cases. Surg Neurol 20:276-279, 1983.

19.

Ori C, Salar G, Giron G: Percutaneous glossopharyngeal thermoco¬ agulation complicated by syncope and seizures. Neurosurgery 13:427—429, 1983.

20.

Sindou M, Henry JF, Blanchard P: Idiopathic neuralgia of the glos¬ sopharyngeal nerve: Study of a series of 14 cases and review of the literature. Neurochirurgie 37:18-25, 1991.

21.

van Loveren HR, Tew JM Jr, Keller JT, Nurre MA: A 10-year experi¬ ence in the treatment of trigeminal neuralgia: A comparison of percu¬ taneous stereotaxic rhizotomy and posterior fossa exploration. J Neurosurg 57:757-760, 1982.

References 1.

Frigyesi T, Siegfried J, Groggi G: The selective vulnerability of evoked potentials in the trigeminal sensory root to graded thermoco¬ agulation. Exp Neurol 49:11-21, 1975.

2.

Jannetta P: Treatment of trigeminal neuralgia by micro-operative de¬ compression, in Youmans J (ed): Neurological Surgery. Philadelphia: Saunders, 1990. pp 3928-3942.

22.

Tew JM Jr. Taha JM: Percutaneous rhizotomy in the treatment of in¬ tractable facial pain (trigeminal, glossopharyngeal, and vagal nerves), in Schmidek HH. Sweet WH (eds): Operative Neurosurgical Tech¬ niques, 3ded. Philadelphia: Saunders, 1995, pp 1469-1484.

Arias MJ: Percutaneous radiofrequency thermocoagulation with low temperature in the treatment of essential glossopharyngeal neuralgia. Surg Neurol 25: 94-96, 1986.

23.

Isamat F, Ferran E, Acebes J: Selective percutaneous thermocoagula¬ tion rhizotomy in essential glossopharyngeal neuralgia. J Neurosurg 55:575-580, 1981.

24.

Mathew NT: Advances in cluster headache. Headache 8:867-890, 1990.

25.

Gybels JM, Sweet WH: Neurosurgical treatment of persistent pain: Physiological and pathological mechanisms of human pain, in Gildenberg PL (ed): Pain and Headache. Basel: Karger, 1988, pp 70-103.

26.

Tew JM Jr, van Loveren HR: Percutaneous rhizotomy in the treat¬ ment of intractable facial pain (trigeminal, glossopharyngeal, and va¬ gal nerves), in Schmidek HH, Sweet WH (eds): Current Techniques in Operative Neurosurgery, 2d ed. Orlando, FL: Grune & Stratton, 1988, pp 1111-1123.

27.

Lazorthes Y, Verdie JC: Radiofrequency coagulation of the petrous ganglion in glossopharyngeal neuralgia. Neurosurgery 4:512-516, 1979.

28.

Giorgi C, Broggi G: Surgical treatment of glossopharyngeal neuralgia and pain from cancer of the nasopharynx: A 20-year experience. J Neurosurg 61: 952-955, 1984.

29.

Pagura JR. Schnapp M, Passarelli P: Percutaneous radiofrequency glossopharyngeal rhizotomy for cancer pain. Appl Neurophysiol 46:154-159, 1983.

30.

Watson CPN, Morley TP, Richardson JC, et al: The surgical treatment of chronic cluster headache. Headache 23:289-295, 1983. Onofrio BM, Campbell JK: Surgical treatment of chronic cluster headache. Mayo Clin Proc 61: 537-544, 1986.

3.

4.

Arbit E, Krol G: Percutaneous radiofrequency neurolysis guided by computed tomography for the treatment of glossopharyngeal neural¬ gia (technical note). Neurosurgery 29:580-582, 1991.

5.

Laitinen L: Trigeminus stereoguide: An instrument for stereotactic approach through the foramen ovale and foramen jugulare. Surg Neurol 22:519-523, 1984.

6.

Goadsby P, Edvinsson L, Ekman R: Release of vasoactive peptides in the extracerebral circulation of humans and the cat during activation of the trigeminovascular system. Ann Neurol 23:193-196, 1988. Broggi G, Franzini A, Lasio G, et al: Long-term results of percuta¬ neous retrogasserian thermorhizotomy for “essential” trigeminal neu¬ ralgia: Considerations in 1000 patients. Neurosurgery 26:783-787, 1990.

7.

8.

9. 10.

11.

Fraioli B, Esposito V, Guidetti B, et al: Treatment of trigeminal neu¬ ralgia by thermocoagulation, glycerolization. and percutaneous com¬ pression of the gasserian ganglion and/or retrogasserian rootlets: Long-term results and therapeutic protocol. Neurosurgery 24: 239-245,1989. Frank F. Fabrizi A: Percutaneous treatment of trigeminal neuralgia. Acta Neurochir (Wien) 97:128-130, 1989. Nugent RG: Surgical treatment: Radiofrequency gangliolysis and rhi¬ zotomy. in Fromm GH. Sessle BJ (eds): Trigeminal Neuralgia: Current Concepts Regarding Pathogenesis and Treatment. Stoneham, MA: Butterworth-Heinemann, 1991, pp 159-184. Siegfried J: Percutaneous controlled thermocoagulation of gasserian ganglion in trigeminal neuralgia: Experience with 1000 cases, in Samii M, Jannetta P (eds): The Cranial Nerves. Berlin: SpringerVerlag, 1981, pp 322-330.

12.

Sweet WH: Treatment of trigeminal neuralgia by percutaneous rhi¬ zotomy, in Youmans J (ed): Neurological Surgery. Philadelphia: Saunders, 1990, pp 3888-3921.

13.

Bruyn GW: Glossopharyngeal neuralgia. Cephalalgia 3:143-157, 1983.

14.

van Loveren HR. Tew JM Jr, Thomas GM: Vago-glossopharyngeal and geniculate neuralgias, in Youmans JR (ed): Neurological Surgery. Philadelphia: Saunders, 1990, pp 3943-3949. Tyttis J: Glossopharyngeal and geniculate neuralgias, in Youmans JR (ed): Neurological Surgery. Philadelphia: Saunders, 1982, vol 6, pp 3604-3612.

15.

16.

King J: Glossopharyngeal neuralgia. Clin Exper Neurol 24:113-121. 1987.

31. 32. 33.

34.

35.

36.

Maxwell RE: Surgical control of chronic migrainous neuralgia by trigeminal gangliorhizolysis. J Neurosurg 57:459-466, 1982. Taha JM, Tew JM Jr: Surgical management of vagoglossopharyngeal and other uncommon facial neuralgias, in Tindall GT, Cooper PR, Barrow DL (eds): The Practice of Neurosurgery. Baltimore: Williams & Wilkins, 1996, pp 3065-3080. Tew JM Jr: Treatment of trigeminal neuralgia by percutaneous rhi¬ zotomy, in Youmans JR (ed): Neurological Surgery, 2d ed. Philadelphia: Saunders. 1982. Tew JM Jr. Taha JM: Treatment of trigeminal and other facial neural¬ gias by percutaneous techniques, in Youmans JR (ed): Neurological Surgery, 4th ed. Philadephia: Saunders, 1995, pp 3386-3403. Tew JM Jr. van Loveren HR: Percutaneous rhizotomy in the treat¬ ment of intractable facial pain (trigeminal, glossopharyngeal, and va¬ gal nerves), in Schmidek HH, Sweet WH (eds): Current Techniques in Operative Neurosurgery, 2d ed. Orlando, FL: Grune & Stratton, 1988.

CHAPTER

1 73

INJECTION OF GLYCEROL INTO THE GASSERIAN CISTERN FOR TREATMENT OF TRIGEMINAL NEURALGIA

Sten Hakanson and Bengt Linderoth

In the clinical management of trigeminal neuralgia there is a need for an inexpensive, highly efficient surgical technique that can safely be used in any age group. Several surgical methods for the treatment of trigeminal neuralgia are available, but the technique of injection of glyc¬ erol into the trigeminal cistern meets with these criteria ex¬ tremely well, as confirmed also by its widespread use. The method can be performed under local anesthesia and its success rate is comparable to that of more invasive techniques. With proper glycerol injection, the risk for substantial loss of facial sensation is very low. The percutaneous nature of the procedure is preferred by many patients who are reluctant to undergo major surgery. The short stay at the hospital and the short absence from work also add to the advantage for the patient. The alleviation of the paroxysmal pain in trigeminal neural¬ gia by the injection of glycerol into the trigeminal cistern was an accidental discovery made during the development of a technique for permanent radiographic marking of the trigemi¬ nal cistern with tantalum dust. This was to be used for stereo¬ tactic target localization of the gasserian ganglion in cases to be treated with the Gamma Knife during the 1970s.1 This observa¬ tion was developed into a method of treatment in trigeminal neuralgia and subsequently recommended for routine use.2 The procedure has now been in common use for more than 15 years.

INDICATIONS The method should be used exclusively in patients suffering from classic trigeminal neuralgia, but patients having paroxys¬ mal pain in association with multiple sclerosis also benefit from the treatment. As troublesome side effects of pharmaco¬ logic treatment in elderly patients and in patients with multiple sclerosis are more common than in middle-aged healthy per¬ sons, the indications for glycerol treatment in these groups can be wide. In patients having a combination of paroxysmal pain and constant pain, it is to be expected that glycerol will have an im¬ pact only on the paroxysmal component of the pain. Patients with other forms of facial pain and those with more or less manifest denervation pain should not be considered for glycerol treatment as it may make the pain condition even

worse. A thorough preoperative evaluation of the patient’s facial sensation as well as an investigation with computed tomography (CT) or magnetic resonance imaging (MRI) is therefore of utmost importance.

PROCEDURE The procedure is preferentially performed under local anesthe¬ sia, as some cooperation from the patient is helpful; but in es¬ pecially anxious patients, general anesthesia can be used. When the procedure is performed with local anesthesia, proper premedication is essential, and the procedure should be discon¬ tinued if the anesthesia is insufficient or the patient is too drowsy. At the Department of Neurosurgery of the Karolinska Hospital in Stockholm, which first described the procedure, glycerol rhizolysis is presently performed as described below. Many modifications of the original performance of the proce¬ dure have been suggested, but no substantial improvement in results or convenience of the technique has, in our opinion, been achieved. In some instances it has even resulted in a less satisfactory outcome.3-6 At least 30 min before the start of the procedure, the patient is premedicated with 5 to 10 mg of morphine hydrochloridescopolamine SC and 2.5 mg droperidol IM, but often the doses have to be reduced due to the patient’s advanced age or the medical condition. Before the premedication is given, the pa¬ tient should be provided with an intravenous line. It is most convenient to perform the procedure in an x-ray suite with a tiltable chair and fluoroscopy as well as the possi¬ bility to obtain radiographs. However, the standard C-arc fluo¬ roscopy, available in most surgical departments, has also proven adequate. The needle is best introduced with the patient in the sitting position, but, since patients sometimes suffer from a drop in blood pressure due to vasovagal reflexes in the initial phase of the procedure, it is essential that the patient can be placed in the supine position for some period of time if needed. Most operat¬ ing tables are not suitable for the procedure. Dentists’ chairs which can easily be tilted to the horizontal position are more appropriate. The needle (preferably 0.7 X 90 to 120 mm; 22 to 23 gauge) is introduced approximately 3.5 cm lateral to the angle of the

1697

1698

Part4/Funotional Stereotaxis

mouth and directed toward the medial border of the pupil and slightly anterior to the temporomandibular joint.

tip of the needle may be placed in the subtemporal subarach¬ noidal space instead, but this location is immediately disclosed

Fluoroscopy in the lateral projection is usually sufficient to identify the site of the foramen ovale indirectly for the intro¬ duction of the needle. In this projection, the foramen is usually to be found about 0.5 cm in front of the cartilage of the tem¬ poromandibular joint. In an infraorbital view in the anteropos¬ terior projection, the tip of the needle may be related to the trigeminal incisura, which is observable on the petrous ridge. Proper intracisternal position of the cannula following penetra¬ tion of the foramen ovale is manifest by a spontaneous exit of cerebrospinal fluid (CSF).

by an anteroposterior x-ray following contrast injection (Fig. 173-4).

CISTERNOGRAPHY However, the free egress of CSF is not a sufficient requisite in itself to prove an intracisternal position of the tip of the needle. A correct position can be confirmed only after injection of con¬ trast medium. We presently use 0.3 to 1 mL of iohexol (Omnipaque 300 mg 1/mL), which is injected with the patient in the sitting position and with the head somewhat flexed. The trigeminal cistern filled with contrast medium is usually well circumscribed and visualizes sensory root filaments in the lat¬ eral as well as in the anteroposterior view (Fig. 173-M and B). The appearance of the cistern may vary as well as its size and location (Fig. 173-2). There are, however, several possible sites of misplacement of the needle tip, as indicated in Fig. 173-3. Deposition of glycerol outside the arachnoid of the cistern is probably ineffective and is discouraged. Not infrequently the

At times, when contrast medium is injected without prior spontaneous CSF drainage, it may accumulate outside the arachnoid within Meckel’s cave (Fig. 173-5). It may also end up in the subtemporal subdural space. Contrast injection with¬ out prior spontaneous CSF drainage is therefore discouraged. After the confirmation of an intracisternal tip position, the contrast medium should be evacuated from the cistern by spon¬ taneous drainage from the needle, followed by tilting the pa¬ tient into the supine position, allowing the remaining contrast medium to drain into the posterior fossa. Some of the less satisfactory results reported may actually be due to a failure to properly drain the cistern prior to glycerol injection.4-5

INJECTION OF GLYCEROL Following the confirmation of an intracisternal tip position and an adequate contrast evacuation, glycerol is slowly injected, using an 1 mL syringe, with the patient in the sitting position. In most cases 0.22 to 0.28 mL of glycerol is an adequate dose. It is advantageous to check the free flow of CSF from the nee¬ dle immediately before the injection of glycerol in order to pre¬ clude dislodgement ot the needle during the procedure. It is possible to obtain some somatotopographic selectivity via four maneuvers: (1) varying the volume of glycerol injected to fill more or less of the cistern; (2) leaving some contrast

Figure 173-1. The appearance of the trigeminal cistern filled with contrast medium in a typical case. Lateral (A) and anteroposterior (/l) projections. Note the root filaments in (A), giving the cistern its striped appearance. In (/l), the second needle (medial) punctured the trigeminal cistern, while the first (lateral) one only pierced the subtemporal subarachnoid space, resulting in a brisk flow of CSF via the needle.

Chapter 173/Injection of Glycerol into the Gasserian Cistern for Treatment of Trigeminal Neuralgia

Figure 173-2. The appearance of the cistern as well as its location may vary considerably. Here a large cistern, partly filled with contrast medium, has been visualized.

medium in the lower part of the cistern, thus preventing the glycerol from reaching the lowermost fibers in the cistern (i.e., the third division); (3) placing the tip of the needle in the part of cistern traversed by the fibers to be treated; and (4) varying the position of the patient’s head during and after the injection.7~9 Immediately after the injection of glycerol, the patient experiences paresthesias in one or more of the branches of the nerve and sometimes, a couple of minutes later, some facial pain may appear, which lasts up to 1 h. This usually indicates a proper glycerol injection and predicts a successful outcome.

Repeated Treatments There is a very high initial success rate (80 to 96 percent) in the patients treated with an adequate volume of glycerol injected in

Figure 173-3. Schematic picture of the different compartments within Meckel’s cave. The arachnoid is indicated by a wavy line. The spaces marked by (*) indicate where extracisternal (extraarachnoidal) deposits of contrast medium and glycerol may be placed. (From Hakanson2 with permission.)

Ill

1699

the proper place. Incomplete pain relief after the initial injec¬ tion is usually the result of technical problems during the pro¬ cedure. In spite of this, reinjections are not recommended within 1 month following glycerol instillation, since late relief of pain has been observed. In order to facilitate the reinjection of glycerol in case of recurrent pain, it is advisable to add a small amount of sterile tantalum dust (Merck, Germany; grain size below 0.042 mm) to the glycerol before the instillation. It will permanently mark the cistern, outlining its bottom. Reinjections due to recurrent pain should be preceded by careful evaluation of facial sensation, with attention paid to the risk of its further impairment. At reinjections, reduced amounts of glycerol should usually be used. Sometimes the repeat cis¬ ternography reveals less satisfactory filling of the cistern, prob¬ ably due to formation of adhesions within the cistern after the previous treatment.10 Cisternal fibrosis may complicate the evacuation of contrast medium from the cistern. Sometimes flushing with 1 to 3 mL of saline with the patient tilted to the anti-Trendelenburg position may be helpful. In such cases it seems especially important to place the needle tip in the part of the cistern traversed by the fibers to be treated.

Postinjection Measures Patients should be kept in the sitting position with the head slightly flexed for about 1 h following the procedure. If intuba¬ tion anesthesia is used, the patient should be extubated while sitting, with the head kept slightly flexed at all times. Re¬ duction of the exposure time to glycerol by trying to withdraw the glycerol through the injection needle is probably futile and is not recommended, as it may damage the root fibers and, at least theoretically, disturb the osmotic mechanisms of loading and unloading glycerol into the rootlets, thereby causing more extensive nerve damage.6,11 The latency period from the time of treatment until com¬ plete pain relief varies from minutes up to a couple of weeks.12 An overwhelming majority of patients get relief from pain within 6 days. The patients usually leave the hospital the day

1700

Part4/Functional Stereotaxis

The recurrence rates vary considerably as shown in Table 173-2. Roughly, it may be said that, within 2 years, no more than 15 to 20 percent of patients with classic trigeminal neural¬ gia should have recurring symptoms requiring neurosurgical treatment. In some series, as seen from the table, the recurrence rates are considerably higher. One responsible factor of impor¬ tance here is probably the technical performance of the proce¬ dure. Another is the selection of patients for treatment. If cases of trigeminal neuropathy with continuous pain are also in¬ cluded, the outcome and recurrence figures are always worse. The cause of this condition is not infrequently a previous de¬ structive procedure directed onto the trigeminal system (see Tables 173-1, 173-2, and 173-3).

Figure 173-4. In this anteroposterior roentgenogram a pure subtemporal contrast injection is illustrated. No contrast filling of the cistern was obtained although spontaneous CSF flow from the needle was observed.

after the treatment. The pharmacologic treatment of their neu¬ ralgia is gradually discontinued during the next 2 to 3 weeks.

OUTCOMES The outcomes of some selected major series of patients treated by glycerol injection for trigeminal neuralgia are presented in Table 173-1.4-12-24 It is readily seen that in most series, the ini¬ tial success rate is in the range 80 to 95 percent.

The original Stockholm series of 100 patients was followed for up to 10 years after their first treatment (average, 5 years, 4 months). At the last follow-up, 53 percent were still pain-free after their initial injection. Twenty-two cases had been rein¬ jected with glycerol and in total 75 percent of the patients in the series were free from pain at the last follow-up. Twenty-three percent of the patients with pain had only mild symptoms easily controlled by medication.25 It should be mentioned that the average volume of glycerol used in this series was only 0.21 mL. As mentioned above, the average risk of recurrence in the short term seems to be about 20 percent but the percentage of late recurrences (within 5 to 10 years) approaches 50 percent. Since the injection is easy to repeat and carries a minimal risk for the patient, the majority of the patients (over 75 percent) may be kept pain-free by a low number of reinjections. In com¬ parison, Jannetta (1991)26 reported 80 percent permanent pain relief in a survey of results after microvascular decompression for tic. An additional 10 percent of patients had some tic at¬ tacks, and there was a 10 percent failure rate. Several modifications have been suggested. The modifica¬ tions of the original technique as described by Hakanson in 19812 have concerned methods to determine intracistemal nee¬ dle position, type of anesthesia, amount of glycerol used, peri¬ operative attempts to evacuate glycerol from the cistern, mix¬ ing the glycerol with contrast media, and the period of time the patients are kept in the sitting position following the procedure. No substantial improvement in results or ease of accomplishing the procedure has been convincingly demonstrated.7 The long-term results as well as the complication rates are markedly influenced by the selection of patients accepted for the treatment and probably also by the amount of glycerol in¬ jected. Since recurrence rate is one of the parameters of most concern in the evaluation of the results, a Kaplan-Meier analy¬ sis is useful to demonstrate the anticipated duration of pain relief. As the goal of treatment in trigeminal neuralgia is complete freedom from paroxysmal pain until death, the age of the patient at treatment also influences the outcome of this analysis.

Figure 173-5. This anteroposterior view demonstrates an ex/racisternal (dense area at needle tip) as well as an w/racisternal deposition of contrast medium.

Immediate pain relief (within 2 weeks; Table 173-1) varies between 67 and 96 percent in different series; this variation can only be explained by the accuracy with which the procedure was performed, and, to a lesser extent, by the amount of glyc¬ erol injected. In case tantalum dust was added to the glycerol, a plain postoperative skull x-ray before the patient leaves the hospital usually reveals whether a proper intracistemal deposi¬ tion of the glycerol was obtained.

Chapter 173/Injection of Glycerol into the Gasserian Cistern for Treatment of Trigeminal Neuralgia

TABLE 173-1.

1701

Outcome of Glycerol Treatment in Some Major Series

Series Hakanson,14 1983 Lunsford,13 1985 Arias,15 1986 Beck et al.,16 1986 Dieckmann et al.,17 1987 Saini,18 1987 Burchiel,4 1988 Young,19 1988 Waltz et al.,20 1989 Fujimaki et al.,5 1990 North et al.,21 1990 Ischia et al.,22 1990 Steiger,23 1991 Slettebo et al.,24 1993 Bergenheim et al.,12 1995

n

Percent with cister¬ nography

Pain-free after first injection percent

Entirely pain-free at follow-up, percent

100

100

96

75

62

100

74

66

100

50

95

95

58

31

67

72

252

100

91

85

550

0

76“

17

46

100

80

53

162

Few

90

78

200

100

73

74

122

100

80

26

85

0

>90

>50

112

100

92

71

122

100

84

59

60

100

93

50

99

100

97

76

“ Most failures previously treated by other lesional technique; otherwise 96%.

Complications In general, glycerol injection in experienced hands carries very little risk and may be used in patients of advanced age (the old¬ est in the Stockholm series was 98 years old) and also in se¬ verely disabled patients. Only anecdotal reports have appeared about serious complication affecting single patients (deaths from heart attack following the procedure;27 intracranial hem¬ orrhage28). The most serious consequence of neurolytic proce¬ dures directed onto the trigeminal pathway is postoperative anesthesia dolorosa. This condition is rarely seen following glycerol injection. An exception to this is the series of Saini (1987)18 of 552 cases performed without preceding cisternogra¬ phy to confirm the localization of the needle tip before glycerol injection. This resulted in a striking 5 percent of patients dis¬ playing anesthesia dolorosa following treatment. In this series there was also a 3 percent incidence of disturbance of the motor function of the third division. In most other series, these types of postoperative sequelae are extremely rare.20-22’28

A review of the sensory complications after glycerol injec¬ tion for trigeminal neuralgia is given in Table 173-3. Transi¬ tory, mild facial hypesthesia is a common phenomenon affect¬ ing 50 to 70 percent of patients following the procedure. Usually the symptoms fade during the 3-month posttreatment period.1519-20-25 Permanent slight hypesthesia after treatment is found in between 20 and 70 percent of the patients. If quantita¬ tive sensory testing is used, an even higher incidence of subtle sensory impairment may be recognized.'5 However, severe hypesthesia should be rare if the procedure is carried out correctly. The use of a larger volume of glycerol than that rec¬ ommended has usually resulted in a more pronounced sensory deficit5-24 without improvement of the outcome. The incidence of dysesthesia should also be low and mostly transient follow¬ ing glycerol injection. As seen from Table 173-3, the incidence generally remains between 0 and 4 percent, but there are series that are unusual also in this respect. Behind the higher figures one should always suspect the additive influence of a previous destructive procedure causing a sensory disturbance not explic-

1702

Part4/Functional Stereotaxis

TABLE 173-2.

Recurrence of Neuralgia After Glycerol Treatment

Series

Percent late recurrence, > 2 years

Follow-up range, months, years

100

26

43

5-10 years

62

21

NA

3-28 months

100

2

10

58 252

11 11

NA 37

2-40 months 2-5 years

550

41

92

1-6 years

46

47

75

3-44 months

162

11

34

6-67 months

200

23

25

25-64 months

122

45

72

38-54 months

85

-40

-55

112

20

26

122

1-96 months

2-3 years

6-54 months 1-5 years

O CO

*

Hakanson,14 1983 Lunsford,13 1985 Arias,15 1986 Beck et al.,16 1986 Dieckmann et al.,17 1987 Saini,18 1987 Burchiel,4 1988 Young,19 1988 Waltz et al.,20 1989 Fujimaki et al.,5 1990 North et al.,21 1990 Ischia et al.,22 1990 Steiger,23 1991 Slettebo et al.,24 1993 Bergenheim et al.,12 1995

n

Percent early recurrence, < 2 years

-41

60

-27

-55

4.5-9 years

99

-33 (1 year)

NA

12 months

itly recorded before the glycerol procedure. Therefore it is es¬ sential to obtain a careful evaluation of facial sensation before and 3 to 6 months after the treatment. Significant dysesthesias after glycerol injection for classic trigeminal neuralgia should not exceed 2 percent in virgin cases.13-20

Postoperative Infections Serious infections following gasserian glycerol injection are rare. The most common is a reactivation of latent herpes sim¬ plex infection. This is a phenomenon previously reported in neurosurgery. However, the symptoms from this herpes infec¬ tion may be minor and easily overlooked both by the doctor and by the patient, explaining why the figures in different series vary considerably. In Table 173-4, infectious complications after glycerol injection are reviewed. Aseptic meningitis was observed in Stockholm in about 2 percent of the earlier cases during the metrizamide (Amipaque) era. Since the replacement ot this contrast medium by iohexol (Omnipaque) in January 1986, very few cases of aseptic meningitis have been recorded. That the contrast medium has been the most likely cause for the sterile meningitis is corroborated also by data reported by Arias (1986),15 who presented a series of 100 cases where 50 percent

were treated without previous contrast medium injection. Among the patients without contrast injection, no case of aseptic meningitis was encountered, while two cases presented with this sequela in the other group. Bacterial meningitis following the Hartel approach to Meckel’s cave is rarely encountered regardless of the intended therapeutic procedure.2529 The bacterial agents found in postop¬ erative CSF have often been those that occur naturally in the up¬ per respiratory tract. Inadvertent penetration of the mucosa to the oral cavity is the most probable cause. In the Stockholm mater¬ ial, the frequency of bacterial meningitis has been about 0.5 per¬ cent, but the international figures vary between 0 and 2 percent (Table 173-4). Usually there is a complete recovery without seri¬ ous sequelae after adequate antibiotic treatment in these cases.

GLYCEROL TREATMENT OF PAROXYSMAL FACIAL PAIN IN MULTIPLE SCLEROSIS The paroxysmal facial pain sometimes affecting patients with multiple sclerosis (MS) is clinically similar to that of classic trigeminal neuralgia. Therefore all procedures with the excep-

Chapter 173/Injection of Glycerol into the Gasserian Cistern for Treatment of Trigeminal Neuralgia

TABLE 173-3.

1703

Sensory Side Effects after Glycerol Treatment"

Series Hakanson,14 1983 Lunsford,13 1985 Arias,15 1986 Beck et al.,16 1986 Dieckmann et al.,17 1987 Saini,18 1987 Burchiel,4 1988 Young,19 1988 Waltz et al.,20 1989 Fujimaki et al.,5 1990 North et al.,21 1990 Ischia et al.,22 1990 Steiger,23 1991 Slettebo et al.,24 1993 Bergenheim et al.,12 1995

Percent severe hypesthesia

Percent dys¬ esthesia

n

Volume of glycerol, ml.

Percent slight hypesthesia

100

0.2-0.3

60

0

0

62

0.15-0.25

21*

0

3C

100

0.1-0.4

13

0

0

58

0.2-0.4

17

2

0

252

0.15-0.4

20

1

2

550

0.2-0.3

NA

5d

11

46

0.15-?

72

7

13

162

0.15-0.55

72

12

3

200

0.2-0.6

37

7

2

122

0.3-0.5

63

29

26

85

0.3-0.4

4

2

4e

112

0.4—0.5

32

0

3

122

0.2-0.35

53*

NA

13

60

0.15-0.70

35

3d

99

0.2-0.35

42

6

-13

5*

“It should be noted that in some series it cannot readily be determined whether the sensory disturbances recorded after glycerol treatment were already present before the procedure. Furthermore, other destructive procedures may have been subsequently used and not recorded.

b Many with previous or additional destructive procedures. c Following herpes reactivation. d Only cases with previous destructive procedures. e Transient. tion of microvascular decompression advocated for sympto¬ matic treatment of this latter condition may also be used in MS. It has been reported that trigeminal paroxysmal pain is present in about 1 to 2 percent of patients suffering from MS30 12 or even up to 8 percent.33-34 Bilateral symptoms are not uncom¬ mon among such cases but are almost nonexistent in classic idiopathic trigeminal neuralgia. The short-term success rate of the procedure is about equal for idiopathic and MS trigeminal neuralgia, but the late results differ considerably between these two conditions.13 The recur¬ rence rate is much higher in the MS group, possibly due to pro¬ gression of the disease, with creation of multiple new lesions along the trigeminal pathway. More than 40 percent of the pa¬ tients experience recurring symptoms during a 2-year follow¬ up.17-33 In comparison, the recurrence rate in classic trigeminal neuralgia is below 20 percent during the same period of time.17

During a longer follow-up period (8 to 79 months after glycerol injection) recurrent tic affects over 60 percent in the MS group33 but only 38 percent in the idiopathic trigeminal neural¬ gia group. Similar recurrence rates have also been observed with other treatment modalities—e.g., selective thermo¬ coagulation35 in MS patients. Since patients suffering from MS tolerate pharmacologic regimens to a much lesser degree than patients without this disease, glycerol injection is recommended early in MS cases in spite of the high recurrence rate. Linderoth and Hakanson (1989)33 reported that over 90 percent of their MS cases with trigeminal neuralgia complained about side effects of drug treatment. Actually, 38 percent of the patients had discontinued taking carbamazepine because of the severe adverse effects. After glycerol instillation, 82 percent of the patients taking carbamazepine preoperatively could discontinue it.

1704

Part4/Functional Stereotaxis

TABLE 173-4.

Infectious Complications after Glycerol Treatment

Series Hakanson,14 1983 Lunsford,13 1985 Arias,15 1986 Beck et al.,16 1986 Dieckmann et al.,17 1987 Saini,18 1987 Burchiel,4 1988 Young,19 1988 Waltz et al.,20 1989 Fujimaki et al.,5 1990 North et al.,21 1990 Ischia et al.,22 1990 Steiger,23 1991 Slettebo et al.,24 1993 Bergenheim et al.,12 1995

n

Percent herpes infection

100

50

0

0

62

13

3

0

100

10

2

0

58

9

4

0

252

77

1

1

550

3

NA

NA

46

5

2

2

162

38

0

1

200

NA

7

1

122

NA

NA

NA

85

NA

NA

NA

112

NA

NA

NA

122

NA

0

0

60

NA

1.6

NA

99

NA

NA

NA

POSSIBLE BASIS OF THE GLYCEROL EFFECT That the high concentration of glycerol used for injection is mildly neurolytic is evident from the side effects, such as hypesthesia. An important issue is whether the effect is selective for a certain group of nerve fibers or not. It seems clear that the trigger mechanism in trigeminal neuralgia involves activity in large-diameter myelinated fibers but that the “final common path” is transmission via the thin fibers subserving pain. The neurolytic action of glycerol is considered to be due to its hypertonicity. Marked structural changes have been observed with glycerol administration to nerve fibers in vitro and after experimental injection in animals.36-40 It seems that the change in osmolarity with glycerol injection constitutes the basis for the damage of the nerve axons. The functional conse¬ quences appear to be minimized by a gradual alteration of the osmolarity—that is, by slowly injecting the glycerol into the cistern, leaving it to dissolve spontaneously in the CSF spaces. Furthermore, it has been reported that glycerol applied to mechanosensitive neuromas in a rat model41 exerted its major action on large-diameter fibers, inducing a short episode of in¬

Percent aseptic meningitis

Percent bacterial meningitis

creased spontaneous firing in the nerve. Rappaport et al. (1986)42 supported the view that the mechanism behind the ef¬ fect in ticlike paresthesia could be a suppression of ectopic im¬ pulses originating in structurally lesioned nervous tissue. Further support for the notion that glycerol affects mainly large-diameter fibers is also given by H&kanson (1991 ),25 who investigated some patients with quantitative sensory testing af¬ ter treatment. In conclusion, the experiments and observations reported above indicate that the glycerol effect is due to hyperosmolarity and that the major part of the effect is exerted on the large myelinated fibers, thus affecting mainly the trigger mech¬ anism. A more thorough discussion of these matters is found in Linderoth and Hakanson (1995).7

GLYCEROL INJECTION FOR OTHER TYPES OF FACIAL PAIN In so-called atypical facial pain, a paroxysmal component may exist in addition to the continuous neuropathic pain. The origin of this condition varies considerably, from trauma, infection, perioperative nerve damage, previous neurolytic treatment for trigeminal neuralgia, to forms of pain of unknown etiology.

Chapter 173/Injection of Glycerol into the Gasserian Cistern for Treatment of Trigeminal Neuralgia

Generally, instillation of glycerol into the trigeminal cistern is contraindicated in the majority of such cases and may actually aggravate the neuropathy to the point where the symptoms severely disrupt activities of daily life for the patient (for discussion, see Ref. 7). A possible exception is when the tic component dominates the picture and diminishes the patient’s quality of life, while the sensory disturbance is minimal. In such cases a very small amount of glycerol may be used (0.15 mL). Glycerol instillation in severe intractable cluster headache (Horton’s syndrome) has been reported by several authors.20-43 In general, the beneficial results of the procedure in these cases have been transitory and at best partial (Sundbarj, 1988, personal communication), so that we consider glycerol injec¬ tion not recommendable in cluster headache.

10. 11.

1129-1137. Bergenheim A, Hariz M: Influence of previous treatment on outcome after glycerol rhizotomy for trigeminal neuralgia. Neurosurgery 36:

13.

303-310, 1995. Lunsford LD: Trigeminal neuralgia: Treatment by glycerol rhi¬ zotomy, in Wilkins RH, Rengachary SS (eds): Neurosurgery. New

14.

douloureux. Adv Pain Res Ther 5:927-933, 1983. Arias MJ: Percutaneous retrogasserian glycerol rhizotomy for trigem¬ inal neuralgia: A prospective study of 100 cases. J Neurosurg 65:

16.

32-36, 1986. Beck DW, Olson JJ, Urig EJ: Percutaneous retrogasserian glycerol rhizotomy for treatment of trigeminal neuralgia. J Neurosurg 65:

Glycerol injection into the trigeminal cistern in typical trigemi¬ nal neuralgia is an inexpensive method requiring very little

18.

20.

21. 22. 23.

24.

References

2. 3.

4.

1985. Burchiel KJ: Percutaneous retrogasserian glycerol rhizolysis in the management of trigeminal neuralgia. J Neurosurg 69:361-366,

5.

1988. Fujimaki T, Fukushima T, Miyazaki S: Percutaneous retrogasserian glycerol injection in the management of trigeminal neuralgia: Long¬

6. 7.

term follow-up results. J Neurosurg 73:212-216, 1990. Sweet WH: Glycerol rhizotomy, in Youmans JR (ed): Neurological Surgery, 3ded. Philadelphia: Saunders, 1990, pp 3908-3921. Linderoth B, Hakanson S: Retrogasserian glycerol rhizolysis in trigeminal neuralgia, in Schmidek HH, Sweet WH (eds): Operative Neurosurgical Techniques, 3d ed. Saunders: Philadelphia, 1995,

8.

pp 1523-1536. Bergenheim AT, Hariz MI, Laitinen LV: Selectivity of retrogasserian glycerol rhizotomy in the treatment of trigeminal neuralgia. Stereo¬

9.

tact Fund Neurosurg 56:159-165, 1991. Bergenheim AT, Hariz MI, Laitinen LV: Retrogasserian glycerol rhi¬ zotomy and its selectivity in the treatment of trigeminal neuralgia. Acta Neurochir 58:174-177, 1993.

Young RF: Glycerol rhizolysis for treatment of trigeminal neuralgia. J Neurosurg 69:39-45, 1988.

25.

Hakanson S, Leksell L: Stereotactic radiosurgery in trigeminal neu¬ ralgia, in Pauser G, Gerstenbrand F, Gross D (eds): Gesichtsschmerz: Schmerzstudien 2. New York: Gustav Fischer Verlag, 1979. Hakanson S: Trigeminal neuralgia treated by the injection of glycerol into the trigeminal cistern. Neurosurgery 9:638-646, 1981. Sweet WH, Poletti CE: Problems with retrogasserian glycerol in the treatment of trigeminal neuralgia. Appl Neurophysiol 48:252-257,

28-31, 1986. Dieckmann G, Bockermann V, Heyer C, et al: Five-and-a-half years ex¬ perience with percutaneous retrogasserian glycerol rhizotomy in treat¬ ment of trigeminal neuralgia. Appl Neurophysiol 50:401-413, 1987. Saini SS: Retrogasserian anhydrous glycerol injection therapy in trigeminal neuralgia: Observations in 552 patients. J Neurol Neuro¬ surg Psychiatry 50:1536-1538, 1987.

19.

neuralgia.

1.

York: McGraw-Hill, 1985, pp 2351-2356. Hakanson S: Retrogasserian glycerol injection as treatment of tic

15.

17.

gia (or similar pain due to demyelinating disease) in patients who are elderly or weak or who suffer from concurrent disease. With meticulous technique, glycerol injection is a relatively in¬ nocuous intervention, carried out under local anesthesia and posing a low risk of severe side effects. It may also be offered to younger patients who are hesitant to undergo the major surgery of microvascular decompression. The recurrence rate of the symptoms is often reported to be slightly higher than that of the more invasive procedure, but it compares well with that of other percutaneous methods directed against trigeminal

Rappaport ZH, Gomori JM: Recurrent trigeminal cistern glycerol in¬ jections for tic douloureux. Acta Neurochir 90:31-34, 1988. Sweet WH: Retrogasserian glycerol injection as treatment for trigem¬ inal neuralgia, in Schmidek HH, Sweet WH (eds): Operative Neuro¬ surgical Techniques, 2d ed. New York: Grune & Stratton, 1988, pp

12.

CONCLUSIONS

special equipment. The procedure may seem simple, but it has to be performed carefully by a surgeon with experience in the technique. The major indication is idiopathic trigeminal neural¬

1705

26.

27.

28.

29.

30.

Waltz TA, Dalessio DJ, Copeland B, Abbott G: Percutaneous injec¬ tion of glycerol for the treatment of trigeminal neuralgia. Clin J Pain 5:195-198, 1989. North RB, Kidd DH, Piantadosi S, Carson BS: Percutaneous retro¬ gasserian glycerol rhizotomy. J Neurosurg 72:851—856, 1990. Ischia S, Luzzani A, Polati E: Retrogasserian glycerol injection: A ret¬ rospective study of 112 patients. Clin J Pain 6:291-296, 1990. Steiger HJ: Prognostic factors in the treatment of trigeminal neural¬ gia: Analysis of a differential therapeutic approach. Acta Neurochir 113:11-17, 1991. Slettebo H, Hirschberg H, Lindegaard KF: Long-term results after percutaneous retrogasserian glycerol rhizotomy in patients with trigeminal neuralgia. Acta Neurochir 122:231-235, 1993. Hakanson S: Surgical treatment: Retrogasserian glycerol injection, in Fromm GH, Sessle BJ (eds): Trigeminal Neuralgia: Current Con¬ cepts Regarding Pathogenesis and Treatment. Boston: ButterworthHeinemann, 1991, pp 185-204. Jannetta PJ: Surgical treatment: Microvascular decompression, in Fromm GH, Sessle BJ (eds): Trigeminal Neuralgia: Current Conc¬ epts Regarding Pathogenesis and Treatment. Boston: ButterworthHeinemann, 1991, pp 145-157. Lunsford LD, Apfelbaum RI: Choice of surgical therapeutical modal¬ ities for treatment of trigeminal neuralgia: Microvascular decompres¬ sion, percutaneous retrogasserian thermal or glycerol rhizotomy. Clin Neurosurg 32:319-333, 1985. Sweet WH: Faciocephalic pain, in Apuzzo MLJ (ed): Brain Surgery, Complication Avoidance and Management. New York: Churchill

Livingstone, 1993, pp 2053-2083. Nugent GR: Surgical treatment: Radiofrequency gangliolysis and rhi¬ zotomy, in Fromm GH, Sessle BJ (eds): Trigeminal Neuralgia: Cur¬ rent Concepts Regarding Pathogenesis and Treatment. Boston: Butterworth-Heinemann, 1991, pp 159-184. Rushton JG, Olafson RA: Trigeminal neuralgia associated with multi¬

31.

ple sclerosis. Arch Neurol 13:383-386, 1965. Brett DC, Ferguson GG, Ebers GC, Paty DW; Percutaneous trigemi¬ nal rhizotomy: Treatment of trigeminal neuralgia secondary to multi¬

32.

ple sclerosis. Arch Neurol 39:219—221, 1982. Jensen TS, Rasmussen P. Reske-Nielsen E: Association of trigeminal neuralgia with multiple sclerosis: Clinical and pathological features. Acta Neurol Scand 65:182-189, 1982.

33.

Linderoth B, Hakanson S: Paroxysmal facial pain in disseminated sclerosis treated by retrogasserian glycerol injection. Acta Neurol Scand 80:341-346, 1989.

1706

34.

35.

36.

Part4/Functional Stereotaxis

Kondziolka D, Lunsford LD, Bissonette DJ: Long-term results after glycerol rhizotomy for multiple sclerosis-related trigeminal neuralgia. Can J Neurol Sci 21:137-140, 1994.

39.

Broggi G, Franzini A: Radiofrequency trigeminal rhizotomy in treat¬ ment of symptomatic non-neoplastic facial pain. J Neurosurg 57: 483-486, 1982.

40.

Robertson JD: Structural alterations in nerve fibers produced

41.

Burchiel KJ, Russell LC: Glycerol neurolysis: Neurophysiological ef¬ fects of topical glycerol application on rat saphenous nerve. J Neurosurg 63:784-788, 1985.

Pal HK, Dinda AK, Roy S, Banerji AK: Acute effect of anhydrous glycerol on peripheral nerve: An experimental study. Br Neurosurg 3: 463^170, 1989.

42.

Rappaport ZH, Seltzer Z, Zagzag D: The effect of glycerol on au-

Freeman AR, Reuben JP, Brandt PW, Grundfest H: Osmometrically determined characteristics of the cell membrane of squid and lobster giant axons. J Gen Physiol 50:423-445, 1966.

43.

Injection of Glycerol. Published dissertation. Karolinska Institute,

Stockholm, 1982.

38.

Rengachary SS, Watanabe IS, Singer P, Bopp WJ: Effect of glycerol on peripheral nerve: An experimental study. Neurosurgery 13: 681-688, 1983.

by hypotonic and hypertonic solutions. J Biophys Biochem Cytol 4: 349-364, 1958. 37.

Hakanson S: Trigeminal Neuralgia Treated by Retrogasserian

totomy. An experimental model of neuralgia pain. Pain 26:85-91, 1986. Ekbom K, Lindgren L, Nilsson BY, et al: Retro-gasserian glycerol in¬ jection in the treatment of chronic cluster headache. Cephalalgia 7:21-27, 1987.

CHAPTER

174

TRIGEMINAL NERVE COMPRESSION FOR NEURALGIA

Arthur M. Gerber and Sean F. Mullan

PERCUTANEOUS MANAGEMENT OF TRIGEMINAL NEURALGIA Since Hartel described a percutaneous technique for penetrat¬ ing the foramen ovale in 1914,' this approach has been used to perform various ablative procedures on the trigeminal ganglion or its preganglionic rootlets to relieve the pain of trigeminal neuralgia. Initially, agents such as alcohol, phenol, boiling wa¬ ter, and glycerol with phenol were injected in order to reduce trigeminal sensory input, the latter by Jefferson2 in 1963. Of these, alcohol injection became the most commonly used, but concern about the high incidence of corneal anesthesia and lack of control over the spread of the solution to nearby structures spurred a search for other modalities. Improved radiological equipment and the availability of the radiofrequency generator then led to the promulgation of the radiofrequency (RF) coagu¬ lation technique by Sweet and Wepsic,3 while Hakanson4 rein¬ troduced the use of percutaneous glycerol injection into the trigeminal cistern in 1981. In 1978 Mullan developed a percutaneous technique for controlled compression of the trigeminal ganglion that could be carried out under a short general anesthetic.5 This effective method, when carried out this way, is painless and readily tol¬ erated by the most anxious patient; it is the simplest of the per¬ cutaneous procedures. The low incidence of corneal anesthesia makes it especially suitable for the patient suffering from firstdivision pain, and the brevity of this procedure is particularly advantageous for the older patient. Like all percutaneous pro¬ cedures, it can be performed on an outpatient basis.

HISTORICAL BASIS FOR TRIGEMINAL COMPRESSION In 1937, Lee6 proposed that the mechanisms causing trigeminal neuralgia and meralgia paresthetica were similar. He suggested that removal of the bone underneath the trigeminal sensory root would relieve the pain while preserving sensation. In 1952, Taarnhpj7 reported relieving trigeminal neuralgia without pro¬ ducing anesthesia in trigeminal territory by decompressing the trigeminal nerve by widely opening the dura over the posterior part of the ganglion and root. In 1954 he described a longer fol¬ low-up of his patients and expressed disappointment with the high incidence of pain recurrence and the need for reoperation.s

Nearly simultaneously, Stender9 and Sheldon et al.10 indepen¬ dently described new procedures. Stender removed the dura propria covering Meckel’s cave, believing that this manipula¬ tion altered the “vasomotor situation,” improving blood supply and eliminating spastic vascular reflexes. Sheldon initially de¬ compressed the peripheral branches of the trigeminal nerve at the foramen ovale and foramen rotundum; but when he ob¬ served that his results were similar to those of Taarnhpj, pain relief with sensory preservation, he concluded that ganglionic compression was the factor common to both procedures. He then successfully relieved trigeminal neuralgia by incising the dura propria and deliberately compressing the posterior root fibers with a blunt dissector. Unfortunately, the compression and decompression methods were accompanied by a high incidence of recurrence. Pain relief after deliberate compres¬ sion was accompanied by a temporary subjective alteration in facial sensation but lasted longer than after decompression. Possibly those patients who had a greater degree of ganglionic manipulation had a better prognosis. In 1954 and 1959 Love and SvienIU2 reported their results in 100 patients operated upon using a modified Taarnhpj de¬ compression procedure. Twenty-two months after decompres¬ sion, 31 patients had suffered recurrence of their trigeminal neuralgia. Of the 91 patients who could be followed up for 4 years, 69 (75.8 percent) had suffered from recurrence of their pain. In the 69 patients whose pain had recurred, 22 suffered recurrence within 3 months and 55 within 18 months. Of the 15 patients who had suffered subjective sensory loss, 5 remained pain-free for 60 to 68 months. While some sensory loss did not preclude recurrence, the authors suggested that their data sub¬ stantiated the prediction by Sheldon et al.10 that some degree of trauma was necessary for worthwhile results. In 1959, Gardner and Miklos13 reported a combined series of 200 patients who had undergone decompression of the trigeminal sensory roots and who were followed for at least 3 years. Complete relief was obtained in 62 percent of the patients, but there was no correlation between presence or absence of sensory loss and the rate of recurrence. They proposed that the critical part ot the operation was a neurolysis or manipulation of the sensory root. Hamby14 compared the effectiveness of various operations for trigeminal neuralgia in 1959. He reported 32 patients treated with a modified Taamhpj procedure and 86 treated with a “Sheldon-Stender” operation, in which he deliberately ma-

1707

1708

Part 4/Functional Stereotaxis

nipulated the rootlets. Sixty percent of the modified Taarnhpj patients required early reoperation, while 8 percent of the Sheldon-Stender group did so. Long-term results were not reported. Four years later, Graf15 reported the results in 100 cases treated with a “compression” procedure, including 70 of the patients reported by Hamby, among whom the recurrence rate was now 24 percent, compared with the earlier figure of 8 percent. Malis16 released fibrous bands crossing the posterior trigem¬ inal root at the petrous apex in order to treat tic in 32 patients. Thirty-one had adherence between dura propria and ganglion or rootlets, making intraoperative root trauma inevitable. He reported a recurrence rate of only 10 percent over an 18-month follow-up period, with all of the recurrences taking place within 6 months of operation. In 1969, Stender and Grumme17 reviewed 986 patients, 590 of whom had been treated by decompression and 355 by com¬ pression. An additional 41 patients had had alcohol applied to the ganglion during compression. Of the 590 decompressed pa¬ tients who were followed 3 months to 8 years, pain recurred in 237 (40 percent), while 67 (19 percent) of the 355 compressed patients suffered recurrences. Review of the literature reporting deliberate compression procedures prior to 1970 suggests a recurrence rate of less than 20 percent during the 5-year period after surgery, most within 18 months. The need for reoperation for recurrence was higher in those patients with normal postoperative sensation that it was in those with postoperative hypesthesia. Despite the elimi¬ nation of deliberate nerve damage, with its consequences, dis¬ satisfaction with the recurrence rate led to the popularization of the RF technique and the posterior fossa microdecompression procedure proposed by Jannetta.18

the lateral wall of the maxillary antrum. Difficulty arises in the patient with calcified dura or osteoporosis whose foramen is radiologically indistinct. If spherical lead shots (standard lead BBs, 0.175 in. in diameter, obtained through hunting-supply stores) are taped over each zygoma 2.5 cm anterior to the tra¬ gus, a line connecting these markers will pass through or adja¬ cent to the foramina ovale, assisting x-ray guidance.33 Using basic mathematical measurements, the relative position of the foramen may be determined on a preoperative submental ver¬ tex skull x-ray (Fig. 174-1 A). The measurements can then be applied to an extended oblique image, facilitating localization of the foramen14 (Fig. 174-IS). Frequently the radiation expo¬ sure needed to show the foramina will be intense enough to overpenetrate the lead markers and make them difficult to see. This problem may be corrected by placing thin sheets of lead on the x-ray cassette holder or on the image intensifier screen behind the patient’s head (Fig. 174- IA). If the lead sheets are placed 12 cm apart parallel to the sagittal plane, the lead markers and the foramen ovale will then be seen clearly (Fig. 174-2). A discarded lead x-ray apron may readily be adapted for this purpose. Most aprons are made from multiple sheets of lead-impregnated material covered with fabric. Removal of half of the lead thickness and cutting the remaining lead with its fabric covering will provide an excellent means of x-ray-beam attenuation.

Mullan5 reexamined the simple concepts of Taarnhpj and Sheldon, uniting them with the speed and safety of the percuta¬ neous approach in the development of the percutaneous microcompression technique. Limiting the percutaneous needle penetration to the depth of the foramen ovale while compress¬ ing the ganglion with a Fogarty-type balloon catheter inserted through the needle into Meckel’s cave provided a safe, effec¬ tive technique for treating trigeminal neuralgia. More than 500 of these procedures have now been reported.19-29

OPERATIVE PROCEDURE Imaging Penetration of the foramen ovale with a balloon catheter is es¬ sential for the successful performance of this procedure and various radiological techniques have been devised to facilitate its localization. Most utiliz.e a lull axial (submentovertex) view of the skull, which shows the position of the foramen ovale and the adjacent foramen spinosum. While this method of imaging the foramen is the most familiar, the necessary positioning could theoretically be hazardous to the anesthetized patient with a narrow spinal canal. Nugent and Berry10 used bony land¬ marks on the anteroposterior and lateral projections of the skull as targets and do not depend on actual visualization of the fora¬ men. lator and Rowed'1 and Whisler and Hill'2 proposed the use of an extended oblique view of the skull that shows the foramen just above the petrous pyramid, medial to the anterior border of the coronoid process of the mandible and lateral to

Figure 174-1. A. Full axial (submental vertex) x-ray of head. Open arrows indicate medial edges of lead strips. Measured on the x-ray. the distance from z to z between the medial surfaces of the zygomatic markers (z) is 179 mm. The distance between the left zygomatic marker (z) and the foramen ovale (0 at the tip of the black arrow is 54 mm. The ratio zF/zz = 54/179 = 0.30 = 30%.

Chapter 174/Trigeminal Nerve Compression for Neuralgia

1709

Equipment Fluoroscopic capability, either biplane fluoroscopy or a portable C-arm unit, preferably with a 9-in image intensifier, is necessary for the balloon compression technique. In the patient with calcified dura or an osteoporotic skull, conventional hard¬ copy x-rays may be needed to visualize the foramen ovale. The necessary large-bore needle can be one of several com¬ mercially available: a liver biopsy needle (Trucut Travenol) or a #13 or thin-wall #14 needle. Concern about advancing a large, sharp needle to the base of the skull led to the use of a modified #13 Cone ventricular biopsy needle35 with the outer cannula shortened 1 cm and a second sharpened stylet pro¬ vided. Once the sharp stylet has penetrated the soft tissues, it is replaced with the blunt one, which may be safely advanced up to and even through the foramen ovale. Risk of damaging arter¬ ies in the region of the pterygoid fossa is reduced. The smooth edges of the Cone cannula also permit safe manipulation of the balloon catheter, decreasing the likelihood of amputating part of it if it is withdrawn through the needle. Compression is produced with a #4 Fogarty catheter; the 40-cm-length model is more convenient to manipulate than longer catheters. It is fitted with a Tuohy-Borst adapter (Cook) as a depth stop to prevent its advancing too far through the needle.

Preoperative Preparation Figure 174-1. B. Right extended oblique image of head. Interzygomatic distance (zz) measured on the x-ray is 173 mm. zf = 30% of zz or 30% of 173 mm; zf = 52. A point 52 mm to the right of the left zygomatic marker overlies the left foramen ovale (tip of black arrow), confirming its identity.

Preoperative x-ray films delineating the foramen ovale should be obtained. Lead markers assist in its localization on the ex¬ tended oblique or submental-vertex views (Fig. 174-1).

Anesthesia Premedication and the anesthesia, which will last 30 to 60 min, are at the discretion of the anesthesiologist. Concern about in-

Figure 174-2. Right extended oblique intraoperative fluoroscopic image. Markers (z) localize a line that passes through or adjacent to left foramen ovale (tip of black arrow). Shadow on right side of image is due to lead sheet used to enhance image of marker.

1710

Part 4/Functional Stereotaxis

traoperative bradycardia has led Belber and Rak19 to use at¬ ropine routinely, while Brown and Preul21 routinely use an external pacemaker in the event of a “depressor response.” Others25 regard bradycardia as a useful reflex indicating that the nerve has been touched by the needle and. during balloon expansion, assuring that a good compression is being achieved. Excessive bradycardia may be relieved by balloon deflation followed by the administration of atropine.

Operative Technique The position of the patient is determined by the imaging technique used. For submental vertex view, the patient is placed semisitting, with the neck fully extended, so that the submental-vertex line is horizontal. This makes it convenient to use a wall-mounted, horizontally directed conventional x-ray tube to obtain hard copies should the fluoroscopic image be in¬ adequate. Another option is to place the patient flat, supporting the occiput on a cerebellar head rest. If the C arm, with the tube overhead, is perpendicular to the operating table on the side of the patient’s pain, the beam direction can readily be adjusted to a sight along the needle path into the foramen ovale. This usu¬ ally entails rotating the C arm 15 to 20° away from the midsagittal plane toward the puncture site and angling the beam upward toward the head at a 55° angle to the canthomeatal line. The foramen ovale will be seen just above the petrous ridge, between the coronoid process and the lateral margin of the maxillary antrum.33 The stylet is withdrawn from the #4 Fogarty catheter and the air inside it replaced by contrast material (Omnipaque or Conray). The depth stop is applied so the balloon will lie a pre¬ determined distance beyond the tip of the needle preventing migration into the posterior fossa, taking care not to over¬ tighten and obstruct contrast flow. A point is selected 1 to 3 cm lateral to the angle of the mouth. The skin is washed and prepped. One mark is placed on the eyelid just below the ipsi-

lateral pupil and another 2.5 cm anterior to the tragus at the level of the top of the zygoma. For guidance, lines may be drawn from the entry spot to each of these points. The largebore needle is first directed slightly laterally so as not to pene¬ trate the buccal mucosa. It is then directed toward the foramen ovale, sighting along the skin lines, and advanced under fluoro¬ scopic guidance aiming for the foramen ovale, which is behind the pupil on a line connecting the “zygoma points” (Fig. 174-3). It is imperative that a shatp needle should only just engage the entry to the foramen. If the Cone cannula with the blunt stylet is used, entering the skin through a small stab wound, it may be advanced gently through the foramen. It is safest to target the anterolateral aspect of the foramen initially and gently “walk” the needle or cannula into the opening, for which maneuver a skull model and preoperative x-ray showing the foramen can be helpful. If a beveled needle is used, the bevel should be kept uppermost to decrease the risk of penetrating the dura. In some patients, sudden transient bradycardia may signal impingement of the needle on the emerging nerve. The C arm may then be adjusted to provide a lateral image to confirm that the sharp needle tip has not penetrated the middle fossa. If a Cone can¬ nula is used, the outer part is advanced along the stylet, which is then removed. The #4 Fogarty catheter is then advanced through the needle or Cone cannula until the stop abuts against the needle hub. If the catheter does not advance properly, the needle or cannula may have to be rotated or advanced a few millimeters under fluoroscopic control. Once the catheter has been inserted, injection of 0.3 mL of contrast will quickly con¬ firm its position, especially on lateral fluoroscopy. This may cause recurrence or deepening of the bradycardia, which may be treated with atropine. More contrast is injected until the bal¬ loon assumes a pear-shaped configuration, with the smaller end protruding posteriorly through the neck of Meckel’s cave to¬ ward the posterior fossa (Fig. 174-4). For this, a volume of 0.7 mL is usually adequate, but occasionally 1 mL or even more is required. Balloon rupture has occurred with such vol¬ umes without incident. When the modified Cone cannula is

Figure 174-3. Intraoperative right extended oblique view. Tip of blunt stylet has engaged left foramen ovale {open arrow).

Chapter 174/Trigeminal Nerve Compression for Neuralgia

1711

Figure 174-4. Lateral fluoroscopy of head with patient in supine position. Tip of pearshaped balloon lies at entry to posterior fossa (tip of arrow).

used, the ruptured catheter may be removed safely and replaced without risk of amputating the catheter tip, but amputation is a distinct hazard if a sharp needle is used. If the catheter does not come out freely, the needle with its protruding catheter is with¬ drawn en bloc and the procedure started all over again. The end point for compression is achievement of the “pear shape,” or a 1-mL volume if the balloon remains ellipsoid. Monitoring of the balloon pressure26,35 may be of assistance in determining adequate compression in those cases in which the balloon does not attain a pear shape. If this occurs, it is often possible to achieve adequate compression by deflating it, deliberately ad¬

Figure 174-5. Lateral intraoperative fluoroscopy of skull. Tip of Cone cannula is engaged in foramen ovale. Dumbbell-shaped balloon lies above cannula tip, partly in middle fossa and partly in posterior fossa.

vancing it into the posterior fossa after the depth stop is loos¬ ened, reinflating it, and pulling it back. Under these circum¬ stances, a balloon distension of less than 0.5 mL usually produces a good dumbbell shape, suggesting sufficient com¬ pression (Fig. 174-5). Compression at the agreed-upon end point is maintained for 1 min and then released. With an obvi¬ ous pear shape and marked bradycardia, more sensory loss and longer pain relief are to be expected. In our earlier experience, compressions longer than 1 min were used in hope of decreas¬ ing the likelihood of recurrence of pain, but these longer compressions increased the incidence of dysesthesia. Two in-

1712

Part 4/Functional Stereotaxis

stances of prolonged corneal anesthesia followed 2 min of compression. Alter deflation of the balloon, the catheter and needle are withdrawn as a unit and pressure is applied at the puncture site and above the zygoma for 5 min to prevent bleeding into the pterygoid space and deep to the temporalis muscle. If deep bleeding with cheek swelling is noted prior to penetration of the foramen, the needle should be removed and compression applied as above before starting again. If the dura is penetrated, the balloon will assume its intrinsic ellipsoidal shape without deforming. If no pain relief is obtained after compression under these circumstances, the procedure may be repeated after al¬ lowing 3 weeks for the dura to seal.

POSTOPERATIVE COURSE The patient usually awakens pain-free except for localized discomfort from the needle track. There is some degree of sub¬ jective or objective numbness, most prominent in the third di¬ vision, which may be due to direct trauma, and some patients may manifest slight hypesthesia. The degree of sensory alter¬ ation appears to parallel the duration of pain relief. The subjec¬ tive numbness is at first disturbing, but most patients adapt to it within 3 to 4 weeks, during which time there may also be some resolution of the hyperesthesia. Although one patient said that she would never have had the operation had she known her face would feel like this and another complained frequently over several years, both requested a repeat procedure when the tic recurred. Corneal sensation may be slightly decreased but is rarely absent; nostril tickle is more commonly decreased. While only one case of corneal anesthesia has been reported,22 at least two others have occurred, both associated with prefer¬ ential sensory loss in the first division. It is not unusual for pa¬ tients to continue to enjoy relief from tic after pinprick and touch perception appear to have returned to normal except for some decrease in two-point discrimination. Weakness ot the ipsilateral temporal and masseter muscles is an almost constant finding and usually resolves in about 3 months. Because of the frequent tic-induced incidence of chewing on the opposite side, this may not be noticed. Originally there is a subjective change or even discomfort re¬ lated to the temporomandibular joint, while occasional pain in the ear may relate to needle impingement on the eustachian tube.

COMPLICATIONS In the authors’ experience, there have been two cases of pro¬ longed corneal anesthesia without complication. Three small pterygoid arteriovenous fistulas have been produced in the re¬ gion of the foramen ovale, giving rise to tinnitus. Only one pa¬ tient consented to transarterial embolization; in one instance, the tinnitus disappeared spontaneously. There have been re¬ ports in the literature of blindness after a 12-min compression36 and of one additional case of corneal anesthesia22 as well as one subarachnoid hemorrhage necessitating shunting for hydro¬ cephalus tollowed by death from shunt infection.29 In the latter case the published radiograph showed that the needle had pene¬ trated the foramen ovale rather than merely engaging it. There was one other case of external carotid artery fistula due to

puncture of the middle meningeal artery near its origin; it closed spontaneously within 19 days.28 Transient sixth nerve palsy may also occur.22,35’37 Patients who have had herpes sim¬ plex in the past will often have a recurrence in the same distri¬ bution, an event usually associated with a good long-lasting result.

RESULTS Immediate relief occurs in all patients in whom the balloon de¬ formed to a pear shape. If the balloon remains ellipsoidal, not all patients obtain such relief. Lack of balloon deformation is believed to occur with either a large Meckel’s cave or intra¬ dural placement of the balloon. In such cases, a repeat proce¬ dure as early as the next day has resulted in a pear-shaped con¬ figuration and pain relief in some patients. Because the dura is usually punctured only with the Fogarty catheter, flow of cere¬ brospinal fluid through the needle may not be observed, so that intradural placement may not be suspected. For patients in whom there is even the slightest degree of balloon deforma¬ tion, the recurrence rate has been 20 percent over 5 years. The recurrence rate peaks during the second year and then drops off resulting in an estimated 10-year recurrence of 30 percent. Most patients with recurrent pain respond to carbamazepine at lower doses than used prior to compression. In the drugrefractory recurrent case or in the patient who cannot tolerate medical treatment, repeat compression or microvascular de¬ compression is suggested. Trigeminal neuralgia due to multiple sclerosis responds to 1 min of balloon compression, exactly as does idiopathic trigem¬ inal neuralgia. Elderly patients tend to be more sensitive to the procedure and more likely to suffer more profound hypesthe¬ sia, but there is no intraoperative parameter that accurately pre¬ dicts the level of postoperative sensory loss. Lobato et al.,26 reporting on 144 patients, found that even with similar radi¬ ographic pictures of the balloon and the same intraluminal bal¬ loon pressure, postoperative sensation varied from almost normal to patchy loss of light touch and decreased pinprick. Patients who have had recurrent pain subsequent to posterior fossa microvascular decompression respond readily to the per¬ cutaneous procedure.

COMPARATIVE EVALUATION The most frequently used operations for the treatment of trigeminal neuralgia are balloon microcompression of the trigeminal ganglion, radiofrequency (RF) rhizotomy, glycerol rhizotomy, and microvascular decompression. Even in the most experienced hands, the mortality rate of microvascular decom¬ pression is 1 percent, along with at least a 1 percent incidence of stroke or cranial nerve palsy, and the recurrence rate after 5 years is probably greater than 25 percent.38 The recurrence rate for RF rhizotomy is probably the same. Glycerol rhizolysis has a high enough recurrence rate that several centers have discon¬ tinued using the procedure.39 The 5-year recurrence rate for percutaneous microcompression is 20 percent. Microvascular decompression rarely results in dysesthesia or other sensory complaints. There is a 5 percent incidence of dysesthesia after the RF technique and 2 percent incidence after 1-min balloon compression. Though longer compressions result in a higher

Chapter 174/Trigeminal Nerve Compression for Neuralgia

incidence of dysesthesia, anesthesia dolorosa or keratitis has not been reported. The microvascular decompression technique with its 1 per¬ cent mortality rate and absence of dysesthesia may be best suited for the younger patient who wishes to avoid any sensory change. The three percutaneous procedures carry essentially no risk of mortality but a definite one of dysesthesia. Of the three, balloon microcompression is the simplest to perform, has the highest 5-year pain-free interval, and produces the lowest inci¬ dence of dysesthesia. Since it can be done under general anes¬ thesia, it is pain-free. Connelly40 comments on the ease of repeating the procedure in the event that further treatment is

19. 20.

21.

22.

23.

required. 24. 25.

References 1. 2.

3.

4. 5. 6. 7.

8. 9. 10.

11. 12.

13.

Hartel F: Uber die intrakranielle Injections—Behandlung der Trigeminusneuralgie. Med Klin 10:582, 1914. Jefferson A: Trigeminal root and ganglion injections using phenol in glycerine for relief of trigeminal neuralgia. J Neurol Neurosurg Psychiatry 26:345, 1963. Sweet WH, Wepsic JG: Controlled thermocoagulation of trigeminal ganglion and rootlets for differential destruction of pain fibers: Part 1: Trigeminal neuralgia. J Neurosurg 40:143, 1974 Hakanson S: Trigeminal neuralgia treated by the injection of glycerol into the trigeminal cistern. Neurosurgery 9:638, 1981. Mullan S, Lichtor T: Percutaneous microcompression of the trigemi¬ nal ganglion for trigeminal neuralgia. J Neurosurg 59:1007, 1983. Lee FC: Trigeminal neuralgia. J Med Assoc Ga 26: 431, 1937. Taamhpj P: Decompression of the trigeminal root and the posterior part of the ganglion as treatment in trigeminal neuralgia: Preliminary communication. J Neurosurg 9:288, 1952. Taarnhpj P: Decompression of the trigeminal root. J Neurosurg 11:299,1954. Stender A: “Gangliolysis” for the surgical treatment of trigeminal neuralgia. J Neurosurg 11:333, 1954. Sheldon CH, Pudenz RH, Freshwater DB, Crue BL: Compression rather than decompression for trigeminal neuralgia. J Neurosurg

26

Belber CJ, Rak RA: Balloon compression rhizolysis in the surgical management of trigeminal neuralgia. Neurosurg 20:908, 1987. Bricolo A, Dalle Ore G: Percutaneous microcompression of the gasserian ganglion for trigeminal neuralgia: Preliminary results (abstr). Acta Neurochir 69: 102, 1983. Brown JA, Preul MC: Trigeminal pressor response during percuta¬ neous microcompression of the trigeminal ganglion for trigeminal neuralgia. Neurosurgery 23:745, 1988. Fiume D, Scarda G, Natali G, Valle GD: La microcompressione percutanea del ganglio di gasser: Una nuova terapia per le nevralgie del trigemino. Riv Neurol 55:387, 1985. Fraioli B, Esposito V, Guidetti B, et al: Treatment of trigeminal neu¬ ralgia by thermocoagulation, glycerolization and percutaneous com¬ pression of the gasserian ganglion and/or retrogasserian rootlets: Long-term results and therapeutic protocol. Neurosurgery 24:239, 1989. Gerber AM: Unpublished data. Lichtor T, Mullan JF: A 10-year follow-up of percutaneous micro¬ compression of the trigeminal ganglion. J Neurosurg 72:49, 1990. Lobato RD, Rivas JJ, Sarabia M, Lamas E: Percutaneous microcom¬ pression of the gasserian ganglion for trigeminal neuralgia. J Neurosurg 72:546, 1990.

27.

Meglio M, Cioni B, d’Annunzio V: Percutaneous microcompression of the gasserian ganglion: Personal experience. Acta Neurochir

28.

39(suppl): 142, 1987. Revuelta R, Nathal E, Balderrama J, et al: External carotid artery fis¬ tula due to microcompression of the gasserian ganglion for relief of

29.

trigeminal neuralgia. J Neurosurg 78:499, 1993. Spaziante R, Cappabianca P, Peca C, deDivitiis E: Subarachnoid hemorrhage and “normal pressure hydrocephalus”: Fatal complica¬ tion of percutaneous microcompression of the gasserian ganglion. Neurosurgery 22:148. 1988.

30.

Nugent GR, Berry B: Trigeminal neuralgia treated by differential per¬ cutaneous radiofrequency coagulation of the gasserian ganglion. J Neurosurg 40:517, 1974.

31.

Tator CH, Rowed DW: Fluoroscopy of foramen ovale as an aid to thermocoagulation of the gasserian ganglion. J Neurosurg 44:254,

32.

1976. Whisler WW, Hill BJ: A simplified technique for the injection of the gasserian ganglion using the fluoroscope for localization. Neurochirurgia 5:167, 1972.

33.

Gerber AM: Improved visualization of the foramen ovale for percuta¬ neous approaches to the gasserion ganglion. J Neurosurg 80:156,

12:123, 1955. Love JG, Svien HJ: Results of decompression operation for trigemi-

34.

nal neuralgia. J Neurosurg 11:499, 1954. Svien HJ, Love JG: Results of decompression operation for trigemi¬ nal neuralgia four years plus after operation. J Neurosurg 16:653,

1994. Gerber AM: Needle for use during percutaneous compression of gasserian ganglion for trigeminal neuralgia. J Neurosurg 71:455,

35.

1959. Gardner WJ, Miklos MV: Response of trigeminal neuralgia to “de¬ compression” of sensory root: Discussion of cause of trigeminal neu-

1989. Brown JA, McDaniel MD, Weaver MT: Percutaneous compression for treatment of trigeminal neuralgia: Results in 50 patients.

36.

14.

ralgia. JAMA 170:1773, 1959. Hamby WB: Effectiveness of various operations for trigeminal neu¬

15.

ralgia. J Neurosurg 17:1039, 1960. Graf CJ: Trigeminal compression for tic douloureux. An evaluation. J

Neurosurgery 32:570, 1993.

37.

Neurosurg 20:1029, 1963.

16.

1713

Malis LI: Petrous ridge compression and its surgical correction. ./

38.

Neurosurg 26:163, 1967.

17.

Stender A, Grumme T: Late results of gangliolysis as a treatment for

39.

18.

trigeminal neuralgia. J Neurosurg 31:21, 1969. Jannetta PJ: Microsurgical approach to the trigeminal nerve for tic

40.

douloureux. Prog Neurol Surg 7:180, 1976.

Sweet WH: Complications of treating trigeminal neuralgia: An analy¬ sis of the literature and response to treatment, in Rovit R, Murali R, Jannetta PJ (eds): Trigeminal Neuralgia. Baltimore, Williams & Wil¬ kins, 1990, pp 251-279. Esposito S, Delitala A, Bruni P, et al: Therapeutic protocol in the treatment of trigeminal neuralgia. Appl Neurophysiol 48:271, 1985. Burchiel KJ: Percutaneous retrogasserian glycerol rhizolysis in the management of trigeminal neuralgia. J Neurosurg 69:361, 1988. Young RF: Glycerol rhizolysis for treatment of trigeminal neuralgia. J Neurosurg 69:39, 1988.

Connelly TJ: Balloon compression and trigeminal neuralgia (letter). MedJAust 2:119, 1982.

CHAPTER

1 75

MICRO VASCULAR DECOMPRESSION FOR TRIGEMINAL NEURALGIA

Jorge Roberto Pagura, Jader Pacheco Rabello, and Wanderley Cerqueira de Lima

Although it is a well-known clinical entity, trigeminal neuralgia (TN) has, over the course of years, been the object of contro¬ versial discussion, not only as regards etiology but mainly as to

Cranial nerves are usually positioned in close relation to ar¬ teries and veins; their proximity probably fluctuates with the degree of pulsation of the vessels and of the cerebrospinal fluid

treatment. Even after Nicholas Andre1 published a description of TN in 1756, it was most probably mistaken for other nosological entities, with diverse modes of treatment attempted.2 After sev¬ eral centuries, despite technological developments affording more precise diagnoses and improved conditions for surgical treatment, this pathology is far from being completely under¬ stood, and the multiplicity of treatments advocated over this

and the position of the head.6 For reasons as yet unknown, the trigeminal, facial, and glos¬ sopharyngeal nerves seem more susceptible to VC than the

period corroborates this. A lack of better anatomic and physiological knowledge and uncertain anesthesia techniques were limiting factors for the surgical treatment of TN in early times. For this reason, the simplest form of treatment invariably proved the best choice, even though it may not always have been the one based on the best pathophysiological concept. In writing on microvascular decompression (MVD), we should like to focus on the work of some authors. Dandy3, in 1932, laid the foundations for MVD when he stood for ap¬ proaching TN by a cerebellar route via the posterior fossa, em¬ phasizing that, in a number of instances, he had found a vascu¬ lar loop in contact with this nerve. It is of interest to note that 27 years elapsed before Gardner and Miklos4 confirmed Dandy’s assumption that the vascular loop might well produce alterations in the myelin at the level of the root entry zone. There were considerable advances in MVD in 1966 with the work of Jannetta and Rand.5 These authors performed what was probably the first MVD with the use of the microscope, us¬ ing the transtentorial subtemporal approach that, in our view, was more complicated than that advocated by Dandy and Gardner. These same authors were later to make use of the cerebellar route through the posterior fossa. There is no doubt that improved anesthesia techniques with routine use of a microscope were factors that were fundamental in popularizing MVD.

other nerves.6 Those who do not accept VC as a causal factor for TN hold that the surgeon is simply uncovering a normal nerve-vessel re¬ lationship that would also be found in persons free of pain. Some authors have tried to elucidate this controversy. Hamlyn and King7 developed clinical and experimental work concomitantly on vascular compression in patients with TN. From the clinical standpoint, they encountered 90 percent of VC in patients submitting to MVD. An experimental study in cadavers of patients who died with no previous background of TN did not show evidence of vascular compression or depres¬ sion of the nerve, although perfusion of the vessels augmented contact of the vascular structures with the nerve. Hardy and Rhoton8 in 1978 referred to finding VC in cadav¬ ers with no history of TN, so that they concluded that there must be asymptomatic compression of the trigeminal nerve. At what moment would compression become symptomatic? Would there be a trigger factor? Jannetta9 holds that TN is typically manifest at an advanced age because cerebral atrophy and the process of arteriosclero¬ sis—with resulting hardened, twisted arteries—would be con¬ ditions fundamental for the onset of TN. How can the presence of young patients with TN in almost all of the series published be explained? How can venous compression be explained? According to the same author, if arterial compression were to occur up to approximately 2.2 mm from the apparent visible emergence of the nerve from the brain stem, it would be taking place within an area of transition from central myelin to periph¬ eral myelin. This area of transition, known as the ObsteinerRedlich (OR) area or root entry zone (REZ), when subjected to contact with a vascular structure, would suffer demyelination with resulting dysfunction of the nerve, manifest clinically as a syndrome of hyperactive dysfunction. If the compression were to take place beyond the REZ, the patient would present with atypical facial pain. In our records, there are various patients with typical TN with VC beyond the

PATHOPHYSIOLOGY Vascular compression (VC) and MVD surgery, even if widely accepted, are still a source of controversy in the literature. 1715

1716

Part 4/Functional Stereotaxis

REZ who submitted to surgery and who presented excellent postoperative results. Short-circuiting between fibers of different diameters sec¬ ondary to demyelination at the REZ may provide the mecha¬ nism for trigger points.10 According to Moller,11 demyelination would lead to alter¬ ations at the level of the nucleus of the spinal tract of the trigeminal nerve. This may be one explanation for the signifi¬ cant percentage of relapses after any method of surgical treat¬ ment for TN. Although a pathophysiological explanation may perhaps en¬ compass several theories, what seems clear to us is that re¬ moval of contact of the vascular loop with the nerve in any po¬ sition in which it may be found results, in the great majority of cases, in relief from the symptomatology with no alteration in sensitivity, signifying decompression without apparent lesion of the nerve. Cases described without confirmation of VC may occur un¬ der some circumstances. The position of the head alters the vessel-nerve relationship, explaining a lesser occurrence of nocturnal TN crises in the majority of patients. In clinical ob¬ servations, Jannetta9 confirmed that the majority of patients lie in lateral decubitus contralateral to the pain, a posture that would tend to disimpact the VC. Besides the positioning of the head and opening of the dura mater, retraction of the cerebel¬ lum and opening of the cistern in the region of the cerebello¬ pontine angle should significantly alter the relationship be¬ tween nerves and vessels in the posterior fossa, so that the operative field may not always reveal the true relationship be¬ tween them. Another limiting factor in identifying VC would be a lack of experience on the part of the neurosurgeon in iden¬ tifying it; several experienced surgeons report a similar fact in literature.1- 15 This controversy may perhaps be summarized in one point: attempts have been made for many years to treat the symptom of TN; MVD is an endeavor to treat a possible cause.

CLINICAL MANIFESTATIONS Paroxysmal stabbing pain of short duration that can be trig¬ gered by a discrete tactile stimulus (trigger point) generally af¬ fecting one or more divisions of the trigeminal nerve are char¬ acteristic of TN. For many years, the vast majority of citations regarded the absence of alteration in sensitivity of the face to be characteristic of TN. In 21 percent of our cases, we found discrete alterations in sensitivity. Pain was generally unilateral and could, in 5 to 10 percent of patients, be bilateral at some stage of the disease. In our experience, we observed the onset of bilateral TN after surgical treatment on the side on which the pain began. Trigeminal neuralgia most often affects women close to age 50.16

INVESTIGATION Classically, investigation of patients with TN was carried out with an x-ray of the skull, examination of the cerebrospinal fluid, and computed tomography (CT) of the brain. In some in¬ stances, we considered brain angiography indicated for the study of the vertebrobasilar system. With the advent of mag¬

netic resonance imaging (MRI) we began to use only this modality, with emphasis, however, on the fact that the result is not a fundamental factor in deciding on the type of treatment. On a few occasions, we had the opportunity to prove with MRI that there was vascular compression of the trigeminal nerve: in the majority of cases, this was an artery of wider than normal gauge. These studies were, of course, carried out in order to ex¬ clude other pathologies, such as tumor, aneurysm, and arterio¬ venous malformation.

SELECTION OF PATIENTS FOR SURGERY All of the patients with TN initially submitted to clinical treat¬ ment with carbamazepine, phenytoin, clonazepam, or baclofen. In the cases that did not respond to the medication or where the collateral effects were very intense, we then went on to con¬ sider surgical treatment. On this point, we share Apfelbaum’s12 concern that the procedure chosen for each case represents the best effort on the part of the doctor, weighing pros and cons of each possible method of treatment. The doctor is responsible for suggesting the appropriate procedure, which must then be discussed extensively with the patient, mainly with regard to the possibility of recurrence or sequelae. We believe, however, that once our basic criteria for suggesting a particular proce¬ dure have been met, the patient may opt for whatever type of surgical treatment he or she chooses. We feel comfortable enough with this because we perform all the main types of surgery for the treatment of TN. Age over 65 years was formerly a contraindication to an ap¬ proach via the posterior fossa. However, after we acquired more experience with the procedure, we did away with this limitation. Today, if the patient is in good clinical condition, age is not a contraindication to MVD, our principal strategy for treating TN. We always recommend MVD as a procedure of choice for young patients, the same being the case for those patients with compromise ol the first division of the trigeminal nerve, owing to the risks of anesthesia of the cornea and a greater incidence of dysesthetic phenomena.

MATERIAL Between January 1981 and May 1995, 203 patients with TN submitted to MVD. Not included in these statistics were pa¬ tients with a diagnosis of aneurysm of the basilar artery, arte¬ riovenous malformation, meningioma, neurinoma, and epider¬ moid tumor. Some of the patients in the series had submitted to MVD in other centers and, owing to persistence of pain, submitted to a second MVD on our service. For purposes of analysis of the material, we considered those patients as having submitted to a first surgery. Second operations in our series are discussed separately. There was a predominance of the female sex: there were 115 women (56.6 percent) and 88 men (43 percent).

Chapter 175/Microvascular Decompression for Trigeminal Neuralgia

The right side was affected 116 times (57.1 percent) and the left side 79 times (38.9 percent); symptomatology was bilateral in 8 patients (3.9 percent). The age of the patients at surgical treatment in our service varied from 19 to 78 years, with an average age of 55.3 years (Table 175-1). In the majority of cases more than one division of TN was affected. The combination of TN in V2 and V3 division was present in 79 (38.9 percent) and was predominant (Table 175-2). Duration of the symptom before surgery varied from 1 to 37 years, averaging 9 years. Of the patients operated upon 43 (21.1 percent) had previ¬ ously submitted to some type of ablation procedure.

SURGICAL TECHNIQUE Each patient submitting to MVD underwent a detailed preoper¬ ative assessment. General anesthesia with orotracheal intubation is used with central venous and arterial access and a Foley catheter placed in the bladder. Trichotomy of the occipital region is restricted to the area of the incision. Earphones are adapted when we use auditory evoked potentials. Corticosteroids and prophylactic antibiotic therapy are uti¬ lized at the onset of surgery. The patient is placed in the lateral decubitus position and se¬ curely fixed with the careful use of straps so that there is no pressure of the neurovascular bundles of the upper limb close to the table. Caudal traction is exerted on the shoulder, which is turned upward in order to augment the space in which the sur¬ geon will work. The head is fixed on the Mayfield support and must be parallel to the floor of the room. Following antisepsis and asepsis of the nuchal and occipital region, we perform a vertical and paramedian incision approximately 8 cm long TABLE 175-1.

Distribution of Patients by Age

Age

Number of Patients

19-30 31-^10 41-50 .51-60 61-70 71-80

4 11 26 53 58 51

TABLE 175-2.

1717

about 3 cm from the mastoid apophysis. Two-thirds of this inci¬ sion must be below the nuchal line and one-third above. With the aid of the electrical scalpel and an orthostatic retractor, we divide and release the nuchal muscles until we have exposed the occipital bone. The emissary veins are coagulated and the bone orifices sealed with bone wax. We effect a burr hole 1 cm below the asterion, which is en¬ larged with the assistance of gouges varying from 2.5 to 3.5 cm. The upper limit of the craniectomy must be the transverse sinus and the lateral edges of the sigmoid sinus. The aerated cavity of the opened mastoid must be sealed with wax and bone powder. The dura mater is opened in a curvilinear fashion, be¬ ginning medially and extending superolaterally to the junction of the transverse and sigmoid sinus and inferolaterally to the edge of the sigmoid sinus. The free edge of the dura mater is sutured to the muscular layer over the mastoid, augmenting the exposure. At this stage of the surgery, we introduce the micro¬ scope. With the aid of a 10-mm spatula, we perform a mild re¬ traction of the upper part of the cerebellum, below the superior petrous vein, opening the arachnoid in the region of the cere¬ bellopontine angle. We place a small sponge and aspirate the fluid over this until the cerebellum is well below the dura mater. If the cerebellum is tense, it is possible to try to drain the cerebellomedullaris cistern located inferomedially. Only after the cerebellum is found to be in an ideally relaxed state, do we commence retraction of the same. The cerebellar surface must be protected with Gelfoam and a sponge to prevent lesions to the parenchyma. The spatula is then advanced progressively until the superior petrosal vein is seen. When we reach the Dandy vein, we shall be able to see the trigeminal nerve in an anteroinferior position. In the great majority of cases, we coagulate the superior petrosal vein, which permits a good view of the nerve. We recommend cau¬ tion at the moment of coagulation and resection. Routinely, at this stage of the proceedings, we place a sponge between the vein and the region of the trigeminal nerve, for, in the event of bleeding, we may safely aspirate, preventing lesions of the nerves in the region. In increasing traction ol the cerebellum, we must keep the arachnoid in the region of the cerebellopon¬ tine angle close to the facial and vestibulocochlear nerves to¬ tally open, thus avoiding traction from being transmitted to those nerves. Removal of the arachnoid around the trigeminal nerve is preceded by careful inspection in the search for the VC. At this phase of the surgery, the lateral inclination of the

Anatomic Distribution of Pain

Trigeminal Nerve

Number of Patients

VI V2 V3 VI-V2 V2-V3 V1-V2-V3

8 38 31 33 79 14

table may be useful to better expose the nerve. Once the VC has been identified, the trigeminal nerve must be completely freed from its arachnoid and the vessel must be separated from contact with the nerve. Then we must position Teflon, totally isolating the nerve. It is important to observe the two free edges of the Teflon with the vessel lying on the middle of its surface. More than one prosthesis was utilized on various occasions. When the compression is venous, the vein must be coagulated. If there is any doubt as to the effectiveness of the venous drainage, which may possibly be prejudiced when veins of large caliber exert pressure on the nerve, dissection may be attempted and isolation with Teflon utilized. In closure, the dura mater must be carefully sutured: biolog¬ ical glue and fragments of muscle must be used to close possi¬ ble orifices. Nuchal muscles are sutured in two layers with non-

1718

Part 4/Functional Stereotaxis

absorbable sutures. The subcutaneous layer is closed with ab¬ sorbable suture, with staples on the skin.

SURGICAL FINDINGS Surgical findings are listed in Table 175-3. The artery most of¬ ten found as the cause of compression of the trigeminal nerve was the superior cerebellar artery, alone or in combination with another artery or vein. In eight cases we could not find any evi¬ dence of compression of the trigeminal nerve.

RESULTS This surgery was effective in alleviating the pain from TN in approximately 95 percent of the patients. The majority awoke from anesthesia without pain; however, a certain number con¬ tinued to experience pain of considerably less intensity that persisted from a few days to weeks. As a routine, we generally continue the specific medication used by the patient in the pre¬ operative stage in much smaller doses for some days and then gradually taper down the dosage depending on how the pa¬ tient’s symptoms evolve. Our results are listed in Table 175-4. The period of follow¬ up varied from 3 to 173 months with an average of 69 months. Results were apparently not influenced by sex, age, duration of symptoms, or type of vascular compression. Patients treated with ablative procedures showed a greater incidence of residual pain or paresthesia immediately postoperatively. Of the 43 patients, 19 (44.2 percent) were included in the group with partial relief of pain. The great majority of the patients were asymptomatic after MVD. The group with partial relief consisted of patients who improved considerably but who nevertheless still required

TABLE 175-3.

Intraoperative Findings Number of Patients

Arterial compression Superior cerebellar artery Anterior inferior cerebellar artery (AICA) Basilar artery Posterior inferior cerebellar artery (PICA) Unidentified artery Mixed compression Unidentified artery/vein Venous compression Vein Negative exploration

TABLE 175-4.

Asymptomatic Partial relief Without response Total

Immediate 151 (74.38%) 41 (20.19%) 11 (05.41%) 203

Of the 11 patients from the group without immediate re¬ sponse, 6 were reoperated upon; in 2 of these there was a tech¬ nical fault in the endeavor to isolate the artery. In 4 cases, we did not observe anything to account for the continued presence of pain. Both cases with technical failure improved on the sec¬ ond attempt and required medication only in small doses. The other four cases continued with pain and another type of proce¬ dure and medication proved necessary. Four patients were reoperated upon owing to late recurrence of pain (over 6 months). The repeated procedure was techni¬ cally more laborious owing to adhesions from the prior inter¬ vention, and the surgical findings were not convincing of VC. All of these submitted to other procedures and required med¬ ication. Since then, we have not subjected patients with recur¬ rence of pain to a further MVD. In our material 9.3 percent of patients were lost to follow-up at the time of late evaluation, including the only death in our series.

COMPLICATIONS The majority of complications in MVD in our experience were transient. A great number of patients complain of headache, nausea, and dizziness, generally in the immediate postoperative period, improving over the subsequent hours. Aseptic meningitis, referred to by Jannetta,13 was not fre¬ quent in our material, possibly because we used corticosteroids routinely postoperatively for 3 days. Table 175-5 lists our main complications. Cerebrospinal fluid fistulas were treated with rest and exter¬ nal lumbar drainage; six cases necessitated reintervention. We later began to make use of biological glue, which practically did away with this complication. Bacterial meningitis was sat¬ isfactorily treated with systemic antibiotic therapy. In the cases where there was a cranial nerve deficit, this was usually tran¬ sient. One patient who awakened after surgery without pain, de¬ veloped drowsiness resulting from cerebellar edema, and died on the sixth postoperative day from pulmonary embolism.

117 28 2 1 21 11 15 8

Results of Microvascular Decompression

Groups

small doses of carbamazepine or clonazepam.

TABLE 175-5.

Postoperative Complications

Cerebrospinal fluid fistula Meningitis Labial herpes Death Nerves affected:

Late, 5 years 93 (67.88%) 25 (18.24%) 19(13.86%) 137

IV V motor V sensitive VII VIII

16 6 18 1 Transient 2 3 —

2 11

Persistent — —

1 1 1

Chapter 175/Microvascular Decompression for Trigeminal Neuralgia

DISCUSSION Pain is a symptom and not a disease.17 The many types of surgery proposed for the treatment of TN, all with reportedly good results and similar recurrence rates, leads us to question what the several surgical procedures used in the treatment of TN have in common that would account for the disappearance of painful symptomatology. Sweet18 believes that all of the pro¬ cedures including MVD inflict a lesion on the nerve. Perhaps, because of this type of explanation, ablative proce¬ dures, which are generally simpler to do, have for very long taken the place of more extensive surgery. Could it be that the simplicity of some of these ablative techniques would justify the loss of facial sensation? It was this question and the findings of Dandy,18 Gardner,1 and Jannetta5 that led to the recommendation that MVD be car¬ ried out in the posterior fossa to minimize the disorders of sen¬ sation occurring in other types of procedure. With the increased experience of several neurosurgeons elaborating its methodol¬ ogy,6,12-15 there has been every endeavor to consider treatment of TN by MVD, which eliminates the cause of its pathology rather than the other procedures that treat only its symptoms. However, although there may be a cause-and-effect relation¬ ship between the finding of a vascular loop compressing the trigeminal nerve and the abolition of pain, because of the con¬ troversy not only about the pathophysiology, but also as to the type of surgical treatment, it has not as yet been possible to change the name idiopathic trigeminal neuralgia to compres¬ sive trigeminal neuralgia. However elegant and probable the VC theory may be in ex¬ plaining TN, a series of questions has as yet remained unan¬ swered: 1.

How does one explain the incidence in young people, al¬

2. 3.

though rare? Why is it unilateral? Why are there frequent periods of spontaneous relief from

4.

pain? Why are there negative surgical explorations in sympto¬

5.

6. 7.

matic patients? What accounts for recurrence or persistence of pain in pa¬ tients after MVD, even in the series of experienced neuro¬ surgeons whose procedure was technically satisfactory? How can asymptomatic vascular compressions found in anatomic studies be explained? If the compression occurred only in the posterior fossa, why does TN improve with manipulation of this nerve in any segment, from its peripheral portion to the region of the nucleus of the spinal tract of the same? These unanswered questions still lead to statements such as

the following: “I do, although I am not sure what it is that I do,”19 and “Microvascular compression or decompression.”20 The absence of simultaneous compromise of divisions I and III of the trigeminal nerve in our material and generally in the literature, reinforces the VC theory, for it would be difficult, in view of their somatotopic relationship, for compression by a single vessel to compromise those two divisions. Two different arteries would be necessary, compressing separately roots V1 and V3, a fact never observed in our material. Any of the other

1719

combinations of compromise of the divisions of the trigeminal nerve are, however, easily explained and are found clinically. Depending on the nerve territory affected, we may anticipate the position of the VC. Although incomplete understanding of VC pathophysiology is undeniable, the great benefit that MVD has brought to pa¬ tients with TN is the possibility of being freed of pain through a safe method, without prior commitment to lesion a nerve. Like Dahle and colleagues,21 we do not consider MVD a cure for TN, but I should dare to say that MVD is the mode of treatment that possibly is closer to the cause. Every time we perform MVD, we neither partially section the pars major nor massage the nerve; any neuropraxis is invol¬ untary and only that needed during dissection. Our patients normally enjoy total pain relief immediately postoperatively, the majority without any clear-cut sensory disorder. Jannetta9,13 believes that VC would cause TN only if it oc¬ curred up to the REZ area, and that if VC were to occur be¬ yond, the patient would present atypical facial pain. Tashiro and co-workers22 consider VC is symptomatic only if it occurs up to the REZ area and proposes straightforward transposition just beyond the REZ in cases such as compression by an artery transfixing the nerve. We do not believe that a neurosurgeon can identify the referred area of transition of the myelin during surgery. In our material, various patients with typical TN pre¬ sented VC situated in the distal third of the trigeminal nerve, defined by us as VC situated beyond the REZ area. In these cases, VC was treated in the usual manner, and patients went on to relief of pain. Venous compression is generally more difficult to identify, and even in cases of compression through tumors, the possibil¬ ity of VC of arterial or venous origin must not be discarded. One instructive case was that of a girl of 9 years not included in this series. The patient had facial pain secondary to an astrocy¬ toma of the brain stem with growth exophytic to the cerebello¬ pontine angle on the same side as the pain. A percutaneous ra¬ diofrequency rhizotomy relieved her pain for some months. Because the pain returned, we chose to approach the posterior fossa and, having removed the exophytic portion of the tumor, we observed the presence of venous compression of the trigem¬ inal nerve that was, in fact, grooved by the vein. This patient has been asymptomatic for the last 5 years. Although routine coagulation of the superior group of veins did not present any clinical repercussions in our cases, we rec¬ ommend that, before coagulation of same, every attempt be made to identify VC. For if the compression on the nerve is of venous origin, it will probably be produced by an inferior ve¬ nous group. In these cases, we try to avoid coagulation of the superior venous group and will do so only if there is no other alternative. Concerning the false diagnostic impressions arising from preoperative investigation, we cite two cases of dolichomegabasilar artery implicated by preoperative MRI as the cause of VC with subsequent TN. However, upon surgical exploration, after the dolichomegabasilar artery had been moved aside, we observed that that structure did not participate in the VC, which was produced instead in one case by AICA and in the other by a nonidentified artery, both cases being treated in the usual fash¬ ion. Retraction of the cerebellum is fundamental for good surgi¬ cal exploration. Lumbar puncture as suggested by Wilkins6

1720

Part 4/Functional Stereotaxis

may be beneficial in reducing the volume of the posterior fossa: we do not carry this out as a routine, but we believe that it is advisable for surgeons with little experience in this procedure. Use of mannitol and furosemide, as proposed by Apfelbaum,12 may also prove useful, but does not substitute for cisternal drainage of cerebrospinal fluid at the start of the procedure. The cerebellum must not be subjected to excessive retraction be¬ cause both Sindou and colleagues23 and we have observed se¬

We are reluctant to reoperate on a patient subjected to MVD, a point of view supported by our experience, and that of other authors.12,24 In the cases of early or tardy recurrence of pain, we have reoperated only upon those cases that were for¬ warded to us from other services. In those treated by us, we suggested another type of procedure.

Figure 175-1. Compression of the trigeminal nerve by the

atrophied.

vere alterations in the auditory evoked potential during the ini¬ tial phase of cerebellar retraction.

Figure 175-3. Compression of the trigeminal nerve, now superior cerebellar artery, probably beyond the REZ.

Figure 175-2. Trigeminal nerve compressed by a dolichomegabasilar artery.

Chapter 175/Micro vascular Decompression for Trigeminal Neuralgia

The death in our series occurred in a patient of 78 years who had been previously subjected to other surgical methods of treatment and who presented with pain that was extremely re¬ sistant to medication. Surgery was completed uneventfully, one artery having been isolated from TN. In the postoperative pe¬ riod, the patient presented cerebellar edema, remained intu¬ bated for a prolonged period of time, and finally died of pul¬ monary embolism. In contrast, another patient of 73 years, also previously operated upon over three times by other methods, submitted to MVD following implantation of an external car¬ diac pacemaker and ended up well and free of pain. Abolishing pain is the final objective of the procedures for the treatment of TN. We know that the greatest complaint of patients in the postoperative phase when they are free of pain revolves around sensory disorders caused by ablative surgery that are at times more undesirable than the very tic for which the operation was done. For this reason, we advocate MVD as a first option for the treatment for TN, a procedure that abolishes pain while preserving facial sensation. The last procedure to be considered is lesioning of the nerve (see Figs. 175-1, 175-2, 175-3, and 175-4).

References 1. 2.

3. 4.

5.

6.

Andre NA: Observations pratiques sur les maladies de Vuretre. Paris: Chez Delaguette, 1756, pp 318-382. Wilkins RH: Historical perspectives, in Rovit RL, Murali R, Jannetta PJ (eds): Trigeminal Neuralgia. Baltimore: Williams & Wilkins, 1990, pp 1-25. Dandy WE: The treatment of trigeminal neuralgia by the cerebellar route. Ann Surg 96:787, 1932. Gardner WJ, Miklos MV: Response of trigeminal neuralgia to “de¬ compression” of sensory root: Discussion of the cause of trigeminal neuralgia. JAMA 170:1773, 1959. Jannetta PJ, Rand RW: Transtentorial retrogasserian rhizotomy in trigeminal neuralgia by microneurosurgical technique. Bull LA Neurol Soc 31:93, 1966. Wilkins RH: Neurovascular decompression procedures in the surgical management of disorders of cranial nerves V, VII, IX and X to treat pain, in Schmidek HH, Sweet WH (eds): Operative Neurosurgical Techniques, 3d ed. Philadelphia: Saunders, 1995, pp 1457-1467.

7. 8. 9.

10. 11. 12.

13.

14.

15.

16.

17. 18.

19. 20. 21. 22.

23.

24.

1721

Hamlyn PJ, King TT: Neurovascular compression in trigeminal neu¬ ralgia: A clinical and anatomical study. J Neurosurg 76:948, 1992. Hardy DG, Rhoton AL Jr: Microsurgical relationship of the superior cerebellar artery and the trigeminal nerve. J Neurosurg 49:669, 1978. Jannetta PJ: Treatment of trigeminal neuralgia by microoperative de¬ compression, in Youmans JR (ed): Neurological Surgery, 3d ed. Philadelphia: Saunders, 1980, pp 3928-3942. Dott NM: Facial pain. Proc R Soc Med 44:1034, 1951. Moller AR: The cranial nerve vascular compression syndrome: II. A review of pathophysiology. Acta Neurochir 113:24, 1991. Apfelbaum RI: Surgical management of disorders of the lower cranial nerves, in Schmidek HH, Sweet WR (eds): Operative Neurosurgical Techniques: Indications, Methods and Results, 2d ed. Orlando, FL: Grune & Stratton, 1989, pp 1097-1109. Jannetta PJ: Microvascular decompression of the trigeminal nerve root entry zone, in Rovit RL, Murali R, Jannetta PJ (eds): Trigeminal Neuralgia. Baltimore: Williams & Wilkins, 1980, pp 201-222. Klun B: Microvascular decompression and partial sensory rhizotomy in the treatment of trigeminal neuralgia: Personal experience with 220 patients. Neurosurgery 30:49, 1992. Rand RW, Hunstock AT: Trigeminal neuralgia: Gardner neuro¬ vascular decompression operation: Glossopharyngeal neuralgia, in Rand RW (ed): Microneurosurgery, 3d ed. St Louis: Mosby, 1985, pp 666-682. Maxwell RE: Clinical diagnosis of trigeminal neuralgia and differ¬ ential diagnosis of facial pain, in Rovit RL, Murali R, Jannetta PJ (eds): Trigeminal Neuralgia. Baltimore: Williams & Wilkins, 1990, pp 53-77. Gardner WJ: Trigeminal neuralgia. Clin Neurosurg 15:1, 1967. Sweet WH: Complications of treating trigeminal neuralgia: An analy¬ sis of the literature and response to questionnaire, in Rovit RL, Murali R, Jannetta PJ (eds): Trigeminal Neuralgia. Baltimore: Williams & Wilkins, 1990, pp 251-279. Adams CBT: Microvascular compression: An alternative view and hypothesis. J Neurosurg 57:1, 1989. Parkinson D: Microvascular compression-decompression: A recollec¬ tion. Neurosurgical forum. J Neurosurg 70:819, 1989. Dahle L, Essen CV, Kourtopoulos H, et al: Microvascular decompres¬ sion for trigeminal neuralgia. Acta Neurochir 99:109, 1989. Tashiro H, Kondo A, Aoyama I, et al: Trigeminal neuralgia caused by compression from arteries transfixing the nerve. J Neurosurg 75:783, 1991. Sindou M, Fobe JL, Ciriano D, Fischer C: Hearing prognosis and in¬ traoperative guidance of brainstem auditory evoked potential in mi¬ crovascular decompression. Laryngoscope 102:678, 1992. Yamaki T, Hashi K, Niwa J, et al: Results of reoperation for failed mi¬ crovascular decompression. Acta Neurochir 115:1, 1992.

1

CHAPTER

1 76

TREATMENT OF FACIAL PAIN

Kim J. Burchiel

SYMPTOMS

This chapter addresses a specific, and in many ways unique, pain problem, facial pain. The discussion includes but is not limited to trigeminal neuralgia, which stands out from other fa¬ cial pain syndromes in that it is relatively easily and reliably di¬ agnosed with a brief history, and it has a number of highlyeffective nonsurgical and surgical treatments. Other facial pain syndromes are often not so easily diagnosed and treated but will nevertheless appear in a clinical practice of neurosurgery from time to time. The present discussion emphasizes the approach to the pa¬ tient with medically intractable facial pain. It also reviews the medical management of trigeminal neuralgia and other facial pain syndromes. We do not cover surgical technique here, since this text is directed toward a sophisticated neurosurgical audi¬ ence, and the technical aspects of the procedures are well cov¬ ered elsewhere in this text. A complete review of the expected outcome and potential morbidity of each procedure is likewise not feasible given the scope of this chapter. Instead, the reader is directed to other chapters that describe the particular surgical procedures as well as to other reviews of the subject.1 This review closely follows the decision analysis pathway presented in Fig. 176-1. This chart seeks to recreate, as much as possible, how we approach patients with facial pain; it is a hier¬ archical and stratified conceptualization from diagnosis to sat¬ isfactory treatment. This approach explicitly places medical management ahead of surgical treatment, involves patient choice in the surgical decision making, and implicitly favors minor procedures over major operations. In most cases, the patient’s history is the most important as¬ pect of the diagnostic evaluation. Therefore, symptoms are of paramount importance. In fact, the critical determinants in sort¬ ing out facial pain syndromes are the temporal quality of the pain and the adjectives used to describe it. The diagnosis is usually fairly apparent from the history and physical exam. If there appears to be a primary etiology, as in the rare case when a cerebellopontine angle tumor causes trigeminal neuralgia, that etiology is dealt with directly by the initial treatment. In most cases, no definite primary etiology can be found and symptomatic medical therapy is then pursued. Failing this, a surgical decision point is reached with the active involvement of the patient, taking into consideration aspects of the case such as patient age, general condition of the patient, and patient preferences.

The symptom of facial pain can be quite specific and diagnostic if an accurate description of its temporal pattern and character¬ istics is obtained. This algorithm divides patients into three groups, (1) those who have paroxysmal pains, (2) those with mixed paroxysmal and constant pains, and (3) those with strictly constant pain. One truism holds that the more paroxys¬ mal pain dominates the patient’s complaint, the more likely it is that medical or surgical intervention may help.

DIAGNOSIS Trigeminal Neuralgia/Atypical Trigeminal Neuralgia Trigeminal neuralgia is typically described as a fleeting, lanci¬ nating pain occurring in the sensory distribution of the trigemi¬ nal nerve. This story is strikingly reproducible and unmistak¬ able. The pain characteristically lasts seconds to minutes and is almost always unilateral. Curiously, the disease course is not static and is notable for pain-free intervals that may last months to years. The pain is described as paroxysmal and electrical in nature. Attacks are usually brought on by such triggering stim¬ uli as talking, eating, oral hygiene, or even cool temperatures or wind on the face. Light tactile stimulation is often all that is needed to provoke a volley of paroxysms, and such an attack can provoke such profound pain that sufferers will neglect grooming on the affected side because of it. This condition usu¬ ally affects older individuals, in their sixties and above, but ranges from the second to the tenth decade. Atypical trigeminal neuralgia differs from typical trigeminal neuralgia in that, in addition to the episodic lancinating pain, there exists a component of a more persistent aching or burning pain. In this setting, careful consideration should be given to the presence of structural pathology in the nerve or to an extrin¬ sic compressive lesion such as a tumor or vascular malforma¬ tion. This is particularly true if sensory loss is detected on the face. Patients with atypical features such as these should undergo computed tomography (CT) or magnetic resonance imaging (MRI) to rule out other pathology.

1723

1724

Figure 176-1.

Treatment of facial pain.

Chapter 176/Treatment of Facial Pain

Postherpetic Neuralgia Pain associated with an acute outbreak of herpetic lesions in the distribution of a branch or branches of the trigeminal nerve does not usually present a diagnostic dilemma. The etiologic agent is herpes zoster or varicella virus and affects middle-aged to elderly individuals, males and females about equally. The pain is described as burning or tingling with occasionally lanci¬ nating components felt in the skin. The pain usually precedes the onset of herpetic eruption by 1 or 2 days or may develop coincident with the eruption. The pain is severe and usually lasts up to several weeks. In the usual case, spontaneous and permanent remission is the rule. However, in the older age group, progression to chronic (postherpetic) neuralgia is more often the rule. Chronic neuralgia that occurs in the distribution of one or more divisions of the fifth cranial nerve subsequent to an acute herpes zoster outbreak is described as postherpetic neuralgia. Pain of this type is usually associated with chronic trophic skin changes or scarring and most commonly occurs in the first (ophthalmic) division. It is a relatively infrequent disorder, pre¬ dominantly seen in patients in their fifties or older, and is more common in males. The pain is described as a burning, tearing, crawling, or itching dysesthesia in the affected area, and it is exacerbated by mechanical contact with the skin. The pain is moderate but is present constantly and may last for years, al¬ though spontaneous remission can occur. Due to the chronic and unremitting nature of the pain, depression and irritability are common associated symptoms. On examination the skin of the painful region may show scarring, loss of normal pigmenta¬ tion, hypesthesia or hyperesthesia, hypalgesia or hyperpathia (allodynia).

POSTTRAUMATIC NEURALGIA From 5 to 10 percent of patients will develop some degree of facial pain following facial fracture or after reconstructive or¬ thognathic surgery and a further 1 to 5 percent of patients after removal of impacted teeth. The quality of the pain is sharp, with episodic triggered paroxysms and dull throbbing or burn¬ ing background pain. Signs of this condition include tender, palpable nodules over peripheral nerves or neurotropic effects. The course of the disorder is characterized by progression over a period of 6 months or so, then by stabilization of the pain un¬ til treatment intervenes. This type of pain may also be termed trigeminal neuropathic pain, to indicate that it is a pain proba¬ bly related to peripheral trigeminal nerve injury.2

Anesthesia Dolorosa Pain that is felt in an insensate region of the face is termed anesthesia dolorosa. The pains are variously described as burn¬ ing, crawling, itching, or even tearing; they are thought to be “central” in origin and thus not dependent upon peripheral stimuli.

Facial Pain and Malignancy Facial pains in the context of a known carcinoma of the head and neck or associated with a known skull-base neoplasm are

1725

usually described as constant, but lancination and intermittency can also characterize their initial onset. These pains are the re¬ sult of direct compression or invasion of the nerve and sur¬ rounding structures (nociceptive element) and central deafferentation from nerve injury (neuropathic element). It is no wonder, then, that adjectives similar to those used for other deafferentation pains can be invoked by the patient and, in fact, these pains may be described as being much like anesthesia dolorosa. Plain radiography, CT, and/or MRI is essential to evaluate the extent of disease and to plan appropriate primary therapy.

Atypical Facial Pain Historically, the term atypical facial pain, or prosopalgia, has been used most commonly to describe diffuse, nonanatomic orofacial pain of unknown pathophysiology. It is vital that neu¬ rosurgeons appreciate this diagnosis, since inappropriate and ill-advised procedures may result from its misdiagnosis. In the author’s opinion, the diagnosis of atypical facial pain should be made only on the following basis: (1) when other etiologies for facial pain have first been considered, evaluated, and excluded where appropriate; (2) when objective evidence for other facial pain syndromes is lacking; and (3) when specific antecedent psychological or behavioral factors can be identified. The predominant characteristic of psychologically induced pain is that it mimics known pain syndromes. It is usually con¬ stant, often bilateral, and not confined to the trigeminal distri¬ bution. The description of the pain quality is often vague and variable, as is the location and precipitating factors. A constant aching or burning sensation is the dominant feature, paroxys¬ mal pain being uncommon. Psychological features (e.g., delu¬ sions, hallucinations, multiple physical complaints with classic conversion or pseudoneurological symptoms, exaggerated symptom reporting, excessive concern or fear of the symptoms, depression, illness behaviors, and excessive treatment seeking or medication usage) are common. The patient often appears morose, with evident suffering. Neurological examination is usually normal except for some poorly localized tenderness and vague sensory loss in the painful region.3

PRIMARY ETIOLOGY It is debatable whether most cases of “idiopathic” trigeminal neuralgia are due to vascular compression of the trigeminal root,4 in which case microvascular decompression should effectively treat the primary etiology. Apart from that issue, the consideration of a primary etiology for other facial pains is quite specific: trigeminal neuralgia is rarely associated with tumor, aneurysm, or arteriovenous malformation of the cerebellopon¬ tine angle. Somewhat more commonly, it is associated with multiple sclerosis. In cases of malignancy, the etiology is com¬ pression, invasion, or destruction of the nerve; in atypical facial pain, depression or other psychogenic causes are responsible.

INITIAL TREATMENT Initial treatment is diagnosis-driven. Across Fig. 176-1, treat¬ able structural etiologies for “secondary” trigeminal neuralgia

1726

Part 4/Functional Stereotaxis

(see above) are dealt with. Pain due to malignancy may be pal¬ liated by local resection and radiation therapy. Psychiatric causes are treated accordingly.

Anticonvulsants such as carbamazepine can alleviate any lanci¬ nating component of the pain. Though antidepressants may be tried, they are rarely effective.

MEDICAL TREATMENT

Anesthesia Dolorosa

Trigeminal Neuralgia

Tricyclic antidepressants may be offered for anesthesia do¬ lorosa, but, as with other deafferentation pains, the outlook for improvement is bleak.

Approximately 70 percent of trigeminal neuralgia patients are well controlled nonoperatively. Perhaps the quintessential drug used is carbamazepine (Tegretol) commencing at 100 mg PO bid and then increasing by 200 mg/day every 2 to 3 days to a final ef¬ fective dose in the range of up to 800 to 1000 mg. This regimen will not only bring a response from most patients but it will also serve as a powerful and reliable modality in the diagnosis of trigeminal neuralgia. That is, if a patient with facial pain re¬ sponds to carbamazepine, the diagnosis of trigeminal neuralgia is assured. Unfortunately, the use of the drug may be limited by the development of hypersensitivity reactions or side effects such as drowsiness, decreased mental acuity, subjective dizzi¬ ness, and ataxia (particularly in older patients), dose-related mild leukopenia, or a very rare non-dose-dependent idiosyncratic bone marrow suppression (aplastic anemia) that can occur early in treatment. For these reasons a baseline white blood cell count is obtained, repeated at 3- to 4-week intervals. In patients who cannot tolerate carbamazepine, other options include the use of baclofen (Lioresal) or phenytoin (Dilantin). Baclofen can be a good choice in patients who get effective relief from carba¬ mazepine but cannot tolerate its side effects; it is usually started at 5 mg tid and increased by 5 to 10 mg every 2 to 3 days to a maximum dose of 80 mg/day. It is usually not effective in patients who do not derive benefit from carbamazepine. Phenytoin is rarely of use when carbamazepine or baclofen have failed but may be helpful in combination with one of the other medications. Although most patients are well controlled initially by medical management, many will become nonresponders in time, drug therapy becoming ineffective accompanied by breakthrough pain. In fact, in the author’s opinion, the majority of patients will even¬ tually fail medical management if followed up carefully over a period of years. Fortunately, most of these patients will subse¬ quently derive excellent relief from surgical modalities.

Postherpetic Neuralgia Treatment of established postherpetic neuralgia is difficult. Fortunately, there is a tendency for the pain to diminish with time. Medications that are effective for trigeminal neuralgia are of little benefit in this disorder, although carbamazepine or clonazepam may be useful in the treatment of that component of postherpetic neuralgia which is described as being paroxys¬ mal and lancinating. For the more typical, constant, burning dysesthetic pain, tricyclic antidepressant medications are prob¬ ably the most effective choices for pharmacological treatment. Amitriptyline 75 mg given at bedtime with fluphenazine 1 mg three times a day is a commonly utilized regimen.

P( )STTR AUM A TIC N EU RALGIA As with postherpetic neuralgia, there is no satisfactory medical treatment lor neuropathic pain in the trigeminal distribution.

Atypical Facial Pain Anticonvulsant medication is particularly unhelpful in these pa¬ tients, psychiatric evaluation with psychotherapy and antide¬ pressant medication being perhaps the only reasonable re¬ course.5 There are no reasonable surgical options in these cases.

SURGICAL DECISION Once it becomes apparent that a patient has failed to benefit from maximal medical management or become refractory to it, a surgical decision point is reached. Particularly in patients with trigeminal neuralgia, numerous surgical options are avail¬ able, and patients must make an informed decision on choice of surgery based on factors such as age, general medical condi¬ tion, and their preferences.

SURGICAL PROCEDURES Trigeminal Neuralgia Minor procedures Percutaneous injection of alcohol into the peripheral trigeminal nerve or its ganglion (ethanol block) and peri/intraganglionic in¬ jection of alcohol (gangliolysis) are rarely performed proce¬ dures that are not discussed further here. Peripheral neurectomy is no longer a state-of-the-art procedure, but it can be employed to provide simple, effective pain relief for very sick, elderly pa¬ tients who would not tolerate other procedures, keeping in mind the fact that pain will almost certainly return within a few years, requiring relesioning. This also is not discussed further. This leaves what are really the three main minor proce¬ dures: percutaneous retrogasserian glycerol rhizolysis (PRGR). percutaneous radiofrequency trigeminal gangliolysis (PRTG), and percutaneous trigeminal ganglion compression (PTGC). The choice of procedure depends on the experience and prefer¬ ence of the surgeon. All are effective, each with relative advan¬ tages and disadvantages. The PTGC procedure is technically simple, causes only mild sensory loss, and has an acceptable recurrence rate. However, it is impossible to restrict the lesion to a single division. Although PRGR causes no or at most mild sensory loss, it is technically more difficult to perform. The failure rate also seems to be higher in most surgeons’ hands, as is the 5-year pain recurrence rate. Finally, PRTG affords imme¬ diate pain relief in a very high percentage of patients with a low recurrence rate, but it produces considerable sensory loss. It is also effective for trigeminal neuralgia associated with multiple sclerosis or tumor. It is easier to perform for V3 than V2 tic be-

Chapter 176/Treatment of Facial Pain

cause of the potential overlap with VI. In general, PTGC and PRGR, with their more minor denervation, are preferable for VI pain, to avoid the complication of corneal keratitis, whereas in V2/V3 pain, PRTG is preferred. One of the primary criticisms of the minor procedures is that they do not address the underlying pathology and remove the cause of the pain. On the other hand, they are effective proce¬ dures with relatively minimal morbidity and almost nonexistent mortality, an important consideration in a nonlethal condition such as trigeminal neuralgia. These procedures offer the substantial benefits of outpatient surgery with minimal anesthetic risk and morbidity/mortality, uti¬ lizing local or brief general anesthesia rather than general endo¬ tracheal anesthesia. For these operations in addition to agents pro¬ vidings an effective short-acting general anesthesia, methohexital (Brevital) and propofol (Diprivan) can also provide an amnestic effect. It is important to note, however, that these agents provide no analgesia, so that their use requires supplementary analgesic agents. The surgical indication for these procedures is medically intractable trigeminal neuralgia, particularly in elderly or ill pa¬ tients who do not desire or would be poor candidates for major operative procedures. However, the pain relief they produce sel¬ dom lasts more than a few years, necessitating repeat procedures. Major procedures The primary major procedures are microvascular decompres¬ sion (MVD) and partial sensory rhizotomy (PSR). In practice, these two procedures are used in tandem. If, on microsurgical exploration, a patient shows no trigeminal root compression or has recurrent pain after MVD, a PSR is performed. The latter may also be performed in a patient with multiple sclerosis or symptomatic trigeminal neuralgia who has failed to gain last¬ ing relief from percutaneous denervation. Although microvascular decompression is the only surgical modality directly addressing the presumed etiology of trigemi¬ nal neuralgia and probably provides the longest-lasting pain re¬ lief, it has several significant drawbacks: it is a major surgical procedure with a reported mortality of 1 percent as well as nonnegligible postoperative complications, including the risk of transient or permanent cranial nerve deficits.6 Several authors have questioned the use of a procedure with defined morbidity and mortality for benign disease; they propose the use of the percutaneous procedures in the surgical management of most cases of trigeminal neuralgia.7 The ultimate choice between major and minor procedures in patients refractory to medical management is a matter for both the patient and physician. Older patients are often biased to¬ ward minor procedures because of considerations such as life expectancy, other health concerns, longer hospital stay, in¬ creased recovery time, and avoidance of a craniotomy. On the other hand, in a young, healthy patient, the longer duration of effective pain relief offered by microvascular decompression may offset these considerations.

Postherpetic Neuralgia

1727

remitting pain that is refractory to medical management. There are no minor procedures that are useful in the surgical manage¬ ment of this disease. Currently, stereotaxic trigeminal tracto¬ tomy and open radiofrequency tractotomy/nucleotomy are probably the only surgical procedures that have been shown, albeit in only a few cases, to be effective for its management.8,9 Destruction of the descending spinal tract of the trigeminal nerve in the dorsal medulla, or trigeminal tractotomy, produces analgesia and thermanalgesia in the distribution of the ipsilateral nerve with preservation of tactile sensation. This can be performed as either an open10 or percutaneous stereotaxic11 pro¬ cedure and can be done bilaterally. Open medullary tractotomy is generally ineffective in cases of deafferentation pain, al¬ though the literature describes mixed success in treating postherpetic neuralgia. Stereotactic trigeminal nucleotomy of the second-order neurons at the oral pole of the nucleus caudalis, on the other hand, has been found to be quite effective in such patients with deafferentation pain.12 Unlike essential trigeminal neuralgia, the degree of dysesthetic pain in deaf¬ ferentation syndromes is directly proportional to the extent of sensory deficit. The theoretical basis for performing dorsal root entry zone (DREZ) lesions at the nucleus caudalis is the belief that central pain is localized to the secondary neurons.12 These are thought to be “hyperirritable,” having become destabilized after de¬ afferentation, so as to fire erratically, resulting in severe pain. Although technically it is not the trigeminal DREZ, the nucleus caudalis of the trigeminal nerve is the first relay station for cen¬ tral transmission of facial pain. Thus, the nucleus caudalis of the trigeminal system is effectively the anatomic equivalent of the spinal dorsal horn. The caudalis DREZ lesion is aimed at destroying the second-order neurons theoretically responsible for maintaining the ongoing pain sensation, and, in this respect, the operation differs from trigeminal tractotomy. In general, DREZ lesions are thought to be most efficacious for de¬ afferentation pain and should probably be limited to patients failing the first line procedures. Deep Brain Stimulation (DBS) directed at ventroposteromedial [(VPM) ventralis caudalis internus (VCi)] may benefit some patients with postherpetic neuralgia. It probably produces somewhat less morbidity than the caudalis DREZ operation, but the efficacy is difficult to gauge from the literature.

POSTTRAUMATIC NEURALGIA Minor procedures Trigeminal neuropathic pain is similar in origin and clinical presentation to other peripheral neuropathic pains. Damage to the distal trigeminal nerve is the common feature of these re¬ lated neuralgias. Although the conclusion is controversial, some patients who respond favorably to local anesthetic block¬ ade of the involved branch may improve after peripheral neurectomy.2 There has also been some evidence that trigemi¬ nal electrical stimulation13 may also produce pain relief, al¬ though implantable systems designed for this indication are currently not available in the United States.

Major procedures

Major procedures

In light of the natural history of postherpetic neuralgia, surgical therapy should be reserved for those patients with severe, un¬

Caudalis DREZ may be used in the most difficult cases, as can deep brain stimulation (DBS).

1728

Part 4/Functional Stereotaxis

Anesthesia Dolorosa

2.

Burchiel KJ: Trigeminal neuropathic pain. Acta Neurochir [Suppl] 58:145,1993.

Major procedures

3.

There are no minor procedures that alleviate this disorder. Surgical therapy is relegated to caudalis DREZ or DBS.

Burchiel KJ, Burgess J: Differential diagnosis and management of orofacial pain, in Tollison CD (ed): Handbook of Pain Management, 2d ed. Baltimore: Williams & Wilkins, 1994, pp 280-293.

4.

Burchiel KJ: Neurovascular compression and trigeminal neuralgia. APS J 2:234, 1993.

5.

Hart RG, Easton JD: Trigeminal neuralgia and other facial pains. Missouri Med 11:683-693, 1981.

6.

Fraoili B, Esposito V, Guidetti B, et al: Treatment of trigeminal neu¬

Facial Pain and Malignancy

ralgia by thermocoagulation, glycerolization. and percutaneous com¬ pression of the gasserian ganglion and/or retrogasserian rootlets: Long-term results and therapeutic protocol. Neurosurgery 24:239, 1989.

Minor procedures Facial pain due to local tumoral invasion can sometimes be man¬ aged by denervation of the area by either percutaneous (PRTG) or open (neurectomy) techniques, assuming that diagnostic local anesthetic blocks have first relieved the pain temporarily. Major procedures If minor procedures are ineffective, intrathecal opioids admin¬ istered into the lumbothoracic theca via a programmable drug delivery system may produce satisfactory analgesia.14 Caudalis

7.

Morley TP: Case against microvascular decompression in the treat¬ ment of trigeminal neuralgia. Arch Neurol 42:801, 1985.

8.

Watson PN, Evans RJ: Postherpetic neuralgia: A review. Arch Neurol 43:836, 1986.

9.

Nashold BS, Lopes H, Chodakiewitz J, Bronec P: Trigeminal DREZ for craniofacial pain, in Samii M (ed): Surgery in and Around the Brain Stem and Third Ventricle. Berlin: Springer-Verlag, 1986, pp 5459. Hosobuchi Y, Rutkin B: Descending trigeminal tractotomy. Neuro¬ physiological approach. Arch Neurol 25:115, 1971. Schvarcz J: Craniofacial postherpetic neuralgia managed by stereo¬ tactic spinal trigeminal nucleotomy. Acta Neurochir [Suppl] 46:62, 1989.

10. 11.

DREZ, mesencephalotomy, or cingulotomy are reserved for the most intractable and desperate cases.12 12.

References 1. Burchiel KJ. Moore KR: Pain and stereotaxis: Trigeminal neuralgia, in Wilden JN, Swash M (eds): Outcomes in Neurological and Neuro¬ surgical Disorders. Cambridge, England: Cambridge University Press, 1996. In press.

Sampson J, Nashold B Jr: Facial pain due to vascular lesions of the brain stem relieved by dorsal root entry zone lesions in the nucleus caudalis. J Neurosurg 71:473, 1992.

13.

Lazorthes Y, Armengaud JP, DaMotta M: Chronic stimulation of the gasserian ganglion for treatment of atypical facial neuralgia. Pacing Clin Electrophysiol 10:257, 1987.

14.

Andersen P, Cohen J, Everts E. et al: Intrathecal narcotics for relief of pain from head and neck cancer. Arch Otolaryngol Head Neck Surg 117:1277, 1991.

CHAPTER

177

TREATMENT OF OCCIPITAL NEURALGIA

Andres M. Lozano

Occipital neuralgia is a painful condition characterized by lateralized paroxysmal lancinating pain from the occipital region to the vertex of the head. This disorder affects neural elements derived from the second cervical (C2) nerves. This syndrome occurs with clear-cut and stereotyped clinical features. Unfortunately, the term occipital neuralgia is used to describe many conditions associated with chronic occipital pain, includ¬ ing migraine, tension headache, and cervical strain, which are usually devoid of the characteristic electric shock-like pain. The underlying mechanisms responsible for occipital neuralgia are unknown, but an understanding of the anatomic substrates for occipital pain offers clues to the etiology of this disorder and provides the basis for therapeutic strategies.

ANATOMY AND PATHOPHYSIOLOGY The dorsal Cl rootlets are absent approximately 70 percent of the time.1 This may explain the apparent lack of Cl dermatomal representation in humans and indicates that the upper¬ most dorsal spinal rootlets most often belong to C2. The C2 dorsal rootlets converge at the C2 dorsal root ganglion. The dural outpouching at C2 blends with the epineurium proximal to the C2 ganglion and the origin of the C2 spinal nerve. The ganglion itself is outside the subarachnoid space and is ex¬ tradural. The short C2 spinal nerve divides almost immediately into primary ventral and dorsal rami (Fig. 177-1). The C2 dor¬ sal ramus divides into four branches: a large sensory medial branch that gives rise to the greater occipital nerve and a lat¬ eral, a superior, and a branch to the obliquus inferior.2 The greater occipital nerve runs transversely across the obliquus in¬ ferior. It is covered by the splenius capitis and cervicis, the longissimus capitis, and the semispinalis capitis.2'3 The nerve turns upward and pierces the fibers of the semispinalis capitis to emerge to the scalp by passing through the aponeurotic at¬ tachment of the trapezius and sternocleidomastoid muscles at the superior nuchal line. Once it passes through the aponeurotic attachment, the greater occipital nerve divides into its terminal branches to innervate the skin of the occipital area and skull vertex up to the coronal suture and the region above the mas¬ toid.2'3 The scalp over the mastoid eminence and the posterior surface of the ear is supplied by the lesser occipital nerve, which is derived primarily from the ventral ramus of the C2 contribution to the cervical plexus. The lesser occipital nerve

pierces the fascia of the posterior triangle of the neck and runs along the posterior border of the sternocleidomastoid muscle before dividing into its terminal sensory branches. The central processes of the nociceptive C2 ganglion neu¬ rons synapse with second-order neurons in the upper cervical dorsal horn. The spinal trigeminal nucleus blends into the up¬ per cervical medullary dorsal horn, and it has been suggested that there may be convergence of nociceptive inputs from the face and upper cervical dermatomes onto spinal cord neu¬ rons.4,5 This may explain in part why some patients with occip¬ ital pain have associated pain in the distribution of the trigemi¬ nal nerve, for example, the temple or the retroorbital area.6-9 Knowing the extent of the C2 sensory dermatome is impor¬ tant for the attribution of pain to the C2 root and the prediction of the area of sensory loss that occurs after neurosurgical pro¬ cedures that interrupt C2 pathways. The C2 dermatome has been mapped in a variety of ways, using embryonic develop¬ ment, herpetic eruptions, areas of vasodilation with nerve stim¬ ulation, anatomic dissection, and areas of sensory deficits after ablative surgery.3,10 The C2 dermatome starts over the posterior superior surface of the neck and extends up toward the occipi¬ tal area to the vertex as far as the coronal suture. Its medial ex¬ tent is the midline; the lateral extent is at the level of the medial margin of the mastoid. The skin over the mastoid and the poste¬ rior surface of the ear is supplied by the lesser occipital nerve and is in the C2 or perhaps the C3 dermatome. Disorders causing occipital neuralgia interfere with the nor¬ mal function of the C2 neural elements. These nerves are sub¬ ject to metabolic disturbances, inflammation, infiltration, and a number of physical injuries, including traction, compression, and entrapment (Table 177-1). Points of vulnerability to injury to or entrapment of the C2 nerve root, the ganglion, or the greater occipital nerve are said to include the areas where (1) the root lies between the laminae of Cl and C2, (2) the posterior ramus is in contact with the lateral edge of the posterior atlantoaxial ligament, (3) the greater occipital nerve pierces the semispinalis capitis muscle, and (4) the greater occipital nerve emerges from the aponeu¬ rotic muscle insertions at the superior nuchal line.11,12 The C2 ganglion is in a position that may predispose it to in¬ jury between the arch of Cl and the lamina of C2 (Fig. 177-1). These structures are joined by a tough posterior atlantoaxial (atlantoepistrophic) ligament, which when hypertrophied is

1729

1730

Part 4/Functional Stereotaxis

C2G

TABLE 177-1.

VERTEBRAL ARTERY

VRAMUS

DRAMUS

Figure 177-1. Anatomic relations of the C2 nerve root and ganglion. The right Cl-C2 interspace is shown. AAFC = atlantoaxial facet joint; Cl = arch of the atlas; C2 = lamina ot the axis; C2G = C2 ganglion; DRAMUS = dorsal primary ramus of C2; PAAL = posterior atlantoaxial ligament; VRAMUS = ventral primary ramus of C2.

said to cause C2 ganglion entrapment.13 The ganglion is imme¬ diately lateral to the dural tube and medial to the C1-C2 facet joint. The proximal portion of the C2 ganglion is inferior to or often covered by the inferior medial aspect of the arch of Cl. It has been suggested that traumatic cervical extension can crush the C2 nerve complex between the arches of Cl and C2.14’15 Other studies, however, suggest that the C2 complex is held deep to the Cl and C2 arches and is not compromised during extension.2 Indeed Weinberger16 denied the existence of C2 in¬ jury by bony elements with cervical movement. The C2 ganglion is immersed in an extensive venous plexus that has also been implicated as a potential source of compres¬ sion through a process of venous engorgement.1718 It has also been suggested that muscle tension and inflammatory processes in muscular attachments may contribute to occipital nerve dysfunction at points where the nerve pierces the poste¬ rior neck muscles or their aponeurotic insertions.6'19

CLINICAL FEATURES It is important to distinguish occipital neuralgia from other oc¬ cipital pain syndromes. The clinical features of occipital pain allow its classification in two main categories: neuralgic and nonneuralgic. Patients with occipital neuralgia have many features in common with patients with trigeminal neuralgia. Patients with occipital neuralgia describe their pain by using “neuralgic” terms. Their pain is electric, shooting, tingling, exploding, jab¬ bing, and “like a bolt.” Neuralgic occipital pain radiates toward the vertex of the head in a manner that follows the branches of the greater occipital nerve. The pain is almost always unilat¬ eral. Attacks are stereotypical and often are triggered by neck movement or palpation along the course of the greater occipital

The Etiology of Occipital Neuralgia

Congenital21 Herniated cerebellar tonsils with Amold-Chiari malformation Traumaticnl5-22-23 Cervical extension and rotation injuries Atlantoaxial instability Fractures of the atlas Hair avulsion injury* Traumatic scars Postsurgical24 Ventriculoperitoneal shunts* Postmastoidectomy neuralgia Neoplastic24,25 Metastatic cancer, Posterior fossa tumors Cervical cord tumors Rheumatic"-26-2* Fibrositis, Myositis Rheumatoid arthritis Gout Myofascial pain Bony pathology26-27-29 Hypertrophic Cl -C3 facet joint C1-C2 arthrosis syndrome Platybasia Arthritic spurs Infectious2630-31 Syphilis Mastoid infections Pachymeningitis Metabolic26-21 Diabetic neuropathy Vascular pathology'1'18>32 Arterial vascular compression Venous vascular compression Other6,24 Muscle entrapment Spasmodic torticollis Idiopathic *Observed by the author.

nerve. Most often there are brief but highly intense attacks of pain that occur in bursts and last several seconds. Between these acute exacerbations patients may be pain-free or may have a baseline of dull aching pain in the occipital area. In some patients, however, the shooting paroxysmal occipital pain is accompanied by other features, particularly after a cervical strain injury, where there can be an underlying aching pain in the neck or occiput that can radiate to the temples or forehead. The pathophysiology of these “extra” features accompanying occipital neuralgia and whether they reflect an independent co¬ existing pathology are not clear. It is important to avoid the pitfall of missing the lancinating component of the pain, which is the key to the diagnosis of neuralgic pain in these patients. In contrast, a large group of patients describe their pain as aching, throbbing, pounding, dull, pulling, and pressure. These patients have “nonneuralgic” occipital pain. In these patients, the pain is nonlancinating and tends to be steadier and less vari-

Chapter 177/Treatment of Occipital Neuralgia

1731

able in intensity, with the differences between pain peaks and valleys not pronounced. The pain is more diffuse, is often bilat¬ eral, and sometimes involves the neck, shoulders, forehead, temples, and retro-orbital area. There may be associated visual or constitutional symptoms, such as nausea, that are also useful in distinguishing this type of pain from occipital neuralgia.

SIGNS OF C2 NERVE DYSFUNCTION Patients with occipital neuralgia have dysfunction in the C2 nerve or its branches. Indeed, the International Headache Society defines occipital neuralgia as “a paroxysmal jabbing pain in the distribution of the greater or lesser occipital nerves, accompanied by diminished sensation or dysesthesia in the af¬ fected area.”20 Although not all patients with occipital neuralgia have sensory abnormalities, many show physical signs sugges¬ tive of C2 nerve dysfunction. There may be decreased sensa¬ tion, of which the patient is usually unaware, in the territory of pain radiation. In some patients, there is hyperpathia in the C2 dermatome. This is characterized by an increased threshold for the perception of a nociceptive stimulus (for example, repeti¬ tive pinpricks) but an exaggerated pain response once the threshold for sensation is reached. Patients and the examiner may trigger an attack by means of neck movements. This sign indicates a susceptibility of the dysfunctional neural elements to mechanical irritability. Similarly, the patient also may ex¬ hibit Tinel’s sign on tapping of the greater occipital nerve.

INVESTIGATION AND TREATMENT A variety of treatments for occipital neuralgia have been sug¬ gested (Table 177-2), but it must be emphasized that therapeu¬ tic interventions should be, whenever possible, directed at the underlying cause (Fig. 177-2). For patients with a precipitating trauma, cervical spine radiographs in neutral position, flexion, and extension are performed to rule out spinal instability. Magnetic resonance imaging (MRI) of the cervical spine may show neural compression, ligamentous injury, or unsuspected abnormalities, each of which may require specific treatment or directed surgery (Fig. 177-2).

TABLE 177-2. Proposed Treatments in the Literature for Occipital Neuralgia Drugs Acupuncture34 Wearing a cervical collar11’33 Local anesthetic infiltration11,35,36 Local steroid infiltration46 Migraine therapy11 Transcutaneous nerve stimulation11 Ligation of the external carotid artery" Ligation of the occipital artery46 Occipital nerve avulsion4,15,34,38,40 Posterior rhizotomy41 Percutaneous neurectomy or rhizolysis39 Root decompression13,37 C2 ganglionectomy45

Figure 177-2. Occipital pain: Diagnostic and therapeutic algorithm.

In patients with spontaneously occurring occipital neural¬ gia, a more extensive search for the causative factors is neces¬ sary. Metabolic and inflammatory causes must be ruled out by the appropriate laboratory investigations. Imaging of the region of the craniocervical junction is important to detect otherwise asymptomatic structural pathology. MRI of the upper cervical spine and the craniovertebral junction can detect abnormalities such as Amold-Chiari malformations, vascular malformations, and tumors that are otherwise asymptomatic. In patients with an underlying structural cause, surgical treatment is directed at the primary abnormality (Fig. 177-2). In patients in whom no underlying structural or metabolic cause can be elicited or in whom there has been an injury that does not require further direct intervention, the initial treatment should be medical. Treatment methods include analgesics, cer¬ vical collars,33 acupuncture,34 and local anesthetic blocks and local steroid infiltration.35,36 One might predict, by analogy to trigeminal neuralgia, that anticonvulsant drugs such as carbamazepine and phenytoin may be helpful for the paroxysmal pain of occipital neuralgia and that anti-inflammatories and muscle relaxants may be help¬ ful in steady nonparoxysmal occipital pain. The appropriate¬ ness of these drugs for painful conditions of the occipital area, however, has not been formally evaluated. Occipital nerve blocks for occipital neuralgia are said to be therapeutic, with many reports of pain relief far outlasting the effect of the local anesthetic.35,36 However, the sensitivity and specificity of local anesthetic blocks, their elicited rate of false¬ positive and false-negative responses, and the rate of pain relief with placebo are unknown. Further, the predictive value of an occipital nerve block for subsequent success with any surgical intervention is unknown. Finally, whereas large volumes of lo¬ cal anesthetics have been used in therapy, diagnostic nerve blocks should be performed with a minimal volume of anes¬ thetic; 0.5 to 1.0 ml should be used to anesthetize only the nerve of interest and not any neighboring nerve branches that also may be involved in mediating pain.

1732

Part 4/Functional Stereotaxis

Surgery of C2 Pathways Patients with occipital neuralgia who fail on medical treatment are candidates for surgical interruption of the nociceptive path¬ ways from the greater occipital nerve terminals to the spinal cord. Both traumatic and nontraumatic occipital neuralgia can be helped by surgery. The surgical options include the release of entrapped C2 nerve branches and neuroablative procedures. The sites of potential entrapment of the C2 nerve and its branches were described above. The decompression procedures have the advantage of not producing denervation. The literature has few reports of long-term successful decompression of C2 elements.1013'17 There has been more experience with interrup¬ tion of nerves transmitting occipital neuralgia pain. These pro¬ cedures include peripheral neurectomy, C2 ganglionectomy, and C2 dorsal rhizotomy. Occipital neurectomies have been carried out in an open fashion and percutaneously under radiological guidance.38 39 This procedure has been said to provide long-term relief of oc¬ cipital neuralgia of traumatic and nontraumatic causes in some patients15-24'34-38 but not others.4041 Oh and associates40 treated 31 patients with occipital neuralgia with occipital neurectomy. They reported an initial 84 percent good response rate. At later follow-up, only 52 percent of the patients continued to be painfree. In another series, 18 of 30 patients had an “excellent” re¬ sult with surgery.24 The advantage of occipital neurectomy is that it is minimally invasive and can be carried out under local anesthesia. Neurectomies have the disadvantage, however, of allowing peripheral nerve regeneration, with the potential for pain recurrence. Peripheral neurectomies also leave proximal neural elements, which can be the site of pathology, intact and free, at least in theory, to generate ongoing dysfunction. Avulsion of the proximal nerve segments addresses this issue but can be associated with the unwanted complication of a spinal cord avulsion injury. Dorsal intradural rhizotomies, by contrast, are designed to interrupt the central process of the dorsal root ganglion. In a survey of 60 cases, Loeser and coworkers42 reported that ap¬ proximately 50 percent of patients with occipital neuralgia ben¬ efited from C2 dorsal rhizotomy. It must be emphasized, how¬ ever, that this is a more elaborate procedure than occipital neurectomy, with a higher surgical risk and with uncertain long-term benefit. Further, there is evidence in humans that some nociceptive fibers enter the cord through the anterior rootlets.4’44 Division of the posterior rootlets would in theory leave afferents traveling in the anterior roots free to continue to transmit nociceptive inputs to second-order neurons. This may explain the high failure rate with this procedure. C2 ganglionectomy overcomes some of the problems of neurectomies and rhizotomies. Because ganglionectomy re¬ moves the neuronal cell bodies, C2 sensory denervation is complete and regeneration of the C2 peripheral nerve processes is not possible. Although percutaneous procedures have been performed,19 the author prefers an open microsurgical resection of the C2 ganglion under direct vision. The operation is done under general anesthesia with exposure of the C1-C2 inter¬ space on the affected side. It is sometimes necessary to remove the medial inferior margin of the Cl arch if it covers the C2 ganglion. The ganglion is immersed in a venous plexus that is

easily dealt with via bipolar coagulation and the application of gelatin sponges. The neural elements are divided proximal and distal to the ganglion. Preliminary observations suggest that microsurgical C2 ganglionectomy is highly effective (approxi¬ mately 90 percent of the cases) for occipital neuralgia charac¬ terized by lancinating pain but not for other occipital pain syn¬ dromes without the shooting pain component45 All ablative peripheral nerve procedures for occipital neu¬ ralgia produce an area of sensory loss in the scalp. In most pa¬ tients, this is imperceptible except on physical examination. Certain patients are aware of the scalp numbness and tend to avoid lying on the denervated side. A dreaded potential compli¬ cation of the procedure is the generation of a deafferentation pain syndrome analogous to anesthesia dolorosa after trigemi¬ nal nerve ablative surgery. Of the 50 patients seen in our clinic with occipital pain, 2 had spontaneous burning pain in the C2 dermatome with touch-evoked pain (allodynia) and hyperpathia characteristic of neural injury with partial deafferenta¬ tion. In one patient, this pain syndrome occurred spontaneously after a cervical extension injury; in the other, it followed a per¬ cutaneous thermocoagulative occipital neurectomy.

CONCLUSION Occipital pain has many causes and comes in many forms. Only patients with lancinating pain have occipital neuralgia caused by a pathological process intrinsic to the C2 elements or branches. The fact that these patients may have sensory abnor¬ malities in the C2 distribution also speaks for a primary dys¬ function of neural elements. In contrast, in nonneuralgic occip¬ ital pain, the nerves of the upper cervical and sometimes facial dermatomes are simply transmission lines relaying information about the state of affairs in the peripheral sensory field. These conditions are easily distinguished from occipital neuralgia, es¬ pecially by the lack of the shooting component of the pain. This distinction is important because nonneuralgic occipital pains have a different etiology, and surgical ablation of C2 pathways is inappropriate. All patients with occipital neuralgia for which a medical or structural cause has been ruled out are initially treated conserv¬ atively with rest, medication, and local anesthetic blocks. Those who fail on medical therapy and have lancinating occip¬ ital pain as a major feature are candidates for interruption of the C2 pathways. A neurosurgeon faced with a patient with med¬ ically intractable occipital neuralgia has a choice of several sur¬ gical procedures. Ablative surgery in the peripheral nervous system pathways can be aimed at the terminal nerve branches, the dorsal rootlets, or the C2 ganglion. Each of these surgical procedures can be effective in relieving occipital pain. Only ganglionectomy removes the neuronal cell bodies to com¬ pletely interrupt the C2 sensory pathway and prevent axonal re¬ generation. All ablative procedures, however, can produce a deafferentation pain syndrome. Because there have not been prospective trials of any of these surgical procedures, it is not possible to assess their safety and efficacy critically or recom¬ mend one as superior to the others. The neurosurgeon should assess each patient individually and determine which proce¬ dure he or she is most comfortable with.

Chapter 177/Treatment of Occipital Neuralgia

References 1.

2. 3. 4.

5.

6.

7.

8.

9.

Rhoton AL, Oliveira E: Microsurgical anatomy of the region of the foramen Magnum, in Wilkins RH, and Rengachary SS (eds): Neuro¬ surgery Update I. New York: McGraw-Hill, 1990, pp 434-460. Bogduk N: The anatomy of occipital neuralgia. Clin Exp Neurol 17:167-184, 1980. Bogduk N: The clinical anatomy of the cervical dorsal rami. Spine 7:319-330, 1982. Chudler EH, Foote WE, Poletti CE: Responses of cat Cl spinal cord dorsal and ventral horn neurons to noxious and nonnoxious stimula¬ tion of the head and face. Brain Res 555:181-192, 1991. Goadsby PJ, Zagami AS, Lambert GA: Neural processing of craniovascular pain: A synthesis of the central structures involved in mi¬ graine. Headache 31:365-371, 1991. Knox DL, Mustonen E: Greater occipital neuralgia: An ocular pain syndrome with multiple etiologies. Trans Acad Ophthal Otol 79: 513-519, 1975. Rosenberg WS, Swearingen B, Poletti CE: Contralateral trigeminal dysaesthesias associated with second cervical nerve compression: A case report. Cephalalgia 10:259-262, 1990. Sessle BJ, Hu JW, Amano N, Zhong G: Convergence of cutaneous, tooth pulp, visceral, neck and muscle afferents onto nociceptive and non-nociceptive neurones in trigeminal nucleus caudalis (medullary dorsal horn) and its implications for referred pain. Pain 27:219-235, 1986. Sjaastad O, Fredricksen TA, Stolt-Nielsen A: Cervicogenic headache, C2 rhizopathy, and occipital neuralgia: A connection? Cephalalgia

23.

24. 25. 26. 27. 28.

29.

30. 31.

32.

33. 34.

10.

6:189-195, 1986. Poletti CE: C2 and C3 pain dermatomes in man. Cephalalgia 11:

11.

155-159, 1991. Hammond SR, Danta G: Occipital neuralgia. Clin Exp Neurol 15: 36.

12.

258-270, 1978. Schultz DR: Occipital neuralgia. J Am Osteopath Assoc 76:335-343, 1977. Poletti CE, Sweet WH; Entrapment of the C2 root and ganglion by the atlanto-epistrophic ligament: Clinical syndrome and surgical anat¬

37.

13.

14. 15. 16. 17.

18.

19. 20.

21. 22.

omy. Neurosurgery 27:288-291, 1990. Hunter CR, Mayfield FH: Role of the upper cervical roots in the pro¬ duction of pain in the head. Am J Surg 48:743-752, 1949. Keith WS: “Whiplash”: Injury of the 2nd cervical ganglion and nerve. Can J Neurol Sci 13:133-137, 1986. Weinberger LM: Cervico-occipital pain and its surgical treatment: The myth of the bony millstones. Am J Surg 135:243-247, 1978. Hildebrandt J, Kansen J: Vascular compression of the C2 and C3 root—yet another cause of chronic intermittent hemicrania? Ceph¬

35.

38.

39. 40. 41. 42.

alalgia 4:167-170, 1984. Jansen J, Markakis E, Rama B, Hikdebrandt J: Hemicranial attacks or permanent hemicrania—a sequel of upper cervical root compression. Cephalalgia 9:123-130, 1989. Hadden SB: Neuralgic headache and facial pain. Arch Neurol Psychiatry 43:405^109, 1940. International Headache Society, Headache Classification Committee: Classification and diagnostic criteria for headache disorders, cranial neuralgias and facial pain. Cephalalgia 8(suppl)7:l-96, 1988. Scott M: Occipital neuralgia. Penn Afed71:85-88, 1968. Evans RW: Some observations on whiplash injuries (Review). Neurol Clin North Am 10:975-997, 1992.

43. 44. 45.

46.

1733

Shoji A, Nakagawa H, Harano H, et al: CT findings and surgical treatment of atlanto-axial rotatory fixation: A case report. No Shinkei Geka 12:987-992, 1984. Murphy JP: Occipital neurectomy in the treatment of headache. Maryland State Med J 18:62-66, 1969. Kerr FWL: A mechanism to account for frontal headache in cases of posterior fossa tumors. JNeurosurg 18:605-609, 1961. Ehni G, Benner B: Occipital neuralgia and the Cl-2 arthrosis syn¬ drome. J Neurosurg 61:961-965, 1984. Ehni G, Benner B: Occipital neuralgia and the C1-C2 arthrosis (let¬ ter). N Engl J Med 310:127, 1984. Graff-Radford SB, Jaeger B, Reeves JL: Myofascial pain may pre¬ sent clinically as occipital neuralgia. Neurosurgery 19:610-613, 1986. Star MJ, Curd JG, Thorne RP: Atlantoaxial lateral mass osteoarthri¬ tis: A frequently overlooked cause of severe occipitocervical pain. Spine 6(suppl):S71-76, 1992. Perelson HN: Occipital nerve tenderness: A sign of headache. South Med J 40:653-656, 1947. Smith DL, Lucas LM, Kumar KL: Greater occipital neuralgia: An unusual presenting feature of neurosyphilis. Headache 27:552-554, 1987. Sharma RR, Parekh HC, Prabhu S, et al: Compression of the C-2 root by a rare anomalous ectatic vertebral artery: Case report. J Neurosurg 78:669-672, 1993. Dugan ME, Locke S, Gallagher JR: Occipital neuralgia in adoles¬ cents and young adults. N Engl J Med 267:1166-1172, 1962. Xie Z: 51 cases of occipital neuralgia treated with acupuncture. Tradit Chin Med 12:180-181, 1992. Bogduk N: Local anesthetic blocks of the second cervical ganglion. A technique with application in occipital headache. Cephalalgia 1:41-50, 1981. Gawel MJ, Rothbart PJ: Occipital nerve block in the management of headache and cervical pain. Cephalalgia 12:9-13, 1992. Poletti CE: Proposed operation for occipital neuralgia: C-2 and C-3 root decompression: Case report. Neurosurgery 12:221-224, 1983. Bovim G, Fredriksen TA, Stolt-Nielsen A, Sjaastad O: Neurolysis of the greater occipital nerve in cervicogenic headache: A follow up study. Headache 32:175-179, 1992. Koch D, Wakhloo AK: CT-guided chemical rhizotomy of the Cl root for occipital neuralgia. Neuroradiology 34:451^452, 1992. Oh S, Tok S, Allemann J, et al: Exeresis in occipital neuralgia. Neurochirurgia 26:47-50, 1983. White JC, Sweet WH: Pain and the Neurosurgeon: A Forty Year Experience. Springfield. IL: Charles C Thomas, 1969, pp 303—343. Loeser JD, Sweet WH, Tew JM, et al: Neurosurgical operations in¬ volving peripheral nerves, in Bonica J, Loeser JD, Chapman CR, and Fordyce WE (eds): The Management of Pain. Malvern, PA: Lea & Febiger, 1990, p 2050. Coggeshall RE: Afferent fibers in the ventral root. Neurosurgery 4:443^448, 1979. Hosobuchi Y: The majority of unmyelinated afferent axons in human ventral roots probably conduct pain. Pain 8; 167-180, 1980. Lozano AM, Vanderlinden G, Rothbart P: Microsurgical C2 ganglionectomy for chronic intractable occipital pain (abstract). J Neurosurg 80:407A^408A, 1994. Mathur JG: Treatment of occipital neuralgia (letter). Med J Aust 2:102, 1980.

CHAPTER

1 7 8

TREATMENT OF HEADACHE

Ninan T. Mathew

The International Headache Society classifies headache disor¬ ders into primary and secondary disorders.1 Table 178-1 lists the primary headache disorders.

ritability, increased appetite, craving for sweets, or excessive yawning, depression, sleepiness, and tiredness, occurs in 30 percent of patients. These symptoms may precede the attack by 12 to 24 h. The prodrome phase may be followed by the aura phase, which consists of specific visual or neurological symp¬

MIGRAINE

toms. The headache phase is the most prominent part of the mi¬ graine attack. The headache is predominantly unilateral in at least 50 percent of patients, although it can be bilateral. It also may start on one side and switch to the other side. A pulsating quality of the head pain is seen in approximately 50 percent of these patients. Nonpulsating headache does not exclude migraine. The headache usually lasts from 4 to 72 h, and occa¬ sionally lasts longer. It is associated with gastrointestinal symptoms such as nausea and/or vomiting and diarrhea in 90 percent of patients. Heightened sensory perception, including phonophobia, photophobia, and increased sensitivity to smell, occurs during the attacks. Patients usually want to be left alone,

In an epidemiological study of migraine2 using a self-adminis¬ tered questionnaire filled out by 23,611 individuals from 9507 American households, 17.6 percent of women and 5.7 percent of men between ages 12 and 80 years had headaches that met a definition of migraine that was based on a modification of the International Headache Society’s criteria.1 Projections from this study to the country as a whole indicate that 18 million women and 5.6 million men over age 12 suffer from severe mi¬ graine headaches. Diagnostic criteria for migraine with and without an aura are given in Table 178-2. Among these individuals, a projected 8.7 million women and 2.6 million men have moderate to severe disability from headache.2 Fifty-five percent of men and 72 percent of women never consult a doctor for a headache problem.3 Among those who seek medical attention, 44.5 percent of men and 46.3 per¬ cent of women consult family practitioners. With increasing awareness of headache as a biological problem, it is expected that a larger number of migraine patients will seek help for this condition. Migraine can occur with or without an aura (warning symp¬ toms). The most common aura is visual in nature, although neurological auras such as hemisensory disturbances, hemiparesis, dysphasia, and changes in memory and state of con¬ sciousness occur occasionally. Migraine without aura is far more common than migraine with aura; approximately 30 per¬ cent of migraine attacks are associated with aura. The same person can have migraine with aura and migraine without aura at different times. Migraine is predominantly a disease of fe¬ males. Identification of trigger factors for attacks of migraine helps in making the diagnosis. The trigger factors are listed in Table 178-3. The severity and frequency of attacks vary over time. Cyclical exacerbations of migrainous episodes are possi¬

and the attacks can be very disabling. The headache of migraine is of moderate or severe intensity (inhibits or prohibits daily activities) as opposed to episodic tension-type headache, in which the intensity is mild to moder¬ ate (may inhibit but does not prohibit daily activities). The headache of migraine is aggravated by any activity that in¬ creases stroke volume or intracranial pressure, such as climb¬ ing stairs, jogging, running, bending down, and coughing. During the headache, at least one of the following characteris¬ tics occurs: (1) nausea and/or vomiting and (2) photophobia and phonophobia. These symptoms are necessary for a diagno¬ sis of migraine. Physical and neurological examinations should rule out any other structural or metabolic condition that can cause headache.

Menstrual Migraine Migraine without aura can occur almost exclusively at a partic¬ ular time in the menstrual cycle. True menstrual migraine oc¬ curs between 2 days before menses and the last day of menses. Migraine also can occur as a part of the late luteal phase disphoric disorder (premenstrual tension). Migraine attacks are not uncommon during ovulation. Menstrual migraine is less re¬ sponsive to prophylactic drug therapy than other types of mi¬

ble during one’s lifetime. A migraine attack is typically episodic, occurring once or twice a month, and is manifested in many phases. The pro¬ drome phase consisting of symptoms of excitation or inhibition of the central nervous system, including elation, excitability, ir¬

graine. Status migrainosus refers to a prolonged migraine attack that usually lasts for more than 72 h and is associated with nau-

1735

1736

Part 4/Functional Stereotaxis

TABLE 178-1. International Headache Society Classifica¬ tion of Primary Headache Disorders

TABLE 178-2. International Headache Society Criteria for Diagnosis of Migraine

1.

1.1

2.

3.

4.

Migraine 1.1 Migraine without aura 1.2 Migraine with aura 1.2.1 Migraine with typical aura 1.2.2 Migraine with prolonged aura 1.2.3 Familial hemiplegic migraine 1.2.4 Basilar migraine 1.2.5 Migraine aura without headache 1.2.6 Migraine with acute-onset aura 1.3 Ophthalmoplegic migraine 1.4 Retinal migraine 1.5 Childhood periodic syndromes that may be precursors to or associated with migraine 1.5.1 Benign paroxysmal vertigo of childhood 1.5.2 Alternating hemiplegia of childhood 1.6 Complications of migraine 1.6.1 Status migrainosus 1.6.2 Migrainous infarction 1.7 Migrainous disorder not fulfilling the above criteria Tension-type headache 2.1 Episodic tension-type headache 2.1.1 Episodic tension-type headache associated with disorder of pericranial muscles 2.1.2 Episodic tension-type headache not associated with disorder of pericranial muscles 2.2 Chronic tension-type headache 2.2.1 Chronic tension-type headache associated with disorder of pericranial muscles 2.2.2 Chronic tension-type headache not associated with disorder of pericranial muscles 2.3 Headache of the tension type not fulfilling the above criteria Cluster headache and chronic paroxysmal hemicrania 3.1 Cluster headache 3.1.1 Cluster headache periodicity undetermined 3.1.2 Episodic cluster headache 3.1.3 Chronic cluster headache 3.1.3.1 Unremitting from onset 3.1.3.2 Evolved from episodic 3.2 Chronic paroxysmal hemicrania 3.3 Cluster headache-like disorder not fulfilling the above criteria Miscellaneous headaches not associated with a structural lesion 4.1 Idiopathic stabbing headache 4.2 External compression headache 4.3 Cold stimulus headache 4.3.1 External application of a cold stimulus 4.3.2 Ingestion of a cold stimulus 4.4 Benign cough headache 4.5 Benign exertional headache 4.6 Headache associated with sexual activity 4.6.1 Dull type 4.6.2 Explosive type 4.6.3 Postural type

sea, vomiting, and dehydration. These patients usually are ex¬ tremely sick and dehydrated and may have to be hospitalized. By the time they come to the emergency room, they may have

1.2

Migraine without aura Previously used term: common migraine Description: Idiopathic, recurring headache disorder manifesting in attacks lasting 4—72 h. Typical characteristics of headache are unilateral location, pulsating quality, moderate or severe intensity, aggravation by routine physical activity, association with nausea, and photo- and phonophobia. Diagnostic criteria: A. At least 5 attacks fufilling B-D B. Headache attacks lasting 4-72 h (untreated or unsuc¬ cessfully treated) C. Headache has at least two of the following charac¬ teristics: 1. Unilateral location 2. Pulsating quality 3. Moderate or severe intensity (inhibits or prohibits daily activities) 4. Aggravation by walking stairs or similar routine physical activity D. During headache, at least one of the following: 1. Nausea and/or vomiting 2. Photophobia and phonophobia E. At least one of the following: 1. History and physical and neurological examinations do not suggest one of the disorders listed in groups 5-11 2. History and/or physical and/or neurological exami¬ nations do suggest such a disorder, but it is ruled out by appropriate investigations 3. Such disorder is present, but migraine attacks do not occur for the first time in close temporal relation to the disorder Migraine with aura* Previously used term: classic migraine Description: Idiopathic, recurring disorder manifesting by attacks of neurological symptoms unequivocally localizable to cerebral cortex or brain stem, usually gradually developed over 5-20 min and usually lasting less than 60 min. Headache, nausea, and/or photophobia usually follow neurological aura symptoms directly or after a free interval of less than an hour. The headache usually lasts 4-72 h but may be completely absent (1.2.5). Diagnostic criteria: A. At least two attacks fulfilling B B. At least three of the following four characteristics: 1. One or more fully reversible aura symptoms indicating focal cerebral cortical and/or brain stem dysfunction. 2. At least one aura symptom develops gradually over more than 4 min or two or more symptoms occur in succession. 3. No aura symptom lasts more than 60 min. If more than one aura symptom is present, the accepted duration is proportionally increased. 4. Headache follows aura with a free interval of less than 60 min. (It may also begin before or simul¬ taneously with the aura.) C. At least one of the following: 1. History and physical and neurological examinations do not suggest one of the disorders listed in groups 5-11

Chapter 178/Treatment of Headache

TABLE 178-2. 2.

3.

(Continued)

TABLE 178-4. International Headache Society Diagnostic Criteria for Cluster Headache

History and/or physical and/or neurological exami¬ nations do suggest such disorder, but it is ruled out by appropriate investigations Such a disorder is present, but migraine attacks do not occur for the first time in close temporal relation to the disorder

A. B. C.

*Aura as used here does not necessarily imply that it precedes the headache or imply a relationship with epilepsy.

already tried large quantities of analgesic medications and/or ergotamine with no benefit.

Cluster Headache Cluster headache is predominantly a disease of males. These headaches are almost always unilateral and short-lived, usually lasting about 45 min to an hour. Multiple episodes occur on a daily basis for periods of 2 or 3 months, with remissions lasting for a number of months to years, with headaches returning in a cluster fashion again for 2 or 3 months. Cluster pattern and re¬ missions are characteristics of the disease, even though in ap¬ proximately 10 percent of patients there are no remissions (chronic cluster headache). Associated with the pain arc auto¬ nomic features such as watering from the eyes, redness of the eyes and congestion of the conjunctiva, and ipsilateral stopping up of the nostrils during the attack. The International Headache Society diagnostic criteria are given in Table 178-4.

Episodic Tension-Type Headache The most common type of headache is the episodic tensiontype headache, for which patients rarely consult a doctor. This type of headache usually is pressing or tightening in quality, bilateral, mild to moderate in severity, and occasionally associ¬ ated with very mild nausea, photophobia, or sonophobia. There is no vomiting, and the patients are able to carry on with their activities. The headache is not aggravated by physical activity.

TABLE 178-3.

Triggers of Migraine

Common Factors Stress, worry, anxiety Menstruation Oral contraceptives Certain foodstuffs and alcohol Hunger Lack of sleep Glare, dazzle Weather or ambient temperature changes Physical exertion, fatigue Head trauma

1737

Less Common Factors High humidity Excessive sleep High altitude Excessive vitamin A Drugs: nitroglycerine, reserpine, estrogens, hydralazine. ranitidine Pungent odors Fluorescent lighting Allergic reactions Cold foods Refractory error

D. E.

At least live attacks fulfilling B-D Severe unilateral orbital, supraorbital, and/or temporal pain lasting 15 to 180 min untreated Headache associated with at least one of the following signs, which have to be present on the pain side: 1. Conjunctival injection 2. Lacrimation 3. Nasal congestion 4. Rhinorrhea 5. Forehead and facial sweating 6. Miosis 7. Ptosis 8. Eyelid edema Frequency of attacks from I every other day to 8 per day At least one of the following: 1. History and physical and neurological examinations do not suggest one of the disorders listed in groups 5-11 2. History and/or physical and/or neurological examinations do suggest such a disorder, but it is ruled out by appropriate investigations 3. Such a disorder is present, but cluster headache does not occur for the first time in close temporal relation to the disorder

Chronic Daily Headache Even though the term chronic daily headache is not included in the International Headache Society classification, from a prac¬ tical point of view it is important. Chronic tension-type headaches are one of the types of chronic daily headache. The clinical features of chronic tension-type headache are essen¬ tially the same as those of Ihe episodic tension-type except that the headache occurs more than 180 days a year. The comorbid factors often seen in chronic tension-type headache include anxiety, depression, excessive intake of pain medications, ab¬ normal personality profiles, inadequate personality, and re¬ pressed anger. Both episodic and chronic tension-type head¬ aches can be associated with pericranial muscle tenderness and a low pain threshold. Digital palpation of the pericranial mus¬ cles, including the neck muscles, reveals increased stiffness and tenderness. The migraine chronic tension-type headache complex (mixed headache) manifests as daily or nearly daily headaches that show features of migraine and chronic tensiontype headache in a mixed form. Many patients have episodes of severe headache with migrainous features, with interictal tension-type headache occurring very frequently. Many of these patients have a history of episodic migraine that gradu¬ ally evolves into daily headache (transformed migraine).4 It sometimes becomes difficult to identify the termination of one type of headache and the beginning of the other type. There are two distinguishable forms in this variety of headache: those associated with analgesic and ergotamine overuse and those not associated with drug overuse. It is well known to specialists in headache that daily or nearly daily use of analgesics and ergotamine in patients with migraine can lead to a chronic daily intractable headache condition that is referred to as an analgesic/ergotamine rebound headache. It is important to look for this disorder in any patient who presents with chronic

1738

Part 4/Functional Stereotaxis

headaches. Analgesic/ergotamine rebound headache is refrac¬ tory to regular treatments. The patients show many associated features, such as early morning awakening with severe headaches; sleep disturbances; tolerance to pain medications over a period of time, requiring larger quantity of medications; and manifestation of withdrawal symptoms when the medica¬ tions are stopped. In addition, prophylactic antimigraine med¬ ications become ineffective as long as the patients are on daily pain medications or ergotamine.

POSTTRAUMATIC HEADACHE Headache can follow relatively minor head and neck trauma, and previously dormant migraine can be aggravated by trauma. Patients with posttraumatic headache usually manifest a mixed form of migraine and tension-type headache with considerable detectable neck muscle spasm and pericranial tenderness. Most headache specialists believe that the various clinical headache types are different manifestations of the same pri¬ mary disorder, which presents as migraine with aura at one end of the spectrum, chronic tension-type headache at the other, and a combination of migraine without aura and tension-type headache in the middle.5 Many patients who present with chronic daily headaches have what is described as “trans¬ formed migraine”; that is, they report a history of clear-cut episodic migraine with increasing frequency of headache until they eventually end up with daily or nearly daily headaches, many of which retain features of migraine.4

BIOLOGICAL BASIS OF MIGRAINE PHARMACOTHERAPY

Neurogenic inflammation is triggered by elaboration of va¬ soactive polypeptides such as substance P, neurokinin A, and calcitonin gene-related polypeptide (CGRP). The neurogenic inflammation consists of platelet aggregation, protein extrava¬ sation, and vasodilatation. These changes initiate nociception through perivascular C fibers. Stimulation of the cranial vascular systems, such as the su¬ perior sagittal sinus, results in an increase in CGRP in the jugular blood in experimental animals.9 Goadsby and Edvinsson10 showed that during a migraine attack the level of CGRP in the external jugular vein increases. These observations undoubtedly prove that the trigeminal vascular system is involved in acute migraine attacks. The ulti¬ mate initiating trigger of a migraine attack may reside in the brain, which in turn activates the trigeminal vascular system.

Central Neuronal Hyperexcitability in Migraine Various observations suggest a CNS origin of migraine. A cen¬ tral neuronal hyperexcitability probably exists in migraine, as evidenced by prominent photic driving during electroen¬ cephalography," augmented high-amplitude visually evoked responses,12 increased contingent negative variation ampli¬ tude,13 and magnetoencephalographic abnormalities of largeamplitude waves with suppression in the direct current shifts.14 Glutamate, an excitatory amino acid, has been implicated in the pathogenesis of migraine, since it may play a role in spreading depression experimentally.14 Abnormalities in platelet glutamate levels have been reported in patients with migraine.15

Brain Stem Migraine Generator The two basic theories that have been postulated to explain the mechanisms of migraine are vascular and neurogenic, with considerable debate about whether migraine is primarily a cephalic vascular disorder or a disorder of the central nervous system (CNS). The vascular theory of migraine proposes that intracerebral vasoconstriction accounts for the aura or migraine, while in¬ tracranial and extracranial vasodilation accounts for the head pain. A lack of correlation between the observed changes in cerebral blood flow6-7 and the occurrence of head pain in pa¬ tients who have migraine with aura has led to the conclusion that vascular reactions may be associated with symptoms of headache but do not necessarily trigger an attack. Instead, re¬ cent clinical and experimental evidence strongly points to mi¬ graine as a disorder initiated in the brain and accompanied by secondary changes in the perivascular nerve endings of the cephalic circulation that result in neurogenic inflammation.

Brainstem structures that are implicated in the pathogenesis of migraine and have relevance to pharmacotherapy include the dorsal raphe nuclei and periaqueductal gray matter. Raskin and coworkers16 indicated that perturbation or dysfunction of the dorsal raphe nuclei, resulting in an increased firing rate of the raphe cells, may be one of the fundamental abnormalities in migraine. Sleep, which reduces the firing rate of dorsal raphe cells, is known to relieve migraine headache. Recently, using positron emission tomography (PET) scanning, increased per¬ fusion of the upper brain stem area close to the dorsal raphe and periaqueductal gray matter was demonstrated in patients during migraine attacks.17 These observations suggest the up¬ per brain stem as a generator of migraine. The dorsal raphe nuclei are one of the major binding sites of dihydroergotamine mesylate (DHE), a very effective therapy lor acute migraine.18 The dorsal raphe nuclei contain large numbers of serotoninergic cells, suggesting that DHE and re¬ lated medications may act through the serotoninergic system.

The Trigeminal Vascular System A series of studies by Moskowitz and colleagues8 established the trigeminal vascular system as the common final pathway lor head pain. The perivascular C fibers of the trigeminal nerve in the cephalic circulation are the site of neurogenic inflamma¬ tion that can be produced by antidromic stimulation of the trigeminal nerve.8

Serotonin and Migraine Serotonin [5-hydroxytryptamine (5-HT)| has long been impli¬ cated in the pathogenesis of migraine. Initial observations in¬ cluded the precipitation of migraine by reserpine, a serotonindepleting agent,19 and relief of migraine by the injection of serotonin even though severe side effects limit its clinical use.20

Chapter 178/Treatment of Headache

Serotonin metabolites are increased in urine during an attack,21 and plasma serotonin levels fall just before a migraine attack.22 Medications that act on the serotonin system have long been used in the treatment of migraine. Table 178-5 shows the chronological order in which serotonin-related medications have been used in migraine. In recent years, there has been a great deal of interest in serotonin pharmacology. At lease three major classes of serotonergic receptors have been identified: 5HTp 5-HT2, and 5-HTy 5-HTm and 5-HT|A are probably the most relevant serotonin receptors in relation to the pharmacol¬ ogy of an acute migraine attack. In general, it appears that medications with an affinity for 5HT, receptors are effective in the treatment of acute migraine attacks and that medications that have an antagonist affinity for 5-HT2 are useful in migraine prophylaxis.23 The relative affini¬ ties for 5-HT! are shown in Table 178-6. It has been shown that pretreatment with sumatriptan and DHE, both of which are 5-HTj agonists, can block the neuro¬ genic inflammation that can be induced by antidromic stimula¬ tion of the trigeminal nerve.24’25 In addition, these medications reduce or prevent the increase in CGRP in the jugular blood induced by craniovascular stimulation9 and during migraine attacks.26 Researchers do not fully agree on the mechanism of action of 5-HT, agonists in migraine. On the basis of their experi¬ ments, Moskowitz and colleagues strongly believe that 5-HT|D receptors are located on the C fibers of the perivascular nerve endings. The agonistic action of sumatriptan and ergot alka¬ loids on 5-HT]D receptors blocks the neurogenic inflammation at the level of the nerve ending. They also have shown that 5HT,d receptor agonists, in addition to blocking neurogenic in¬ flammation, may reduce pain transmission through the trigemi¬ nal nerve; this conclusion was based on experiments using c-fos markers.27 However, Humphrey and coworkers28 believe that the effect of sumatriptan is primarily due to craniovascular vasoconstriction and closure of the arteriovenous anastomosis, which is postulated to be one of the mechanisms of migraine head pain.29 It should be noted that sumatriptan has very little peripheral vasoconstrictive effect and is predominantly a selec¬ tive craniovascular agent.

TREATMENT OF ACUTE MIGRAINE ATTACKS Factors that determine the choice of medications for acute mi¬ graine are time to reach maximum headache (time to peak),

TABLE 178-5. Chronological Order in Which 5-HT Medica¬ tions Were Introduced into Migraine Therapy Serotonin-Related Drug Ergotamine Dihydroergotamine Methysergide Cyproheptadine Pizotifen Amitriptyline Sumatriptan

TABLE 178-6. Antimigraine Drug Relative Potencies at 5-HT1D Receptor Subtypes Relative Affinity for 5-HT1D Receptor

Antimigraine Drug Acute Sumatriptan Dihydroergotamine Prophylactic Methysergide Pizotifen, alprenolol, amitriptyline, cyproheptadine, nifedipine, pindolol, propranolol, verapamil, timolol, atenolol, or diltiazem

17 19 120

>1000

Adapted from Peroutka SJ: Development of 5-hydroxytriptamine receptor pharmacology in migraine. Neurol Clin 8:831, 1990. With permission.

severity, and associated symptoms such as nausea and vomit¬ ing. The frequency of attacks combined with their severity de¬ termine prophylactic pharmacotherapy. The main principle of the treatment of acute migraine is the use of medications early in an attack. This is especially relevant for oral medications, which should be administered long before nausea and vomiting set in. For practical purposes, it may be worthwhile to divide acute migraine attacks into different treat¬ ment categories, depending on the severity of the attack (Table 178-7).

Mild to Moderate Attacks For mild to moderate attacks, simple analgesics such as as¬ pirin and acetaminophen may be all that is necessary. There is an associated gastroparesis in migraine that results in poor ab¬ sorption of aspirin from the large intestine.30 Phenothiazines such as promethazine, which are commonly used as antiemet¬ ics, have a tendency to reduce gastric motility further, resulting in delayed absorption of aspirin. Therefore, metoclopramide, which increases gastric motility and enhances the absorption of aspirin, is the antiemetic of choice in patients with acute migraine attacks.

TABLE 178-7.

Aborting Headache Treatment Options

Time to Peak, h 3

Options • • • •

Sumatriptan 6 mg subcutaneous DHE 1 mg intramuscular Nasal butorphanol 1-2 mg Sumatriptan tablets 50 mg; repeat 50 mg at 2 h • Ergotamine suppository 2 mg (Wigraine, Cafergot) • DHE nasal spray 2 mg • Isometheptene compounds (Midrin); 2 capsules, repeat 1 in If h • Ergotamine tablets 2 mg or ergotamine 1 mg with naproxen 550 mg or meclofenamate 200 mg • Sumatriptan 50-mg tablets; repeat 1 in 2 h

1740

Part 4/Functional Stereotaxis

Nonsteroidal anti-inflammatory drugs (NSAlDs) such as rapidly absorbed naproxen sodium are effective for the abor¬ tive treatment of mild to moderate cases of migraine. Isometheptene mucate (available in combination with dichloralphenazone and acetaminophen) is also a very useful agent for abortive migraine treatment. Isometheptene is a sympath¬ omimetic vasoconstrictor, and its exact mechanism of action is unknown. Since it is well tolerated by most people, it is the drug of choice for mild to moderate attacks.

Moderate to Severe Attacks Until recently, ergotamine tartrate was the drug of choice for moderate to severe episodes of migraine. Ergotamine, alone or in combination with caffeine, is available in oral and rectal forms. If the patient is not nauseated, oral ergotamine is useful and can be combined with NSAIDs such as naproxen sodium and meclofenamate. Meclofenamate alone has been shown to have an antimigraine effect comparable to that of ergotamine,31 and we find this combination useful. Injectable ketorolac has been very effective in some patients with moderate to severe migraine and has been recommended as a practical alternative to narcotic injections.32 If the patient is nauseated, metoclopramide is often the antiemetic of choice. Since metoclopramide is a dopamine ago¬ nist, it may cause extrapyramidal reactions in the form of akathisia and restlessness.

Drugs Used to Treat Migraine Sumatriptan Sumatriptan is a 5-HTm agonist that blocks neurogenic inflam¬ mation at the trigeminal vascular system and causes vasocon¬ striction. It is available in tablet and subcutaneous forms. Sumatriptan has become the drug of choice in the treatment of moderate to severe cases of migraine. Our knowledge of sumatriptan use in acute migraine is based on major clinical trials.33-35 With subcutaneous injection, the onset of relief occurs in 10 to 15 min; 50 percent of patients get relief in 30 min. More than 80 percent show relief in less than 2 h, and 60 percent become pain-free in 2 h. With tablets, the onset of relief occurs in 30 min. Sixty percent of these pa¬ tients show improvement in I h, and 75 percent by 4 h. Nearly 50 percent are pain-free in 4 h. Sumatriptan is effective any time during an attack, unlike ergotamine, which is most effective in the early part of an at¬ tack. Another important advantage of sumatriptan over ergota¬ mine is that the accompanying symptoms of migraine, such as nausea and vomiting, are relieved by sumatriptan, obviating the need for a separate antiemetic agent. With sumatriptan, patients are able to return to their normal activities very rapidly. Sumatriptan studies have shown that most of the adverse events are mild to moderate, occur early after the treatment, are of short duration, and resolve spontaneously. Electrocardio¬ gram monitoring showed no more abnormalities with sumatrip¬ tan than with placebo. There are very few adverse reactions of any consequence, and as the data indicate, this is a relatively safe drug from a cardiovascular point of view. Typical adverse

effects after subcutaneous injection of sumatriptan include tingling, a warm or hot feeling, heaviness of the upper part of the body, flushing, and a burning sensation of the head, but all these symptoms are mild and transient. Transient or pressure symptoms in the chest occur in 3 to 5 percent of these patients. There is no evidence that the pressure is of cardiac origin. In the postmarketing surveillance, the incidence of cardiac is¬ chemia has been extremely low, occurring in 1 in 1 million mi¬ graine attacks treated with sumatriptan. Some of the cardiac symptoms reported were related to the use of sumatriptan in patients with preexisting cardiac disease or concomitant risk factors. Misinterpretation of clinical symptomatology (e.g., misdiagnosing a stroke in evolution for a migraine attack) and inappropriate dosing were also factors in previously reported complications of therapy with sumatriptan. For subcutaneous injection, a 6-mg dose is the most effec¬ tive and has the fewest side effects. For oral dosing, 25- or 50mg tablets are used. Approximately 35 percent of patients have recurrence of the pain in 24 h, but data indicate that sumatrip¬ tan can be repeated in such cases with prompt relief of the re¬ currence. A practical way of using sumatriptan is as an injec¬ tion followed by tablets. The injection gives immediate relief and the tablets continue to maintain adequate blood drug lev¬ els, and so pain does not recur within the first few hours.

Dihydroergotamine For the treatment of severe to very severe migraine, parenteral medications may have to be used, since these patients are ex¬ tremely sick with nausea and vomiting. Intravenous DHE is the drug of choice in such a situation. Dihydroergotamine can be combined with intravenous (IV) metoclopramide, prochlorper¬ azine, or chlorpromazine. Dihydroergotamine is a highly effective medication for acute migraine attacks but is underutilized. Its advantages in¬ clude minimal arterial constriction and intravenous administra¬ tion with far less nausea compared with ergotamine. One study comparing DHE with narcotics showed that DHE is superior to meperidine and butorphanol tartrate in the acute treatment of migraine headache in the emergency room.36 No physical dependence has been reported with DHE use. Peak plasma levels are attained in 15 to 45 min with subcuta¬ neous injection, 30 min with intramuscular injection, 2 to 11 min with IV injection, and 30 to 60 min with intranasal admin¬ istration. Self-injection by patients is possible. Dihydroergotamine has an affinity for 5-HT|A and 5-HT|D receptors, and this probably accounts for its antimigraine ef¬ fects. It also has an affinity for 5-HT, adrenergic receptors and dopaminergic receptors. Its affinity for dopaminergic receptors may account for the nausea that can occur as a side effect. The advantage of sumatriptan over DHE is that it has specific affin¬ ity tor 5-HT, receptors only and has no effects on adrenergic or dopaminergic receptors; this accounts for the lack of nausea and vomiting as a side effect. As was discussed earlier. DHE not only acts at the 5-HT; re¬ ceptor sites and the trigeminal vascular system but also is bound to dorsal raphe nuclei and other brain stem serotoninergic nuclei. Therefore, the action may also be central.18 Status migrainosus is defined in the International Headache Society’s classification as a prolonged migraine attack that lasts

Chapter 178/Treatment of Headache

more than 72 h; is associated with nausea, vomiting, and other gastrointestinal (GI) symptoms; and is totally incapacitat¬ ing. The patient usually presents to the physician after having taken fairly large quantities of pain medications and usually is dehydrated. Hospitalization, IV fluids, and repeated injections of intra¬ venous DHE for about 24 to 72 h may be necessary to relieve the headache. Various protocols are available for the use of repetitive injections of DHE.38,39 In all of them, an initial test dose of 0.34 mg of DHE plus 5 mg of metoclopramide or prochlorperazine is given, followed by 0.5 mg of DHE with ei¬ ther of the two antiemetics every 6 h for 48 to 72 h. Most patients are able to tolerate the medications used in these protocols. Intolerance to DHE can occur in a few patients because of severe nausea or vomiting in spite of antiemetics. Very rarely, its use may be limited by acute myalgia involving the lower extremities and numbness or paresthesia. Vasospastic reaction with angina has been reported but is rare. Repetitive IV DHE is the mainstay in the treatment of status migrainosus at present. The concomitant use of narcotics is not recommended. In fact, analgesics and narcotics have no place in the treatment of status migrainosus and very little place in the treatment of recurrent episodes of acute migraine. Frequent use of analgesics and narcotics may result in the transformation of episodic migraine into chronic daily headache.40

ALTERNATIVE THERAPY FOR ACUTE MIGRAINE Intravenous Prochlorperazine Patients who are not responsive to sumatriptan or IV or intra¬ muscular DHE can be given IV prochlorperazine (Compazine).37 Five to 10 mg of Compazine can be given intravenously in an emergency room setting. Dystonic reactions are possible in some patients who receive Compazine and can be counteracted by intramuscular injection of 1 mg of benztropine mesylate (Cogentin). Intravenous chlorpromazine (Thorazine) may also be worth trying in patients who do not respond satisfactorily to sumatriptan or DHE. From 12.5 to 25 mg (0.1 mg/kg) of chlor¬ promazine given in a piggy back IV is effective in many pa¬ tients with acute migraine. Repeat dosing every 15 min up to a total of three doses may become necessary. Orthostatic hy¬ potension is a distinct side effect, and patients have to be moni¬ tored for a while before they are allowed to get up and walk around or go home. They have to be warned about the possibil¬ ity of orthostatic hypotension.

Narcotics and Sedatives in Acute Migraine Most migraine attacks can be manageu without narcotics, using the medications mentioned above. The reasons why narcotics are not preferred in migraines are as follows: 1. Serotonin mechanisms are disturbed in migraine, and med¬ ications such as sumatriptan, ergotamine, and dihydroergotamine are 5-HT|D receptor agonists that reduce the neuro¬ genic inflammation associated with migraine attacks in

2.

3.

1741

addition to their vasoconstrictive effect, whereas narcotics reduce pain without having any specific effects on the neu¬ rogenic inflammation or vasodilatation. Narcotics and analgesics with sedatives may in fact pro¬ duce rebound headache phenomena and perpetuate the chronicity of migraine. With frequent use, habituation occurs.

For these reasons, narcotics are very rarely recommended for acute attacks of migraine. However, in a person who is totally nonresponsive to sumatriptan, ergotamine, DHE, and phenothiazines, one may use parenteral narcotics such as meperidine (Demerol) in a limited way; however, it should not be pre¬ scribed on a routine basis. Combination of analgesics with sedatives A number of preparations are available that contain butalbital with acetaminophen or aspirin and caffeine with or without codeine, including Fiorinal, Fiorinal #3, Fioricet, Fioricet with Codeine, Esgic, Esgic with Codeine, Esgic Plus, and Phrenilin. While these preparations are useful for a person with oc¬ casional migraine, they are certainly not recommended for patients with frequent episodes of migraine or tension-type headache. Not only do these medications have a potential for abuse, they also invariably produce rebound headache phenom¬ ena when used frequently. The excessive use of medications containing butalbital results in lethargy, sleepiness, lack of con¬ centration, and an overall sedated feeling. One of the other ma¬ jor dangers in the use of butalbital-containing medications is that abrupt discontinuation may result in withdrawal phenom¬ ena such as increased headache, nausea, irritability, sleepless¬ ness, and even seizures. Because of these problems with the combination medications containing butalbital, the author does not recommend them for routine use. If one has to use a nar¬ cotic oral pain medication, a combination of acetaminophen with 30 mg of codeine is probably the least controversial.

PROPHYLAXIS OF MIGRAINE HEADACHES Prophylactic Pharmacotherapy The decision to start prophylactic pharmacotherapy, which has to be made on a daily basis, depends totally on the impact of migraine on the patient. This impact depends on the frequency, the severity, the disability headache produces, and the comorbid factors. In general, the following are the broad indications for prophylactic pharmacotherapy: 1. 2.

Two or more attacks per month that are disabling and result in inability to work or function Severe, prolonged, disabling attacks even if they occur less

3. 4. 5. 6.

than twice a month Inability to cope with migraine episodes Failure of abortive therapy Serious side effects from abortive therapy Failure of nonpharmacological approaches

Table 178-8 lists the currently used prophylactic agents for mi¬ graine.

1742

Part 4/Functional Stereotaxis

TABLE 178-8.

Medications Used in the Prophylactic Treatment of Migraine

Medication Beta-adrenergic blocking agents Propranolol (Inderal) Propranolol long-acting (Inderal-LA) Nadolol (Corgard) Timolol (Blocadren) Metoprolol (Lopressor) Pindolol (Visken) Atenolol (Tenormin) Antidepressants Tricyclic antidepressants Amitriptyline (Elavil, Endep) Doxepin (Sinequan, Adapin) Nortriptyline (Aventyl, Pamelor) Imipramine (Tofranil) Desipramine (Pertofrane, Norpramin) Selective serotonin reuptake inhibitors Fluoxetine (Prozac) Sertraline (Zoloft) Paroxetine (Paxil) Monoamine oxidase inhibitors Phenelzine (Nardil) Isocarboxazid (Marplan) Calcium channel blockers Verapamil (Calan, Isoptin, Verelan) Flunarizine (Sibelium)* Diltiazem (Cardizem) Nicardipine (Cardene) Nimodipine (Nimotop) Serotonin antagonists Methysergide (Sansert) Cyproheptadine (Periactin) Pizotifen (Sandomigran)* Anticonvulsants Divalproex sodium (Depakote) Phenytoin (Dilantin) Alpha-adrenergic agonist Clonidine (Catapres)

Dosage

40-160 mg/day in divided doses 60-160 mg once daily 40-160 mg once daily Up to 20 mg twice daily 50-100 mg/day 10-30 mg/day 50-100 mg/day

25-200 mg at bedtime 10-100 mg at bedtime 10-50 mg at bedtime 25-150 mg at bedtime 25-50 mg, at bedtime 20 mg daily in the morning 50 mg at bedtime 20 mg daily in the morning 15 mg three times daily 10 mg four times daily 80-360 mg/day 10-30 mg/day 60-90 mg three times/day 20 mg three times/day 30 mg three times/day 4—8 mg/day 8-16 mg/day

500-1500 mg/day 100-300 mg/day 0.1-0.2 mg three times a day

*Not available in the United States.

Steps before Prophylactic Pharmacotherapy The following steps should precede prophylactic pharmacology: 1 2. 3.

Women of childbearing age should practice contraception, preferably barrier contraception. Vasodilators should be avoided as much as possible. Concomitant daily analgesics should be avoided.

One should be alert to the fact that many of these patients have comorbid disorders, making the treatment difficult and the prognosis less than satisfactory. The comorbidity includes de¬ pression, anxiety, panic episodes, bipolar illness, and neuroticism. Analgesic and ergotamine rebound must be recognized, and those who are on daily analgesics or ergotamine should be detoxified from those medications before prophylactic pharma¬ cotherapy is instituted. It is difficult to assess the success of prophylactic therapy because of variability in migraine fre¬ quency and severity and the tendency for spontaneous im¬

provement for prolonged periods. In addition, it is well known that migraine can come in cycles in an unpredictable fashion, and this also makes the assessment of prophylactic therapy difficult. In some situations, tachyphylaxis to medications is observed. It is important to give adequate time for prophylactic ther¬ apy to work. To judge the effectiveness of any medication used, one should treat the patient at least for 2 to 3 months, particu¬ larly in the case of calcium channel blockers, which should be given for at least 3 months in adequate doses before they are judged to be ineffective. It is always good to start with small doses and gradually increase the dose in accordance with the tolerance of the patient. When patients are withdrawn from prophylactic therapy, this has to be done gradually. Some reasons for prophylactic TREATMENT FAILURE There are several possible reasons for treatment failure:

Chapter 178/Treatment of Headache

1. 2. 3. 4. 5. 6.

Wrong diagnosis Not recognizing comorbidity Not recognizing analgesic rebound phenomena Inadequate dose Inadequate treatment period Unrealistic expectations on the part of the patient as well as the physician

Beta-Adrenergic Blocking Agents Beta-adrenergic blockers are considered the first line of treatment for migraine prophylaxis at present. Propranolol and timolol have been approved by the U.S. Food and Drug Admin¬ istration (FDA), whereas the other agents, such as nadolol, have not been specifically approved. It is better to start with small doses and increase the dose gradually. If a person is not adequately responsive to one particular beta blocker, another can be tried. There is no correlation between the efficacy of beta blockers and their ability to enter the CNS, their membrane stimulating properties, their 5-HT-blocking properties, or beta receptor se¬ lectivity. Beta blockers are best suited for patients with mi¬ graine who are under stress and are anxious. They are suitable for patients with migraine and hypertension. Contraindications and adverse EFFECTS OF BETA BLOCKERS Beta blockers are contraindicated in patients with active asthma, hypotension, congestive cardiac failure, and diabetes mellitus. Their main drawback is the side effects, which in¬ clude weight gain, lethargy, extreme tiredness, and depression. Many patients have associated depression as a comorbid disor¬ der, and beta blockers are not suitable for such patients.

Tricyclic Antidepressants Tricyclic antidepressants, particularly amitriptyline, are widely used for migraine. They are not as efficacious as beta blockers. The side effects, which include weight gain and sleepiness, an¬ ticholinergic effects such as dry mouth, blurred vision, and dysuria, may become a problem. In selecting a tricyclic, one should take into consideration the anticholinergic effects. If a person has many symptoms pointing to anticholinergic activity, the patient may be switched from amitriptyline to nortriptyline, which has less of an anticholinergic effect. Those who want se¬ dation at night may be tried on doxepin. Tricyclic antidepres¬ sants, particularly amitriptyline, have a central analgesic effect that has been shown to reduce the firing rate of the trigeminal nucleus caudalis. The antidepressant effect helps patients with migraine, and the hypnotic effect is helpful in many patients. Tricyclic antidepressants are particularly useful in patients with frequent attacks of migraine, migraine with medication over¬ use, migraine with sleep disorders, migraine with tension-type headache, and migraine with depression.

Serotonin Reuptake Inhibitors Many patients prefer specific serotonin reuptake inhibitors (SSRIs) such as fluoxetine and sertraline. The less sedating ef¬

1743

fect of these medications make them attractive. They have not clearly been shown to have any antimigraine effect; however, they are good adjuncts in the treatment of migraine, especially in patients who cannot tolerate tricyclic antidepressants or ex¬ perience unpleasant side effects. Occasionally there can be a complication referred to as serotonin syndrome in patients who are on SSRIs, lithium, or monoamine oxidases and also receive 5-HT, agonists such as sumatriptan and DHE for acute attacks. We recently reported six patients with such a syndrome.41 The manifestations of the syndrome consist of a combination of acute mental changes and neurological symptoms that include motor weakness, inco¬ ordination, myoclonus, and hyperreflexia. There may also be autonomic symptoms such as increased sweating, tachycardia, and fever. These are usually transient phenomena that occur in close proximity to the intake of the acute abortive agent. The recovery is complete. An increase in the available serotonin at the central synapses is thought to be the cause of this syndrome.

Calcium Channel Blockers There are no good, adequately controlled studies on calcium channel blockers; however, many physicians with long-term experience find calcium channel blockers such as verapamil useful, especially in patients with complicated migraine (mi¬ graine with neurological symptoms such as basilar or hemi¬ plegic migraine). Verapamil does cause water retention and constipation and should be used with care in patients with car¬ diac disorders. Verapamil is, of course, the most useful for the prophylaxis of cluster headache.

Serotonin Antagonists Methysergide (Sansert) is probably the most effective medica¬ tion for the prophylaxis of migraine. Seventy percent of pa¬ tients benefit from it, usually with doses of about 6 to 8 mg daily. The immediate side effects include muscle pains in the leg, water retention, swelling, discoloration, and telangiectasia of the ankle area. The most worrisome side effects are fibrotic reactions, which may occur in the retroperitoneal or pulmonary tissue or in the cardiac valves. The overall incidence of fibrotic reactions is very low. It appears that this is an idiosyncratic re¬ action and does not have any relation to the dose used or the length of treatment. However, the FDA has special instructions for using methysergide, which include a drug holiday for 2 months after 6 months of use. Patients who receive repeated courses of methysergide, have to be monitored carefully with chest x-ray, echocardiogram, and computed tomography (CT) of the abdomen to rule out fibrotic reactions. Very rarely, renal failure occurs without any warning; therefore, these patients have to be followed carefully.

Cyproheptadine Cyproheptadine is useful for children, especially young chil¬ dren, with migraine. Four milligrams three or four times a day is the dose in children; weight gain is sometimes a problem, and drowsiness may occur.

1744

Part 4/Functional Stereotaxis

Divalproex Sodium in the Prophylaxis of Migraine

ishes, a change has to be made to another suitable medication. Side effects have to be monitored, and drug interactions must be kept in mind.

Divalproex sodium (valproic acid) is the latest addition to the armamentarium of drugs for the prophylaxis of migraine. Sodium valproate has been shown to reduce the neurogenic in¬ flammation in Moskowitz’s experimental model.42 It also has been shown to cause attenuation of c-fos activation in the trigeminal nucleus caudalis in Moskowitz’s experimental ani¬ mals.43 Valproate is known to increase gamma-aminobutyric acid (GABA) levels in the brain. In four separate double-blind studies, sodium valproate and divalproex sodium were shown to be superior to placebo.44-47 Divalproex sodium also has been shown to be as effective as propranolol.48

Comorbid conditions such as depression, anxiety, and neu¬ rotic behavior have to be treated with medications as well as with nonpharmacological approaches. Stress management, biofeedback therapy, and individual counseling may help in some patients.

Divalproex sodium usually is given in small doses to start with, such as a 250-mg tablet twice a day, to be increased to a total of 1000 to 1500 mg per day. Starting with small doses and gradually increasing them in smaller increments will prevent the excess nausea and vomiting that may occur in some pa¬ tients. The side effects of sodium valproate include asthenia, weight gain, hair loss, and tremor. Patients show an all-or-none response to valproate. Those who respond, respond very well and remain responsive for long periods. There is no point con¬ tinuing the medication in those who do not show any response in a few weeks. Divalproex sodium is the only approved drug for migraine prophylaxis that has no direct cardiovascular ef¬ fects. It can be used as a second-line drug in many patients and a first-line drug in the prophylactic treatment in the following situations:

Attacks of Cluster Headache

1.

2. 3.

When beta blockers are contraindicated, as in asthma, con¬ gestive cardiac failure, low blood pressure, cardiac conduc¬ tion defects, depression, patients with immunotherapy for allergies who cannot take beta blockers, patients who can¬ not tolerate excercise intolerance on beta blockers When the patient has comorbid migraine and epilepsy When the patient has comorbid migraine and bipolar ill¬ ness

It should be noted that valproate has been approved for use in bipolar illness as well as epilepsy and will soon be available for migraine prophylaxis.

PRIORITIZATION OF PROPHYLACTIC PHARMACOTHERAPY Table 178-9 is a summary that helps to prioritize prophylactic migraine therapy. Clinical efficacy, scientific proof of efficacy, and side effect potential are graded from + to + + + +, with + + + + being the highest grade. This is an empirical grading based on a review of the literature and the experience of the au¬ thors and is modified from Tfelt-Hansen and Welch.49 The beta blockers methysergide and valproate are the most effective. One has to choose between them on the basis of their side effect potentials. Because the side effect potential of methysergide is high, it is not considered a first-line drug. On the basis of this assessment, beta blockers and valproate are more or less equal in performance.

Continuity of Care Patients with migraine need continuity of care. Tachyphylaxis to medications is possible: therefore, if the effectiveness dimin¬

TREATMENT OF CLUSTER HEADACHE Abortive Treatment of Acute

In the treatment of an acute attack of cluster headache, oxygen is the preferred agent.50 Oxygen inhalation at 8 liters per minute for 10 min using a mask will abort the attacks of cluster headache in approximately 70 percent of patients. Our patients with cluster headaches rent portable oxygen tanks. Oxygen may simply delay the headache in some patients; the headache will return after an hour or so. Oxygen inhalation can be combined with ergotamine in a form that is absorbed very rapidly. Ergotamine inhalation, which results in rapid plasma peak levels, is no longer avail¬ able; therefore, one has to rely on sublingual, suppository, or oral preparations. Plasma peak levels after oral administration take longer time to achieve in acute attacks of cluster headache. Sublingual preparations are erratic in their absorption pattern and thus are not very reliable. Suppositories are inconvenient for administration in cases of cluster headache, which comes on rapidly without any warning and ceases rapidly. In spite of these disadvantages, some patients respond to a combination of oxygen and ergotamine in an oral, sublingual, or rectal form. One-milligram ergotamine tablets, 2-mg sublingual tablets, or 2-mg suppositories may be tried. Sumatriptan is the drug of choice for acute episodes of clus¬ ter headache.51-53 It is available in 100-mg tablets and 6-mg subcutaneous preparations. Subcutaneous sumatriptan pro¬ duces a dramatic effect within 15 min of administration. It also can be combined with oxygen. With this combination, the pa¬ tient should get relief almost immediately and acute attacks should be aborted totally. Repeat administration of sumatriptan is possible, and the drug has not led to tolerance even after re¬ peated use for more than approximately a year in patients with chronic cluster headache. Injectable sumatriptan is available in an autoinjector form and is very easy for patients to self-administer. The advantage of sumatriptan is its rapidity of action. Lack of nausea and vomiting is also a distinct advantage, as it is a specific 5-HT1D agonist without any effects on other neuro¬ transmitter receptors. Upper chest discomfort, a burning sensation at the site of in¬ jection, and a hot feeling in the body for a short period are the relatively minor side effects of sumatriptan. As the majority of patients with cluster headache are men and usually are heavy smokers, cardiac status has to be evaluated before drug therapy is started. Sumatriptan and ergotamine should not be used in pa¬ tients with proven coronary artery disease and those who have multiple risk factors for coronary heart disease. Appropriate in¬ vestigations to exclude ischemic heart disease have to be done before ergotamine, sumatriptan, and DHE are prescribed.

Chapter 178/Treatment of Headache

TABLE 178-9.

Clinical Efficacy, Scientific Proof of Efficacy, and Potential for Side Effects

Drug Beta blockers Propranolol, nietoprolol, atenolol, nadolol, timolol Antiserotonin drugs Methysergide

Pizotifen Calcium antagonists Flunarizine

Verapamil

NSAIDs Naproxen Tolfenamic acid Miscellaneous Amitriptyline Clonidine Dihydroergotamine Anticonvulsants Valproate

1745

Clinical Efficacy*

Scientific Proof of Efficacyf

Side Effect Potential*

Examples of Side Effects (Examples of Contraindications)

++++

++++

++

Tiredness, cold extremities, vivid dreams, depression (asthma, brittle diabetes, atrioventricular conduction defects)

++++

++

++++

+++

++

+++

+++

++++

+++

+

+

+

Chronic use: fibrotic disorders (cardiovascular diseases) Weight gain, sedation (obesity) Sedation, weight gain, depression (depression, parkinsonism) Constipation (bradycardia, atrioventricular conduction defects)

++

+++

++

+ 4-

+++

++

++

++

++

+ ++

+ +

+ ++

++++

++++

++

Dyspepsia, peptic ulcers (active peptic ulcers)

Sedation, dry mouth, weight gain (glaucoma) Dry mouth Nausea, diarrhea (ischemic heart disease) Nausea, vomiting, weight gain, tremor, hair loss

*The rating is based on a combination of the published literature and the author’s personal experience. f As judged by the authors (apparently conflicting with the overwhelming majority of comparative trials claiming equipotency of the two drugs; this claim of comparability is probably due to small trials).

DHE administered intramuscularly relieves cluster headache attacks effectively but acts more slowly than does sumatriptan. Since cluster headache occurs one to three times a day on an average, repeated intramuscular injections are painful and impractical. A nasal spray of DHE is under trial. Analgesics and narcotics have no real place in the treatment of cluster headache. It should be noted that the total period of pain from each cluster headache is approximately 45 min and that by the time an oral narcotic is absorbed and takes effect, the pain is usually over. The prescription of narcotic medica¬ tions will simply lead to excessive use and habituation without any major benefit in terms of pain relief. Combination anal¬ gesics containing barbiturate and caffeine (Fiorinal prepara¬ tions) have no place in the treatment of acute cluster headaches.

Prophylactic Treatment of Cluster Headache Table 178-10 lists the medications used for the prophylactic treatment of cluster headache.

Verapamil Among all the medications used for the prophylaxis of cluster headache, verapamil (Calan, Isoptin, Verelan) appears to be the most effective and is the drug of choice. The usual dose is 120 mg three to four times a day, but the dose may have to be in¬ creased in some patients. Verapamil should be continued for at least 2 to 3 weeks after the patient becomes totally free of headaches of the episodic variety. In chronic cluster headache, the length of treatment has to be determined by trial-and-error. Most patients with chronic cluster headache require verapamil for an indefinite period. Ergotamine Combinations of ergotamine and verapamil are known to pro¬ duce very good results in patients with cluster headache. The dose of ergotamine is 1 mg twice a day, and unlike in migraine, its use in cluster headache does not appear to result in rebound phenomena. However, caution is necessary concerning daily ergotamine use in patients with risk factors for cardiovascular disease. Most cluster headache patients are heavy smokers, and

1746

Part 4/Functional Stereotaxis

TABLE 178-10. Headache

Prophylactic Pharmacotherapy of Cluster

Medication

Dosage

Verapamil (Calan, Isoptin, Verelan) Lithium carbonate (Lithobid, Eskalith, Lithane)* Methysergide (Sansert) Ergotamine (Wigraine, Cafergot) Prednisonef

Valproate (Depakote) Indomethacin (Indocin)j:

120-480 mg per day 600-900 mg per day 4-8 mg per day 1-2 mg per day 40 mg per day to start with. 2- to 3-week course in decremental doses. 500-1500 mg per day 50-150 mg per day

*Recommended for chronic cluster headache. tRecommended only in short courses to break the cycle if patient is unresponsive to other prophylactic agents. fUseful only in chronic paroxysmal hemicrania.

some have hypertension; therefore, these patients have an in¬ creased risk for vascular disease. Lithium carbonate Lithium carbonate is useful for both episodic and chronic clus¬ ter headache prophylaxis. Lithium is administered in divided doses of 300 mg two to three times a day. Lithium becomes ef¬ fective in less than a week. If it is to be continued, monitoring of the lithium level to keep it in the low therapeutic range of about 0.5 to 0.6 mEq per liter is necessary. The plasma level of lithium should never exceed 1.2 mEq per liter. Lithium is rea¬ sonably well tolerated by most patients. While on lithium, these patients should not take sodium-depleting diuretics, as hyponatremia leads to lithium toxicity. The common side ef¬ fects of lithium include nausea, vomiting, tremor, and lethargy. Neurotoxicity occurs at higher plasma levels, resulting in ataxia, blurred vision, confusion, and altered consciousness. Lithium can be combined with verapamil or ergotamine tar¬ trate. Combinations of lithium and verapamil are the drugs of choice in the treatment of chronic cluster headache.

be reserved for short courses to break the cycle of headache when agents such as verapamil, ergotamine, lithium, and methysergide are not helpful. The usual dose of prednisone is 20 mg two to three times a day to start with, reduced gradually over a period of 2 to 3 weeks and then discontinued. The mech¬ anism of action of corticosteroids in cluster headache is not clear; they may suppress the synthesis or release of humoral agents that mediate an attack of cluster headache or may influ¬ ence neurotransmitters involved in the headache. Cortico¬ steroids modulate serotoninergic pathways in the brain and may affect the hypothalamic biological clock that is disrupted in patients with cluster headache. Some headache specialists use prednisone at the onset of the cluster period along with verapamil. Then the prednisone is ta¬ pered off after 2 weeks, and the verapamil is continued for the duration of the cluster period. This is a reasonable alternative approach; however, as was mentioned above, exacerbation of the headache can occur after prednisone is discontinued, even though the chance of that happening is lower when the patients are continued on verapamil. Indomethacin Indomethacin is specific for and always successful in the treat¬ ment of chronic paroxysmal hemicrania, which is a variant of cluster headache that occurs mostly in women. The attacks are short-lived, lasting on average 5 to 10 min, as opposed to clus¬ ter headache, which lasts for 45 min to an hour. Multiple at¬ tacks (15 to 20 per day) occur, and autonomic symptoms may accompany the headache. The headache is always unilateral, and there are no remissions, resembling the pattern seen in chronic cluster headache. The therapeutic response to in¬ domethacin can be used as a diagnostic test for chronic parox¬ ysmal hemicrania. The usual dose of indomethacin is 25 to 50 mg three times a day. As with other NSAIDs, gastric side ef¬ fects are common with indomethacin. Misoprostol (Cytotec) may help protect the upper GI tract from the effects of in¬ domethacin in patients with chronic paroxysmal hemicrania who need to continue indomethacin for an indefinite period. Those on long-term indomethacin (Indocin) should have renal function tests periodically. Beta blockers and antidepressants

Methysergide Methysergide is useful in patients with episodic cluster headache, whereas patients with chronic cluster headache are less responsive to it. One tablet (2 mg) three to four times a day is the standard dose. The side effects of methysergide are de¬ scribed in the section on the treatment of migraine, above.

Some of the medications that have been proved to be effective in the prophylaxis of migraine, such as beta-adrenergic block¬ ing agents and tricyclic antidepressants, are not particularly useful in the treatment of cluster headache. However, an occa¬ sional patient may respond to these medications. In patients with chronic cluster headache who are also depressed, antide¬ pressants may be of value as an adjunct.

Corticosteroids Corticosteroids, particularly prednisone, have a definite place in the prophylactic treatment of cluster headache. The effect is usually dramatic, and these patients stop having cluster headache attacks within a day or two. However, when the corti¬ costeroids are discontinued, the headache may recur with the original frequency. Because of exacerbation after the discontin¬ uation of prednisone and the possibility of hypercorticism de¬ veloping after frequent and prolonged use, prednisone should

DlHYDROERGOTAMINE DHFi is useful in breaking the cycle of headache in those with intractable cluster headache attacks that do not respond to regu¬ lar prophylactic therapy. DHE given intravenously every 6 h will invariably break the cycle in 2 to 3 days. The remission ob¬ tained with DHE gives the physician an opportunity to adjust the prophylactic therapy. A course of DHE may put a patient into remission for a considerable period.

Chapter 178/Treatment of Headache

SURGICAL TREATMENT OF CHRONIC INTRACTABLE CLUSTER HEADACHE Approximately 10 percent of cluster headaches are chronic. By definition, chronic cluster headache patients have no remission of their headaches for at least a year. The headaches occur more frequently than in the episodic variety and are more difficult to treat medically. Prophylactic medical therapy includes combi¬ nations of agents such as verapamil, lithium, ergotamine, methysergide, and valproate and occasional short courses of corticosteroids. Triple therapy using any three of these agents may be the last pharmacotherapeutic strategy in some chronic cluster headache patients. When adequate trials of medical therapy fail completely, surgical treatment may be considered.

Indications for Surgery in Chronic Cluster Headache There are several indications for surgery in chronic cluster headache patients: 1. 2. 3.

Total resistance to medical treatment Strictly unilateral cases Stable psychological and personality profiles, including low proneness to addiction

Over the last few decades, a number of procedures have been tried for the surgical treatment of cluster headache (Table 178-11).

Radiofrequency Trigeminal Rhizotomy Among the procedures listed in Table 178-11, those directed to¬ ward the trigeminal nerve, particularly percutaneous radiofre¬ quency trigeminal rhizotomy, have been the most effective.54-59 Radiofrequency trigeminal rhizotomy utilizes thermocoagula¬ tion of the pain-carrying fibers of the trigeminal nerve. It is a stereotactic procedure. A needle is advanced through the fora¬ men ovale under light general anesthesia. Once the needle is in place in the trigeminal ganglion region, the needle tip can be placed selectively, guided by electrical stimulation, in the indi¬ vidual VI, V2, or V3 roots of the sensory trigeminal nerve. Radiofrequency current is passed to the area of interest produc-

TABLE 178-11.

ing thermocoagulation and resulting in selective destruction of the pain fibers but maintaining touch sensation. Experience in many centers indicates that approximately 70 to 75 percent of patients benefit from radiofrequency trigemi¬ nal rhizotomy. In the majority, the cluster headache attacks stop. In a smaller percentage, there is substantial improvement with occasional mild episodes. The results are not completely satisfactory, however, with failure occurring in approximately 15 percent of patients, often for technical reasons. Those with excellent and good results retain the improve¬ ment for a number of years, and even long-term follow-up for more than 20 years has shown continuing benefit. However, re¬ currence of pain occurs in approximately 20 percent of those who initially had excellent or very good results, in which case surgery can be repeated. The recurrence may occur on the op¬ posite side of the head; in our experience, patients with a his¬ tory of occasional headache on the opposite side may be the candidates to develop significant recurrence on the opposite side. Therefore, we recommend selecting patients with a strictly unilateral history of headache. A number of relatively minor complications can occur, es¬ pecially in the immediate postoperative period, including tran¬ sient diplopia, stabbing pain in the distribution of the trigemi¬ nal nerve, difficulty in chewing on the side of the lesion, and jaw deviation. These complications are usually transient, and complete recovery is the rule. A more troublesome complica¬ tion is anesthesia dolorosa, although its incidence is very low. In our series of 98 patients with long-term follow-up, only 2 had moderately severe anesthesia dolorosa symptoms. Corneal analgesia may be produced by the radiofrequency lesion, in which case the patients have to be instructed to take particular care of their eyes after surgery and to consult an ophthalmolo¬ gist if there is any sign of corneal infection. Untreated corneal infections can easily result in corneal opacification because of a lack of corneal sensation. The beneficial effects of this proce¬ dure, however, far outweigh the complications. Some observations Some of our observations over the last 13 years in 98 patients who have received radiofrequency lesions are as follows: 1.

2.

Surgical Procedures for Cluster Headache

Procedures directed toward sensory trigeminal nerve Alcohol injection into supraorbital and infraorbital nerves Alcohol injection into gasserian ganglion Avulsion of infraorbital, supraorbital, and supratrochlear nerves Retrogasserian glycerol injection Radiofrequency trigeminal gangliorhizolysis Trigeminal sensory root sections Procedures directed toward autonomic pathways Section of greater superficial petrosal nerve Section of nervus intermedius Section or cocainization of sphenopalatine ganglion

1747

Complete analgesia is necessary to ensure adequate benefi¬ cial effects. By comparison, in trigeminal neuralgia, partial analgesia is all that is required. If the pain is confined to the orbital, retro-orbital, infraor¬ bital, or supraorbital area, a lesion involving the VI and V2 divisions of the trigeminal nerve is adequate. If the pain also occurs in the temples and in the area of the ear, a le¬ sion of the third division is necessary because the auricular branch of the mandibular nerve supplies the temples and the ear.

Retrogasserian Glycerol Injection Retrogasserian glycerol injection was once a popular proce¬ dure.59-60 The disadvantages of this technique, however, are as follows: 1.

Analgesia is, at most, not as complete as with radiofre¬ quency lesioning.

1748

2.

3.

Part 4/Functional Stereotaxis

It is difficult to control the glycerol lesion, whereas with radiofrequency lesions, selective destruction of VI, V2, or V3 is possible. Glycerol may seep outside of Meckel’s cave and cause chemical meningitis.

Many authors with experience with both radiofrequency le¬ sions and glycerol injections prefer the former procedure. In summary, surgical treatment of cluster headache is a last resort and should be restricted to patients with medically resis¬ tant disabling chronic cluster headache. Radiofrequency trigem¬ inal rhizotomy is the surgical treatment of choice. In view of the disability and suffering of chronic cluster headache patients, the benefits of this procedure far outweigh the complications.

19.

20. 21.

22.

23. 24.

25.

References 1.

2.

3.

4. 5. 6.

7.

8.

9.

Headache Classification Committee of the International Headache Society: Classification and diagnostic criteria for headache disorders, cranial neuralgias and facial pain. Cephalalgia 8(suppl 7):9-96, 1988. Stewart WF, Lipton RB, Celentano DD, et al: The epidemiology of severe migraine headaches from a national survey: Implications of projections to the United States population. Cephalalgia 11 (suppl 11):87—88, 1991. Linet MS, Steward WF, Celentano DD, et al: An epidemiologic study of headache among adolescents and young adults. JAMA 261:2211-2216, 1989. Mathew NT, Reuveni U, Perez FP: Transformed or evolutive mi¬ graine. Headache 27:102-106, 1987. Raskin NH: Headache, 2d ed. New York: Churchill Livingstone, 1988.

Saito K. Markowitz S, Moskowitz MA: Ergot alkaloids block neuro¬ genic extravasation in dura mater: Proposed action in vascular headache. Ann Neurol 24:732-737, 1988. Goadsby PJ, Edvinsson L, Ekman R: Release of vasoactive peptides in the extracerebral circulation of humans and the cat during activa¬ tion of the trigeminovascular system. Ann Neurol 23:193-196, 1988.

14.

Welch KM, D’Andrea G, Tepley N, et al: The concept of migraine as a state of central neuronal hyperexcitability. Neurol Clin 8:817-828, 1990.

15.

D'Andrea G, Cananzi AR. Joseph R, et al: Platelet glycine, glutamate and aspartate in primary headache. Cephalalgia 11:197-200. 1991. Raskin NH, Hosobuchi Y. Lamb S: Headache may arise from pertur¬ bation of brain. Headache 27:416-420, 1987.

18.

30. 31.

32.

34.

Slatter KH: Some clinical and EEG findings in patients with mi¬ graine. Brain 91:85-98, 1968. Gawel M. Connolly JF, Rose FC: Migraine patients exhibit abnormal¬ ities in the visual evoked potential. Headache 23:49-52, 1983. Schoenen J. Maertens de Noordhout A, Timsit-Berthier M, et al: Contingent negative variation and efficacy of beta-blocking agents in migraine. Cephalalgia 6:229-233, 1986.

17.

29.

Olesen J: Cerebral and extracranial circulatory disturbances in mi¬ graine: Pathophysiological implications. Cerebrovasc Brain Metab Rev 3:1-28, 1991.

11.

16.

28.

33.

Goadsby PJ, Edvinsson L: Sumatriptan reverses the changes in calci¬ tonin gene-related peptide seen in the headache phase of migraine. Cephalalgia 11 (suppl 11 ):3—4, 1991.

13.

27.

Lauritzen M, Olesen J: Regional cerebral blood flow during migraine attacks by Xenon-133 inhalation and emission tomography. Brain 107:447-461, 1984.

10.

12.

26.

May A, Weillcr C, Juptner M, et al: Brainstem activation in human migraine attacks: A PET study. Cephalalgia 15(suppl 14): 122, 1995. Goadsby PJ, Gundlach AL: Localization of 'H-dihydroergotaminebinding sites in the cal central nervous system: Relevance to mi¬ graine. Ann Neurol 29:91 -94. 1991.

35.

36.

37.

38. 39.

40.

41. 42.

43.

44.

Curzon G, Barrie M, Wilkinson MI: Relationship between headache and amine changes after administration of reserpine to migraineurs subjects. J Neurol Neurosurg Psychiatry 32:555-561, 1969. Kimball RW. Friedman AP. Vallego E: Effect of serotonin in migraine patients. Neurology 10:107-111, 1960. Sicuteri F, Testi H, Anselmi B: Biochemical investigations in headache: Increase in hydroxyindolacetic acid excretion during mi¬ graine. Int Arch Allergy Appl Immunol 19:55-58, 1961. Curran DA, Hintenberg H, Lance JW: Total plasma serotonin, 5 hy¬ droxyindolacetic acid and p-hydroxi-m-methoxymandelic acid excre¬ tion in normal and migrainous subjects. Brain 88:997-1010, 1965. Peroutka SJ: 5-hydroxy try ptamine receptor subtypes. Annu Rev Neurosci 11:45-60, 1988. Buzzi MG, Moskowitz MA: The antimigraine drug, sumatriptan (GR43175), selectively blocks neurogenic plasma extravasation from blood vessels in dura mater. Br J Pharmacol 99:202-206, 1990. Markowitz S, Saito K. Moskowitz MA: Neurogenically mediated leakage of plasma protein occurs from blood vessels in dura mater but not brain. J Neurosci 7:4129-4136, 1987. Goadsby PJ, Edvinsson L, Ekman R: Vasoactive peptide release in the extracerebral circulation of humans during migrain headache. Ann Neurol 28:183-187, 1990. Buzzi MG, Moskowitz MA: Evidence for 5-HT|Rm) receptors mediat¬ ing the antimigraine effect of sumatriptan and dihydroergotamine. Cephalalgia if: 165-168, 1991. Humphrey PP, Fenink W, Perren MJ, et al: The pharmacology of the novel 5HT,-like receptor agonist, GR43175. Cephalalgia 9(suppl 9):23—33, 1989. Heyck H: Pathogenesis of migraine. Res Clin Stud Headache 2:1-28, 1969. Volans GN: Research review: Migraine and drug absorption. Clin Pharmacokinet 3:313-318, 1978. Hakkarainen H, Vapaatalo H, Gothoni G, et al: Tolfenamic acid is as effective as ergotamine during migraine attacks. Lancet 2:326-328, 1979. Klapper JA, Stanton JS: Ketorolac versus DHE and Metoclopramide in the treatment of migraine headaches. Headache 31:523-524, 1991. Doenicke A, Brand J, Perrin VL: Possible benefit of GR43175, novel 5-HT^like receptor agonist, for the acute treatment of severe mi¬ graine. Lancet 1:1309-1311, 1988. Cady RK, Wendt JK, Kirchner JR, et al: Treatment of acute migraine with subcutaneous sumatriptan. JAMA 265:2831-2835, 1991. The Subcutaneous Sumatriptan International Study Group: Treatment of migraine attacks with sumatriptan. N Engl J Med 325:316-321, 1991. Belgrade MJ, Ling LJ, Schleevogt MB. et al: Comparison of single¬ dose meperidine, butorphanol and dihydroergotamine in the treatment of vascular headache. Neurology 39:590-592, 1989. Jones J, Sklar D, Dougherty J, et al: Randomized double-blind trial of intravenous prochlorperazine for the treatment of acute headache. JAMA 261:1174-1176. 1989. Raskin NH: Repetitive intravenous dihydroergotamine as therapy for intractable migraine. Neurology 36:995-997, 1986. Silberstein SD, Schulntan EA. Hopkins MM: Repetitive intravenous DHE in the treatment of refractory headache. Headache 30:334-339, 1990. Mathew NT, Kurman R. Perez F: Drug induced refractory head¬ ache—clinical features and management. Headache 30:634-638, 1990. Mathew NT, Tietjen GE, Lucker C: Serotonin syndrome complicating migraine pharmacotherapy. Cephalalgia. In press. Lee WS, Limmroth V, Ayata C, et al: Peripheral GABAa receptormediated effects of sodium valproate on dural plasma protein ex¬ travasation to substance P and trigeminal stimulation. Br J Pharmacol 116:1661-1667, 1995. Curter FM, Limmroth V. Ayata G. Moskowitz MA: Attenuation by valproate of C-FOS immunoreactivity in trigeminal nucleus caudalis induced by intracisternal capsaicin. Br J Pharmacol. In press. Hering R, Kuritzky A: Sodium valproate in the prophylactic treat¬ ment of migraine: A double blind study versus placebo. Cephalalgia 12:81-84. 1992.

Chapter 178/Treatment of Headache

1749

45.

Jensen R, Brinek T, Oleson J: Sodium valproate has a prophylactic ef¬ fect in migraine without aura: A triple blind placebo cross over study. Neurology 44:647-651, 1994.

53.

Ekbom K. Monstad I, Prusinski A, et al: Subcutaneous sumatriptan in the acute treatment of cluster headache: A dose comparison study. Acta Neurol Scand 88:63-69, 1993.

46.

Mathew NT, Saper JR, Silberstein SD, et al: Migraine prophylaxis with divalproex. Arch Neurol 52:281-286, 1995. Klapper J: Divalproex sodium in the prophylactic treatment of mi¬ graine (abstract). Headache 35:290, 1995.

54.

Maxwell RE: Surgical control of chronic migrainous neuralgia by trigeminal gangliorhizolysis. J Neurosurg 57:459^166, 1982. Onofrio BM, Campbell JK: Surgical treatment of chronic cluster headache. Mayo Clin Proc 61:537-544, 1986.

Kanieck RG: A comparison of sodium valproate to propranolol hy¬ drochloride and placebo in the prophylaxis of migraine without aura (abstract). Headache 35:305, 1995. Tfelt-Hansen P, Welch KMA: Prioritizing prophylactic treatment in the headaches, in Olesen J, Tfelt-Hansen P, Welch KMA (eds): The Headaches. New York: Raven Press, 1993, pp 403-405. Kudrow L: Response of cluster headache attacks to oxygen inhala¬ tion. Headache 21:1-4, 1981.

56.

47. 48.

49.

50. 51. 52.

The Sumatriptan Cluster Headache Study Group: Treatment of acute cluster headache with sumatriptan. N Engl J Med 325:322-326, 1991. Ekbom K, Cole JA: Subcutaneous sumatriptan in the acute treat¬ ment of cluster headache attacks. Can J Neurol Sci 20(suppl 4):F61, 1993.

55.

57.

Sweet WH, Wepsic JG: Controlled thermocoagulation of trigeminal ganglion and rootlets for differential destruction of pain fibers: I. trigeminal neuralgia. J Neurosurg 40:143-156, 1974. Mathew NT, Hurt W: Percutaneous radiofrequency trigeminal gan¬ gliorhizolysis in intractable cluster headache. Headache 28:328-331, 1988.

58. 59. 60.

Taha JM, Tew JM: Long-term results of radiofrequency rhizotomy in the treatment of cluster headache. Headache 35:193-196, 1995. Waltz TA, Dalessio DJ, Ott KH, et al: Trigeminal cistern glycerol in¬ jections for facial pain. Headache 25:354-357, 1985. Ekbom K, Lindgren L, Nilsson BY, et al: Retro-Gasserian glycerol in¬ jection in the treatment of chronic cluster headache. Cephalalgia 7:21-27, 1987.

'

I

Section

19

Evaluation of Epilepsy

CHAPTER

179

INTRODUCTION TO EPILEPSY

Jerome Engel, Jr.

Epilepsy or, more correctly, the epilepsies, can be defined as a family of disorders characterized by the occurrence of epileptic seizures. Epileptic seizures are defined as transient paroxysmal events caused by abnormal hyperexcitable and/or hypersynchronous neuronal discharges involving the cerebral cortex.1 These events are symptoms in a variety of conditions. A single insult such as head trauma, fever, alcohol withdrawal, or sleep deprivation can provoke a reactive epileptic seizure, which is a natural, although pathological, response of a normal brain, not evidence of an epileptic disorder. A diagnosis of epilepsy im¬ plies the existence of an enduring cerebral disturbance that gives rise to recurrent epileptic seizures. Consequently, indi¬ viduals who experience a single epileptic seizure usually are not considered to have epilepsy and are not treated with antiepileptic drugs.1 Instead, if a specific precipitating cause can be identified, they are counseled to avoid exposure in the future and to be aware of the risks associated with the occur¬ rence of another event. This chapter deals with individuals who have epilepsy, that is, a chronic condition associated with re¬ current epileptic seizures.

HISTORICAL PERSPECTIVE Throughout history, virtually all cultures have harbored pre¬ dominantly negative concepts, both natural and supernatural, concerning the causes and significance of epilepsy. These inter¬ pretations have given rise to stereotypes that continue to con¬ tribute to the disabilities of those who have this condition. The modem biological view of epilepsy originated at the end of the nineteenth century, and the most important advances can be at¬ tributed to the observations of John Hughlings Jackson.2 Jackson recognized that some epileptic seizures involve only a part of the brain and that epilepsy consists of much more than generalized convulsions. He carried out clinicopathological correlations that permitted him to use initial symptoms to pre¬ dict the location in the cerebral cortex of the underlying epilep¬ togenic lesion. His work led directly to the mapping of the cor¬ tical function in the human brain and to resective surgical treatment for intractable epileptic seizures. Localization of the epileptic abnormality for surgical treat¬ ment was based initially on ictal signs and symptoms as well as direct visualization of structural pathology.3 The development of radiological techniques, including angiography and pneu¬

1753

moencephalography, offered increased opportunities to identify structural lesions; however, it was the advent of electroen¬ cephalography (EEG) that revolutionized diagnosis in epilepsy. Gibbs and colleagues4 first recognized that generalized convul¬ sions, absences, and psychomotor seizures could be distin¬ guished by their typical ictal EEG patterns, but it was Jasper and Kershman5 who pointed out that the location rather than the pattern of the interictal and ictal disturbances characterized partial seizures. EEG criteria were then developed to guide sur¬ gical resections in the absence of obvious structural lesions, leading in particular to an increase in surgical treatment for temporal lobe epilepsy.6'7 Over the past 20 years, the develop¬ ment of structural and functional neuroimaging has led to a second revolution in the diagnosis of epileptic disorders and an even greater application of surgical treatment.

TYPES OF EPILEPSY The international classification of epileptic seizures8 divides ictal events into partial if the epileptic discharge begins in part of one hemisphere and generalized if the onset is simultaneous in both hemispheres (Table 179-1). Partial and generalized seizures are further categorized according to electroclinical phenomenology. Partial seizures are considered simple if con¬ sciousness is retained and complex if consciousness is lost. When partial seizures evolve to generalized convulsions, they are referred to as secondarily generalized seizures. Generalized seizures can be convulsive, including tonic-clonic, tonic, and clonic ictal events, or nonconvulsive, including absences, myo¬ clonic seizures, atonic seizures (also called drop attacks), and brief tonic seizures. The international classification of epileptic disorders9 is based largely on the type of associated epileptic seizures and, like the classification of seizures, is divided into partial (re¬ ferred to as localization-related) and generalized epilepsies (Table 179-2). Each of these broad categories is further divided into idiopathic (primary) and symptomatic (secondary) disor¬ ders on the basis of the presumed etiology. Idiopathic disorders are inherited, largely benign conditions that are not associated with structural lesions or specific neurological disturbances. The well-defined idiopathic epileptic syndromes are agerelated (neonatal, childhood, or juvenile onset), and many re¬ solve spontaneously. Symptomatic epilepsies are due to spe-

1754

Part 4/Functional Stereotaxis

TABLE 179-1. Seizures

International Classification of Epileptic

I. Partial (focal, local) seizures A. Simple partial seizures 1. With motor signs 2. With somatosensory or special sensory symptoms 3. With autonomic symptoms or signs 4. With psychic symptoms B. Complex partial seizures 1. Simple partial onset followed by impairment of consciousness 2. With impairment of consciousness at onset C. Partial seizures evolving to secondarily generalized seizures 1. Simple partial seizures evolving to generalized seizures 2. Complex partial seizures evolving to generalized seizures 3. Simple partial seizures evolving to complex partial seizures evolving to generalized seizures II. Generalized seizures (convulsive or nonconvulsive) A. Absence seizures 1. Typical absences 2. Atypical absences B. Myoclonic seizures C. Clonic seizures D. Tonic seizures E. Tonic-clonic seizures F. Atonic seizures (astatic seizures) III. Unclassified epileptic seizures

TABLE 179-2. International Classification of Epilepsies, Epileptic Syndromes, and Related Seizure Disorders 1.

2.

source: From Commission on Classification and Terminology of the International League against Epilepsy,8 with permission.

cific structural disturbances of the brain, which can be well lo¬ calized, giving rise to partial seizures, or widespread, diffuse, or multifocal, giving rise to generalized seizures. Patients with symptomatic epilepsies can have other neurological signs and symptoms in addition to epileptic seizures, and the treatment and prognosis often are determined by the nature of the under¬ lying lesion. When patients have a form of epilepsy that does not fit into any known idiopathic disorder and is very likely to be due to an underlying structural lesion but neither history nor diagnostic testing reveals the etiology, the condition is referred to as cryp¬ togenic. Cryptogenic epilepsies therefore are symptomatic epilepsies for which a cause has not been demonstrated. For these patients, the structural substrate is not detectable by the available diagnostic tests, but careful pathological examination of brain tissue and postmortem or postsurgical resection should identify the lesion.

3.

CAUSES OF EPILEPSY The distinction between idiopathic genetic disorders and symp¬ tomatic lesional disorders is somewhat artificial because both genetic and lesional factors contribute to the manifestation of epileptic seizures in many patients. In addition, environmental

4.

Localization-related (focal, local, partial) 1.1 Idiopathic (primary) Benign childhood epilepsy with centrotemporal spikes Childhood epilepsy with occipital paroxysms Primary reading epilepsy 1.2 Symptomatic (secondary) Temporal lobe epilepsies Frontal lobe epilepsies Parietal lobe epilepsies Occipital lobe epilepsies Chronic progressive epilepsia partialis continua of childhood Syndromes characterized by seizures with specific modes of precipitation 1.3 Cryptogenic, defined by Seizure type Clinical features Etiology Anatomic localization Generalized 2.1 Idiopathic (primary) Benign neonatal familial convulsions Benign neonatal convulsions Benign myoclonic epilepsy in infancy Childhood absence epilepsy (pyknolepsy) Juvenile absence epilepsy Juvenile myoclonic epilepsy (impulsive petit mal) Epilepsies with grand mal seizures on awakening Other generalized idiopathic epilepsies Epilepsies with seizures precipitated by specific modes of activation 2.2 Cryptogenic or symptomatic West syndrome (infantile spasms, Blitz-Nick-Salaam Krampfe) Lennox-Gastaut syndrome Epilepsy with myoclonic-astatic seizures Epilepsy with myoclonic absences 2.3 Symptomatic (secondary) 2.3.1 Nonspecific etiology Early myoclonic encephalopathy Early infantile epileptic encephalopathy with suppression bursts Other symptomatic generalized epilepsies 2.3.2 Specific syndromes Epileptic seizures may complicate many disease states Undetermined epilepsies 3.1 With both generalized and focal seizures Neonatal seizures Severe myoclonic epilepsy in infancy Epilepsy with continuous spike waves during slow-wave sleep Acquired epileptic aphasia (Landau-Kleffner syndrome) Other undetermined epilepsies 3.2 Without unequivocal generalized or focal features Special syndromes 4.1 Situation-related seizures (Gelgenheitsanfalle) Febrile convulsions Isolated seizures or isolated status epilepticus

Chapter 179/Introduction to Epilepsy

TABLE 179-2. International Classification of Epilepsies, Epileptic Syndromes, and Related Seizure Disorders (Continued) Seizures occurring only when there is an acute or toxic event caused by factors such as alcohol, drugs, eclamp¬ sia, and nonketotic hyperglycemia source: From Commission on Classification and Terminology of the

International League against Epilepsy,9 with permission.

and intrinsic precipitating factors are responsible for the mani¬ festation of a seizure at any given time. This complicated mul¬ tifactorial nature of seizures and epilepsy is diagrammed in Fig. 179-1.

Genetic Contributions to Epilepsy Genetic factors influence epileptogenesis in three ways. The degree of cortical excitability and the propensity for synchro¬ nization in the normal brain depend in part on variations in neuronal function and structure that are genetically determined.

1755

Consequently, individuals who have inherited a low threshold for epileptic activity develop epileptic seizures with less provo¬ cation than do individuals with a high threshold. As was noted previously, there are specific idiopathic epileptic disorders that are familial. The inheritance pattern has been determined for some, and the gene locus is known for a few.10 Penetrance is incomplete in all these conditions, how¬ ever, and it is generally assumed that the conditions determin¬ ing the manifestation of the phenotype are multifactorial. There are also genetic causes of symptomatic epilepsies be¬ cause some conditions associated with epileptogenic cerebral lesions are inherited. These conditions include disorders that affect the metabolism of amino acids, proteins, lipids, vitamins, and carbohydrates; dysgenetic syndromes; growth of abnormal brain tissue such as tuberous sclerosis and neurofibromatosis; and progressive myoclonus epilepsies. Even though these spe¬ cific diseases are inherited, the epileptic seizures are secondary to brain lesions, and the resultant disorders are therefore symp¬ tomatic epilepsies.

Acquired Causes of Epilepsy Virtually any cerebral insult that causes localized or diffuse brain damage can alter neuronal excitability and synchroniza¬ tion, predisposing an individual to the occurrence of sponta¬ neous epileptic seizures. Routinely encountered epileptogenic insults and lesions include anoxia, trauma, cerebrovascular dis¬ turbances, brain tumors, infections, congenital defects, migra¬ tion disorders, toxic and metabolic disturbances, and hippo¬ campal sclerosis.11 Hippocampal sclerosis is probably the most common epileptogenic lesion, occurring in approximately 70 percent of all patients with medically refractory complex par¬ tial seizures who are treated with anterior temporal lobec¬ tomy.12 The cause of hippocampal sclerosis is unknown, but the neuronal cell loss presumably occurs early in childhood, result¬ ing in a synaptic reorganization that is responsible for epilepto¬ genesis.13

Basic Mechanisms of Epilepsy

Figure 179-1. Schematic diagram illustrating interactions of the fluctuating threshold for seizures determined by nonspecific predisposing factors (A), independent fluctuations of a specific epileptogenic disturbance (B), and intermittent precipitating factors (Q. With a high threshold, epileptogenic disturbances and precipitating factors alone (Dl, D2) and combined (D3) fail to generate seizures. With an intermediate threshold, epileptogenic disturbances and precipitating factors alone (D4, D5) fail to generate seizures, but seizures (arrows) occur when these factors are combined (D6). With a low threshold, epileptogenic disturbances and precipitating factors alone (D7, D8) are each capable of generating seizures and, when combined (D9), generate even more seizures, perhaps constituting status epilepticus. (From Engel,1 with permission.)

Most of our understanding of the fundamental neuronal mecha¬ nisms of epilepsy derives from investigations with experimen¬ tal animal models. For the most part, these are models of epileptic seizures rather than chronic conditions that might be considered epilepsy. Consequently, the neuronal substrates of ictal events have been well defined, but the mechanisms by which areas of the brain become epileptogenic over time and give rise to spontaneous seizures at irregular intervals are poorly understood. A characteristic feature of epilepsy is the interictal EEG spike and wave, which reflects pathological hypersynchronous discharges of neurons in an epileptogenic region. Intracellular recordings from experimental epileptic foci have revealed that the EEG spike results from abnormally large membrane depol¬ arization shifts occurring synchronously in a number of af¬ fected neurons, while the slow wave results from abnormally large synchronized afterhyperpolarizations. The depolarization shift is associated with rapid action potential discharges, while the afterhyperpolarization inhibits neuronal firing (Fig. 179-2). A paroxysmal depolarization shift is best explained by an in-

1756

Part 4/Functional Stereotaxis

Part 4/Functional Stereotaxis

This so-called recruiting pattern can be viewed as a disinhibitory type of ictal onset and is typified by the EEG changes

Figure 179-2. Neuronal basis of the EEG spike and wave. A. Excitatory input opens channels on dendrite for Ca2+ entry, seen as a large paroxysmal depolarization shift (PDS) on intracellular recording (IC) and as burst unit firing on extracellular recording (EC). Summated outside-negative membrane events appear in the EEG as a negative spike. B. Prolonged afterhyperpolarizations caused not only by K+ currents but also by recurrent inhibition induced Cl— current at the soma are outside¬ positive membrane events (IC) but summate to appear as a slow negative wave in the EEG because of a dipole effect (the soma and apical dendrites maintain opposite polarity). (From Engel,1 with permission.)

flux of calcium that could be due to excessive excitatory synap¬ tic input or increased susceptibility of a neuron to excitation. Excitatory amino acid neurotransmitters, particularly gluta¬ mate, acting on the /V-methyl-D-aspartate (NMDA) receptors have been implicated as a possible mechanism for producing the paroxysmal depolarization shift seen in epilepsy.14 The af¬ terhyperpolarization results in part from calcium-dependent potassium currents and in part from activation of inhibitory in¬ terneurons, causing predominantly gamma-aminobutyric acid (GABA)-mediated chloride currents.15 Although there are undoubtedly many mechanisms for tran¬ sition to ictus, two broad categories are commonly encoun¬ tered.16 In one, the afterhyperpolarization deteriorates, permit¬ ting the neuron to remain depolarized for prolonged periods, during which there is continuous action potential discharge, re¬ cruiting adjacent neurons into the process. The resultant EEGrecorded ictal onset pattern begins with low-voltage fast activ¬ ity, which evolves into rapid spiking with increasing amplitude.

that accompany the onset of a generalized convulsion. In the second type of ictal event, the afterhyperpolarization persists and each afterhyperpolarization is followed immediately by an¬ other depolarization, giving rise to EEG-recorded repetitive spike-and-wave discharges. This hypersynchronous type of ictal event requires enhanced inhibition as well as enhanced ex¬ citation and is exemplified by the three-per-second EEG spikeand-wave pattern of typical absence seizures. There is evidence that low-threshold calcium currents in pacemaker neurons of the thalamus drive the synchronous cortical discharges ob¬ served in some forms of absence epilepsy.17 Partial seizures can begin with either pattern. With hippocampal sclerosis, the onset is more often hypersynchronous, usually evolving to a recruit¬ ing pattern that then is associated with propagation to other ipsilateral and contralateral limbic structures (Fig. 179-3). Current concepts about the neuronal substrates responsible for chronic epilepsy have been derived largely from research on human hippocampal sclerosis and comparable animal mod¬ els caused by the induction of excitotoxic damage to the hip¬ pocampus.16 With the loss of specific types of neurons, there is a reorganization of the surviving neuronal elements, including sprouting of axon collaterals, which produce recurrent excita¬ tory circuits, and enhanced inhibitory influences that predis¬ pose to hypersynchronization (Fig. 179-4). It is likely that these changes constitute a substrate for seizure generation. It has been postulated that recurrent epileptic activity then produces distant structural and functional changes that may give rise to other features of the syndrome of mesial temporal lobe epi¬ lepsy.1819 Whether similar changes account for neocortical epileptogenicity associated with other structural lesions, such as tumors, hamartomas, and cortical dysplasias, remains to be determined. It is likely, however, that many neuronal mecha¬ nisms give rise to spontaneous seizures and that the various types of epilepsy eventually will be found to reflect a number of different pathophysiological disturbances. Whereas current antiepileptic drug treatment acts nonspecifically to increase in¬ hibition, decrease excitation, or decrease synchrony, elucida¬ tion of specific neuronal disturbances in individual types of epilepsy will ultimately permit more directed pharmacological and surgical approaches to treatment and perhaps provide new opportunities for cure and prevention.

DIAGNOSIS AND TREATMENT There are several levels of diagnosis in epilepsy (Fig. 179-5).1 First, it is important to determine whether the events in ques¬ tion are epileptic or are intermittent disturbances resulting from another systemic, neurological, or psychiatric condition. If it can be concluded with a high degree of certainty that a patient has suffered an epileptic seizure, it is then necessary to deter¬ mine whether this is a single event or whether there have been recurrent episodes. If only a single seizure has occurred, a diag¬ nosis of epilepsy usually is not warranted, as was noted previ¬ ously. Because of the stigmata and societal limitations associ¬ ated with a diagnosis of epilepsy, when there is doubt, it is better to wait for the subsequent course to reveal the nature of the disorder. When it is clear that a patient has had a single or recurrent epileptic seizure, the next step in diagnosis is to find

Chapter 179/Introduction to Epilepsy

1757

ivi

Figure 179-3. Segments of telemetry recordings from two patients showing EEG activity at selected depth electrode bipolar tips during the onset of complex partial seizures. A. The classical depth electrode recorded ictal onset consists of a buildup of low-voltage fast discharge, here beginning in a single channel (arrow). B. Three continuous segments show a more common ictal onset pattern, beginning with rhythmic high-amplitude sharp and slow transients (arrow) and eventually giving way to a low-voltage fast discharge that then evolves into higher-amplitude repetitive spikes or spikes and waves. L = left; R = right; A = amygdala; AH = anterior hippocampus; MH = midhippocampus; PS = presubiculum; PG = posterior hippocampal gyrus. Calibration, 1 s. (From Engel,16 with permission.)

an underlying treatable cause. If a treatable cause is found, such as an infectious process or a brain tumor, and treatment is suc¬ cessful in abolishing seizures, the patient should not be consid¬ ered to have epilepsy. Once the diagnosis of an epileptic condition has been estab¬ lished, the differential diagnosis then consists of determining the types of seizures that are occurring and, when possible, identifying a specific epileptic syndrome. Treatment usually is based on the type of epileptic seizures a patient is experiencing (Table 179-3), whereas the diagnosis of a specific syndrome can provide additional information about prognosis and occa¬ sionally suggests a specific therapeutic approach.1 For instance, the idiopathic localization-related syndrome of benign child¬ hood epilepsy with centrotemporal spikes can manifest only with nocturnal seizures that are so rare and mild that treatment with antiepileptic drugs is not necessary, particularly because

this condition invariably resolves spontaneously by later ado¬ lescence. By contrast, some of the idiopathic generalized epi¬ lepsies, such as juvenile myoclonic epilepsy, do not remit with age, but in most cases seizures can be controlled completely with valproic acid. Patients with symptomatic generalized epilepsies have diffuse brain damage and usually are disabled by neurological deficits and mental retardation in addition to recurrent seizures. With symptomatic localization-related epilepsies, the prognosis depends on the size, location, and na¬ ture of the underlying structural lesion, but seizures usually are best controlled with carbamazepine or phenytoin. Of particular importance here is the fact that patients with symptomatic epilepsies and seizures that do not respond to antiepileptic drugs may be candidates for surgical treatment.20 A major recent advance in epileptology has been the recog¬ nition that some surgically remediable epileptic syndromes can

1758

Part 4/Functional Stereotaxis

Figure 179-4. Reciprocal innervation of a hypothetical neuronal system is shown schematically (above). This is the typical synaptic organization of the neocortex and hippocampus. Excitatory afferent input terminates on the dendrites of principal neurons (filled triangles). Axon collaterals from the principal neurons terminate on inhibitory interneurons (empty circles), which in turn make hyperpolarizing synapses on the soma of the same and adjacent (not shown) principal neurons. With cell loss, a number of synaptic reorganizations are likely to occur, as shown schematically below. Fewer afferent input fibers sprout to innervate more principal neurons, predisposing to hypersynchronization. Because the dendrites of principal neurons are shorter, these excitatory influences are closer to the axon hillock and are more likely to induce neuronal firing. Neuronal excitability is further increased by the establishment of monosynaptic excitatory recurrent circuits, as shown in the figure. Although this has not been definitively demonstrated, inhibitory interneurons may sprout terminals to produce more powerful and/or more extensive recurrent inhibitory influences, further enhancing the potential for hypersynchronization. (From Engel,'6 with permission.)

be easily diagnosed noninvasively, respond poorly to anti¬ epileptic drugs, but can be cured or greatly relieved by surgical

treatment.21 The implication of this concept is that surgical therapy is not necessarily an option of last resort; rather, when such syndromes are diagnosed and treatment with first-line antiepileptic drugs fails, early surgical intervention provides the best opportunity for a good outcome with respect to both epileptic seizures and psychosocial rehabilitation. Many surgically remediable epileptic syndromes begin in infancy and early childhood.22 For instance, patients with se¬ vere medically intractable unilateral or generalized seizures originating in a diffusely abnormal hemisphere who already have hemiparesis and a useless hand usually become com¬ pletely seizure-free with little or no additional neurological deficit after hemispherectomy.23 This situation is most com¬ monly encountered in infants and small children with hemimegencephaly, Sturge-Weber syndrome, and Rasmussen’s encephalitis. Patients in the same age group who have cata¬ strophic symptomatic generalized epilepsies that resemble West syndrome (infantile spasms) and a unilateral localized area of structural abnormality are candidates for multilobar re¬ section. These children often have focal cortical dysplasia in the posterior part of one hemisphere and can become seizurefree with reversal of developmental delay after combined uni¬ lateral removal of the temporal, occipital, and parietal lobes.24 Older children with Lennox-Gastaut syndrome and other symptomatic generalized epilepsies associated with multiple seizure types, including drop attacks, can be considered for corpus callosotomy if drop attacks are the most disabling ictal symptom.25 In this situation, an anterior two-thirds, or occa¬ sionally a complete, section of the corpus callosum can abolish or greatly reduce the occurrence of drop attacks; however, other seizure types are rarely improved. Consequently, corpus callosotomy is regarded as a palliative rather than curative sur¬ gical intervention. Nevertheless, freedom from drop attacks can greatly enhance the quality of life for children who have multiple disabilities. Surgically remediable symptomatic localization-related epilepsies are seen in patients with epileptic disorders resulting from well-defined structural lesions that can be removed with¬ out inducing additional neurological deficits26 and patients with mesial temporal lobe epilepsy, which is the syndrome associ¬ ated with hippocampal sclerosis.19-27 Patients with features of the latter syndrome (Table 179-4) who have ictal EEG onsets localized to one temporal lobe, associated with either hip¬ pocampal atrophy on that side identified with magnetic reso¬ nance imaging (MR1) or temporal hypometabolism on that side identified by positron emission tomography (PET), and no con¬ flicting data derived from ictal semiology, structural imaging, or other tests of focal function deficit, have a 70 percent chance of becoming seizure-free after a standardized anterior temporal lobectomy. Patients with symptomatic localization-related epilepsy who are candidates for a tailored surgical resection rather than a standardized anterior temporal lobectomy or a lesionectomy for a specific structural lesion must undergo further diagnostic testing. This testing is aimed at determining the extent of the epileptogenic zone, which is defined as the area of brain tissue necessary and sufficient for the generation of spontaneous seizures.29 The epileptogenic zone is the minimal area of resec¬ tion that will eliminate habitual ictal events; however, this is a theoretical concept, and the boundaries cannot be defini-

Chapter 179/Introduction to Epilepsy

Is the event epileptic?

NO

1759

Diagnose and treat systemic.

YES

Is this a chronic condition?

Patient does not have epilepsy

YES

Is there a treatable cause?

YES

Is specific treatment for cause successful in curing seizures?

NO

Figure 179-5. Steps in the evaluation of paroxysmal events. (.From Engel,1 with permission.)

Patient has epilepsy. Diagnose seizure type and, if possible, epileptic syndrome. Institute specific treatment for epilepsy.

tively determined. Instead, they are derived through a variety of diagnostic studies designed to identify related disturbances (Table 179-5). The irritative zone is the area of the brain that generates interictal spike activity. This zone can be roughly determined noninvasively with interictal EEG recordings and magnetoen¬ cephalography (MEG); however, definite delineation requires

TABLE 179-3. Therapeutic Classification of Epileptic Seizures and Myoclonus

Seizure Type Partial seizures

Generalized convulsive seizures

Absences

Myoclonus Mixed seizures

Preferred Drugs Carbamazepine Phenytoin Valproic acid Felbamate Gabapentin Phenobarbital Primidone Carbamazepine Phenytoin Valproic acid Felbamate Gabapentin Phenobarbital Primidone Ethosuximide Valproic acid Clonazepam Clonazepam Valproic acid Valproic acid Felbamate Combination of other drugs

Possibility of Surgery Local excision

None*

None

None Callosal section (for drop attacks)

*Hemispherectomy and mutilobar resections are occasionally beneficial in patients with localized pathology whose seizures appear to be generalized. source:

Adapted from Engel,' with permission.

the use of intraoperative or chronic direct brain recording. The scalp EEG-recorded spike focus indicates an area where inter¬ ictal epileptiform transients are maximal, but the actual irrita¬ tive zone is usually widespread and often involves areas of the hemisphere contralateral to the epileptogenic zone. The ictal onset zone is the area where electrographic seizures appear to begin. Mesial temporal ictal onsets usually can be identified with scalp and sphenoidal EEG recordings, and scalp EEG can occasionally delineate lateral neocortical ictal onsets; however, definitive localization often requires chronic intracranial recordings. An epileptogenic lesion is the structural abnormality re¬ sponsible for epileptic seizures. It can now be identified in most patients with high-resolution MRI. It is important to rec¬ ognize, however, that patients with symptomatic localizationrelated epilepsy occasionally have structural lesions that are not epileptogenic and therefore do not help identify the epilep¬ togenic zone. The symptomatogenic zone is the part of the brain responsi¬ ble for generating the initial clinical signs and symptoms of the ictal event. Although epileptic seizures often arise in so-called silent areas of the brain and although their ictal clinical mani¬ festations result from distant propagation, knowledge of prefer¬ ential pathways permits initial ictal signs and symptoms to be of confirmatory value in localizing the epileptogenic zone. The epileptogenic zone and areas of direct projection can exhibit enduring nonepileptiform dysfunction: the functional deficit zone. These localized disturbances can be demonstrated by neurological examination and neuropsychological testing when primary cortical areas are involved, functional imaging such as PET and single photon emission computed tomography (SPECT), and EEG in the form of focal slow waves and attenu¬ ation of normal rhythmic activity. When the epileptogenic zone selected for resection is adja¬ cent to or encroaches on primary cortical areas, it is also neces¬ sary to carry out functional mapping to delineate the extent of cortex that cannot be damaged without inducing an additional neurological deficit.30 Functional mapping can be performed during intraoperative electrocorticography or extraoperatively using subdural grids. Noninvasive approaches to functional

1760

Part 4/Functional Stereotaxis

TABLE 179-4. A.

B.

C.

D.

E.

The Syndrome of Mesial Temporal Lobe Epilepsy

History 1. Increased incidence of complicated febrile convulsions. 2. Increased incidence of a family history of epilepsy. 3. Onset in latter half of first decade of life. 4. Auras common and occur in isolation. 5. Secondarily generalized seizures occur infrequently. 6. Seizures often remit for several years until adolescence or early adulthood. 7. Seizures often become medically intractable. 8. Interictal behavioral disturbances can occur (most commonly depression). Clinical seizure 1. Aura is usually present: Most common is epigastric rising, often other autonomic or psychic symptoms, with emotion (e.g., fear), can be olfactory or gustatory sensation (several seconds). 2. Complex partial seizure: Often begins with arrest and stare; oroalimentary automatisms and complex automatisms common. Posturing of one upper extremity may occur contralateral to the ictal discharge (1 to 2 min). 3. Postictal phase: Usually includes disorientation, recent memory deficit, amnesia for the event, and dysphasia if seizures begin in the languge-dominant hemisphere (several minutes). Neurological examination 1. Usually normal. 2. May have recent memory deficit. EEG 1. Unilateral or bilateral independent anterior temporal spikes; maximum amplitude in basal electrodes. 2. May have intermittent or continuous rhythmic slowing in one mesial temporal area. 3. Extracranial ictal activity appears only with complex partial symptoms, usually initial or delayed focal onset pattern of 5 to 7 s rhythmic activity, maximum amplitude in one basal temporal derivation. 4. Depth electrode ictal onset most often high-amplitude rhythmic spikes or sharp waves, less commonly low-voltage fast or suppression. 5. Propagation to contralateral side is slow (> 5 s but may be minutes) or does not occur. Focal functional deficits 1. 2. 3.

Usually temporal lobe hypometabolism on interictal 18F-fluorodeoxyglucose-PET (FDG-PET); often involves ipsilateral thalamus and basal ganglia. Usually temporal lobe hypoperfusion on interictal SPECT and characteristic pattern of hyper- and hypoperfusion on ictal SPECT. Usually material-specific memory disturbances on neuropsychological testing and amnesia with contralateral intracarotid sodium amobarbital injection.

4.

F.

G.

H.

Mesial temporal EEG slowing and attenuation of normal rhythms can be seen with scalp/sphenoidal electrodes, but more common with depth electrodes; exacerbated by IV pentothal test. Structural imaging 1. May have small hippocampus on one side (on MRI). 2. May have small temporal lobe on one side. 3. May have enlarged temporal horn on one side. Pathophysiology 1. Hippocampal sclerosis (> 30% cell loss with specific patterns). 2. Sprouting of dentate granule cell mossy fibers. 3. Selective loss ot certain hilar neurons (somatostatin and neuropeptide Y (NPY)-containing cells). 4. Hamartomas and heterotopias may occur as “dual pathology.” 5. Microdysgenesis common. 6. Seizures may originate in sclerotic hippocampus, but much larger area appears to be included in the epileptogenic region. Features that place diagnosis in doubt 1. History ot severe head trauma, encephalitis, or other specific causal events. 2. Focal motor or specific sensory symptoms at seizure onset or postictally. 3. Interictal focal neurological deficits. 4. Marked cognitive impairment on neuropsychological testing. 5. Bilaterally synchronous, generalized, or extratemporal focal EEG spikes. 6. Diffuse or extratemporal focal EEG slowing. 7. Cerebral lesion other than hippocampal sclerosis on MRI.

source:

From Engel,2* with permission.

Chapter 179/Introduction to Epilepsy

TABLE 179-5.

Definition of Abnormal Brain Areas Definition

Epileptogenic zone

Irritative zone Ictal onset zone

Epileptogenic lesion

Symptomatogenic zone Functional deficit zone

source:

1761

Measures

Area of brain that is necessary and sufficient for initiating seizures and whose removal or disconnection is necessary for abolition of seizures Area of cortex that generates interictal spikes Area of cortex where seizures are generated (including areas of early propagation under certain circumstances) Structural abnormality of the brain that is direct cause of epileptic seizures Portion of brain that produces initial clinical symptomatology Cortical area of nonepileptic dysfunction

Theoretical concept

Electrophysiological (invasive and noninvasive) Electrophysiological (invasive and noninvasive)

Structural imaging and tissue pathology Behavioral observation and patient report Neurological examination and neuropysychological testing: EEG, PET, SPECT

From Liiders et al,29 with permission.

mapping using magnetic stimulation, MEG, PET, and func¬ tional MRI are under investigation.

PSYCHOSOCIAL ISSUES Epilepsy can be associated with other neurological deficits and cognitive impairment, and this contributes greatly to the asso¬ ciated disability. Whereas reduction or elimination of epileptic seizures can simplify the management of such patients, the other problems may require attention that is beyond the scope of this chapter. Epilepsy uncomplicated by additional neurolog¬ ical and mental disturbances, however, can still cause psy¬ chosocial disabilities that compromise the quality of life far be¬ yond what is expected from the physical complaint.31 Stigmata and other misconceptions result in prejudices against persons with epilepsy that impair social interactions and damage self¬ esteem. Parents’ tendencies to overprotect their children create unnecessary dependence. The possibility that a seizure can oc¬ cur at any time without warning produces anxiety, insecurity, and obstacles to the performance of many ordinary activities of daily living. These consequences of epilepsy are particularly damaging during adolescence and early adulthood, when they interfere with the development of a positive self-image and prevent the acquisition of social and vocational skills. In addition, society places limits on individuals with epilepsy that keep them from driving automobiles, pursuing certain occupations, participat¬ ing in insurance programs, and carrying out many other func¬ tions necessary for normal socialization and financial security. Persons with epilepsy can develop interictal behavioral distur¬ bances as a result of these environmental stresses and in some cases as a result of the underlying disease process,32 further jeopardizing their quality of life. Consequently, psychiatric, psychological, and social evaluation and, if necessary, inter¬

vention are essential parts of the diagnosis and treatment of pa¬ tients with epilepsy. Physicians can often do more to help pa¬ tients with epilepsy by taking the time to listen to their prob¬ lems and offer suggestions and by educating family, social, school, and work groups about the disorder than by dispensing medications or performing surgical procedures.

ACKNOWLEDGMENTS Original research reported by the author was supported in part by Grants NS-02808, NS-15654, and GM-24839 from the National Institutes of Health and Contract DE-AC03-76SF00012 from the Department of Energy.

References 1. 2. 3. 4. 5. 6. 7.

8.

9.

Engel J Jr: Seizures and Epilepsy. Philadelphia: Davis, 1989. Taylor J (ed): Selected Writings of John Hughlings Jackson. New York: Basic Books 1958, vol 1. Horsley V: Brain surgery. Br Med J 2:670, 1886. Gibbs FA, Gibbs EL, Lennox WG: Cerebral dysrhythmias of epi¬ lepsy. Arch Neurol Psychiatry 39:298, 1938. Jasper H, Kershman J: Electroencephalographic classification of the epilepsies. Arch Neurol Psychiatry 45:903, 1941. Bailey P, Gibbs FA: The surgical treatment of psychomotor epilepsy. JAMA 145:365, 1951. Jasper H, Pertuisset B, Flanigin H: EEG and cortical electrograms in patients with temporal lobe seizures. Arch Neurol Psychiatry 65:272, 1951. Commission on Classification and Terminology of the International League against Epilepsy: Proposal for revised clinical and electroen¬ cephalographic classification of epileptic seizures. Epilepsia 22:489, 1981. Commission on Classification and Terminology of the International League against Epilepsy: Proposal for revised classification of epilep¬ sies and epileptic syndromes. Epilepsia 30:389, 1989.

1762

10. 11.

12.

13.

Part 4/Functional Stereotaxis

Leppert M, McMahon WM, Quattlebaum TG, et al: Searching for hu¬

22.

man epilepsy genes: A progress report. Brain Pathol 3:357, 1993. Vinters HV, Armstrong DL, Babb TL, et al: The neuropathology of human symptomatic epilepsy, in Engel J Jr (ed): Surgical Treatment of the Epilepsies, 2d ed. New York: Raven Press, 1993, pp 593-608. Babb TL, Brown WJ: Pathological findings in epilepsy, in Engel J Jr (ed): Surgical Treatment of the Epilepsies. New York: Raven Press, 1987, pp 511-540.

Shields WD, Duchowny MS, Holmes GL: Surgically remediable syn¬ dromes of infancy and early childhood, in Engel J Jr (ed): Surgical Treatment of the Epilepsies, 2d ed. New York: Raven Press, 1993, pp 35-48.

23.

Engel J Jr, Van Ness P, Rasmussen TB, Ojemann LM: Outcome with respect to epileptic seizures, in Engel J Jr (ed): Surgical Treatment of the Epilepsies, 2d ed. New York: Raven Press, 1993, pp 609-621. Chugani HT, Shields WD, Shewmon DA, et al: Infantile spasms: I. PET identifies focal cortical dysgenesis in cryptogenic cases for sur¬ gical treatment. Ann Neurol 27:406, 1990.

24.

DeLanerolIe NC, Brines ML, Kim JH, et al: Neurochemical remodel¬ ing of the hippocampus in human temporal lobe epilepsy. Epilepsy Res (suppl 9):205, 1992. Mody I, Stanton PK, Heinemann U: Activation of V-methyl-D-aspartate receptors parallels changes in cellular and synaptic properties of dentate granule cells after kindling. J Neurophysiol 59:1033, 1988. Giaretta D, Avoli M, Gloor P: Intracellular recordings in pericruciate neurons during spike and wave discharges of feline generalized peni¬ cillin epilepsy. Brain Res 405:68, 1987.

16.

Engel J Jr: Functional explorations of the human epileptic brain and their therapeutic implications. Electroencephalogr Clin Neurophysiol 76:296, 1990.

28.

17.

Coulter DA, Huguenard JR, Prince DA: Specific petit mal anticonvul¬ sants reduce calcium currents in thalamic neurons. Neurosci Lett 98:74, 1989.

14.

15.

18.

19.

Engel J Jr, Shewmon DA: Impact of the kindling phenomenon on clinical epileptology, in Morrell F (ed): Kindling and Synaptic Plasticity: The Legacy of Graham Goddard. Cambridge, MA: Birkhauser Boston, 1991, pp 195-210. Engel J Jr: Recent advances in surgical treatment of temporal lobe epilepsy. Acta Neurol Scand Suppl 86:71, 1992.

20.

Engel J Jr (ed): Surgical Treatment of the Epilepsies, 2d ed. New York; Raven Press, 1993.

21.

Engel J Jr, Shewmon DA: Overview: Who should be considered a surgical candidate? in Engel J Jr (ed): Surgical Treatment of the Epilepsies, 2d ed. New York; Raven Press, 1993, pp 23-34.

25.

Gates JR, Wada JA, Reeves A, et al: Re-evaluation of corpus callosotomy, in Engel J Jr (ed): Surgical Treatment of the Epilepsies, 2d ed. New York: Raven Press, 1993, pp 637-648.

26.

Cascino GD, Boon PAJM, Fish DR: Surgically remediable lesional syndromes, in Engel J Jr (ed): Surgical Treatment of the Epilepsies, 2d ed. New York: Raven Press, 1993, pp 77-86.

27.

Wieser HG, Engel J Jr, Williamson PD, et al: Surgically remediable temporal lobe syndromes, in Engel J Jr (ed): Surgical Treatment of the Epilepsies, 2d ed. New York: Raven Press, 1993, pp 49-63. Engel J Jr: Update on surgical treatment of the epilepsies. Neurology 43:1612, 1993.

29.

Liiders HO, Engel J Jr, Munari C: General principles, in Engel J Jr (ed): Surgical Treatment of the Epilepsies, 2d ed. New York: Raven Press, 1993, pp 137-153.

30.

Ojemann GA, Sutherling WW, Lesser RP, et al: Cortical stimulation, in Engel J Jr (ed): Surgical Treatment of the Epilepsies, 2d ed. New York: Raven Press, 1993, pp 399^114.

31.

Taylor D: Epilepsy as a chronic sickness: Remediating its impact, in Engel J Jr (ed): Surgical Treatment of the Epilepsies, 2d ed. New York: Raven Press, 1993, pp 11-22. Engel J Jr, Bandler R, Griffith NC, Caldecott-Hazard S: Neurobiological evidence for epilepsy-induced interictal disturbances, in Smith D, Treiman D, Trimble M (eds): Advances in Neurology. New York: Raven Press, 1991, vol 55, pp 97-111.

32.

CHAPTER

180

CLASSIFICATION OF EPILEPTIC SEIZURES AND EPILEPTIC SYNDROMES

Soheyl Noachtar and Hans Otto Liiders

Systems used to classify signs, symptoms, syndromes, and dis¬ eases have been continuously evolving since the origin of clin¬ ical medicine. This was the consequence of a better under¬ standing of the pathological conditions we were classifying and/or the availability of progressively better diagnostic proce¬ dures. Epileptic syndromes and the main symptom associated with epilepsy—namely, the epileptic seizure—have been sub¬ ject to innumerable classification attempts dating back to the early days of medical literature.1 In 1970, the International Classification of Epileptic Seizures (ICES) provided for the first time a more generally ac¬ cepted classification system, which facilitated communication among epileptologists.2 The current version of this classifica¬ tion system (1981), which is mainly based on clinical semiol¬ ogy and electroencephalographic criteria, employs a double di¬ chotomy that divides the seizures into generalized and partial seizures on one side and further subdivides the partial seizures into complex and simple partial seizures, depending on whether consciousness is altered or preserved during the ictal event.3 This classification has been criticized by some authors,4 but compared to the older classification systems, which focused on the highly variable seizure symptomatology, the ICES system represented a major simplification that permitted even nonex¬ perts to classify seizures correctly. For pharmacological treat¬ ment decisions, the dichotomy “generalized” versus “partial” actually provides the essential information needed to select the anticonvulsant most likely to be effective. Alteration of con¬ sciousness during an ictal event serves as a criterion to assess the impact of seizures on the quality of life. Therefore, a reduc¬ tion of “complex partial seizures” is usually a good index of therapeutic efficacy. However, this classification system inte¬ grates very little localizing information, which is essential for epilepsy centers concerned with epilepsy surgery, as also for clinicians trying to define the location of a lesion by analyzing the clinical characteristics of seizures.5 A recently published proposal for a seizure classification was developed to serve the special needs of epilepsy surgery centers and is currently in use in several selected epilepsy cen¬ ters.5-6 This classification system is exclusively based on the ic¬ tal seizure semiology and provides detailed localization infor¬ mation. The objective of this classification system is to provide the essential clinically relevant information about an epileptic seizure and an epileptic syndrome in (1) a standardized and (2) the shortest possible format.

1763

THEORETICAL CONSIDERATIONS Neurosurgical procedures have given us extensive material to define the effects of electrical stimulation of the human brain. Electrical stimulation can serve as a model to define epileptic seizure symptomatology. The seizure onset zone has been de¬ fined as the area of cortex from which seizures originate. It usually also includes the region of cortex, which is involved earliest in the spread of seizures. However, it is important to recognize that an epileptic discharge will not be associated with any clinical symptomatology unless it spreads to eloquent cortical areas (Fig. 180-1). The symptomatogenic zone is the area of cortex that, when activated by the epileptic discharge (or experimentally by electrical stimulation), produces the clin¬ ical symptomatology of the epileptic seizure.7

CLASSIFICATION OF EPILEPTIC SEIZURES The classification of epileptic seizures presented here is based exclusively on the clinical semiology of an epileptic event. The electroencephalographic (EEG) data, if available, are classified separately and for the purpose of seizure classification are used only to decide whether we are dealing with an epileptic seizure or not.8 As outlined above, the semiology of an epileptic seizure will depend on the symptomatogenic zone. Almost all focal and some generalized seizures are characterized by some seizure evolution. Focal ictal epileptic discharges tend to spread to contiguous cortical areas, and there are typical spread patterns that reflect common seizure evolutions. The initial seizure symptomatology is usually the most important informa¬ tion for the localization of the epileptogenic zone. The follow¬ ing seizure types are distinguished (Table 180-1): I.

Auras Auras are defined as subjective symptoms that are not associated with any objective signs. Autonomic symp¬ toms produced by epileptic discharges are also included as “auras” even if they can be documented objectively (see discussion below). The expression aura should be used only if there is sufficient additional information (usually specific EEG abnormalities) to suggest that the

1764

Part 4/Functional Stereotaxis

TABLE 180-1. 1.

2. 3. 4. 5.

6. 7.

Epileptic Seizures"

Aura a. Somatosensory aura b. Visual aura c. Auditory aura d. Gustatory aura e. Olfactory aura f. Experiential aura g. Abdominal aura Absence seizure Automotor seizure Hypermotor seizure Motor seizure a. Clonic seizure b. Tonic seizure c. Tonic-clonic seizure d. Atonic seizure e. Akinetic seizure f. Myoclonic seizure g. Versive seizure Epileptic seizure Unclassifiable event

“The following can be applied to the above seizures: Modifiers to be used preceding the seizure type:

Figure 180-1. This figure shows some eloquent cortex in humans as identified by electrical stimulation. Note that electrical stimulation of some cortical regions is not associated with any consistent clinical symptomatology. SNMA = supplementary negative motor area; SSMA = supplementary sensorimotor area; Ml = primary motor area; SI = primary sensory area; PNMA = primary negative motor area; BTL = basal temporal language area. (Modified from Ltiders and Nachter,6 with permission.)

1. In absence, automotor, and hypermotor seizures: left hemispheric or right hemispheric 2. In somatosensory and visual auras, motor seizures, epileptic seizures and unclassifiable events (indicate portion of the body participating in the seizure symptomatology): (a) generalized; (b) left; (c) right; (d) somatotopic: face, hand, arm, foot, leg. Evolution: Arrow linking two seizure types indicates seizure evolution (see “Seizure Evolution” in this chapter).

symptoms are of epileptic origin. The existence of an aura reliably points to a focal seizure onset. A. Somatosensory aura

B.

This aura is characterized by paresthesias with a clearly somatotopic distribution. The patients de¬ scribe the paresthesias usually as a “numbness” or “vibration” but occasionally use nonspecific terms like an “unusual sensation.” Pain as an expression of somatosensory aura is extremely rare.9 Somatosensory auras, by definition, are always lo¬ calized to a clearly defined somatosensory area. “Whole body sensation” or “sensations” that can¬ not be localized are classified as experiential auras. Unilateral paresthesias, limited to a portion of the hand, face, arm, trunk, leg, or foot, are usually the expression of epileptic activation of the contralat¬ eral somatosensory region (Brodmann’s areas 1, 2, and 3).10 Epileptic activation of the supplementary sensorimotor region or the secondary sensory region usually produces more extensive paresthe¬ sias, which can have a bilateral distribution.10 Visual aura Visual auras usually consist of simple phosphenes and may be described as “bright spots” of either white or colored light or, less frequently, “dark spots.” These phosphenes tend to blink but may also be steady. The visual impression tends to be re¬

C.

D.

E.

stricted to a portion of the visual field but may move within this portion. Visual auras are usually an expression of an ictal epileptic discharge in Brodmann’s area 17 or 18. Activation of the occipi¬ tal and temporal association cortex is associated with more complex hallucinations like seeing ob¬ jects, animals, or human beings. These hallucina¬ tions frequently appear distorted. Auditory aura Auditory auras consist of auditory hallucinations (hearing noises) and reflect epileptic activation of Heschl’s gyrus. More complex auditory hallucina¬ tions, like hearing voices or melodies, are ex¬ tremely rare and point to an epileptic activation of the temporal association cortex. Olfactory aura Olfactory auras consist of a smell, usually unpleas¬ ant, and are relatively rare. They are most probably an expression of the epileptic activation of the orbitofrontal rectal gyrus. Experiential aura This type of aura involves unusual sensations in which patients perceive the external or "internal” environment in a distorted manner. It includes the typical and frequent sensation of d£jti vu and jamais vu. These experiences consist of a “feeling" that an object, environment or individual has never been

Chapter 180/Classification of Epileptic Seizures and Epileptic Syndromes

F.

seen before or is extremely familiar even when the patient knows that these feelings do not correspond to reality. The feeling that an object appears far away or smaller than it actually is should be in¬ cluded here. Emotional experiences such as fear are also experiential auras of another type, frequently seen in patients with mesial temporal sclerosis. Available data suggest that these auras are a reflec¬ tion of epileptic activation of the basal temporal cortex. Abdominal aura

G.

This frequent aura type is described as a “funny feeling” in the stomach, which is usually unpleasant and tends to rise to the throat and head. It is set apart in a special category because of its frequent occurrence in patients with mesial temporal scle¬ rosis. It is most probably produced by epileptic activation of the insular cortex and is frequently as¬ sociated with autonomic symptoms like nausea. Occasionally actual ictal vomiting may occur.11 Autonomic aura

Autonomic changes like tachycardia, respiratory changes, or sweating are included as auras because, unless special recordings are performed, it is usually impossible to document the autonomic change ob¬ jectively; we only become aware of the autonomic change when the patient reports the symptoms expe¬ rienced in relation to such a change. The typical example is the patient who reports an aura of palpita¬ tions and EEG and electrocardiographic (ECG) mon¬ itoring documents a tachycardia. There is evidence that epileptic activation of the frontal basal region and also of the anterior cingulate area may produce autonomic symptoms in the absence of any other aura or motor symptomatology. Tachycardia is observed with most epileptic seizures shortly after seizure onset and can effec¬ tively serve to detect seizures. However, these tachycardias are most probably causally related to the initial seizure symptomatology, as opposed to being induced by the epileptic discharge itself (au¬ tonomic aura). The typical example is a patient who experiences an aura consisting of fear and reacts to it with a marked tachycardia, pupillary dilatation, and sweating. Similar reactions can be seen in pa¬ tients who suffer other auras or focal motor seizures but are afraid of the secondary generalization that may follow such seizure symptomatology. These autonomic reactions should not be classified as au¬ tonomic auras. II. Absence seizure Absence seizures consist of episodes of loss of con¬ sciousness during which the patient has limited respon¬ siveness to external stimuli and for which the patient is partially or totally amnesic. These episodes are not asso¬ ciated with any significant loss of motor tone. Motor activity is usually reduced to a minimum, although occa¬ sionally some myoclonic jerking of the eyelids or poorly defined automatisms may occur. Patients may, however, continue doing the same activity they were doing before the seizure started, but invariably at a lower speed and with loss of motor skills. Cases in which the loss of mus¬

III.

1765

cle tone or the positive motor activity during the seizure overshadows the loss of consciousness should not be classified as absence seizures but as psychomotor, hy¬ permotor, or one of the other types of motor seizures listed below (Table 184-1). Automotor seizure Automotor seizures are characterized by the occurrence of automatisms. Automatisms in this classification are defined as well-organized movements that are involun¬ tary and are inappropriate to the environmental situation. Frequently these involuntary movements are repetitive. Typical examples include oroalimentary automatisms such as chewing, lip smacking, or swallowing and man¬ ual automatisms like fumbling. The automatisms are usu¬ ally associated with loss or alteration of consciousness, but there are well-documented exceptions.12 Automotor seizures are distinguished from hy¬ permotor seizures by the type of associated automa¬ tisms. In automotor seizures, the automatisms affect pri¬ marily the distal portions of the extremities and the lips

IV.

V.

or tongue. In hypermotor seizures (see below), the prox¬ imal segments of the limbs and trunk are involved in the automatisms, giving rise to more extensive movements such as body rocking, pedaling, or running automatisms. There is no clear agreement on which brain structure gives rise to automotor seizures. Stimulation studies suggest that epileptic activation of the anterior cingulate will elicit “distal” automatisms.13 It is possible, there¬ fore, that the automatisms are an expression of seizure spread within the limbic system with activation of the anterior cingulate gyrus. Automotor seizures are most frequently seen in patients with temporal lobe epilepsy and less frequently in patients with frontal lobe epilepsy, particularly patients with lesions in the fronto-orbital re¬ gion. In addition, automotor seizures may be produced by spread of the seizure discharge into the temporal re¬ gion from the parietal or occipital lobe (Fig. 184-1). It is also interesting to notice that patients who have auto¬ motor seizures without loss of consciousness almost in¬ variably suffer from epilepsy in the nondominant tempo¬ ral lobe.14 This indicates that the alteration of consciousness is due to mechanisms other than the au¬ tomatisms.4 Hypermotor seizure Hypermotor seizures are characterized by automatisms affecting mainly the proximal portions of the limbs and trunk. The distinction from automotor seizures is not necessarily clear-cut because it is occasionally difficult to tell whether the automatisms affect predominantly proximal or distal limbs. As in automotor seizures, con¬ sciousness may be well preserved during the seizure but this feature has no known lateralizing significance. Hypermotor seizures are classified as a type separate from automotor seizures because there is sufficient evi¬ dence to suggest that hypermotor seizures are more fre¬ quently associated with frontal lobe epilepsy, whereas automotor seizures are seen most frequently with tempo¬ ral lobe epilepsy. Motor seizure Motor seizures consist of involuntary muscle contrac¬ tions that do not imitate normal movements or postures because of their unnatural speed or temporal sequence or

1766

Part 4/Functional Stereotaxis

because the patient adopts an unnatural posture. Similar movements can be elicited by electrical stimulation of the primary motor cortex (Brodmann’s areas 4 and 6), the supplementary sensorimotor cortex (mesial frontal Brodmann’s area 6), or the cingulate gyrus. A. Clonic seizure Clonic seizures consist of intermittent, short con¬ tractions of variable groups of muscles that tend to recur at regular intervals. Focal clonic seizures most frequently affect the distal segments of the limbs, the face, and the tongue. They are usually an expression of epileptic activation of the primary motor region (Brodmann’s areas 4 and 6). Electrical stimulation of the supplementary sensorimotor area may also, though less frequently, elicit distal clonic movements. However, it is not yet established whether epileptic activation of the supplementary sensorimotor cortex may result in focal clonic seizures. Generalized clonic seizures are usually associ¬ ated with generalized epileptiform discharges. The cortical discharge usually has a one-to-one relation¬ ship to the muscle twitch. It is generally assumed that generalized clonic seizures are the result of an intermittent “generalized activation of the motor cortex” by the epileptic discharge. It is, however, not yet clear which region of area 4 or 6 gives rise to the type of movement commonly seen with gen¬ eralized clonic seizures. B. Tonic seizure This seizure type is characterized by sustained in¬ voluntary contraction of one or more muscle groups, resulting in posturing. Focal tonic seizures are usually the result of epileptic activation of the supplementary sensorimotor area. These tonic seizures affect mainly proximal limb muscles bilat¬ erally, but usually in an asymmetrical fashion. The contralateral side tends to be more prominently in¬ volved, but ipsilateral involvement is not infre¬ quent.34 Consciousness is consistently preserved at the initial phase of the seizure.

C.

D.

Generalized tonic seizures are associated with generalized epileptiform discharges. As in the case of generalized tonic seizures, the cortical structures whose activation may lead to generalized tonic seizures has not yet been elucidated. They are prob¬ ably generated by activation of the cortical motor areas (Brodmann’s areas 4 and 6), which, in turn, excite brain-stem motor-activating centers. Tonic-clonic seizure This seizure type comprises the classic generalized tonic-clonic seizure, which is also called a “grand mal” seizure in the literature. The patients initially show a generalized tonic posturing, which later de¬ velops into generalized clonic movements with a progressively slower repetition rate but larger am¬ plitude. The pathogenic mechanisms already dis¬ cussed for tonic and clonic seizures also apply to this type of seizure. Atonic seizure Atonic seizures are characterized by a sudden loss of muscle tone that leads to “drop attacks” or "head

VI.

drops.” This seizure type is frequently associated with generalized epileptiform discharges. The pathogenesis is still unclear. Usually patients pre¬ senting with this seizure type also have tonic seizures, suggesting that atonic and tonic seizures may share a common pathogenic mechanism. Frequently atonic seizures are preceded by a brief myoclonic jerk, which propulses or retropulses the patient, causing falls with injuries rather than just “slumping down.” Epileptic “negative myoclonus,” which repre¬ sents a focal atonic seizure, should be included here. The mechanisms involved in the generation of this seizure type are still unclear, but it is likely that the “silent period” elicited by cortical activa¬ tion is responsible for the negative myoclonus seen in patients in whom the negative myoclonus is pre¬ ceded by a focal cortical spike in the EEG.15 E. Akinetic seizure This seizure type consists of the inability to perform voluntary movements. This inability to move may affect only selected muscle groups and lead to in¬ ability to move one hand or to speak, but it may also have a generalized distribution. Akinetic seizures are not associated with alteration of con¬ sciousness. A typical example is a patient who, dur¬ ing a seizure, experiences a generalized inability to move. Focal akinetic seizures are probably due to epileptic activation of the negative motor areas.16 However, a generalized inability to move may also be due to a focal epileptic activation of the negative motor area. A similar generalized inability to move can be elicited by focal electrical stimulation of the negative motor area. F. Myoclonic seizure These seizures consist of isolated, rapid jerks that may have a generalized or focal distribution. They are produced by isolated epileptiform discharges that activate any of the cortical motor areas. The epileptiform discharges frequently consist of poly¬ spikes which, due to the temporal facilitation, are more likely to activate the motor cortex. The patho¬ genesis of myoclonic seizures is probably very sim¬ ilar to that of clonic seizures, essentially consisting of repetitive myoclonic jerks. G. Versive seizure These seizures are usually characterized by conju¬ gate lateral deviation of the eyes. Usually, when the eyes reach the extreme position, a deviation of the head and eventually also of the trunk may oc¬ cur. The lateral deviation of the eyes may be smooth (tonic) or saccadic. Lateral deviation of the head or trunk without preceding eye deviation is infrequent. Almost invariably these seizures are produced by epileptic activation of the frontal eye field (contralateral to the side to which the eyes deviate). Epileptic seizure Spells that cannot be classified as auras, absence, auto¬ motor, hypermotor, or motor seizures but in which the epileptic nature of the event has been established by EEG criteria and/or other signs (consistent elevation of

Chapter 180/Classification of Epileptic Seizures and Epileptic Syndromes

VII.

creatine phosphokinase (CPK) and/or prolactin, typical evolution into generalized tonic-clonic seizures after withdrawal of anticonvulsants, etc.) should be classified as epileptic seizures. Unclassified event The expression unclassified event is used when the com¬ plete clinically available information does not permit the classification of a “spell” as of epileptic or nonepileptic origin. Included in this category are psy¬ chogenic pseudoseizure and syncope.

SOMATOTOPIC LOCALIZATION OF ICTAL SIGNS AND SYMPTOMS The clinical manifestation of an epileptic seizure may contain valuable lateralizing or somatotopic information. This informa¬ tion should be included in the seizure classification. Based on ictal EEG-video recordings, several ictal lateralizing signs have been described.17 A dystonia of one hand in the course of an au¬ tomotor seizure points to a contralateral seizure origin.18 Other lateralizing signs include ictal speech and postictal aphasia, pointing to a seizure onset in the nondominant and dominant hemispheres respectively.19 The hemisphere of seizure origin will be mentioned before the seizure classification in the fol¬ lowing seizure types: absences, automotor, and hypermotor seizure. For example: Left hemisphere absence refers to a seizure during which a pa¬ tient was unresponsive without any motor manifestation and postictally demonstrated an expressive aphasia. Left hemisphere automotor seizure refers to a seizure consist¬ ing of loss of consciousness and fumbling automatisms dur¬ ing which a dystonia on the right is observed. In visual and somatosensory auras and in motor seizures, the peripheral seizure manifestation will be included. In this classification system, a visual aura in the left visual field will be classified as left visual aura. Accordingly, a somatosensory aura in the left hand would be classified as left-hand so¬ matosensory aura. These modifiers can also be applied to epileptic seizures that are not further classified and unclassi¬ fied events. They indicate the somatotopic distribution of the motor, somatosensory, or visual phenomenon or the unclassi¬ fied event and epileptic seizure. The modifiers generalized, left, left face, left hand, left arm, left foot, left leg, right, right face, right hand, right arm, right foot, and right leg can be used with all the motor seizures except the versive seizures. For versive seizures only, the modifiers left or right should be used, indicating the side toward which the eyes and head move. The classification specifies the first localizing or lateral¬ izing sign or symptom when the seizure has a spreading soma¬ totopic evolution. For example: Generalized clonic seizure refers to a seizure with bilateral syn¬ chronous clonic jerks. Left clonic seizure refers to a seizure with left-sided clonic jerks. Left visual aura refers to an aura with visual hallucinations or illusions in the left visual field.

1767

SEIZURE EVOLUTION Epileptic seizures frequently evolve from one seizure type to another. In this seizure classification system, the seizure evolu¬ tion is specified by linking different seizures by arrows. For example: Abdominal aura —> left hemisphere automotor seizure Right visual aura —► right clonic seizure Sequential motor seizures of different types should be linked by arrows. For example, a poorly defined tonic seizure with bilateral, asynchronous involvement followed by a clonic seizure of the right hand should be classified as follows: Tonic seizure —> right hand clonic seizure However, as mentioned above, if the same type of seizure shows a change in somatotopic distribution, only the initial so¬ matotopic distribution is specified. For example, a clonic seizure starting in the left hand and then evolving into a left face clonic seizure and eventually into a generalized tonicclonic seizure would be classified as follows: Feft hand clonic seizure —> generalized tonic-clonic seizure In other words, the detailed “jacksonian march” is seldom used to avoid complexity. Also to avoid complexity, the fre¬ quently observed evolution from a motionless stare (“absence seizure”) to an automotor seizure or hypermotor seizure should be classified just as an automotor seizure or hypermotor seizure. In automotor seizures, we not infrequently may observe a ver¬ sive eye and head deviation that reliably points to a contralat¬ eral seizure origin.20 This seizure evolution will be classified as follows: Automotor seizure —»left (or right) versive seizure Generalized epileptic seizures may also demonstrate a seizure evolution. A typical example is the evolution from a generalized myoclonic seizure to a generalized tonic-clonic seizure, frequently seen in patients with juvenile myoclonic epilepsy: Generalized myoclonic seizure —► generalized tonic-clonic seizure

EPILEPTIC SEIZURES AND EPILEPTIC SYNDROMES Epileptic seizures are spells characterized by a constellation of symptoms and/or signs that are the consequence of an epileptic discharge activating the cortex and/or subcortical structures. A wide variety of signs and symptoms may occur in epileptic seizures (Table 180-1). As we discussed elsewhere, it is impor¬ tant to define the epileptic seizure exclusively by the clinical signs and/or symptoms observed during the “spell.”5 Otherwise

1768

Part 4/Functional Stereotaxis

it is unclear what clinical information was used to classify the seizure, making it difficult to decide whether there is conver¬ gence of results (many test results pointing to the same anatomic region). This is critical in assessing the results of presurgical epilepsy testing. Terminology in which an epileptic seizure is identified by an anatomic region should not be used, because it is unclear whether the anatomic region defines the epileptogenic or symptomatogenic zone.7 For example, when epileptologists refer to temporal lobe seizures, they usually re¬ fer to the epileptogenic zone (even if the symptomatogenic zone tends to be extratemporal), but when they talk of supple¬ mentary sensorimotor area seizures, they refer to the sympto¬ matogenic zone (even if the epileptogenic zone almost always tends to be outside the supplementary sensorimotor area).21 However, in defining the epileptic syndrome, it is appropriate to define an anatomic region that defines the epileptogenic zone (area of cortex capable of generating seizures, the surgical re¬ section of which results in freedom from seizures). To define the epileptic syndrome, all the available information (clinical data, functional and imaging test results) are taken into ac¬ count. Thus, an epileptic syndrome constitutes a summary of etiologic and clinical data and information derived from func¬ tional and structural tests. Some epileptic syndromes, particu¬ larly those produced by well-defined and consistent etiologies, are associated with a certain prognosis (e.g., good prognosis in juvenile myoclonic epilepsy, poor prognosis in Lennox-Gastaut syndrome). Generalized epilepsies are those in which the epileptogenic zone involves a significant portion of the cerebral cortex of both hemispheres. This does not necessarily mean that a given seizure may not originate from a relatively localized cortical region (“secondary generalization”). It implies only that seizures could also potentially originate from many other corti¬ cal areas on both hemispheres. From a practical point of view, there is a diffusely abnormal cortex, and resection of only a re¬ gion of cortex would not eliminate the seizures, since other areas even on the opposite hemisphere would take over as “pacemakers.” Focal epilepsies are epileptic syndromes in which the epileptogenic zone is limited. By definition, resection of these limited epileptogenic zones renders the patient seizure-free. Seizure spread occurs slowly and may remain restricted to a limited region of cortex for an indefinite time. The ictal onset zone is usually imbedded in a regional irritative zone, which is capable of generating epileptiform discharges.7 The tendency of restricted seizure spread is probably related to the fact that the adjacent cortex is normal and mechanisms to restrict the seizure spread are preserved.

CLASSIFICATION OF EPILEPTIC SYNDROMES In this classification, epileptic syndromes are diseases of the central nervous system associated with or manifest by clinical seizures and characterized by a cluster of signs and symptoms usually occurring together. Some syndromes are actually dis¬ eases (i.e., have a common etiology, like juvenile myoclonic epilepsy), but for the majority of the syndromes there is no common etiology and/or prognosis. The signs and symptoms may be clinical (e.g., case history, age of onset, seizure type,

modes of seizure recurrence, and neurological and psychologi¬ cal findings) or findings detected by ancillary studies—e.g., EEG, x-ray, computed tomography (CT), magnetic resonance imaging (MR1), etc. Paroxysmal events that are not epileptic in nature or for which there is no clear evidence as to whether they are epileptic or not are not included here. Table 180-2 shows 21 different types of epilepsy syndromes defined with different degrees of precision. The table also shows that some syndromes are subsets of others, which are less precisely classified. For example, mesial temporal lobe epilepsy is a subset of temporal lobe epilepsy, which, in turn, is a subset of focal epilepsy and of epilepsy respectively. As shown in Table 180-2 for each of the 21 epileptic syndromes, the etiology and the type of seizures should be specified. Following are descriptions of these 21 syndromes. 1. Epilepsy This category includes patients in whom there is clear evidence of the epileptic nature of the “spell,” but the epileptic syndrome cannot be further classified. The cause of the epileptic syn¬ drome may be unknown or a clearly defined cause may be identified (symptomatic). 2. Focal epilepsy This syndrome includes patients in whom there is clear evi¬ dence that the epileptogenic zone is regional, but its exact loca¬ tion cannot be defined. The patients may have different types of seizures. The epilepsy may be symptomatic or of unknown eti¬ ology. A typical example is a patient with a poorly defined aura with secondary generalized seizures in whom the EEG and available neuroimaging tests show no focal abnormality. 3. Temporal lobe epilepsy Patients in whom there is clear evidence that the seizures arise from a temporal lobe are included here. Typically these patients suffer from automotor seizures that may or may not be pre¬ ceded by abdominal, experiential, autonomic, or olfactory auras. Secondary generalized tonic-clonic seizures may occur. The EEG seizure may originate unilaterally or bilaterally. In this syndrome, there is not sufficient information to decide whether the seizures originate from the mesial temporal area or neocortical temporal cortex. 4. Mesial temporal lobe epilepsy These patients usually suffer from abdominal, experiential, au¬ tonomic, or olfactory auras that evolve into automotor seizures characterized by behavioral arrest as well as oroalimentary and manual automatisms. The patients not infrequently also have secondary generalized tonic-clonic seizures. The seizures tend to appear in the second half of the first decade of life. A high percentage of these cases have bilateral disease. Pathological examination frequently shows sclerosis of the mesial temporal structures with a variable degree of involvement of the basal temporal and even lateral convexity of the temporal lobe. The structural abnormality may be detected by MRI studies and may appear as an area of hypometabolism on positron emission tomography (PET). There is no tendency toward remission with time. 5. Neocortical temporal lobe epilepsy Patients with this syndrome have seizures arising from the neo¬ cortex of the temporal lobe. The clinical symptomatology of this group is similar if not identical to that of the seizures de¬ scribed in mesial temporal lobe epilepsy, but EEG evidence points to a temporal focus outside the mesial region. Complex

Chapter 180/Classification of Epileptic Seizures and Epileptic Syndromes

visual or auditory and experiential auras have been related preferentially with seizures of extramesial temporal origin.22 6. Frontal lobe epilepsy Patients with this syndrome have seizures in which there is clear evidence of origin from the frontal lobes. The clinical symptomatology of the seizures is still poorly defined but prob¬ ably includes frequent tonic, hypermotor, and automotor seizures of short duration, preferentially occurring during sleep. Absence seizures and secondary generalized tonic-clonic seizures are also seen in these cases.23 7. Supplementary sensorimotor area epilepsy The patients with this epilepsy syndrome usually suffer from tonic seizures and/or hypermotor seizures that may evolve into focal clonic seizures with variable degrees of alteration of con¬ sciousness and generalized tonic-clonic seizures. Tonic seizures due to activation of the supplementary sensorimotor area tend to (a) be sudden in onset, (b) be short in duration (10 to 20 s), (c) involve proximal muscle segments bilaterally (even if predominantly contralateral), (d) cause no alteration of consciousness, and (e) occur preferentially during sleep. Version of the eyes, head, and body or focal clonic seizures im¬ mediately before secondary generalization consistently indi¬ cate that the seizure originates contralateral to the version and clonic jerks. The ictal EEG is usually obscured by electromyographic (EMG) artifacts. Postictal generalized slowing occurs fre¬ quently when the seizures evolve to focal versive or clonic seizures. 8. Perirolandic area epilepsy Patients with this syndrome have an epileptogenic zone in the pericentral cortex resulting in focal clonic seizures involving most frequently the face, hand, and foot. The seizure sympto¬ matology may include contralateral version of the eyes, head, and body, particularly when there is involvement of the face muscles. A “jacksonian march” of the clonic jerks as the seizure discharge spreads over the precentral cortex may occur. Infrequently, the focal clonic seizures may be preceded by a so¬ matosensory aura. 9. Parieto-occipital lobe epilepsy This syndrome includes patients with seizures arising from the parieto-occipital region. Seizures include visual auras, which may evolve into focal clonic or automotor seizures.24 25 The semiology of seizures arising from the parietal lobe is still poorly defined but may include somatosensory auras and neu¬ ropsychological disturbances.26 Because of the close anatomic relationship and the poorly defined differentiation between seizures arising from the parietal and occipital lobes, in this classification the occipital and parietal lobes are included in

1769

11. Benign epilepsy of childhood Patients with this syndrome usually experience their first seizures between the ages of 3 and 14 years. The seizures are focal and tend to be nocturnal and infrequent. Secondary gener¬ alized tonic-clonic seizures may occur. This disorder is labeled benign because the seizures tend to be infrequent and consis¬ tently disappear after the age of 15 years. Patients with benign focal epilepsy of childhood have a higher incidence of febrile convulsions. The EEG shows uni- or multiregional benign epileptiform discharges of childhood, which have a typical morphology.28 Neurological exam and neuroimaging studies are normal. 12. Generalized epilepsy Patients with generalized seizures who do not fit into the other more specific syndromes of generalized epilepsies are included in this classification. 13. Absence epilepsy This syndrome is a subtype of generalized epilepsy in which the main seizure type is an absence seizure. Seizure onset is at school age with a peak at 6 to 7 years of age (range, 3 to 12 years). Typically, frequent daily absences occur. Generalized tonic-clonic seizures may occur later in adolescence. Absences may remit or, more rarely, persist as the only seizure type. There is a strong genetic predisposition. The children tend to have a normal IQ. The EEG shows generalized 3-Hz spike-and-wave com¬ plexes, usually triggered by hyperventilation, and a normal background activity. Neuroimaging is normal. 14. Juvenile myoclonic epilepsy This subtype of generalized epilepsy presents with generalized myoclonic seizures as the predominant seizure type. The seizures tend to occur shortly after awakening and are typically precipitated by sleep deprivation. Repetitive myoclonic jerks may evolve into generalized tonic-clonic seizures. The condi¬ tion shows a strong genetic predisposition. Development and neurological exam are normal. Seizures usually start at puberty and persist with age but are very responsive to anticonvulsants. Interictally and ictally, there are generalized polyspikes or fast spike-and-wave complexes in the EEG. 15. Grand mal epilepsy Patients with this syndrome usually have their first seizures in the second decade of life. Not infrequently, generalized tonicclonic seizures occur shortly after awakening and are precipi¬ tated by sleep deprivation. The neurological examination and imaging studies are normal. The EEG is normal or, less frequently, shows interictal gen¬ eralized spike-and-wave complexes.

one epilepsy syndrome. 10. Rasmussen syndrome This syndrome includes patients with a slowly progressive neu¬ rological deterioration usually including hemiparesis, homony¬ mous hemianopsia, and mental retardation (dysphasia if the dominant hemisphere is involved) associated with unilateral or predominantly unilateral brain atrophy on neuroimaging. This is associated with recurring focal seizures that tend to be med¬ ically intractable and frequently present as epilepsia partialis continua. The syndrome occurs primarily in childhood (1 to 14 years).27 Brain pathology reveals a microscopic pathological picture suggesting a viral encephalitis, although this has not yet

16. West syndrome Patients with this syndrome have “infantile spasms” (general¬ ized tonic or myoclonic seizures) appearing before 1 year of age. The syndrome is classified as symptomatic if there is a known etiology for the occurrence of seizures or there is evi¬ dence of psychomotor retardation or of neurological and/or ra¬ diological abnormalities indicative of brain damage preceding the appearance of the “spasms.” If there is no evidence of pre¬ vious brain damage and no cause for the seizures can be uncov¬ ered, the etiology is classified as unknown. In symptomatic cases, the prognosis is poor. Some of the patients with un¬ known etiology may develop favorably. The EEG typically shows a generalized epileptiform pattern

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70% reduction (patient with tumor).

Improvement in patient with frontoparietal language areas treated.

Zonghui, Quanjun, Shiyue, Zengmin, Yuehan, Haili15

50 Not clear if resection was also performed.

Precentral 13/50 Postcentral 5/50 Broca’s 12/50 Wernicke’s 5/50 Visual 5/50 Combined 10/50

32/50 (64%) seizure-free. 13/50 (26%) >50% reduction. 3/50 (6%) 90% reduction. 8/45 (18%) no benefit. MST + resection was slightly better than MST alone.1'

“Progressive disease includes Rasmussen’s encephalitis, tumors, and subacute sclerosing panencephalitis. '’Progressive disease occurred in 32%. Recurrent seizures arose in new cortical areas. ‘However, progressive cerebral disease patients were included in this group.

tients from those who had “MST plus resection.”7'11'21'22 No significant differences can be extrapolated from these data, since the number of patients is small and the indications and cortical foci vary among patients. Patients undergoing MST plus a focus resection may have better seizure outcomes, since a more extensive and definitive surgery was performed, although their functional outcomes may be less good than for MST alone.27 No conclusions based on these two treatment groups can yet be drawn. Incomplete MST surgery was per¬ formed in some cases where access to medial cortical struc¬ tures prevented abolition of electrocorticographic spikes, but clinical results were good nonetheless: “Subtotal transection of the discharging area did not preclude clinical improve¬ ment.”11 When all patients are considered, seizure frequency reduction and often complete seizure relief were seen. Very few patients exhibited no benefit. These results improve fur¬ ther when patients with progressive neurological diseases are excluded.:o No cases were reported where seizure disorders became worse save for patients with progressive diseases.

Follow-up for seizure outcome data has varied among se¬ ries, making comparison of patient groups unreliable. Longer follow-up periods have not been associated with diminishing percentages of patients with control of epilepsy. Again, return of epileptiform activity (electrically and/or clinically) may be seen in patients with progressive neurological diseases, yet the seizure foci are different than the original presenting foci.417 There was no discernible way of comparing resection alone versus MST plus resection or versus MST alone; however, one author reported that the result of MST alone was nearly compa¬ rable to resection.22 Further cohort-controlled studies are needed to answer these questions. Functional outcomes (Table 195-1) varied with cortical lo¬ cation and are poorly reported in some series. When present, deficits were most often seen in the patients undergoing resec¬ tion of an epileptogenic lesion plus MST.11 Most deficits were found only on objective testing, not being apparent to the pa¬ tients, or at least they were not bothersome. Most series found a small incidence of deficits without debilitation.2-4'717 Many

Chapter 195/Subpial Transections for the Surgical Management of Epilepsy

deficits were transient.12-14'27 Patients may be underreporting symptoms because they may perceive a mild functional deficit to be an improvement over persistent seizures.4 Deficits pertaining to language areas were usually naming and reading paraphasias and word-finding problems.1213 Many of these symptoms were transient.13 Residual deficits occurring after MST performed in the pre- and postcentral gyri were usu¬ ally manifest as impairment of the fine movement of the fin¬ gers.4 Patients with preoperative deficits typically exhibited no change in their symptoms after MST. Excitingly, patients with the Landau-Kleffner syndrome (an acquired aphasia) exhibited marked return of speech function after MST.18 These patients demonstrated that MST may be used to restore neurological functions to cortical areas formerly prevented from carrying out their normal roles due to epilepsy. Thus, neurological func¬ tion can be preserved or restored by MST for the treatment of intractable epilepsy. Measuring the overall functional outcome for a wide variety of patients is difficult. With respect to particular progressive disease processes such as Rasmussen’s encephalitis, SSPE, and tumors, the functional outcome after MST usually demon¬ strates progression of symptoms, although some initial benefit from seizure reduction or abolition is seen.4 Many patients had transient postoperative functional symptoms or signs that im¬ proved with time and with physical or speech therapy.12 No deficits were defined as disabling and no postoperative neuro¬ logical states were inferior to those that existed preoperatively.2*11 Preoperative functional deficits were usually left un¬ changed except in the special case of patients with Landau-Kleffner syndrome. In one series, two patients demon¬ strated postoperative neuropsychological changes,16 yet in an¬ other study, neuropsychological improvement was seen after MST.15 Permanent deficits were mild if present, and not found to be impeding the performance of the activities of daily living for most patients, if not normal activity.1117 The worst neuro¬ logical deficits reported from MST were hemipareses in the im¬ mediate postoperative period in patients in whom motor cor¬ tices had been treated.11 This symptom usually resolved.11 The most lasting language deficits from MST were in long-term storage of unrelated words in a verbal learning task, confronta¬ tion naming, repetition, and verbal learning tasks.12 These also improved with time.12 Patients with Landau-Kleffner syndrome typically had im¬ provement or complete return of speech function after MST was performed in electrically active areas (F,T). These patients did not exhibit any new functional deficits, although some had residual paraphasias that continued to improve with speech therapy. It is not known if these residua are related to the pri¬ mary disease process or to the surgical therapy. It is not clear from the results whether epileptic or func¬ tional outcomes varied based on the cortical location of MST. Comparison of functional outcomes in individual patients and in patients between studies is not easy because of the hetero¬ geneity of the population.27 The variation in follow-up periods and methods of measurement also makes comparison of the se¬ ries difficult. However, all authors advocated MST as an ad¬ junct or primary therapy for refractory epilepsy in or near elo¬ quent cortex based on excellent functional and epileptic outcomes.

1899

Discussion Evidence from animal studies and clinical series indicates that MST is effective in limiting the local spread of epileptiform ac¬ tivity on the cerebral cortex by destroying horizontal interneu¬ ronal connections. One author proposes that local neuronal damage cannot be avoided by subpial transections and that this destruction may be at least partly responsible for the therapeu¬ tic and side effects of MST.12 Damage to cortical neurons is ac¬ companied by limitations in the function of their vertical fibers, thus providing a possible mechanism for long-term neurologi¬ cal symptoms after MST. Small subcortical hemorrhages occur as a complication of MST, and vertically oriented fibers are compressed as a result. As the hemorrhages resolve, so does impairment of neurological function. Such bleeding may ac¬ count for transient symptoms after MST. Since MST does not prevent the spread of electrical activity to deeper or distant cor¬ tical areas, it is unlikely that this minimal neuronal loss will slow epilepsy progression in patients with progressive neuro¬ logical disease. However, loss of these neurons may partially explain the disappearance of spikes and the reduction of elec¬ trical spread after MST.12 Postoperative symptoms vary with the cortical area tran¬ sected, indicating that association cortices (e.g., language areas) differ functionally from primary somatosensory areas.12 Language areas are known to associate other sensory and mo¬ tor cortices, and the function of association areas may rely more critically on superficial horizontal fibers. Transection of language areas has been associated with more postoperative neurological dysfunction than transection in primary cortices.12 These symptoms improve only gradually, providing credence for the augmented functional importance of horizontal connec¬ tions in association cortices. Gradual improvement of language skills after MST may be due to the change in neuronal routing through nontransected horizontal fibers or deeper white matter tracts. Also, association cortex, like the language areas, does not have a functional-anatomic relationship like that of the primary sensorimotor cortices.12 Edema is probably not in¬ volved in the postoperative language dysfunction in patients undergoing MST in language areas, since the symptoms are long-lasting. Thus, future studies must compare the neuro¬ physiology and outcomes of MST on association and primary cortices. Resection of cortical areas coincident with MST may lead to an increased incidence of postoperative neurological symp¬ toms. This is especially marked in patients undergoing MST af¬ ter resection in association areas like the supramarginal gyrus.12 Only postoperative functional mapping will allow a better un¬ derstanding of the individual functional relationships of MST in particular gyri, with defined resections of functionally quies¬ cent cortex determined by preoperative mapping. Postoperative mapping will also enable the study of shifts oi function from resected or transected cortex to other areas.28 This technique will also allow a better comparison of the plasticity of the cere¬ bral cortices in children and adults.28 Long-term follow-up will also be necessary to help deter¬ mine the true epileptic and functional efficacy of MST and to document delayed complications pathologically. Application of MST has already allowed a better understanding of neocortical function and the pathophysiology of the spread of epilepsy.

1900

Part 4/Functional Stereotaxis

Much is not known and further experimental and clinical stud¬ ies are needed to elucidate the mechanisms of the columnar or¬ ganization of the cerebral cortex, its function, and the physiol¬ ogy of neuropathological processes. Perhaps mathematical models using neural networks will aid the theoretical study of neocortical connectivity and pathophysiology.

SURGICAL TECHNIQUE The original surgical technique was described by Morrell et al. in 1989.4 Only subtle modifications have been described.12,13’15 Often MST is referred to as the “Morrell procedure.” His tran¬ secting instrument was made of heavy steel wire, with a 4-mm right-angle hook at the end similar to a blunt right-angled hook. The instrument needed to be stiff to complete the corti¬ cal transection tangentially to the surface yet springy enough to allow different orientations to be achieved around difficult gyri and to give the surgeon a feel of the tissue during the tran¬ section maneuver. Morrell describes the end to be smooth and rounded to 0.3 mm, but others have described a 0.5-mm ball tip.15 Although not mentioned in the original description, micro¬ scopic guidance and a comfortable microsurgical armchair is recommended for complete control and surgical comfort dur¬ ing a procedure that may consist of many transections.13 Surgery should be done under general anesthesia and cran¬ iotomies and dural openings should be made generous enough to allow appropriate monitoring and surgical access. Multiple subpial transections are planned by careful electrocorticography and, in some cases, stimulation trials during a monitoring period, using a subdural grid.4,12,1315 The informa¬ tion obtained from these trials and monitoring as well as from careful neuropsychiatric testing and functional mapping should be transferred to the cortical surface with a series of paper tick¬ ets.13 Multiple subpial transection was advocated in areas di¬ rectly involved in ictal onset that occurred in or near eloquent cortical regions.13 Furthermore, in most MST cases, the proce¬ dure is continued until sharp waves are no longer recorded.15 To enter a sulcus prior to subpial transection, Morrell de¬ scribes making a pinhole incision with the tip of a No. 11 blade. Modifications to this include the use of a No. 9 injection syringe,15 and, recently described, a complete dissection of the sulcus on either side of the transection.13 Whether the entry is a hole or a complete sulcal dissection, care must be taken to avoid the traversing vessels. To begin a dissection, the instrument is placed into the sul¬ cus (again avoiding the nearby vessels) and the tip oriented across the gyrus to be transected. The instrument is swept tan¬ gentially under the gyrus while keeping the blade vertically ori¬ ented. Once the opposite sulcus is reached, the instrument is drawn back across the gyrus, this time keeping the tip in view below the pia. Care is taken to avoid vessels in the distal sulcus as well as on the cortical surface while pulling the instrument back. Transections are made until no further sharp wave activ¬ ity is noted from the area planned for transection.15 Transections are made 5 mm apart and are kept paral¬ lel.411'' The depth of 4 mm described by Morrell has remained constant except in one series of patients in which the surgeons described the depth of transection as being 4 to 5 mm.13

Multiple transection “stripes” are typically seen along the dissections and arise from capillary damage. These stripes can help guide the measurement for the next transection. Topically placed thrombin-soaked sponges can be used to abate exces¬ sive capillary hemorrhage. If a resection is also planned, the transections should be per¬ formed afterwards, since seizure foci in resectable cortex may directly modulate the epileptogenicity of the eloquent cortex where transection is planned. Each patient should have the lesioning planned individually, since no two cases are identical. The main difficulty from this procedure lies in the “blind¬ ness” of the transection. The surgeon must use a supersensitive touch in performing the transection in order to prevent damage to underlying cortical vessels.27

COMPLICATIONS No surgical procedure is without the risk of complications. Besides the myriad of complications associated with an in¬ tradural craniotomy, certain problems are specific to MST. The neurological changes associated with MST on the eloquent cor¬ tices will not be considered complications per se and are dis¬ cussed elsewhere. The need for invasive, subdural EEG monitoring involves an increased risk of infection in the perioperative period. Often, antibiotics are used prophylactically. This has not been a prob¬ lem in the published series of MST. Parallel transection “stripes” are evidence of subpial capil¬ lary rupture. These are typically seen across the cortex and pro¬ vide horizontal landmarks for planning the distance to the next transection. They may function as a “fire wall” of gliosis, pre¬ venting epileptiform activity, but they may also be a site of continued bleeding. Thrombin-soaked microsponges may be used topically to diminish stripe oozing.4 Interestingly, prior ra¬ diation therapy prevented the transection stripes from becom¬ ing dark or bloody.12 Hematomas have been reported from the transected areas.19 This complication appears to be related to damage to cortical vessels during the performance of a transection. Because the transections are made blindly, occasional small hematomas may be expected; they typically resolve.27 Symptoms pertain¬ ing to such hemorrhages are particularly evident due to the elo¬ quence of the cortex involved and comprise many of the tran¬ sient symptoms seen after MST.27 Based on the columnar organization of the cortex, the vertically oriented fibers are probably transiently injured by these bleeds.7 One author indi¬ cated that these subcortical local hemorrhages were the “main cause of permanent hemorrhages,”27 yet no evidence for this is offered. The highest reported incidence of these small hema¬ tomas was 6 out of 45 patients operated upon in one series.7 Larger hematomas have been reported at sites distant from transection which are presumed unrelated to MST, specif¬ ically.7 No wounds or related infections were reported in the pub¬ lished series. Prophylactic antibiotics were typically used perioperatively to help prevent infectious complications. One small subcortical infarction distant from the site of MST was re¬ ported. This was presumed not to be directly related to MST. There has been no reported mortality from MST.

Chapter 195/Subpial Transections for the Surgical Management of Epilepsy

Neurological problems associated with the eloquent cortices are more marked in association cortices due to a proposed critical dependence on horizontal connections. Functional symptoms in language areas, for example, recover more gradu¬ ally12’29 than those found after MST in primary sensorimotor cortices. Although certain cases were presented with incomplete MST due to limitations imposed by anatomic exposure, pa¬ tients improved. It is not known if this subset of patients will progress and have poorer seizure outcomes. Thus, complete transection of electrically active cortex should be attempted. Complications particular to children have not been fully elucidated.28 The evaluation of MST in children may vary from that in adults due to the excellent plasticity seen in pediatric nervous systems.28 Furthermore, long-term complications of MST have not been described.28 Histological and electrophysiological studies of MST patients after many years have not been reported. It is possible that return of seizures in new foci may occur, or in the same foci from possible subpial fibrogliosis. This remains to be evaluated. Since the number of patients is typically small in each series and because outcome measurements have varied, risk percent¬ ages are not reliable, yet each patient should be advised of all

3.

4.

5.

6.

7.

8.

9. 10.

11.

12.

possible adverse outcomes. 13.

CONCLUSION Multiple subpial transections have been shown to be effective and safe for the treatment of epilepsy recorded in or near elo¬ quent cortical areas. Neurosurgeons have multiple surgical tools that can be combined to treat refractory epilepsy effec¬ tively with minimal functional deficits. Modern recording tools and preoperative planning allow customization of the use of these tools to best treat epileptic patients. Future improvements and expansion in indications for MST are expected. Improvement in the knowledge of the function of association cortices may be accompanied by modifications or conventions related to MST in these areas. Experimental ad¬ vancements in electrophysiology and functional anatomy of the neocortex will be rapidly applied to the further development of MST and clinical observations will best guide the direction of laboratory experiments. Computer models of neuronal connec¬ tivity will likely be used to study the effects of MST and perhaps one day be utilized for surgical planning in individual patients. Such databases would incorporate electrophysiological, imaging, neuropsychological, and functional testing to be used in the operating room. Improvements in instrumentation and technique may help prevent damage to underlying cortical ves¬ sels, possibly accomplished by intraoperative ultrasonic or opti¬ cal imaging. Multiple subpial transection is an exciting and use¬ ful neurosurgical procedure for the control of refractory epilepsy.

14.

15. 16.

1.

Dichter M: Cellular mechanisms of epilepsy and potential new treat¬

2.

ment strategies. Epilepsia 30 (suppl 1 ):S3—S12, 1989. Morrell F, Hanbery JW: A new surgical technique for the treatment of focal cortical epilepsy. Electroencephalogr Clin Neurophysiol 26:117-121, 1969.

Asanuma H: Recent developments in the study of the columnar arrangement of neurons within the motor cortex. Physiol Rev 55: 143-156, 1975. Morrell F, Whisler W, Bleck T: Multiple subpial transection: A new approach to the surgical treatment of focal epilepsy. J Neurosurg 70:231-239, 1989. Sugiyama S, Fujii M, Ito H: The electrophysiological effects of multi¬ ple subpial transection (MST) in an experimental model of epilepsy induced by cortical stimulation. Epilepsy Res 21:1-9, 1995. Reichenthal E, Hocherman S: A critical epileptic area in the cat’s cor¬ tex and its relation to the cortical columns. Electroencephalogr Clin Neurophysiol 47:147-152, 1979. Fisher R, Uthman B, Ramsay R, et al: Alternate surgical techniques for epilepsy: Second Palm Desert Conference on Surgical Treatment of the Epilepsies, Palm Desert, California, Feb. 22, 1992. Leuders H, Bustamante L, Zablow L, Goldensohn ES: The indepen¬ dence of closely spaced discrete experimental spike foci. Neurology 31:846-851, 1981. Duysens J, Mclean DR: The effect of subpial vertical cortical incision on a cobalt-gelatin focus. Epilepsia 15:579-591, 1974. Zhao Q, Liu Z, Tian Z, et al: Experimental study of multiple subpial transections for treatment of intractable focal epilepsy. Epilepsia 34(suppl 2): 128, 1993. Sawhney IM, Robertson IJ, Polkey CE, et al: Multiple subpial tran¬ section: A review of 21 cases. J Neurol Neurosurg Psychiatry 58: 344-349, 1995. Devinsky O, Perrine K, Vasquez B, et al: Multiple subpial transec¬ tions in the language cortex. Brain 117:255-265, 1994. Dogali M, Devinsky O, Luciano D, Perrine K: Invasion intracranial monitoring, cortical resection and multiple subpial transection for the control of intractable complex partial seizure of cortical onset. Stereotac Fund Neurosurg 62:222-225, 1994 Dogali M, Devinsky O, Perrine K, Beric A: Experiences with multi¬ ple subpial transections for the control of intractable epilepsy in ex¬ quisite cortex. Epilepsia 33 (suppl 3): 100, 1992. Liu Z, Zhao Q, Li S, et al: Multiple subpial transection for treatment of intractable epilepsy. Chin Med J 108:539-541, 1995 Liu Z, Zhao Q, Li S, et al: Clinical application of multiple subpial transections for treatment of intractable focal epilepsy. Epilepsia 34

17.

(suppl 2): 128, 1993. Morrell F, Whisler WW: Multiple subpial transections for epilepsy eliminates seizures without destroying the function of the transected

18.

zone. Epilepsia 23:440, 1982. Morrell F, Whisler WW, Smith MC, et al: Clinical outcome in Landau-Kleffner syndrome treated by multiple subpial transection.

19.

20.

Epilepsia 33 (suppl 3): 100, 1992. Shimizu H, Suzuki I, Ishijima B, et al: Multiple subpial transection (MST) for the control of seizures that originated in unresectable corti¬ cal foci. Jpn J Psychiatry Neurol 45:354—356, 1991. Whisler WW: Multiple subpial transection. Techn Neurosurg

22.

1:40-44, 1995. Honaver M, Janota I, Polkey CE: Rasmussen’s encephalitis in surgery for epilepsy. Dev Med Child Neurol 34:3-14, 1992. Smith JR, King DW: Current status of epilepsy surgery. J Med Assoc

23.

Georgia 82:177-180, 1993. Piatt J: Multiple subpial transection in treatment of focal epilepsy. J

24.

Neurosurg 71:629-630, 1989. Devinsky O, Pacia S: Epilepsy surgery. Neurol Clin 11:951-971,

21.

25. 26.

References

1901

27.

28. 29.

1993. Haglund M, Ojemann G: Extratemporal resective surgery for epilepsy. Neurosurg Clin North Am 4:283-292, 1993. Rossi GF: Principles of surgery for epilepsy. Acta Neurochir Suppl 50:58-63, 1990. Rossi G: Innovations in surgical approaches that extend the indication for surgical treatment of the epilepsies. Crit Rev Neurosurg 6:6-12, 1996. Madsen J, Adelson D, Haglund M: The future of pediatric epilepsy surgery. Neurosurg Clin North Am 6:589-597, 1995. Pilcher W, Rusyniak WG: Complications of epilepsy surgery. Neurosurg Clin North Am 4:311-325, 1993.

.

CHAPTER

196

CORPUS CALLOSOTOMY FOR SURGICAL MANAGEMENT OF EPILEPSY

Robert E. Maxwell

RATIONALE

posterior temporal and striate occipital cortices, which tend to show relatively independent discharges.

The rationale for sectioning the corpus callosum to control gen¬ eralized seizures rests on the tenets that seizures evolve in the cerebral cortex, secondarily spread through commissural path¬ ways to the opposite cerebral hemisphere, and that therefore such generalization or bilateral synchronization can be reduced or eliminated by sectioning the main commissural bundle.4 The corpus callosum, hippocampal commissure, and anterior com¬ missure transmit interhemispheric discharges. The corpus cal¬ losum is by far the largest of the three, developing in propor¬ tion to the size and complexity of the neocortex and reaching maximal size in humans, where it contains somewhat on the or¬ der of 180 million axons.52 The number of callosal connections varies from one cortical region to another. Definitive data on the topography of commissural fibers in humans are not available, though the issue has been investigated in the rhesus monkey by Pandya and others using degeneration and autoradiographic techniques. The vast majority of corpus callosum fibers connect homotypic regions of the two hemi¬ spheres, but heterotypic connections occur. Motor and associa¬ tion cortex mediating the head, trunk, and proximal limbs has more robust connections through the callosum than do the distal appendages. This may partially explain why secondarily gener¬ alized seizures with rapid bisynchronization often result in sud¬ den drop attacks and traumatic falls. Pandya and Rosene have studied the topography of the interhemispheric connections us¬ ing dark-field microscopy to trace the transport of radioactive amino acids along callosal fibers.37 There are relatively few cal¬ losal connections between the anterior and inferior temporal re¬ gions, but those fibers originating in the temporal lobes cross in the posterior part of the body and in the underlying hippocampal commissure. Fiber tracts originating in the frontal cingulate re¬ gions traverse the anterior half of the corpus callosum, includ¬ ing the rostrum, genu, and anterior body. Parietal connections cross to the opposite hemisphere through the posterior body and anterior splenium, and occipital connections occur through the most posterior and inferior portions of the splenium. The gen¬ eral rule of cortical excitability and spread of discharges is that the pattern of bilateral electrical discharge and spread is influ¬ enced by the density of callosal connections between corre¬ sponding areas of the two hemispheres. Therefore, regions with many callosal connections, such as the premotor and precentral cortices, will show well-synchronized bilateral discharges more readily than those with fewer callosal connections, such as the

Experimental Rationale Electrical stimulation of the primate cortex evokes a biphasic wave in the contralateral cortex, with the largest potentials seen in homotopic areas, but heterotopic responses can also be recorded. These responses are obtained by stimulating almost any cortical region but are abolished by sectioning the corpus callosum.10 It has clearly been shown that the corpus callosum transmits excitatory potentials between the cerebral hemi¬ spheres, but inhibitory effects are even more pronounced under some experimental conditions. Asanuma and Okuda found that transcallosal stimulation in cats was inhibitory of contralateral pyramidal tract activity over a much wider area than was the case with excitatory potentials.2 A sentinel report was that of Erickson in 1940, who studied afterdischarges produced by electrical stimulation of the mon¬ key cerebral cortex before and after sectioning the corpus cal¬ losum. He found that afterdischarges initially spread through¬ out the ipsilateral motor area, producing ipsilateral clonic movements before crossing to the opposite hemisphere when bilateral clonic movements occur. Complete section of the cor¬ pus callosum stopped the spread of discharges to the opposite hemisphere and clonic movements remained contralateral to the discharges.12 Subsequent experimental studies in both fe¬ line and primate models have shown that sectioning the corpus callosum can disrupt bilaterally synchronous discharges in¬ duced by topical or systemic epileptogenic agents.27'2932 The corpus callosum is by far the most significant of the commissures connecting the cerebral hemispheres. Experimen¬ tal studies of epilepsy in both feline and primate models have clearly demonstrated the role of the corpus callosum in mediat¬ ing bilateral synchrony.26 Complete section of the corpus callo¬ sum and contiguous hippocampal commissure produces dis¬ ruption of bilateral synchrony and the reestablishment of an independent discharge in each hemisphere in acute cats whose seizures were induced with 0.5% strychnine.29 Musgrave and Gloor demonstrated in the cat that they could abolish penicillin-induced bilaterally synchronous epileptic discharges by completely sectioning the corpus callo¬ sum and anterior commissure.32 Incomplete callosal section did not completely disrupt synchrony. This helped confirm the 1903

1904

Part 4/Functional Stereotaxis

important role of the corpus callosum in the propagation of 3-Hz spike-and-wave discharges in animal models of general¬ ized epilepsy. In the kindling model, Wada and his associates showed the anterior two-thirds of the corpus callosum to be important for the occurrence of generalized convulsive seizures after chronic amygdaloid stimulation.56 Corpus callosotomy also disrupts the synchrony of spike-wave discharges in rodents and in the pho¬ tosensitive baboon.33'55 There have been acute and chronic studies, using epilepto¬ genic feline and primate models, suggesting increased epilepti¬ form activity after corpus callosum sectioning. Kopeloff et al. found that chronic seizure foci induced by aluminum oxide cream increased in frequency and severity after the corpus cal¬ losum was sectioned.23 Dividing the corpus callosum also in¬ creases cats’ susceptibility to seizures following acetylcholine and pentylenetetrazol administration.50 Wada and Sato also found that division of the corpus callosum facilitated the pro¬ gression of generalized seizures induced by daily electrical stimulation of the amygdala.58 Experimental studies suggest al¬ ternate pathways to the corpus callosum that may account for the bilateral synchrony occurring with motor seizures. Wada and Sato reported evidence that afterdischarges occurred in the midbrain reticular formation before generalized discharges, and seizures were seen in the amygdala-kindled cat.57 Seizures induced in rats by topical application of penicillin to a unilat¬ eral focus have been found to spread bilaterally by first increas¬ ing bilateral activation of intrathalamic pathways until transsynaptic stimulation of medial and orbital frontal cortices occurred.0 Kusske and Rush found that corpus callosotomy ac¬ celerated thalamic spread.24 It was therefore concluded that the cortical thalamic pathway is perhaps as important or even more important for bilaterally synchronous seizure spread than the pathway through callosal fibers.44

giomas was found to have tumor projecting into the corpus cal¬ losum. Retrospective analysis of his medical history revealed frequent seizures at the beginning of his symptomatology but fewer as the tumor progressed. Another observation was made at the time of a postmortem examination on a patient who had suffered seizures for 25 years and then experienced relief from the seizures following a cerebral hemorrhage. Examination of the brain revealed that the hemorrhage had destroyed most of the corpus callosum. Therefore, based on these clinical obser¬ vations and the tenet that consciousness is not usually lost when the spread of the epileptic discharge is limited to one cerebral cortex, they decided to section the corpus callosum in an effort to confine spread of the seizure to one hemisphere. It has been pointed out that although significant experimental work regarding the role of the corpus callosum in epilepsy was being pursued at the time, there is no indication that Van Wagenen and Herren were aware of it, and it is not alluded to or referenced in their article.22After the initial 10 patients were reported in 1940, Van Wagenen subsequently operated on 14 additional patients, sometimes including the anterior commis¬ sure in the commissurotomy. Over the subsequent three decades, several disconnection procedures were tried as variations on Van Wagenen’s original concept. Division of interhemispheric fiber tracts was per¬ formed that included various combinations of the corpus callo¬ sum, hippocampal commissure, anterior commissure, and fornix. Most of the reported series were small but provided substantial evidence that the frequency and severity of general¬ ized seizures could be unequivocally improved after callosot¬ omy or commissurotomy.25'56 The slow acceptance and reluc¬ tant rush to embrace such an otherwise promising technique for managing severe, intractable, generalized epilepsy was primar¬ ily due to the comparatively high morbidity and even mortality experienced at some centers attempting procedures where sev¬ eral forebrain commissures and even the massa intermedia were divided.

There is also evidence that the brain stem is important in the mediation of generalized motor seizures. Electrical activity is propagated to the substantia nigra during kindled seizures.58 Increases in multiple unit activity of the midbrain and pontine reticular formations have been recorded at the onset of pentylenetetrazol-induced tonic seizures.7 Experimental para¬ digms therefore suggest that the corpus callosum conducts both excitatory and inhibitory potentials and that although the spread and synchronization of epileptic discharges is mediated by the corpus callosum, there are other propagation pathways that involve the thalamus, substantia nigra, and brain-stem reticular formation.

Two factors made commissurotomy safer: the advent of microsurgical techniques as promoted by Donald Wilson and the realization that division of the corpus callosum (with the hip¬ pocampal commissure) was as effective as sectioning multiple commissures for achieving control of secondarily generalized seizures.60 61 The development of the operating microscope and improvements in presurgical evaluation and surgical tech¬ niques encouraged epilepsy centers to reevaluate callosotomy, with more emphasis on the neurophysiological and neuro¬ psychological consequences of the procedure.

Clinical Rationale

PATHOPHYSIOLOGY

The origin of the operation of corpus callosotomy for treating epilepsy and the articulation of a clinical rationale for the pro¬ cedure can both be credited to the neurosurgeon William P. Van Wagenen. In 1940 Van Wagenen and Herren defined a ra¬ tionale for corpus callosotomy based on their clinical observa¬ tions and reported the clinical study of 10 patients with a brief follow-up.54

The purpose of epilepsy surgery is of course, where possible, to achieve the cure or at least complete control of all seizures. It must be recognized that there are important secondary reasons to evaluate patients for seizure surgery. One such purpose is to re¬ duce the frequency and severity of particularly disabling and dev¬ astating seizures that cause falls and frequent injuries. Another purpose is to improve control of seizures so that the number and dosages of anticonvulsant medications can be reduced in order to limit or eliminate disabling side effects or toxicity. The goal of seizure surgery is to eliminate epileptogenic tis¬ sue where possible or confine the spread of seizure discharges so they do not become generalized with alterations of con-

They observed that patients with malignant gliomas often had generalized seizures early in the course of the illness, but as the tumor enlarged and involved the corpus callosum, the seizures were often unilateral without loss of consciousness and were fewer in number. A patient with multiple menin¬

Chapter 196/Corpus Callosotomy for Surgical Management of Epilepsy

sciousness and muscle tone. Whereas temporal lobectomy for partial complex seizures has the potential, or even the likelihood in well-selected cases, for cure or complete control of epilepsy, commissurotomy can only confine or desynchronize the spread of the epileptic discharges. Corpus callosotomy is therefore al¬ most always palliative rather than curative and is not an appro¬ priate choice when focal resection of an epileptogenic lesion is feasible. Corpus callosotomy is considered for patients with medically intractable epilepsy where the seizure focus is unapproachable, widespread, or multifocal. The secondarily generalized dis¬ charges result in tonic, atonic, tonic-atonic, or tonic-clonic seizures. The epileptic events must be well documented and significantly interfering with the patient’s health and well¬ being. Many of the patients are suffering repeated falls with re¬ peated lacerations and fractures. Medical intractability is docu¬ mented when intensive and methodical anticonvulsant therapy, verified by adequate drug levels, is proven inadequate to con¬ trol the seizures and provide the patient with satisfactory home, school, and job adjustments. A variety of seizure types have been reported to benefit from callosotomy, but results are considerably better among patients where clinical and electroencephalographic evidence suggests rapid secondary generalization and bilateral synchro¬ nization of the seizure discharges by means of propagation through the corpus callosum. These patients will usually have asymmetrical abnormalities on neurological examination and focal lesions seen on neuroimaging studies.21’61 Sudden head-drops and falls are associated with an atonic event, with loss of muscle tone in the axial or proximal limb musculature. Close observation often discloses a preceding tonic or myoclonic phase of the seizure, however. In Minnesota, only patients suffering frequent and disabling falls with re¬ peated injuries have been selected for corpus callosotomy. Several authors have suggested that patients suffering general¬ ized seizures associated with unilateral structural lesions seen by neuroimaging are better candidates for corpus callosotomy than those with no lateralizing features.16'30’31’38’49 Mental retardation is rarely a contraindication to corpus cal¬ losotomy. The humanitarian benefits of sparing the patient, family, and caregivers from the physical and psychological trauma of experiencing or witnessing repeated head-drops and falls is reason enough in some cases for considering the proce¬ dure even in the severely retarded. Furthermore, it is well rec¬ ognized and documented that many retarded patients demon¬ strate gains in attentiveness, sociability, and behavior following callosotomy. This is not to say that mental retardation is not a factor in outcome. Clinical investigators who have studied this issue re¬ port that severe mental retardation is associated with a poor outcome.4-31’38’61 Patients with lower IQ’s have less success with seizure reduction consistent with the widespread and multifo¬ cal nature of their cerebral pathology. Using the Minnesota cri¬ teria for patient selection—which include medical intractabil¬ ity, unresectability, and frequent generalized seizures causing falls and repeated injuries—it is unusual to have a candidate for callosotomy with an IQ greater than 75. The higher¬ functioning patients tend to have a smoother recovery, shorter convalescence and better seizure outcome after callosotomy. Section of the corpus callosum has been proposed as an al¬ ternative to hemispherectomy in patients with infantile hemi¬ plegia.25'59 This recommendation was primarily predicated on

1905

the higher immediate and delayed complication rates experi¬ enced with hemispherectomy. Furthermore, hemispherectomy is not an ideal option in patients with intact visual fields or with lesser degrees of hemiplegia with preserved finger movements and a somewhat functional hand. In intractable cases where a widespread, unilateral epileptogenic process has resulted in an otherwise nonfunctional hemisphere with a useless con¬ tralateral hand, hemispherectomy is almost always preferable to callosotomy and is one of the most effective procedures in the epilepsy surgeon’s repertoire. Investigators who have studied seizure control after callosot¬ omy and hemispherectomy in comparable patient groups with lateralized epileptogenic lesions have reported hemispherec¬ tomy to be more effective and in some cases curative.20’51 With the advent of modern surgical techniques and modified ap¬ proaches to hemispherectomy, the rate of complications from superficial cerebral hemosiderosis with delayed bleeding and late-developing hydrocephalus has been reduced.39 One of the vexing problems for clinical epileptologists is the identification of a seizure and EEG pattern that would bet¬ ter predict those patients likely to benefit from corpus callosot¬ omy. Most patients considered for callosotomy have one of several interictal electroencephalographic (EEG) patterns: mul¬ tifocal spikes or slow waves with secondary generalization, fo¬ cal spikes with secondary bilateral synchrony, or generalized spike-and-wave discharges with or without a normal back¬ ground. No interictal pattern has been identified that clearly portends a good outcome, but the presence of multifocal, inde¬ pendent interictal spike patterns apparently suggests a poor seizure outcome and an increased risk for developing more fre¬ quent and intense partial seizures after callosotomy.38’47 The identification of an ictal EEG pattern with unilateral on¬ set and rapid secondary generalization and bilateral synchro¬ nization is critical for patient selection. The most favorable ic¬ tal pattern shows epileptiform fast activity at the onset of the seizure.13 Patients with a slow spike-and-wave pattern with a fast, generalized polyspike activity and an electrodecremental response at the onset of this seizure do well after callosotomy. Much poorer results are seen in patients whose seizures have a complex partial onset of frontal lobe origin with a strong tonic component and considerable asymmetry in the tonic activity. There is a consensus in the experimental and clinical litera¬ ture that sectioning the corpus callosum disrupts EEG bisyn¬ chrony to some (albeit variable) degree and that this is corre¬ lated with a diminished generalization of clinical seizures in carefully and well-selected patients. The categories of patients considered for corpus callosot¬ omy include those with multifocal or unresectable focal gener¬ alized epilepsy, progressive epileptic hemiplegic encephalitis (Rasmussen’s syndrome), Forme-Fruste infantile hemiplegia with a functional hand, and the Lennox-Gastaut syndrome.

TECHNIQUE Preoperative Considerations It is important that the preoperative evaluation clearly define the seizure frequency, type, and severity by video-EEG. The precise nature of the seizure(s) to be treated is documented by ictal video-EEG using safety harnesses when necessary to record and correlate the clinical seizure and the onset and pat-

1906

Part 4/Functional Stereotaxis

tern of discharge spread. The preoperative neuropsychological level of function and the existence of preexisting deficits must be recognized and documented. Magnetic resonance imaging (MRI) is done to define the structural integrity and configura¬ tion of the corpus callosum and identify structural lesions and focal or diffuse pathology.

pathology extending beyond the boundaries of the frontal lobes, or a strong bias by the family, guardian, or caregivers against the possibility of having to consider a second-stage pro¬ cedure because of psychosocial issues.

All patients considered for corpus callosotomy are classified according to seizure type(s) based upon clinical documentation of multiple ictal events and concomitant EEG recordings. This often requires sleep-deprived as well as routine EEG with mul¬ tiple 4- to 6-h video-EEG or telemetered sessions. Other ad¬ juncts include sphenoidal leads, hyperventilation, and photic stimulation. Carefully monitored and systematic anticonvulsant drug withdrawal is rarely necessary in this population because of the frequency of the seizures. Pharmacological activation is avoided because of the risk of provoking status epilepticus or nonstereotypical epileptic events.

rior commissure and one limb of the fornix were sometimes in¬ cluded in the early series, but these more extensive commis¬ surotomies did not result in noticeably better seizure outcome and were associated with increased morbidity.

The preoperative evaluation occurs in three phases and may occur over a few weeks up to several years, depending upon the frequency and severity of the seizures and psychoso¬ cial issues. Phase 1 is concerned with categorizing the seizure type(s), establishing compliance with the anticonvulsant med¬ ical regimen, confirming intractability, and defining social and psychological issues. Phase 2 concerns the acquisition of data that support or contraindicate corpus callosotomy as a thera¬ peutic option. Neuropsychometric studies, MRI, video-EEG and possibly positron emission tomography (PET) or single photon emission tomography (SPECT) studies are usually suf¬ ficient to rule out a surgically resectable lesion or seizure focus and define a secondarily generalized seizure pattern amenable to callosal section. The third-phase studies are invasive tests such as the sodium amytal (Wada) test to document language and memory dominance prior to making the final decision to proceed with callosotomy. The MRI is necessary not only for identifying cerebral pathology and congenital defects, but for preoperative planning of the surgery. The configuration and dimension of the corpus callosum can be determined and, more importantly, the loca¬ tion of cortical bridging veins in the region of the surgical ap¬ proach determined and the position of the bone flap adjusted in order to avoid the risk of cortical venous infarction. Preoperative studies are important for deciding and plan¬ ning the extent of callosotomy. Section of the anterior twothirds of the corpus callosum carries little risk of permanent disconnection and is, therefore, the procedure of choice for pa¬ tients in whom neuropsychometric studies indicate a relatively high IQ and level of performance. Many patients achieve sig¬ nificant improvement in their seizure control following anterior callosotomy, and the risk of total section is probably not war¬ ranted in the highly functioning patient. It is well recognized that a second-stage completion of the posterior corpus callo¬ sum can be performed at a later date if the seizure control after anterior callosotomy does not meet expectations. There are pa¬ tients, however, in whom preoperative EEG and neuroimaging studies have demonstrated posterior cerebral pathology, where the propagation of seizure activity is likely occurring through the splenium and posterior body of the corpus callosum. In these cases the callosotomy should be completed as a primary procedure. Other factors promoting complete section of the corpus callosum in one stage include severe mental retardation and a low level of function that makes increased disability from disconnection unlikely, the presence of diffuse multifocal

No attempt is made to spare the hippocampal commissure on the underside of the body of the corpus callosum. The ante¬

Anticonvulsant drug levels and a coagulation battery in¬ cluding a bleeding time are obtained preoperatively. Patients on valproate often have a prolonged bleeding time; this drug is discontinued and an appropriate anticonvulsant drug substi¬ tuted if necessary at least 2 weeks before the scheduled surgery.

Surgical Considerations The operative technique varies little from institution to institu¬ tion. The procedure is performed under general anesthesia. In instances where EEG monitoring is used to determine the ex¬ tent of section where generalized epileptiform discharges be¬ come lateralized, the montages are placed prior to preparing and draping the field. The isoflurane level in EEG-monitored cases is kept at a concentration of around 0.5%. At Minnesota, the patient is placed in the supine position with the table slightly flexed and the skull secured by three-point skeletal fix¬ ation. This gives the surgeon a comfortable vantage, looking straight down on the vertex. Some surgeons prefer a lateral de¬ cubitus position in the belief that gravity acting on the depen¬ dent hemisphere aids exposure. The author prefers to trephine the skull on either side of the midline rather than directly over the sagittal sinus. The free bone flap is turned with a high-speed air drill or Gigli saw. The latter provides a beveled edge, allow¬ ing for a nice cosmetic closure in the frontal region. It is impor¬ tant that the craniotomy cross the midline so that brain retrac¬ tion is minimal while exposing the corpus callosum through the interhemispheric fissure. The dura mater is opened far enough laterally so that there is little danger of injuring the large bridging veins as they ap¬ proach the sagittal sinus. Large dural venous lakes and pac¬ chionian bodies are also less conspicuous a few centimeters off the midline. The dura mater is opened to the edge of the sagittal sinus and dural retraction sutures are placed to assist the sur¬ geon in obtaining exposure. A bicoronal incision is made with the right limb extending to the level of the top of the auricle and the left limb extending to the top of the insertion of the temporalis muscle. The skull is exposed by subperiosteal retraction of the scalp. The precise position of the bone flap is determined by preoperative assess¬ ment of the location of the bridging cortical veins. Usually the free bone flap is two-thirds in front and one-third behind the coronal suture. If a complete callosotomy is planned, it is better to have more exposure in the sagittal than in the coronal plane. It may be necessary to tamponade venous ooze from the dura mater over the sagittal sinus with pledgets of Avitene, Surgicel, or Geifoam. Bridging veins are spared, and this is usually pos¬ sible if the bone flap is well placed and long enough in the sagittal plane. Mannitol is administered in a dosage of I g/kg at least 20 min prior to beginning the interhemispheric exposure. Hyper-

Chapter 196/Corpus Callosotomy for Surgical Management of Epilepsy

ventilation to an end-tidal CO, of 22 and the reverse Trendelenburg position may all assist with brain relaxation. If the ventricles are generous and the brain remains tight in spite of the above measures, the ipsilateral ventricle can be tapped as a last resort for relaxing the brain and avoiding excessive trac¬ tion on the interhemispheric cortex. The surface of the cerebral cortex is protected with moist pledgets, and a self-retaining re¬ tractor system is gently positioned once the brain is relaxed. The operating microscope is brought into the field and stan¬ dard microsurgical technique is used to take down inter¬ hemispheric adhesions. These adhesions may be quite dense in older patients who have had numerous falls and small bleeds or a prior episode of meningeal encephalitis. This dissection is usually much easier in young children. In cases where the cin¬ gulate gyri are densely adherent beneath the lower edge of the falx cerebri, some trauma to the pia mater and cingulate cortex may be unavoidable, but every effort should be made to limit such injury to one side. It is important to identify the callosal marginal and perical¬ losal arteries both for the purpose of avoiding injury to the ves¬ sels and for anatomical orientation. The pericallosal vessels lie immediately dorsal to the nacreous fibers of the corpus callo¬ sum. Division of the cotpus callosum between the paired peri¬ callosal arteries assures the surgeon proximity to the midline and often exposes the cavum between the two leaves of the septum pellucidum once the corpus callosum is divided. Transection of the callosal fibers to either side of the paired pericallosal arteries will usually result in exposure of either the right or left lateral ventricle. The exposure is carried forward until the paired pericallosal arteries are seen merging with the anterior cerebral vessels where the frontopolar artery is given off and the anterior cerebral vessels dive down and around the genu and beneath the rostrum. Callosal fibers are divided and these vessels exposed until the anterior commissure is visual¬ ized to assure the surgeon that the genu and rostrum have been completely sectioned. Occasionally a single azygous anterior cerebral artery supplies both hemispheres. Various instruments are used to section the callosal fibers, including microsuckers, microdissectors, the ultrasonic aspirator, and laser. Micro¬ suction is safe and cost-effective. Exposure is facilitated by periodically adjusting the operating table into the reverse Trendelenburg position when working on the genu and the Trendelenburg position when working on the splenium of the corpus callosum. In cases where there has been ventriculitis or ependymitis, the ependyma is quite firm and the integrity of the ventricles protected. Often, however, the ependyma is a gossamer struc¬ ture that is easily fenestrated. With microsurgical technique and meticulous hemostasis, no complications or side effects are ap¬ parent when the ependyma is violated. Aseptic ventriculitis has not been a recognized problem in the Minnesota series. The extent of the ongoing section may be assessed in a number of ways and is, of course, not an issue when complete section is planned. It is helpful to study the midline sagittal cut of the MRI in order to appreciate the length and configuration of the corpus callosum. The inferior tip of the splenium can be a long reach in those cases where the corpus callosum takes the shape of an upside-down “U” and the splenium is quite bul¬ bous. In such cases, it is necessary for the surgeon to visualize the arachnoid membrane over the vein of Galen and internal cerebral veins before concluding that all the fibers of the sple¬ nium are sectioned. Distinctive anatomic features of the corpus

1907

callosum are recognizable on the MRI and guide the surgeon as to the extent of the section. MRI measurements can also be cor¬ related with surgical measurements. One approach is to mark the posterior extent of the section and obtain an intraoperative plain skull film using the glabella, inion, and bregma as anatomic landmarks in conjunction with an MRI obtained be¬ fore surgery.3 A useful landmark is the isthmus of the corpus callosum that marks the boundary between the posterior body and the splenium. The experienced neurosurgeon can usually recognize this segment as the callosotomy progresses. If in doubt, however, a radiographic marker can be placed at the posterior point of the section and a lateral skull film obtained. A perpendicular line is then drawn from the marker to a line connecting the bregma and inion and compared with a similar line drawn from the isthmus on the preoperative MRI. The sec¬ tion can then be extended as necessary to assure a four-fifths partial callosotomy with sparing of the splenium.46 After irrigation of the wound and meticulous attention to hemostasis, the self-retaining retractors are removed and the anesthesiologist is asked to raise the patient’s venous pressure to see if this elicits any intradural bleeding. If not, the dura mater is closed with a running 4-0 nylon suture and dural tacking sutures are applied. The bone flap is secured with a 0 Tevdek or wire sutures, and the galea is closed with inter¬ rupted inverted 2-0 Vicryl or similar suture. The dermis is closed with staples and a sterile dressing is applied. Postoperative care is consistent with standard craniotomy precautions. The endotracheal tube is left in place until the pa¬ tient is breathing well and has good protective reflexes. A naso¬ gastric tube is often necessary during the early postoperative period for the administration of anticonvulsant medications. Children can usually be mobilized and discharged from the hospital more rapidly than adults.

Results The EEG changes are quite dramatic after complete section of the corpus callosum with desynchronization of the bilateral EEG abnormalities and the more clear-cut demonstration of fo¬ cal abnormalities.17 It is difficult if not futile to try to compare seizure outcomes between reported series of corpus callosotomy because of the differences in inclusion criteria among the epilepsy centers. Almost all reporting centers have found that partial or complete callosotomy is of significant benefit for patients with tonic/atonic seizures characterized by repeated falls and for generalized tonic-clonic seizures.’■'81940 Callosotomy for com¬ plex partial seizures is much more controversial, but a few in¬ vestigators have reported successful outcomes for this seizure type.1543 There is considerable variation in the literature with regard to the effectiveness of partial callosotomy. Investigators agree that complete callosotomy is effective in reducing or eliminat¬ ing bilaterally synchronous generalized discharges, but is this benefit worth the risk of neurological deficit? Comparing series of “anterior callosotomy” is difficult because of the variation in extent of callosotomy. At Minnesota, the extent of anterior cal¬ losotomy has evolved from a 50 percent section to two-thirds section and currently an 80 percent section. In children with a Lennox-Gastaut syndrome and severe mental retardation, a complete section is performed.

1908

Part 4/Functional Stereotaxis

An early age of seizure onset and callosotomy during child¬ hood correlate well with a favorable outcome.31-49 The operation is better tolerated, seizures are more readily ameliorated, and the children avoid the risk of repeated falls and injuries as they grow. Education and training are also enhanced by the improved attentiveness, sociability, and behavior improvement seen after callosotomy. There is general agreement in the literature that a good seizure outcome is favored by a higher IQ.4-49-61 Mental retarda¬ tion is often associated with more severe and widespread brain damage, and the seizure disorder is accordingly more complex and refractory to both medical and surgical treatment. The ma¬ jority of patients considered for corpus callosum section are mentally retarded, because this is the group of patients most in need of relief. Mental retardation is not a contraindication to corpus callosotomy. Purves et al. reported that the mentally re¬ tarded with diffuse cerebral pathology responded less well to anterior callosotomy than patients with unilateral pathology, but 40 percent of these patients were still classified as having an excellent seizure outcome.38 Cendus et al. reported a series of children undergoing corpus callosotomy, and 32 of the 34 patients were mentally retarded. Satisfactory seizure control was achieved in 73.5 percent of this population.8 This inci¬ dence of mental retardation in the pediatric population con¬ sidered for callosotomy is consistent with the Minnesota experience where there is a predominance of patients with Lennox- Gastaut syndrome and mental retardation. Patients with severe attentional disturbance of a frontal lobe type show improvement after either anterior or complete callosotomy. Attention disorders with frontal lobe epilepsy in¬ clude incomplete retention of commands, easy distraction from tasks, and abrupt interruption of task in progress. The families and caregivers of patients undergoing corpus callosot¬ omy are invariably enthusiastic about the improvement they witness in attentiveness, memory, sociability, verbalization, school performance, and integration with family, friends, and peers. They report that “we feel like we have our child back,” or “he seems more human.” This improvement has been as¬ cribed to the relief of a frontal syndrome induced by frequent bilateral generalized seizures. The improvement in behavior is correlated with changes in frontal blood flow confirmed by SPECT imaging.45 Spencer et al. reported that total corpus callosotomy pre¬ vented secondarily generalized seizures in at least 75 percent of patients, which is consistent with other series.49 They found that total callosotomy was more than twice as effective as par¬ tial section. They also found that the presence of two or more seizure types, a verbal IQ less than 80, and diffuse ictal EEG patterns were significantly more common in the patients who failed with anterior callosotomy and that these patients could benefit by extending and completing the callosotomy.48 Fuiks et al. found that 70 percent of their 80 patients under¬ going anterior callosotomy had significant improvement in their seizures, and 12.8 percent were cured. Eighty-six percent ot patients with generalized tonic-clonic seizures and 83 per¬ cent ot patients with atonic seizures were markedly better. Ten patients with either atonic, tonic-clonic, or mixed seizures who failed to improve underwent subsequent completion of the callosotomy and in no case was the improvement sufficient to move the patient from one outcome category to another.15 Other investigators have found worthwhile improvement in seizure outcome by completing a partial section.41

Intraoperative EEG monitoring throughout the act of sec¬ tioning the corpus callosum showed that 78 percent of patients with generalized epileptiform discharges at the outset of the procedure became lateralized when somewhere between twothirds and all of the callosum was divided.14 All of the 37 pa¬ tients with tonic-atonic seizures with “drop” attacks had at least an 80 percent reduction in their seizure frequency. Those pa¬ tients with the greatest decrease in generalized discharges had the greatest decrease in seizures (95.5 percent), but six patients with no lateralization of generalized discharges showed an 88 percent decrease in seizures. Patients with a mild or moderate decrease in generalized discharges had an 85 percent decrease in seizures. It therefore appears that although lateralization of generalized epileptiform discharges is evident in more than three-fourths of patients, the degree of lateralization does not correlate well with the degree of tonic-atonic seizures. Intra¬ operative surface EEG monitoring was therefore not consid¬ ered particularly helpful as a guide to determining the extent of the callosal section.

COMPLICATIONS In 1936 Walter Dandy described his experience with sectioning the corpus callosum to approach third ventricular and pineal tu¬ mors. “The corpus callosum is split longitudinally from its pos¬ terior extremity to a point anteriorly where the third or lateral ventricle comes into view; this incision is bloodless. Usually this incision takes most and sometimes all of this structure to its downward bend. No symptoms follow its division. This simple experiment at once disposes of the extravagant claims to function of the corpus callosum.”11 Barely a year later, however, Trescher and Ford reported alexia in the left visual field in a patient of Dandy’s upon Whom a third ventricular colloid cyst was approached transcallosally. They offered a number of explanations for this finding in the face of Dandy’s earlier disclaimer, suggesting that the section was perhaps more extensive for this lesion than that necessarjl for approaching pineal tumors. They also noted that “special methods of examination are required to demonstrate the essen¬ tial symptoms.”53 While it is true that sectioning the corpus callosum can result in side effects and complications, these are usually quite tran¬ sient and do not interfere with the quality of the patient’s dayto-day activities. In well-selected patients, particularly those suffering severely from repeated falls and injuries, it is probably preferable to be aggressive rather than timid in considering the extent of the section, because the disconnection syndrome is rarely significant in the daily life of these patients. Children tol¬ erate callosal section better than adults, have fewer complica¬ tions and side effects, and have a shorter convalescence. Neurological deficits following corpus callostomy are best distinguished by whether they are transient or permanent, sig¬ nificant or only apparent by means of sophisticated neuropsy¬ chometric testing, expected or unexpected, a side effect of cal¬ losal disconnection or a complication of the operation such as infection, hemorrhage, or infarction. During the immediate postoperative period, which can be a few hours in a young child or 2 to 3 weeks in a severely men¬ tally retarded adult, a number of transient neuropsychological phenomena are observed. The patient lacks spontaneity of speech and motion. If any speech occurs, it is often one or two

Chapter 196/Corpus Callosotomy for Surgical Management of Epilepsy

primitive words or short phrases occurring only in response to verbal or physical stimulation. The patient shows a paucity of motion, and if asked to raise an arm or squeeze a hand, there is often a prolonged delay between the request or command and the response. There is a variable degree of left-sided neglect, more pronounced in the leg than in the arm. The inexperienced observer may interpret this as a paresis, but true weakness is unusual unless a cortical venous infarction or severe retraction edema in the posterior frontal lobe has occurred. Adult patients tend to sit slumped, with reduced postural tone; the head often deviates toward the left side; and the face wears a full, apa¬ thetic expression. The etiology of these transient findings is not clearly established but may be caused by disruption of commis¬ sural fibers between the frontal lobes and supplementary motor cortices. This syndrome can be seen after anterior or total cal¬ losotomy and is distinct from the permanent disconnection syn¬ drome documented by specific neuropsychometric stimulus testing after complete callosotomy. The left visual and tactile agnosia detected by specific and artificial testing paradigms is of no significance to the typical candidate for callosotomy. There are several specific situations, however, where cal¬ losotomy has a particular affinity for producing significant fo¬ cal deficits. One such situation is where the early onset of hemispheric damage results in an acquired right hemispheric dominance for language in a right-handed individual who writes with the right hand. An analogous risk occurs when a ge¬ netically determined left-handed person is left hemisphericdominant for speech. A disconnection deficit also occurs when hemianopsia or alexia exist in the visual field contralateral to the hemisphere dominant for language. If an early hemispheric injury causes speech and verbal memory to be located in con¬ tralateral hemispheres, corpus callosotomy produces a signifi¬ cant risk for language deficits.35 New seizure types are sometimes first apparent or appreci¬ ated after corpus callosotomy.18'36’43'47 These “new” seizures are not common and are usually described as being either complex partial, simple partial, or myoclonic. Simple partial seizures and focal myoclonic seizures may be recognized for the first time after a corpus callosotomy.34 These seizures may represent an active focus that is no longer generalizing or an irritable re¬ gion of cortex no longer subjected to inhibitory influences. On occasion these “new” seizures are sufficiently frequent to con¬ cern the patient or family. The simple partial seizures tend to improve over time or with adjustments of medication. Analysis of patients from the Minnesota experience follow¬ ing partial callosotomies allows us to reach several conclusions relevant to permanent disconnection syndromes. Patients with two-thirds of the corpus callosum sectioned demonstrate left ear suppression of verbal information under conditions of dichotic stimulation. Patients with only the splenium and most posterior portion of the body of the callosum intact are able to execute complex motor sequences involving the left hand and arm to verbal command and are capable of the interhemispheric transfer of visual, tactile, and kinesthetic messages. Patients with only the splenium intact exhibit a disconnection for all modalities tested except vision, which remains com¬ pletely intact.42 These findings underscore the importance of the posterior body and splenium of the corpus callosum for ba¬ sic and sensorimotor interhemispheric integration. Patients whose surgical sections have spared these areas do not demon¬ strate a permanent disconnection syndrome or any impairment of intellectual ability, suggesting that the practical significance

1909

of uncomplicated anterior callosum section is minimal. The topographic arrangement of callosal fibers accounts for the se¬ lective nature of the disconnection syndromes. As with any intracranial operation, a full spectrum of surgi¬ cal complications is possible though rarely seen, as the experi¬ ence of the epilepsy surgery team grows. The Minnesota expe¬ rience has included one death among the first 170 patients having craniotomy for section of the corpus callosum. This pa¬ tient was a severely debilitated, diabetic middle-aged man who was recommended for callosotomy only after he fractured both legs during a tonic-atonic drop attack in which his caregivers caught him before he hit the ground. During the postoperative period, he was unable to swallow effectively and developed fulminant peritonitis and septic shock following jejunostomy complicated by a bowel perforation. As patient selection criteria have been refined and modem neurosurgical and microsurgical technology developed, the complications and risks of callosal sectioning have lessened considerably. Surgical complications include aseptic and sep¬ tic ventriculitis that can result in delayed hydrocephalus. The risk of ventricular contamination by blood and tissue debris is less since Wilson introduced the operating microscope and the use of microsurgical techniques to callosotomy in the 1970s.59 Wilson recommended that every effort be made to maintain the integrity of the ependyma in order to reduce ven¬ tricular soilage. Recognition that anterior commissurotomy, fornicotomy, and section of the massa intermedia are of little benefit also led to constructive advances in the avoidance of this complication. The risk of postoperative intracranial bleeding in the epidural or subdural spaces is reduced by preoperative atten¬ tion to the coagulation studies and discontinuation of anticon¬ vulsant drugs, such as devalproex (Depakote), known to pro¬ long the bleeding time well before the day of the surgery. Cortical venous infarction with secondary edema and hemor¬ rhage is avoided by sparing the bridging cortical veins. Careful positioning of the craniotomy after analysis of the venous anatomy on preoperative scans or angiograms lessens this risk. The risk of air emboli is controlled by careful attention to the venous sinuses, waxing the bone edges, avoiding the sitting po¬ sition, and utilizing the Doppler for detection of air throughout the procedure. Injury to the sagittal sinus is reduced by aware¬ ness of the skull thickness in a patient on chronic anticonvul¬ sant therapy and by not placing burr holes directly over the sagittal sinus. The risk of corpus callosotomy at major epilepsy centers ex¬ perienced with this procedure is comparable to that of resective surgery and is no longer a contraindication in patients meeting appropriate selection criteria.

References 1. 2. 3.

4.

Amacher AL: Midline commissurotomy for the treatment of some cases of intractable epilepsy. Childs Brain 2:54-58, 1976. Asanuma H, Okuda O: Effects of transcallosal volleys on pyramidal tract cell activity of cat. J Neurophysiol 25:198-208, 1962. Awad IA, Wyllie E, Luders H, Ahl J: Intraoperative determination of the extent of corpus callosotomy for epilepsy: Two simple techniques. Neurosurgery 26: 102-106, 1990. Blume, WT: Corpus callosum section for seizure control: Rationale and review of experimental and clinical data. Cleve Clin Q 51: 319-332, 1984.

1910

Part 4/Functional Stereotaxis

5.

Bogen JE, Fisher ED, Vogel PJ. Cerebral commissurotomy: A second case report. Am J Med 194: 1328-1329, 1965.

6.

Bogen JE, Vogel PJ: Treatment of generalized seizures by cerebral com¬ missurotomy. Surg Forum 14:431-433, 1963.

7.

Bremer F: Nouvelle recherches dans le mecanisme du sommeil. CR Soc Biol (Paris) 122:460-464, 1936.

8.

Cendes F, Ragazzo P, daCosta V, Martins L: Corpus callosotomy in

9. 10.

treatment of medically resistant epilepsy: Preliminary results in a pe¬ diatric population. Epilepsia 34:910-917, 1993. Collins R, Kennedy C, Sokoloff L, Plum F: Metabolic anatomy of fo¬ cal motor seizures. Arch Neurol 33: 536-542, 1976. Curtis HJ, Bard P: Intercortical connections of the corpus callosum as indicated by evoked potentials. Am J Physiol 126:473, 1939. Dandy WE: Operative experiences in cases of pineal tumors. Arch Surg 33:19-46, 1936.

31.

Murro AM, Flanigan HF, Gallagher BB, et al: Corpus callosotomy for the treatment of intractable epilepsy. Epilepsy Res 2:44-50, 1988.

32.

Musgrave J, Gloor P: The role of the corpus callosum in bilateral in¬ terhemispheric synchrony of spike and wave discharge in feline gen¬ eralized penicillin epilepsy. Epilepsia 21:369-378, 1980. Maquet R, Manini CH, Catier J: Photically induced epilepsy in Papio Papio: The initiation of discharges and the role of the frontal cortex and of the corpus callosum, in Petsche H, Brazier M (eds): Synchro¬ nization of the EEG in the Epilepsies. Vienna: Springer-Verlag, 1972, pp 347-367.

33.

34.

Nordgren R, Reeves A, Viguera A, Roberts D: Corpus callosotomy for intractable seizures in the pediatric age group. Arch Neurol 48:364-372, 1991.

35.

Novelly R, Lifrak M: Forebrain commissurotomy reinstates effects of pre-existing hemisphere lesions: An examination of the hypothesis, in Reeves AG (ed): Epilepsy and the Corpus Callosum. New York: Plenum Press, 1985, pp 467-500.

36.

changes during corpus callosotomy in predicting surgical results. Epilepsia 34:74-78, 1993.

Oguni H, Olivier A, Andermann F, Comair J: Anterior callosotomy in the treatment of medically intractable epilepsies: A study of 43 pa¬ tients with a mean follow up of 39 months. Ann Neurol 30:357-364, 1991.

37.

15.

Fuiks KS, Wyler AR, Hermann BP, Somes G: Seizure outcome from anterior and complete corpus callosotomy. J Neurosurg 74:573-578, 1991.

38.

16.

Garcia-Flores E: Corpus callosum section for patients with intractable epilepsy. Appl Neurophysiol 50: 390-397, 1987.

Pandya DN, Rosene DL: Some observations on trajectories and topography of commissural fibers, in Reeves AG (ed): Epilepsy and the Corpus Callosum. New York: Plenum Press, 1985. pp 21-39. Purves SJ, Wada JA, Woodhurst WB, et al: Results of anterior corpus callosum section in 24 patients with medically intractable seizures. Neurology 38:1194-1201, 1988.

17.

Gates JR, Maxwell R, Leppik IE, et al: Electrographic and clinical ef¬ fects of total corpus callosotomy, in Reeves AG (ed): Epilepsy and the Corpus Callosum. New York: Plenum Press, 1985, pp 315-328. Gates JR, Rosenfeld WE, Maxwell RE: Response of multiple seizure types to corpus callosum sectioning. Epilepsia 28:28-34, 1987. Geoffroy G, Lassonde M, Delisle F: Corpus callosotomy for control of intractable epilepsy in children. Neurology 33:891-897, 1983.

11. 12.

Erickson TC: Spread of the epileptic discharge; an experimental study of the afterdischarge induced by electrical stimulation of the cerebral cortex. Arch Neurol Psychiatry 43:429—452, 1940.

13.

Fiol ME, Gates JR: EEG studies and corpus callosotomy results. EEG Clin Neurophysiol 58:34, 1984.

14.

Fiol M, Gates J, Mireles R, et al: Value of intraoperative EEG

18. 19. 20.

21.

22.

23.

24. 25.

39.

Rasmussen T: Hemispherectomy for seizures revisited. Can J Neurol Sci 10:71-78, 1983.

40.

Rayport M, Ferguson SM, Corrie SW: Outcome and indications of corpus callosotomy section for intractable seizure control. Appl Neurophysiol 46:47-51, 1983.

41.

Goodman RN, Williamson PD, Reeves AG, et al: Interhemisphere commissurotomy for congenital hemiplegics with intractable epi¬ lepsy. Neurology 35:1351-1354, 1985.

Routens D, Bye A, Hopkins I, et al: Corpus callosotomy for in¬ tractable epilepsy: Seizure outcome and prognostic factors. Epilepsia 34:904-909, 1993.

42.

Harbaugh RE, Wilson DH, Reeves AG, Gazzaniga MD: Forebrain commissurotomy for epilepsy: Review of 20 consecutive cases. Acta Neurochir 68:263-275, 1983.

Risse GL, Gates JR, Lund G, et al: Interhemispheric transfer in pa¬ tients with incomplete section of the corpus callosum. Arch Neurol 46:437^143, 1989.

43.

Joynt RJ: History of forebrain commissurotomy, in Reeves AG (ed): Epilepsy and the Corpus Callosum. New York: Plenum Press, 1985, pp 237-241.

Roberts DW, Reeves AG: Effect of commissurotomy on complex par¬ tial epilepsy in patients without a resectable seizure focus. Appl Neurophysiol 50: 398^400, 1987.

44.

Kopeloff N, Kennard M, Pacella B, et al: Section of corpus callosum in experimental epilepsy in the monkey. Arch Neurol Psychiat 63: 719-727, 1950.

45.

Schwartzkroin P, Mutani R, Prince D: Orthodromic and antidromic effects of a cortical epileptiform focus on ventrolateral nucleus of the cut. J Neurophysiol 38:795-811, 1975. Septien L, Giroud M, Sautreaux J, Dumas R: Corpus callosotomy for intractable seizures in the pediatric age group: Influence on frontal syndrome. Childs Nerv Syst 8:2-3, 1992. Shimizu H, Ohta Y, Suzuki I, et al: Anterior extensive corpus callo¬ sotomy including resection of the isthmus. Jpn J Psychiatry Neurol 47:264-266, 1993.

Kusske J, Rush J: Corpus callosum and propagation of afterdischarge to contralateral cortex and thalamus. Neurology 28:905-912, 1978. Luessenhop AJ: Interhemispheric commissurotomy (the split brain operation) as an alternative to hemispherectomy for control of in¬ tractable seizures. Am Surg 36:265-268, 1970.

26.

Marcus EM: Generalized seizure models and the corpus callosum, in Reeves AG (ed): Epilepsy and the Corpus Callosum. New York: Plenum Press, 1985, pp 131-206.

27.

Marcus EM, Watson CW: Bilateral synchronous spike wave electro¬ graphic patterns in the cat: Interaction of bilateral cortical foci in the intact, the bilateral cortical-callosal, and diencephalic preparation. Arch Neurol 14:601-610, 1966.

28.

Marcus EM, Watson CW: Symmetrical epileptogenic foci in mon¬ key cerebral cortex: Mechanisms of interaction and regional varia¬ tions in capacity for synchronous discharges. Arch Neurol 19' 99-116, 1968.

29.

Marcus EM, Watson CW, Simon SA: An experimental model of some varieties of petit mal epilepsy: Electrical-behavioral correlation of acute bilateral epileptogenic foci in cerebral cortex. Epilepsia 9233-248, 1968.

30.

Marino R Jr, Ragazzo PC: Selective criteria and results of selective partial callosotomy, in Reeves AG (ed): Epilepsy and the Corpus Callosum. New York: Plenum Press, 1985, pp 281-301.

46.

47.

Spencer SS, Spencer DD, Glaser GH, et al: More intense focal seizure types after callosal section: The role of inhibition. Ann Neurol 16:686-693, 1984. 48. Spencer S, Spencer D, Sass K, et al: Anterior, total, and two-stage corpus callosum section: Differential and incremental seizure re¬ sponses. Epilepsia 34: 561-567, 1993. 49. Spencer SS, Spencer DD. Williamson PD, et al: Corpus callosotomy for epilepsy: I. Seizure effects. Neurology 38:19-24, 1988. 50. Stavraky GW: Supersensitivity Following Lesions of the Nervous System. Toronto: University of Toronto Press, 1961, pp 33-38. 51. Tinuper P, Andermann F, Villemerre JG, et al: Functional hemi¬ spherectomy for treatment of epilepsy associated with hemiplegia: Rationale, indications, results and comparisons with callosotomy. Ann Neurol 24:27-34. 1988. 52. Tomasch J: Size, distribution, and number of fibres in the human cor¬ pus callosum. Anat Rec 119:119-135, 1954. 53. Trescher JH, Ford RR: Colloid cyst of the third ventricle: Report of a case: Operative removal with section of posterior half of the corpus callosum. Arch Neurol Psychiatry 37:959-973, 1937.

Chapter 196/Corpus Callosotomy for Surgical Management of Epilepsy

54.

55.

56. 57.

Van Wagenen WP, Herren RY: Surgical division of commissural path¬ ways in the corpus callosum: Relation to spread of an epileptic attack. Arch Neurol Psychiatry 44:740-759, 1940. Vergnes M, Marescaux CL, Depaulis A, et al: Spontaneous spike and wave discharges in Wistar rats: A model of genetic generalized nonconvulsive epilepsy, in Avoli M, Gloor P, Kostopoulos G, Naquet R (eds): Generalized Epilepsy, Neurobiological Approaches. Boston:

58.

Birkhauser, 1990, pp 238-253. Wada JA, Nakashima T, Kaneko Y: Forebrain bisection and feline amygdaloid kindling. Epilepsia 23: 521-531, 1982. Wada JA, Sato M: Generalized convulsive seizures induced by daily electrical stimulation of the amygdala in cats: Correlative electro¬ graphic and behavioral features. Neurology 24:565-574, 1974.

60.

59.

61.

1911

Wada JA, Sato M: The generalized convulsive seizure state induced by daily elevctrical stimulation of the amygdala in split brain cats. Epilepsia 16:417M30, 1975. Wilson DW, Culver C, Waddington M, Gazzaniga M: Disconnec¬ tion of the cerebral hemispheres: An alternative to hemispherectomy for the control of intractable seizures. Neurology 25: 1149-1153,1975. Wilson DH, Reeves AG, Gazzaniga MS, Culver C: Cerebral commis¬ surotomy for control of intractable seizures. Neurology 27:708-715, 1977. Wilson DH, Reeves AG, Gazzaniga MS: “Central” commissurotomy for intractable generalized epilepsy: Series two. Neurology 32: 687-697, 1982.

CHAPTER

197

HEMISPHERECTOMY FOR SURGICAL MANAGEMENT OF EPILEPSY

Jean-Guy Villemure

HISTORICAL BACKGROUND

In 1933, W. J. Gardner6 reported his experience with hemi¬ spherectomy for tumor in 3 cases; 2 patients died of hyperther¬ mia within 36 h following the operation and the other was alive 21 months postoperatively at time of the report. Gardner em¬ phasizes the early postoperative return of function in the af¬ fected leg, so that the patient could flex and extend it, allowing her to walk without assistance within 2 months following

Dandy was the first surgeon to carry out cerebral hemispherectomy in humans.1 Between 1923 and 1928, he proceeded to hemispherectomy in 5 patients suffering from a right hemi¬ sphere glioma, the objective of the operation being to eradicate the tumor. In his preliminary report, published in 1928, Dandy relates the patients’ histories and physical findings pre- and postoperatively and describes the technique of anatomic hemi¬ spherectomy. Dandy insists that mentation is not impaired post¬ operatively. The hemiplegia, while complete in the arm and leg, is only partial in the face. He reports a patient surviving 3 'A years postoperatively who regained some flexion and extension of the knee and thigh. He goes on to describe that patients de¬ velop mild rigidity of the paralyzed limbs following an initial period of flaccidity; deep sensation is preserved, while epicritic and protopathic sensations are lost. Hemianopsia is the rule, and Dandy noted little if any impairment of the cranial nerves. The technique utilized required, as a first step, ligation of the middle and anterior cerebral arteries at the carotid bifurcation, which “causes a considerable lessening of the cerebral bulk”; the main veins were ligated. Dandy removed the hemisphere in fragments; first, the frontal lobe was sectioned, requiring “only a sweep of the scalpel.” The corpus callosum was divided; the incision through the internal capsule was then carried through

surgery. Contrary to Dandy, Gardner did not excise the basal gan¬ glia; the early motor recovery in his patient led him to conclude that the “function present in the leg is due to basal ganglion innervation.” This same patient was discussed again by J. D. O’Brien7 when, in 1936, he reported deterioration occurring after a fall. The clinical evolution (days or weeks) led to trephination and drainage of a subdural hematoma on the side opposite to hemi¬ spherectomy and repeated drainage of bloody spinal fluid from the hemispherectomy cavity; initially these punctures improved the patient’s condition, but this therapy eventually failed and she expired 4 months following the onset of deterioration. This represents the first report of the late complications that may be encountered following anatomic hemispherectomy, in this case, the presence of a subdural hematoma following a fall; it is also possibly the first clinical case of superficial cerebral hemosiderosis (SCH). No autopsy could be obtained to docu¬ ment the pathological findings further. We owe to Kenneth McKenzie the credit for having carried out the first hemispherectomy for control of seizures,8 as pre¬ sented at the American Medical Association Annual Session in 1938. The patient, a female aged 16 years at time of surgery, had sustained a head injury at age 3 weeks and developed a left hemiplegia and seizures. After the en bloc hemispherect¬ omy, she showed no clinical aggravation and the seizures

the depth of the temporal lobe. Dandy’s patients expired from 48 h to 3 'A years postopera¬ tively from hemorrhage, pneumonia, or tumor progression. Throughout his report, he insists that the operation did not create any mental impairment. While hemispherectomy for glioma has been abandoned, Dandy pioneered the technique and demonstrated that half the brain could be removed without intellectual changes and in those of his patients who were already hemiplegic, without

stopped. By 1949, a total of 13 cases of hemispherectomy for tumor had been reported in the literature, according to Bell and Kamosh,9 whose paper reviews the major postoperative clini¬ cal features encountered in these patients and report a case with

physical deterioration. Contrary to what has been reported by Rasmussen,2 Good¬ man,3 and Davies,4 Jean Lhermitte never did a hemispherect¬ omy.5 In his 1928 paper on hemispherectomy published in L’Encephale (the same year as Dandy’s report), Lhermitte dis¬ cusses Dandy’s clinical observations from an anatomophysiological point of view and points out their significance, taking stands which in some instances were completely opposed to some of the current theories.

a 10-year follow-up. In 1950, R. A. Krynauw reported a series of 12 patients with infantile hemiplegia treated by hemispherectomy10 for seizures and/or behavior disturbances; two patients without a history of seizures underwent hemispherectomy. In his paper, Krynauw

1913

1914

Part 4/Functional Stereotaxis

discusses all his 12 cases individually in detail as to the history as well as the preoperative, operative, and postoperative find¬ ings. The operative technique consisted of dividing the hemi¬ sphere into four fragments and dissecting them from within the ventricle. The results of these operations were dramatic, with complete seizure control in all cases and improved personality and behavior. This paper by Krynauw led many neurosurgical centers in Europe and America to carry out hemispherectomy as well, so that, by 1961, White found 261 cases recorded in the litera¬ ture." His paper discusses the clinical syndrome of infantile hemiplegia, gives a review of the literature, and presents two cases of his own. In the decade of the 1950s, many papers from multiple surgeons were published describing small series of patients op¬ erated upon or describing the technique utilized.12-16 While hemispherectomy consisted of the anatomic removal of the hemisphere, this was done either en bloc or in fragments (Table 197-1; Fig. 197-1). This choice of technique had no physiologi¬ cal complications, but the issue of leaving or excising the basal ganglia was more controversial. Gardner6 had already postu¬ lated that preservation of the basal ganglia in his cases was re¬ sponsible for their better motor performance postoperatively, in contradistinction to Dandy’s patients, who had these structures removed and did not seem to regain much motor function.1 Both French14 in the United States and Laine17 in France noted no long-term effects of either the ablation or the preservation of the basal ganglia on their patients’ motor performance. Complications such as hemorrhage, infection, and hydro¬ cephalus were reported in the series published in the 1950s,18 but it was only in the mid-1960s,19 following the recognition of superficial cerebral hemosiderosis as a late complication of anatomic hemispherectomy, that this operation lost its popular¬ ity. The first clinical report of the condition with pathological correlates was published in the Revue Neumlogique by Ulrich in 1965.20 The same year, Griffith delivered the Hunterian Lecture at the Royal College of Surgeons of England entitled “Cerebral Hemispherectomy for Infantile Hemiplegia in the Light of the Late Results.”21 Griffith reviewed the Oxford expe¬ rience of 18 cases operated upon between 1950 and 1961; after a general discussion of the syndrome of infantile hemiplegia, mention of the technique and results, Griffith went on to dis¬ cuss “The three cases,” who followed a stereotyped clinical pattern after hemispherectomy “with an initial period of well being, succeeded by a steady deterioration over some years, and at postmortem all have presented a rare picture—that of

TABLE 197-1.

Hemispherectomy en Bloc or in Fragments

En Bloc French14 McKenzie8 Obrador16 Rasmussen23 White"

Fragments Cairns12 Dandy1 Feld13 Griffith21 Krynauw10 McKissock15 Penfield41 Ransohoff22

hydrocephalus and haemosiderosis of the central nervous sys¬ tem.” Brief mention of the pathological findings follows, which was the object of a more extensive paper published a year later by Oppenheimer and Griffith.19 Griffith concluded his report by stating that “the act of re¬ moving the hemisphere may be the important one beginning the fatal sequence.” He went on by saying “I suggest that we are now presented with the opportunity, and indeed the obliga¬ tion, to try other manoeuvers and modifications of hemi¬ spherectomy for these unfortunate children.” The concept of disconnection rather than excision began to emerge and Griffith suggested some techniques of undercutting tracts and sparing of the posterior (less epileptogenic) portion of the brain. The paper “Persistent Intracranial Bleeding as a Complica¬ tion of Hemispherectomy,” published in 1966 by Oppenheimer and Griffith, describes in great detail the clinical and pathologi¬ cal (autopsy and histology) findings encountered in the three patients who died of superficial cerebral hemosiderosis (SCH).19 The similarities in these three cases were striking and are summarized as follows by the authors: 1.

Infantile hemiplegia, treated in childhood by hemispherect¬ omy.

2. 3.

A trouble-free period lasting for some years. A period of deterioration, extending over several years and ending in death. During this period there was evidence of bleeding into the cerebrospinal fluid pathways and later of obstructive hydrocephalus.

4.

Postmortem findings of superficial hemosiderosis of the central nervous system; chronic granular ependymitis, leading to obstruction of cerebrospinal fluid pathways; and evidence of multiple bleeding points in the membrane that had replaced the missing hemisphere and in the extension of this membrane onto the lining of the ventricular system (Fig 197-2).

The authors then discuss the physiopathology of SCH and conclude that repeated spontaneous small hemorrhages from the membranes are responsible for the siderosis and the hydro¬ cephalus, both of which lead to neurological deterioration. These observations led the authors to propose a modifica¬ tion of the hemispherectomy technique by which “the abnor¬ mal hemisphere could be disconnected from the rest of the brain, leaving it in place, with an intact ventricular lining,” or to “attempt to close off the cavity from the ventricles, taking up the space in the cavity with a biologically inert prosthesis.”19 Following the description of the clinical pattern and patho¬ logical findings of SCH, other surgeons reported the occur¬ rence of this late complication following anatomic hemi¬ spherectomy. In 1967, Griffith21 reported that Falconer and Scoville had indicated that they had also encountered the con¬ dition. Four years later. Falconer and Wilson18 reported “Complications related to delayed hemorrage after hemi¬ spherectomy”; 4 of their 18 patients presented the complica¬ tion, which they attempted to control by evacuation of the membrane, lavage of the cavity, and shunting procedures. Ransohoff22 and Rasmussen23 also reported their experience with SCH. This complication has been found in 15 to 35 per¬ cent of cases, associated with a high incidence of clinical dete¬ rioration and death. The median interval between anatomic hemispherectomy and SCH has been 8 years (Table 197-2).

Chapter 197/Hemispherectomy for Surgical Management of Epilepsy

1915

Figure 197-1. A. Anatomic specimen, en bloc hemispherectomy. (Courtesy ofT. Rasmussen.) B. Operative photograph demonstrating the hemispherectomy cavity following anatomic hemispherectomy. (Courtesy of I Rasmussen.) (From Theodore,42 with permission.)

The ensuing years saw fewer anatomic and more subtotal hemispherectomies, in an attempt to provide the benefit of the surgical removal of the most epileptogenic brain tissue to con¬ trol seizures while avoiding the late complications. In keeping with this more conservative surgical approach, new methods of hemispherectomy started emerging in the 1970s, and they are still the object of debate today. These techniques, discussed in another section of this review, are described briefly below. In 1967, Ignelzi and Bucy described the surgical technique of hemidecortication and reported 4 cases.24 The principle of this operation consists of avoiding the opening of the ventricle but still completely removing the cortex of the affected

hemispheric removal, but with complete hemispheric disconnec¬ tion, which are the principles of functional hemispherectomy.2 Modifications of these three basic techniques of hemi¬ spherectomy have been proposed over the past 25 years, but the underlying surgical principles of each of these operations have been preserved and elaborated. Current techniques of hemi¬ spherectomy are discussed in another section of this review.

hemisphere. In 1968, Gibbs and Wilson25 introduced the concept of mod¬ ified hemispherectomy now popularized by Adams,26 where the hemispherectomy cavity is isolated from the ventricular system by obstructing the foramen of Monro with muscle and made smaller by stripping the dura and stitching it to the falx, tento¬ rium, and basal dura at the expense of creating a large

The use of cerebral hemispherectomy for control of seizures implies that the pathological processes of the epileptogenic brain, the seizure foci, are lateralized to one hemisphere, and that the other hemisphere has preserved its anatomic and phys¬ iological integrity. In that respect, hemispherectomy may be considered as the most radical focal (unilateral) brain excision. While the pathological process responsible for the seizures will have classically produced a contralateral neurological deficit characterized by complete hemiplegia and hemianopsia, one may consider that, from the standpoint of producing a neu¬ rological deficit, the hemispherectomy has already been achieved by the disease process. However, in progressive con¬ ditions such as progressive chronic encephalitis, extensive Sturge-Weber syndrome, and infantile spasms, in which we may invariably anticipate a clinical deterioration that will lead to a maximum contralateral neurological deficit, early hemi¬ spherectomy will cause an aggravation of the neurological deficit in exchange for complete or improved seizure control, which in turn is accompanied by an important psychosocial

extradural cavity. It was after analyzing the results of subtotal hemispherec¬ tomies, done in patients who might have been candidates for hemispherectomy, that Rasmussen noted the absence of the late complication of SCH. This led him to consider subtotal anatomic

TABLE 197-2.

Superficial Cerebral Hemosiderosis

Surgeon Griffith21 Falconer,18 White" Ransohoff22 Rasmussen41

Incidence 3/18 4/16 5/18 9/27 21/79 (26%)

RATIONALE AND PATHOPHYSIOLOGY

improvement. In more than half the patients who are candidates for hemi¬ spherectomy, electroencephalography (EEG) demonstrates epileptic activity originating from the good hemisphere; this is either secondary or independent. In many instances where it

1916

Part 4/Functional Stereotaxis

Figure 197-2. Photomicrographs in superficial cerebral hemosiderosis following anatomic hemispherectomy. A. Section at level of fourth ventricle demonstrating granular ependymitis (arrow) with hemosiderin deposit. B. Section at level of aqueduct showing gliosis (arrow) and hemosiderin deposit. (Courtesy of K. Meagher-Villemure.) (From Villemure,38 with permission.)

appears independent, it disappears posthemispherectomy and the patient may remain seizure-free off medication. It is possi¬ ble that this phenomenon represents an intermediate form of secondary epileptogenesis.27 In most instances of hemispherec¬ tomy, the EEG investigation reveals not only one hemispheric focus but multiple independent hemispheric foci. It is for that reason that focal cortical excision is usually not as successful in controlling seizures in these instances. The processes by which hemispherectomy controls seizures are of two types: excision and disconnection. Surgical removal of the neurological tissue responsible for the seizures—the cerebral cortex—can be accomplished by anatomic hemi¬ spherectomy or hemidecortication. The mechanical eradication of the epileptogenic tissue should be accompanied by a cessa¬ tion of the seizures. The same objective may be reached by dis¬ connecting the epileptogenic tissue from the effectors, in this instance, the diseased hemisphere, from the rest of the brain— i.e., the contralateral hemisphere and the brain stem. This dis¬ connection can be achieved according to the principles of func¬ tional hemispherectomy. In this instance, neurons can still generate epileptic potentials but they have nowhere to go be¬ cause of the disconnection, so that patients remain seizure-free. These epileptic potentials are recorded on posthemispherec¬ tomy corticography and also on posthemispherectomy conven¬ tional EEG done even years later. In cases where seizures with the same or a different clinical pattern persist postoperatively, we should suspect that the good hemisphere may not have been as normal as expected and that it continues to trigger seizures.

PREOPERATIVE EVALUATION The decision to proceed to hemispherectomy should be based on a critical preoperative evaluation of the intractability and types of seizures, the etiology of the underlying condition, the neurological examination, the EEG, and the imaging studies.28

When a patient is being considered for hemispherectomy, usually seizures have not been controlled pharmacologically despite multiple drug trials or the use of combinations of drugs. Seizure frequency will vary from a few a day to over 100 per day in some cases. Seizures are not only refractory to pharma¬ cological treatment but also incapacitating, interfering with normal life, having repercussions on social and psychological development. Most patients who are candidates for hemi¬ spherectomy have a focal motor component to their seizure pattern even though they may exhibit many seizure types, i.e., generalized, focal motor, drop attacks, etc. Epilepsia partialis continua is usually characteristic of chronic encephalitis. The etiological factor responsible for the seizures and the neurological deficits are classified in two major groups: con¬ genital and the acquired. Congenital etiologies regroup condi¬ tions such as infantile hemiplegia from prenatal or perinatal insult, migrational disorder, cerebral dysplasia, and SturgeWeber disease, while acquired conditions such as cerebrovas¬ cular accident (hemorragic or embolic), head injury, cerebral infection, or chronic encephalitis of Rasmussen occur after early normal development. Close to 50 percent of our patients have suffered from an acquired condition responsible for their seizures (Table 197-3).

TABLE 197-3. Etiology of Disease Responsible for the Author’s Series of Functional Hemispherectomies (50 Patients) Perinatal insult Hemimegalencephaly Migrational disorder Chronic encephalitis Infection(viral, bacterial) Sturge-Weber syndrome Vascular accident Head injury

15 5 2 15 2 3 4 4

Chapter 197/Hemispherectomy for Surgical Management of Epilepsy

1917

The neurological findings on examination are of primary importance in the decision to carry out hemispherectomy. In most instances, the neurological deficit is fixed, static, non¬ evolving and, generally speaking, characterized by complete hemiplegia and hemianopsia. In these instances, where the pa¬ tient is unable to do foot tapping or to use the fingers individu¬ ally, the hemispherectomy will not worsen the motor perfor¬ mance except possibly for temporary hypotonia. In other instances, possible neurological dysfunction is traded for seizure control with the accompanying benefit of psychosocial development. In conditions known to be progressing and where a progressive hemispheric deficit will undoubtedly develop, such as extensive Sturge-Weber disease or active chronic en¬ cephalitis and infantile spasms, serious consideration to early hemispherectomy, prior to the development of maximal deficit, should be given. In these cases, especially in the young age group, early hemispherectomy with aggravation of the neuro¬ logical dysfunction is justifiable for seizure control and im¬ proved psychosocial development; the hemiplegia and hemi¬ anopsia are easily compensated for. The tone of the affected limbs is usually increased preoperatively secondary to the underlying brain pathology. Postoperatively, tone is either unchanged, markedly reduced with loss of movements for a few days to 1 week, or chronically improved, so that some movements become easier. Voluntary movements are present at proximal joints in the upper and lower extremi¬ ties in hemiplegic patients or postoperatively. Patients who can walk preoperatively but who are unable to perform repeated foot tapping usually walk within a week postoperatively. The sensory examination, which is impaired preoperatively if there is significant hemispheric involvement, remains un¬ changed postoperatively, with impaired proprioception, stereognosis, and two-point discrimination. Pain and light touch sensations are present but altered. Mentally, most patients present some degree of mental re¬ tardation preoperatively, usually proportional to whether the good hemisphere is involved or not, the frequency and severity of the seizures, and whether the social milieu in which they de¬ velop is favorable. The EEG gives evidence of diffuse hemispheric damage characterized by low voltage, slow waves, and multifocal inde¬ pendent epileptic spikes. Depending upon whether there are fo¬ cal anatomic changes within the damaged hemisphere, these changes may be more pronounced in some areas. Not infre¬ quently (50 percent of cases) epileptic abnormalities are recorded from the good hemisphere; these may be either secondary or independent. The presence of independent spikes should raise some concerns about the integrity of the good hemisphere but do not represent an absolute contraindication to hemispherectomy. They may represent evidence of sec¬ ondary epileptogenesis or of diseased brain from the primary condition; posthemispherectomy, they often disappear or are asymptomatic. Imaging—skull x-ray, computed tomography (CT), or mag¬ netic resonance imaging (MRI)—usually demonstrates atrophy characterized by a thick, flattened skull, widened sulci, small gyri, and enlarged ventricles. According to the underlying pathology responsible for the seizures, the radiological findings may be more specific. Superficial calcifications may be seen in cases of Sturge-Weber; an enlarged hemisphere and an abnor¬ mal gyral pattern may be seen in cases of hemimegalencephaly

B Figure 197-3. Magnetic resonance image, ^-weighted, in a case of hemimegalencephaly. A. Axial view: note the smaller right lateral ventricle and the abnormal gyrus pattern in the right parietooccipital area. B. Sagittal view: obvious abnormal gyrus formation in the centroparietal area.

1918

Part 4/Functional Stereotaxis

Figure 197-4. Magnetic resonance image, T,-weighted, axial view, demonstrating severe atrophy of the right hemisphere (large porencephaly), characteristically seen in infantile hemiplegia and resulting from perinatal vascular insult.

(Fig 197-3); marked porencephaly is encountered in infantile hemiplegia secondary to prenatal or perinatal cerebrovascular problems (Fig. 197-4); progressive diffuse hemispheric atrophy may be documented in the active phase of chronic encephalitis (Fig. 197-5). The pathology is usually strikingly unilateral; the atrophy, even though it predominates on one side, may also in¬ volve the other hemispheres, but to a lesser degree. The preoperative investigation should indicate clearly if the candidate for hemispherectomy is likely to benefit from the op¬ eration. Assessement of the criteria discussed above (i.e., seizures, neurological function, etiology, EEG, and radiology) should lead to a firm decision without much hesitation. Ideally, the operation and the choice of the candidate should aim at obtaining a cure of the seizures. There are instances where the investigation predicts improvement in seizure con¬ trol without cure: patients with more severe psychomotor retar¬ dation. indicating a more diffuse brain involvement, and those where the EEG or the imaging indicates bilateral impairment. We have learned that although these patients may not become seizure-free, they may benefit from a major improvement (over 80 percent) in their seizure tendency.

Figure 197-5. Magnetic resonance image, T,-weighted, axial view, demonstrating mild to moderate atrophy of the left hemisphere in a patient with chronic encephalitis.

rate, namely SCH. There are currently three types of hemi¬ spherectomy technique: “hemidecortication,” proposed by Ignelzi and Bucy;24 “modified hemispherectomy,” described by Adams;26 and “functional hemispherectomy,” described by Rasmussen1 2 3 4 (Table 197-4). The anatomic hemispherectomy consists of the anatomic re¬ moval of one cerebral hemisphere with or without the basal ganglia: the end result is the creation of a large subdural cavity. The procedure may be done with resection en bloc or in frag¬ ments, depending on the surgeon’s preference. All vascular in¬ put and output must be interrupted, complete callosotomy car¬ ried out, and the corona radiata sectioned superior to the thalamus. The posteroinferior frontal cortex as well as the me¬ dial temporal structures are excised. Complications encoun¬ tered following this method of hemispherectomy have led many centers to abandon it in its original form.29 “Hemidecortication” (Fig. 197-6) consists of removal of the whole cerebral cortex with sparing of the white matter, thus avoiding opening of the lateral ventricle; this reduces the size of the hemispherectomy cavity created and reduces the mixing of bloody material and debris from the surgery with the ven-

SURGICAL TECHNIQUES TABLE 197-4. Surgical techniques of hemispherectomy are classified in two main categories historically: the classic “anatomical hemi¬ spherectomy" with its variations, as practiced from the time of Dandy to that of Griffith, and the “modifications” proposed since the mid-1960s that aim at decreasing the complications

1. 2. 3. 4.

Hemispherectomy Techniques

Anatomic Hemidecortication Modified hemispherectomy Functional hemispherectomy

Chapter 197/Hemispherectomy for Surgical Management of Epilepsy

1919

Falx

Figure 197-6. Hemidecortication. Schematic representation demonstrating removal of the cortex (hatched area) and sparing of the ventricle. (Adaptedfrom Ignelzi and Bucy,24 with permission.) Figure 197-7. Schematic representation of “modified hemispherectomy.” (From Adams,26 with permission.) tricular cerebrospinal fluid (CSF). This method of hemispherectomy has been used and reported by Ignelzi and Bucy,24 Hoffman in Toronto,30 Carson in Baltimore,31 and Winston in Boston.32 In the technique used by Welch and reported by Winston and coworkers,32 large slabs of cortex are undermined and removed, rather than proceeding piecemeal with suction or ultrasonic aspirator. Hoffman30 reduces the volume of the hemispherectomy cavity further by plicating the dura and morcellating the skull. “Modified hemispherectomy” (Fig. 197-7) as developed by Adams26 consists of anatomic hemispherectomy followed by occlusion of the ipsilateral foramen of Monro with muscle to prevent communication between ventricular CSF and the hemi¬ spherectomy cavity, plus reduction of the volume of the hemi¬ spherectomy cavity by tacking the convexity dura to the falx, the basal dura, and the tentorium, creating a large extradural space. “Functional hemispherectomy” (Fig. 197-8) consists of an anatomic subtotal but physiologically complete hemispherect¬ omy.2 The operation is based on principles of disconnection rather than excision. The classic form requires the excision of the central frontoparietal cortex including the parasagittal tis¬ sue from the level corresponding to the genu of the corpus cal¬ losum to the splenium. A temporal lobectomy with excision of amygdala and hippocampus is carried out. The residual frontal and parietooccipital lobes are disconnected medially by inter¬ rupting all fibers entering the corpus callosum and proceeding to interruption of all ipsilateral connections by aspirating from within the ventricle all tissue down to the orbital surface of the sphenoid wing in the frontal region and to the tentorium in the posterior part of the hemisphere. This technique has been further developed by Villemure,33 with marked reduction in the volume of tissue excised in the

central region except for a suprasylvian window allowing ac¬ cess to the ventricle, through which the suprasylvian portion of the hemisphere can be disconnected (Fig. 197-9). Folowing the principle of hemispherectomy by disconnec¬ tion (functional hemispherectomy), Delalande and colleagues34 proposed hemispherotomy. The hemisphere is disconnected through a posterior frontal transcortical approach to the lateral ventricle. From within the ventricle, the callosotomy is carried out, the fornix sectioned, and an incision made through the basal ganglia, reaching the temporal horn. Peri-insular hemispherotomy (Villemure) is part of a contin¬ uum in the technical variations of functional hemispherect¬ omy,33'333 with the highest disconnection-versus-excision ratio (Fig. 197-10). The procedure is carried out through suprasyl¬ vian and infrasylvian windows. The whole lateral ventricle (frontal horn, body, trigone, and temporal horn) is exposed by removal of the opercular cortex and sectioning through the white matter. Once the lateral ventricle is entered, the parame¬ dian callosotomy can be carried out, as well as the frontoorbital and parietooccipital disconnections. Since the temporal stem has been incised from the trigone to the tip of the temporal horn to enter the ventricle, the temporal disconnection is completed by removal of the uncus, including as much of the superomedial portion of the amygdala and the anterior hippocampus as possible up to the point where choroidal fissure is reached. The hippocampus may either be excised or its output interrupted. We prefer to interrupt it at the fimbria-fornix level immediately opposite the inferior portion of the splenium; this is done by as¬ piration from within the ventricle of the medial tissue, starting from the callosotomy incision, which is prolonged forward across the fimbria-fornix to reach the choroidal fissure. This

1920

Part 4/Functional Stereotaxis

Figure 197-8. Left “functional hemispherectomy.” A. Schematic representation. B. Operative photograph. Note the excision of the central region, including the parasagittal tissue, the temporal lobectomy (T), and the disconnection of the frontal (F) and parietooccipital (PO) lobes from the corpus callosum (C). (From Schmidek and Sweet,43 with permission.)

last step isolates the whole frontoparietooccipitotemporal cor¬ tex from any contralateral or ipsilateral connections. The insu¬ lar cortex may or may not be removed. Some surgeons have removed the insular cortex routinely while others have spared it. In analyzing a series of 55 hemi¬ spherectomy patients who had the insular cortex removed or spared, we found that there were more seizure-free patients in the group with the insula preserved, suggesting that its routine removal is not essential to the success of the operation.35 There

A

have been occasional references to the necessity of removing this structure.30 In recent practice, we have removed the insula only when corticography done after hemispherectomy demon¬ strated spiking activity from this cortex. In principle, whichever method of hemispherectomy is uti¬ lized for the same indications, the resulting seizure control should be identical, since these techniques either by removal or disconnection, completely eliminate the epileptogenic influ¬ ence of the diseased hemisphere. These methods of hemi-

B Figure 197-9. Functional hemispherectomy. 4. Visualization of the parasagittal callosotomy from within the lateral ventricle (arrows). B. Magnetic resonance imaging (axial view) demonstrating the frontal and parietooccipital disconnection following left functional hemispherectomy (arrows).

Chapter 197/Hemispherectomy for Surgical Management of Epilepsy

A

1921

B Figure 197-10. Peri-insular hemispherotomy. A. Schematic representation, coronal view. Suprainsular window; I = infra-insular window. Parasagittal callosotomy (arrow). B. Operative photograph, left peri-insular hemispherotomy.

spherectomy differ principally in the way they aim at reducing early and late postoperative complications.

COMPLICATIONS Complications associated with hemispherectomy are of three types: perioperative, early postoperative, and late postoperative (more than 30 days postoperative).

should be preserved to assure viability of the tissue and to avoid further brain atrophy. The best way to avoid perioperative complications is for the surgeon to have a perfect understanding of the threedimensional surgical anatomy necessary for the method of hemispherectomy utilized; this may be even more important in techniques where the hemisphere is not removed.

Early Postoperative Complications Perioperative Complications The skin incision and bone flap should be planned to avoid the superior sagittal sinus; a bone flap slightly away from the midline allows easy access to the parasagittal region and falx and prevents opening over and damaging the superior sagit¬ tal sinus. Bleeding from or thrombosis of the superior sagittal sinus may be dramatic and possibly fatal. The skin incision and bone flap should be as small as possible, varying according to the method of hemispherectomy utilized and influencing anes¬ thesia time and blood loss. Few papers discuss perioperative complications; Brian et al.36 reported the anesthetic manage¬ ment of 10 hemispherectomy children operated upon over a 5year period and pointed out that “massive and sudden blood loss was a common finding . . . fluid rescuscitation frequently was an ongoing process.” These hemorrhages requiring blood replacement were associated with coagulopathy, hypokalemia, and hypothermia. Technically, subpial aspiration is recommended in the me¬ dial regions—i.e., in the neighborhood of the optic apparatus and the medial temporal structures as well as at the time of cal¬ losotomy to avoid damage to the pericallosal arteries. These risks are further reduced with the utilization of fiber-optic illu¬ mination and magnification. In hemispherectomy techniques where brain is left in the hemispherectomy cavity, as many arteries and veins as possible

The syndrome of aseptic meningitis is invariably present in the early postoperative period and is discussed under this heading, even though it is not a complication but rather a phenomenon expected to occur. The clinical picture is characterized by lethargy, irritability, and low-grade fever, usually seen follow¬ ing excisions where the ventricle is opened. It is suspected to be secondary to blood products mixing with CSF and creating meningeal irritation. It rarely lasts more than 1 week to 10 days and appears to be less severe with surgical techniques with smaller degrees of brain removal. Failure to control seizures should not be considered a com¬ plication of the operation, since this is more the result of selec¬ tion of patients than of the technique used. Early postoperative seizures occurring within hours do not preclude a good progno¬ sis and may be related to chemical and pharmacological changes associated with the surgery and anesthesia; they may also reflect some degree of epileptogenicity outside the oper¬ ated hemisphere. Early postoperative wound infection and hemorrhage in the hemispherectomy cavity have been recorded.10 Considering the extent of the operation, these complications are relatively rare. Meningitis (CSF infection) occurred in up to 10 and 17 percent of patients respectively in the published series from UCLA30 and Johns Hopkins;31 Adams reported an 18 percent incidence of bone flap infection in his cases of “modified hemispherec-

1922

Part 4/Functional Stereotaxis

tomy.”26 Villemure30 reported one case of a brain abscess (2 percent) in the residual brain following functional hemispherectomy successfully treated with antibiotics. There were no wound. CSF or bone infections in the Montreal series of 49 functional hemispherectomies. Early postoperative brain shift, herniation and death has been reported following anatomical hemispherectomy. Cabiese37 postulated that this complication was secondary to the development of hydrocephalus of the good hemisphere, combined with displacement of the residual hemisphere toward the hemispherectomy cavity. The creation of a large cavity fol¬ lowing anatomic hemispherectomy may predispose to such mechanical shift. Early hydrocephalus following hemispherectomy is mani¬ fested by deterioration of neurological function days to a few weeks after the surgery; lethargy and intellectual changes char¬ acterize this complication. It has been recorded in 33 percent of patients undergoing hemispherectomy for Rasmussen’s en¬ cephalitis in the Johns Hopkins’s series.31 Other series of hemicorticectomy32 and functional hemispherectomy29 report an in¬ cidence of 8 and 9 percent respectively. Early hydrocephalus may develop because of the surgical method utilized, which in¬ volves, in modified hemispherectomy and hemidecortication, removal of half the supratentorial subarachnoid space and in functional hemispherectomy as much as 35 percent or as little as 5 percent, according to technical variations. The possible mixture of blood and blood debris from the hemispherectomy cavity with CSF may contribute to the development of hydro¬ cephalus. It may also result from the underlying cause of the seizures, such as head injury or infection, which may have al¬ tered the processes of CSF circulation and absorption.

Late Postoperative Complications Infection and spontaneous and posttraumatic hemorrhages have been reported to occur late following hemispherectomy. The presence of a large empty space following anatomic hemi¬ spherectomy has been suspected to favor the development of hematoma after even minor head injury. The main late complication has been SCH, discussed earlier in this review. Its occurrence at a median interval of 8 years postoperatively in 15 to 33 percent of cases has raised serious concerns about anatomic hemispherectomy. No such cases have been reported with the techniques of hemidecortication, modified hemispherectomy, or functional hemispherectomy. What these methods of hemispherectomy have in common as opposed to anatomic hemispherectomy may be summarized as follows; reduction of ventricular exposure and of the volume of the hemispherectomy cavity. These two features seem to ac¬ count for the success in preventing SCH. Late hydrocephalus, not related to SCH, has been reported in up to 18 percent of patients with long-term follow-up.38 It is to be suspected that the incidence of late hydrocephalus should be lower following functional hemispherectomy, since large surfaces of subarachnoid space on the operated side remain undisturbed. Factors contributing to the development of late hydrocephalus following hemispherectomy are identical to those responsible for early hydrocephalus and have already been discussed. The mortality rale following hemispherectomy was reported by White in 1961 to be about 6 percent." Brian'6 reported 1

death in a series of 10 patients, while in a series of 49 func¬ tional hemispherectomies, 2 deaths have occurred (Villemure). Wilson in 197025 reported a mortality of 39 percent following anatomic hemispherectomy, taking into account all the deaths secondary to hemispherectomy whether in the early or late postoperative period. Hemispherectomy represents a major sur¬ gical procedure and the perioperative period remains critical.

Results For the same indications, the benefit of hemispherectomy should be identical and independent of the choice of technique. For hemispherectomy either by excision (anatomic or hemi¬ decortication) or disconnection (functional), the variations re¬ side not in the surgical benefit but rather in the incidence of complications. The outcome of the operation should be mea¬ sured according to its primary objective: seizure control. Outcome figures must consider the different surgical tech¬ niques, the underlying pathology responsible for the seizures, as well as variability in the selection criteria for surgery. Long-term improvement in seizure control following hemi¬ spherectomy is anticipated in 90 to 95 percent of patients. This benefit can be further divided into two categories: those pa¬ tients who become and remain seizure-free (70 to 85 percent) and those who continue to have some seizures but benefit from at least an 80 percent reduction in seizure frequency (10 to 20 percent). These figures reflect the experience of different sur¬ geons using techniques for different pathologies and are useful for discussion with patients and their families. Depending on the underlying pathology, selection criteria and surgical experi¬ ence with a particular method of hemipsherectomy, these re¬ sults may vary slightly within the general range described. While hemispherectomy is ideally carried out only in the pres¬ ence of unilateral cerebral seizure onset, it is obvious that in many instances it might not be easy to lateralize the epileptogenicity strictly. For instance, the EEG may show bilateral epileptic abnormalities in over 50 percent of patients who are otherwise candidates for hemispherectomy; there might be in¬ dependent contralateral epileptic activity, which has been shown to disappear after hemispherectomy; the condition re¬ sponsible for the seizures may affect one hemisphere only or both hemispheres but to different degrees. Considering these features, it is not surprising to observe that some patients do not become seizure-free. Another reason for persistent seizures is related to the surgeon’s experience with a specific technique and the completeness of the hemispherectomy from a physio¬ logical point of view, eliminating by excision or disconnection the influence of the diseased hemisphere. While the control of seizures represents the first and ulti¬ mate objective of hemispherectomy, there are secondary bene¬ fits from improved seizure control in the sphere of psychoso¬ cial development, including improvement in behavior. These are documented by formal measurements of psychosocial func¬ tioning as well as by observations by health care professionals and patients’ families. In hemispherectomy patients, Lindsay et al have clearly demonstrated the ill effects of repeated seizures which are accompanied by intellectual deterioration. Beardsworth and Adams40 have documented not only intellec¬ tual stabilization following hemispherectomy but also contin¬ ued intellectual improvement. These benefits are secondary to better seizure control and possibly, as well, to the reduction or

Chapter 197/Hemispherectomy for Surgical Management of Epilepsy

elimination of anticonvulsant medication. Similar psychosocial gains have been observed to follow less extensive surgery for focal epilepsy. The social gains are characterized by better and easier inte¬ gration in the family and at school. Control of seizures allows patients to develop confidence, interact with others, communi¬ cate more easily, and make friends. While in the minority, some patients with strictly unilateral brain damage and a supportive family may, after hemispherectomy, be able to earn a living and be autonomous.

4.

5. 6. 7. 8. 9. 10.

CONCLUSION Hemispherectomy is a very effective method of controlling pharmacologically refractory seizures originating from a dif¬ fusely damaged hemisphere. Its indications depend on the eval¬ uation of the seizures, neurological function, the etiological factor responsible for the seizures, imaging, and the EEG in¬ vestigation. The preoperative evaluation should establish as clearly as possible the degree of damage of the diseased hemi¬ sphere and the degree of integrity of the good hemisphere. In well-selected cases, hemispherectomy is among the most effective procedures for the control of refractory seizures. It provides complete seizure control in some 70 to 85 percent of patients and almost complete control in 90 to 95 percent. These results are independent of the surgical method used which, whether by excision or disconnection, eliminates the epileptic foci of one hemisphere, thus achieving the same end result. The various hemispherectomy techniques differ in the technical strategies used to reduce complications. All techniques except anatomic hemispherectomy share the objective of reducing the volume of the hemispherectomy cavity. In the Oxford-Adams modification, the subdural hemispherectomy cavity is reduced at the expense of a large extradural space. In hemidecortication techniques, preservation of white matter and avoidance of ven¬ tricular exposure reduce the volume excised. In functional hemispherectomy, disconnection is favored over excision, thus reducing the volume of the cavity left behind. For seizure control and improved psychosocial integration, hemispherectomy should be performed as early as possible once a patient is shown to meet the necessary selection criteria. In progressive neurological conditions with intractable epilepsy, whose natural course will lead eventually to a hemi¬ spheric syndrome (i.e., chronic encephalitis, infantile spasms, extensive Sturge-Weber syndrome), hemispherectomy should be considered before the patient reaches maximal hemispheric deficit, because control of seizures improves psychosocial de¬ velopment, which is most beneficial in the first decade of life. The surgical technique chosen should expose the patient to the lowest possible complication rate.

11. 12. 13. 14.

15. 16. 17.

18. 19.

20. 21. 22.

23.

24.

3.

1956. Obrador A: About the surgical technique of hemispherectomy in cases of cerebral hemiatrophy. Acta Neurochir 3:57-63, 1952. Laine E, Pruvot P, Osson D: Resultats eloignes de l’hemispherectomie dans les cas d’hemiatrophie cerebrale infantile generatrice d’epilepsie. Neurochirurgie 10:507-522, 1964. Falconer MA, Wilson PJE: Complications related to delayed hemor¬ rhage after hemispherectomy. J Neurosurg 30:413-426, 1969. Oppenheimer DR, Griffith HB: Persistent intracranial bleeding as a complication of hemispherectomy. J Neurol Neurosurg Psychiatry 9:229-240, 1966. Ulrich J, Isler W, Vassalli L: L’effet d’hemorragie leptomeningee repdtees sue le systeme nerveux. Rev Neurol 112:466-471, 1965. Griffith HB: Cerebral hemispherectomy for infantile hemiplegia in the light of late results. Ann R Coll Surg Engl 41:183-201, 1967. Ransohoff J, Hess W: Discussion, in Rasmussen T (ed): Post-opera¬ tive superficial hemosiderosis of the brain:” Its diagnosis, treatment and prevention. Am Neurol Assoc 98:133-137, 1973. Rasmussen T: Post-operative superficial hemosiderosis of the brain: Its diagnosis, treatment and prevention. Am Neurol Assoc 98: 133-137,1973. Ignelzi RJ, Bucy PC: Cerebral hemidecortication in the treatment of infantile cerebral hemiatrophy. J Nerv Ment Dis 147:14-30,

26.

Brain 93:147-180, 1970. Adams CBT: Hemispherectomy: A modification. J Neurol

27.

Neurosurg Psychiatry 46:617-619, 1983. Morrell F: Varieties of human secondary epileptogenesis. J Clin

28.

29.

Dandy W: Removal of right cerebral hemisphere for certain tumors with hemiplegia. JAMA 90:823-825, 1928. Rasmussen T: Hemispherectomy for seizures revisited. Can J

31.

Neurol Sci 10:71-78, 1983. Goodman R: Hemispherectomy and its alternatives in the treatment of intractable epilepsy in patients with infantile hemiplegia. Dev

32.

Med Child Neurol 28:251-258, 1986.

hemiplegia. Conf Neurol 21:1-50, 1961. Cairns H: Hemispherectomy in the treatment of infantile hemiple¬ gia. Lancet 2:411-415, 1951. Feld M: L’hemispherectomie totale et subtotale: Considerations de technique operatoire. Rev Neurol 87:525-532, 1952. French LA, Johnson DR, Brown IA, Van Bergen FB: Cerebral hemi¬ spherectomy for control of intractable convulsive seizures. J Neuro¬ surg 12:154-164, 1955. McKissock W: Infantile hemiplegia. Proc R Soc Med 46:431-434,

1968. Wilson PJE: Cerebral hemispherectomy for infantile hemiplegia.

30.

2.

Davies KG, Maxwell RE, French LA: Hemispherectomy for in¬ tractable seizures: Long-term results in 17 patients followed for up to 38 years. J Neurosurg 78:733-740. 1933. Lhermitte J: L’ablation complete de [’hemisphere droit. Encephale 23:314-323, 1928. Gardner WJ: Removal of the right cerebral hemisphere for infiltrat¬ ing glioma. JAMA 12:154-164, 1933. O’Brien JD: Further report on case of removal of right cerebral hemisphere. JAMA 107:657, 1936. McKenzie KC: The present status of a patient who had the right cerebral hemisphere removed. JAMA 111:168, 1938. Bell E, Karnosh LJ: Cerebral hemispherectomy. J Neurosurg 6:285-293, 1949. Krynauw RA: Infantile hemiplegia treated by removing one cerebral hemisphere. J Neurol Neurosurg Psychiatry 13:243-267, 1950. White HH: Cerebral hemipsherectomy in the treatment of infantile

25.

References 1.

1923

33.

Neurophysiol 6:227-275, 1989. Villemure JG: Hemispherectomy, in Resor SR, Kutt H (eds): The Medical Treatment of Epilepsy. New York: Marcel Dekker, 1992, pp 243-249. Villemure JG: Hemispherectomy : Techniques and complications, in Wyllie E (ed): The Treatment of Epilepsy: Principles and Practice. Philadelphia: Lea & Febiger, 1993. pp 1116-1119. Villemure JG, Adams CBT, Hoffman HJ, Peacock WJ: Hemi¬ spherectomy, in Engel J Jr (ed): Surgical Treatment of the Epilepsies. New York: Raven Press, 1993, pp 511-518. Vining EPG, Freeman JM, Brandt J, et al: Progressive unilateral en¬ cephalopathy of childhood (Rasmussen’s syndrome): A reappraisal. Epilepsia 34:639-650, 1993. Winston KR, Welch K, Adler JR, Erba G: Cerebral hemicorticectomy for epilepsy. J Neurosurg 77:889-895, 1992. Villemure JG, Mascott C: Hemispherotomy: The peri-insular ap¬ proach. Technical aspects. Epilepsia 34(suppl 6):48, 1993.

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33a. Villemure J-G, Mascott CR: Peri-insular hemispherotomy: Surgical principles and anatomy. Neurosurgery 37:975-981, 1995. 34. Delalande O, Pinard JM, Basdevant C, et al: Hemispherotomy: A new procedure for central disconnection. Epilepsia 33(suppl 3):99—100, 1992. 35. 36. 37.

Villemure JG, Mascott C, Andermann F, Rasmussen T: Hemispherectomy and the insula. Epilepsia 30:5, 1983. Brian JE, Deshpande JK, McPherson RW: Management of cerebral hemispherectomy in children. J ClinAnesth 2:91-95, 1990. Cabiese F, Jeni R, Landa R: Fatal brain-stem shift following hemi¬ spherectomy. J Neurosurg 14:74-91, 1957.

38. 39. 40. 41.

Villemure JG: Hemispherectomy techniques, in Liiders HO (ed): Epilepsy Surgery. New York: Raven Press, 1992, pp 569-578. Lindsay J, Ounsted C, Richards P: Hemispherectomy for childhood epilepsy: A 36 years study. Dev Med Child Neurol 29:592-600, 1987. Beardsworth ED, Adams CBT: Modified hemispherectomy for epilepsy: Early results in 10 cases. Br J Neurosurg 2:73-84, 1988. Rasmussen T: Personal communication.

42.

Theodore WH: Surgical treatment of epilepsy. Epilepsy Res (suppl 5):209-215, 1992.

43.

Schmidek HH, Sweet WH: Operative Neurosurgical Techniques, 2d ed. Philadelphia: Saunders, 1988.

CHAPTER

198

THE ROLE OF RADIOSURGERY IN THE TREATMENT OF EPILEPSY

Juan L. Barcia-Salorio and Juan A. Barcia

CLINICAL EXPERIENCE

The clinical use of radiosurgery instead of conventional resective surgery for the treatment of medically resistant epilepsy was derived from observations of the beneficial effects of radi¬ ation therapy, brachytherapy, and radiosurgery on the sympto¬ matic seizures produced by lesions of several pathologies [mainly tumors or arteriovenous malformations (AVMs)] even before there was an effect on the primary lesion. A considera¬ tion on the possible doses received by the epileptogenic brain tissue surrounding the lesion, which were lower than those re¬ ceived by the lesion, led us to consider the therapeutic use of low-dose focal irradiation. Two main problems were dealt with in the first clinical trials: case selection and focus localization. The cases had to be patients not suitable for conventional resective surgery because of (1) focus located in eloquent areas, (2) multiple or bilateral foci, (3) specific contraindications for epilepsy surgery, or (4) failed previous conventional resection. This led to too small a sample to draw definitive conclusions, while selection was biased toward a group with a poorer out¬ come. The other problem with this bloodless technique is that the procedure necessary for focus localization is too aggressive in comparison with the treatment procedure and may also be too imprecise. Contrary to what happens with resective surgery, in which anatomic localization may be sufficient or a direct electrocorticographic confirmation can be made at the very mo¬ ment of resection, focus location for radiosurgery must locate the source stereotactically within a very small volume without

Effect of Focal Irradiation on Symptomatic Epilepsy Effect on seizures associated WITH BRAIN

AVMS

Stereotactic radiosurgery has become one of the most accept¬ able means of treating deeply seated intracranial AVMs.1'2 As the clinical experience with radiosurgery for AVMs has grown, several reports have been published on the beneficial effect of this form of treatment on the seizures associated with these le¬ sions. Interestingly, several authors observed that in some cases those seizures had not responded to previous anticonvulsant medication and that seizures sometimes disappeared or im¬ proved before any angiographic evidence of an effect on the AVM. Kjellberg and coworkers3 reported 24 patients with cerebral AVMs who had seizures as the first symptom and were treated with stereotactic Bragg-peak proton-beam radiosurgery. After more than 2 years of follow-up, 8 did not have further seizures, 11 improved with respect to seizure frequency, and 5 appeared about the same; none reported being worse. A subsequent pa¬ per4 reported 118 patients with seizures as the initial symptom; after treatment, nearly half of them were improved and onefifth were the same; in two patients, seizures were apparently worse. In a series of 129 patients with AVMs treated with stereotac¬ tic proton-beam radiosurgery, Heikkinen and associates5 re¬ ported the cessation of symptomatic epilepsy in 16 of 29 pa¬ tients (55.17 percent). These patients remained seizure-free during the follow-up period (2 to 8 years; mean, 55 months). In nine of these patients, anticonvulsants were discontinued after 6 to 9 months. Temporal lobe epilepsy was significantly more resistant to both medical and irradiation therapy (two of seven patients seizure-free). Among the factors that favored control of seizures by irradiation was the area of the AVM included within the 20 percent isodose field. As angiographic changes took place after irradiation in 41 percent of these patients while relief of seizures did so in 55 percent, they concluded that irra-

in situ confirmation. However, several reports from other groups seem to confirm the efficacy of this treatment. This can be, in the future, a promising complement to conventional resective surgery for epilepsy when better methods for focus localization are achieved, a greater number of cases can be analyzed, and the exact mechanism of irradiation on the epileptogenic focus ac¬ tivity can be ascertained. This chapter reviews the clinical experience with the effect of irradiation on seizures, either symptomatic or idiopathic, and the experimental studies that have been performed. It also out¬ lines a hypothesis about its possible mechanism and possible indications.

1925

1926

Part 4/Functional Stereotaxis

diation therapy by itself could arrest the epileptogenic activity around the lesion. In a further series of cerebral AVMs treated by Heikkinen6 with fractionated stereotactically guided photonbeam irradiation from a linear accelerator,7 nine patients pre¬ sented with symptomatic epilepsy before treatment. Of these patients, one became seizure-free after irradiation without any medication (with complete obliteration of the AVM) and four are totally seizure-free continuing on similar or reduced anti¬ convulsant medication, while their AVMs have not been angiographically obliterated. The maximal doses given were 10 frac¬ tions of 4 Gy or 23 fractions of 2 Gy each. Follow-up periods ranged between 4 and 8 years. Of particular interest is the fact that the main indication for treatment was the huge size of the AVM and its location near an eloquent area (mostly motor area) and that no neurological deficits were recorded after treatment. Lance and Smee8 reported the cessation of medically resis¬ tant partial seizures associated with a right occipital cavernous hemangioma after treatment with a course of fine-beam radio¬ therapy directed to the lesion. Similar observations have been reported in large series of AVMs treated with stereotactic radiosurgery. Steinberg, Fabrikant, and coworkers9'10 found a 63 percent improvement of symptomatic seizures in their series of 89 patients with AVMs treated with helium ion Bragg-peak radiation. Lindquist, Steiner, and coworkers111 reported the effects of radiosurgery in 59 patients with symptomatic epilepsy in a series of 247 pa¬ tients harboring AVMs who were treated with the gamma knife. After 4 or more years of follow-up, 11 (18.64 percent) were seizure-free without anticonvulsants and 41 (69.49 percent) were seizure-free but were still receiving anticonvulsants. Three patients were seizure-free although their AVMs did not show any radiological change. Sutcliffe and coauthors12 reported on the possible com¬ plications of stereotactic radiosurgery for AVMs in a series of 160 patients and observed that epilepsy was improved in 29 of 48 (60.4 percent) patients presenting with seizures and wors¬ ened transiently in only 3 of these patients. These observations suggest that the effect of irradiation on seizures may be inde¬ pendent of the direct effect on the AVM. Effect on seizures associated WITH BRAIN TUMORS Rossi and coworkers13 reported improvement of seizures in 15 patients with various types of surgically inaccessible epilepto¬ genic cerebral neuroepithelial tumors who were treated with stereotactic interstitial irradiation. Seizures were abolished in six cases and were markedly reduced in another seven. A simi¬ lar result was observed by DeRiu and Rocca14 with interstitial irradiation of malignant supratentorial gliomas. External irradiation has been reported to produce similar re¬ sults. Goldring and associates15 observed that external irradia¬ tion reduced seizures in four patients with low-grade gliomas (one of them with anaplastic foci) associated with medically in¬ tractable epilepsy. Rogers and colleagues16 reported the effects on seizures in five patients with surgically unresectable biopsy-proven lowgrade astrocytomas and medically intractable epilepsy who un¬

derwent fractionated focal irradiation with 54 to 61.2 Gy. Interestingly, four patients had tumors that appeared stable on magnetic resonance imaging (MRI) or computed tomography (CT), and radiation was given only because of the intractable epilepsy. Another patient was irradiated because of tumor pro¬ gression. After treatment, seizure frequency was reduced by more than 90 percent in three patients (one of whom became seizure-free) and by more than 75 percent in one patient. One patient showed no response in seizure frequency. In one of the patients, seizures improved in spite of the lack of reduction in tumor size. The doses of anticonvulsants could be reduced in all patients. The patient who became seizure-free remained so over 8.2 years, until the tumor again progressed and she began to experience the same type of seizures that had occurred be¬ fore irradiation. The rest of the patients had follow-up periods of 1 to 1.5 years.

Stereotactic Radiosurgery Performed for the Treatment of Medically Intractable Epilepsy Experience at the University of Valencia Between 1982 and 1993, we treated 19 patients diagnosed with medically intractable epilepsy with stereotactic radiosurgery; 14 presented with clinically observable seizures, and five were diagnosed with epileptic psychoses.17"19 Stereotactic radio¬ surgery was performed using a single conventional 60Co gamma source, except in two patients in whom a betatron was used. In all cases, the maximal central doses ranged between 10 and 20 Gy (with a 5- or a 10-mm collimator) in a single ses¬ sion, except in one patient who was bilaterally irradiated. Another patient received two fractions of 10 Gy. In two pa¬ tients in whom the foci were located superficially under the convexity of the brain (one parietal and one occipital) with an epileptogenic area estimated to be large, irradiation was done using electrons of 10 to 15 MeV from a 45-MeV betatron, yielding an estimated dose of 10 Gy at the target from only a one-beam entrance direction. Among the 14 patients with observable seizures, 2 were lost to follow-up. Among the 12 patients who were followed, 4 are now seizure-free off medication. Two are almost seizure-free and are still on medication (reduced in one). One patient has had 85 percent reduction of seizures compared to the status be¬ fore treatment, and two have had about a 75 percent reduction. Mean follow-up was 98 months. Three patients now suffer the same seizure frequency as ex¬ isted before irradiation. One of the patients with a poor out¬ come presented with a left mesial temporal hyperintense lesion on MRI, and the target point was selected from the MRI image instead of from electrophysiological recordings. Another pa¬ tient presented with a large parietal posttraumatic gliotic scar, and the electrocorticographic studies were not completely con¬ clusive. These two patients did not experience any change in seizure frequency. Another patient who had initially responded with complete suppression of seizures stopped anticonvulsant medication suddenly, after which seizures returned with the same frequency as before.

Chapter 198/The Role of Radiosurgery in the Treatment of Epilepsy

Seizure reduction began after a period of at least 2 months

1927

frequency reduction compared with the preoperative rate. Two

It is important to stress that the doses that have been effec¬ tive for suppression of epileptic activity are much lower than those used for producing lesions in the brain tissue and that the aim is to modify the behavior of the epileptic focus, not to in¬ duce focal necrosis tit the epileptogenic site or in pathways that spread the epileptie activity to other regions of the brain.

patients responded immediately after irradiation and achieved complete cessation of seizures, but seizures ensued again in

Experience at other centers

and up to 1 year except in two cases, and in most cases the seizure rate decreased progressively, stabilizing after a period of 6 months postoperatively (range, 3 months to 4 years). Figure 198-1 shows the evolution in time of the mean seizure

both cases, in one patient being related to early withdrawal of medication. The indications for using radiosurgery instead of conven¬ tional resective surgery in these cases were failed previous con¬ ventional resective surgery in three patients, failed previous surgery with a focus near eloquent areas in two patients, failed previous surgery with bilateral independent discharges in one patient, severe behavioral disturbances with temporal foci in three patients, location near eloquent areas in four patients, and refusal to undergo conventional surgery in one patient. The patients with epileptic psychoses were diagnosed as such by our psychiatrists, and in all cases epileptiform interictal activity could be recorded arising from one temporal lobe. The existence and location of a focus were confirmed in every case with chronic depth electrode recordings. Among the five patients irradiated, one was lost to follow-up. Of the remaining four, three have been reported to be greatly improved in the psychiatric reports and almost back to a normal life and one is unchanged. However, the analysis of these patients is obscured by a lack of clinically observed seizures. We did not record any complication related to irradiation in terms of focal neurological worsening or radionecrosis. In one of the patients, there was a neurological deficit (leg monoparesia) caused by the cortical electrode implantation, but it was present before irradiation.

After we reported our clinical series,17 other authors published the results of pilot studies on the use of radiosurgery instead of conventional surgery to medically resistant epilepsy. In 1991, Lindquist and associates11 reported treatment with radiosurgery of four patients who met the criteria for conven¬ tional resective epilepsy surgery. Of these patients, one did not show any pathological lesion on CT or MRI and the other three presented with mesial temporal structural lesions (one a biopsy-proven low-grade astrocytoma, one a radiologically suspected low-grade astrocytoma, and one a cystic partly cal¬ cified lesion). The target for radiosurgery was selected with magnctocncephalographic (MEG) interictal recordings and confirmed with long-term subdural (three patients) or depth electrode recordings (one patient). In two of these patients, 8month follow-up data were available. Of these patients, one had begun to experience amelioration of the seizures 3 months after radiosurgery and had complete disappearance five months after irradiation. The other patient experienced ame¬ lioration during the last 6 months after irradiation. For the other two patients there were no conclusive data because of the shortness of follow-up. In a subsequent publication,20 the Karolinska group reported a series of six patients with com¬ plex partial seizures whose target for radiosurgery with the gamma knife was selected by stereotactic MRI and MEG. After a follow-up period of I to 2 years, all these patients had experienced a reduction in seizure frequency. The reported dose in one of the patients with epileptogenic low-grade astro¬ cytoma was in the range of 10 Gy to the periphery (maximal central dose 33 Gy) using an 18-mm collimator in four over¬ lapping fields.21 Heikkincn22 reported one patient with a left temporal focus and medically intractable partial seizures who underwent stereotactic irradiation from a linear accelerator (6 MeV) in five fractions to a total dose equivalent of 10 Gy in a single shot. Two months after irradiation, the frequency of seizures began to improve, and they stopped completely at the seventh month after irradiation. This patient stayed seizure-free for 3 years until his seizures recurred after a febrile respiratory infec¬ tion. He was operated on using conventional surgery, with

Months

f igure 198-1. Evolution in lime of the percentage of seizures remaining compared with the preoperative rate. The mean percentage of all the patients is plotted, except for two nonresponding patients and one with recurrence after medication withdrawal. Seizure frequency reduction begins after the second month and stabilizes after the sixth month. (Modified with permission from Barcia et al./v)

good results.6 Alexander and colleagues21 reported three additional pa¬ tients, one of them a 5-year-old boy with a nontumoral poste¬ rior temporal lesion and complex partial seizures and two cav¬ ernous angiomas near eloquent areas. Radiosurgery was performed with a 6-MeV modified linear accelerator. Doses were in the range of 15 to 17.5 Gy to the 90 percent or 17 Gy to the 80 percent isodose surface, using 35- to 20-mm collimators. One of the patients is seizure-free, and the other two have ex¬ perienced marked improvement. Seizures began to improve progressively after a delay of 2 weeks to 6 months. In one of the patients, there was transient immediate improvement 48 h

1928

Part 4/Functional Stereotaxis

after radiosurgery. Follow-up periods ranged between 14 months and 4 years.

lar to the findings of other authors in experimental foci pro¬ duced by metals.25 The experimental group consisted of 10 animals that un¬ derwent the same procedure as the control group and exhib¬ ited similar clinical and ECoG signs of epileptiform seizures. Three months after cobalt oxide implantation, they were irra¬ diated by means of a gamma source with a total target dose of 10 Gy. Three to 4 days after irradiation, ECoG recordings showed marked slowing and decreased amplitude of the traces in frontotemporal areas and a persistence of epilepti¬ form bursts in the rest of the channels. Twelve to 18 days after irradiation, all their ECoG recordings returned to normal, un¬ til the sixth month, when the animals were necropsied (Fig. 198-2). Histologically, arachnoidal fibrosis, edema, and neu¬ ronal loss were found with a more discrete glial proliferation, with the glial scar being less consistent. In Golgi prepara¬ tions, a high number of nerve fibers was seen. Neurons ap¬ peared more stylized and had a higher degree of dendritic branching. The observations revealed a higher number of dendritic spines, although a technique for spine counting was

EXPERIMENTAL BACKGROUND Experimental Studies on Animal Models of Chronic Epilepsy An experimental study was conducted at the authors’ labora¬ tory2324 to confirm the clinical results and ascertain possible mechanisms for focal irradiation in the relief of epileptic seizures in a model of chronic epilepsy using cobalt oxide in the cat. The study confirmed that focal irradiation with low doses such as 10 Gy stopped the clinical seizures and improved the electrocorticographic (ECoG) recordings in all the epileptic animals. In this experimental work, a control group of 10 cats were anesthetized and had their heads fixed to a stereotactic frame. A 6-mm-diameter left frontal craniotomy was performed, and 30 mg of cobalt oxide powder was placed in the epidural space over the left motor strip. Twenty-one stainless steel screws were symmetrically inserted and distributed throughout the skull to be used as epidural electrodes. All the animals exhib¬ ited focal and sometimes generalized seizures lasting for 15 to 20 days. Three weeks after implantation, epileptic bursts and spikes predominated in the cobalt area (Fig. 198-2). ECoG traces then progressively worsened until the sixth month, when the animals were killed. Brains were studied with hematoxylin-eosin, Luxol fastblue, and modified Golgi techniques. A dural granuloma and cobalt particle debris and arachnoidal fibrosis were observed. Most animals presented edema of the molecular layer that spared the structure of all layers, discrete neuronal loss, and as¬ trocyte proliferation. In a few cases, a glial scar with giant as¬ trocytes and neuronal loss was found. In the white matter, there was axonal loss, vacuolization, demyelinization, and vascular and glial proliferation. Golgi preparations showed a loss of higher-order (III to V) dendritic prolongations, apical dendrite edema, and a loss of synaptic spines (Fig. 198-3), a result simi¬

not performed (Fig. 198-4). A sham group of five normal ani¬ mals underwent the same irradiation procedure and showed no clinical or electroencephalographic (EEG) abnormalities over 6 months. Ronne-Engstrom and associates26 reported an experiment in which 16 rats were intracortically injected with ferrous chloride, 14 of which showed EEG epileptiform changes. Six of the latter animals were focally irradiated with the gamma unit with doses between 50 and 100 Gy, using a 4-mm collimator. In these animals, the EEG epileptic signs dimin¬ ished and electric stimulation failed to provoke epileptiform activity.

Possible Mechanisms Involved Although the number of patients treated is still too low to draw conclusions, some features of therapy in which radiosurgery af¬ fects seizures can be outlined. First, very low doses (10 to 20 Gy) compared with those normally used to provoke brain

-

a: Before irradiation

b: 6 months after irradiation

Figure 198-2. Electrocortico¬ graphic recording of an epileptic animal before irradiation (4) and 6 months after irradiation (5). The black spot reveals where the convulsant agent was placed. (Modified from Barcia-Salorio et al.23)

Chapter 198/The Role of Radiosurgery in the Treatment of Epilepsy

Figure 198-3. Epileptic neuron: loss of dendritic prolongations, dendrite edema, and loss of synaptic spines.

Figure 198-4. Irradiated neuron. Npte the increase in dendritic spines.

1929

1930

Part 4/Functional Stereotaxis

tissue destruction have proved effective for suppression of epileptogenic activity. Second, the effects are delayed in time and appear progressively. In our series, seizures began to de¬ crease after 2.5 months to 1 year and stabilization occurred progressively after 3 months to 4 years. Similar results have been reported in the other series. Third, these doses seem to produce no functional neurological deficits even when applied near eloquent areas. These features support the hypothesis that a long-term functional or structural effect may be induced by radiation in the epileptic focus. Clinical recurrences after total cessation of seizures may favor a functional effect only. Some studies suggest an effect of irradiation on neurotransmitters involved in epilepsy mechanisms.27 In an experimental work, extracel¬ lular levels of aspartate and glutamate, two neurotransmitters involved in epilepsy mechanisms, were decreased in the tar¬ get areas of normal rats focally irradiated with doses between 50 and 250 Gy.26 A selective influence on epileptic neurons is possible, since normal neurons apparently are not affected by low irradiation doses. Normal rats receiving focal irradiation with 50 to 100 Gy do not show any signs of epileptiform ac¬ tivity or any histological alteration, while rats receiving 150 to 250 Gy show epileptiform spike activity over the target area.26 Doses up to 20 Gy with a single 4-mm collimator isocenter seem to cause no electrophysiological changes in the optic chiasm of the normal rat as tested with visual evoked potentials.28 Another possible explanation is an indirect effect on neu¬ ronal excitability through changes in the glia. Gliosis, or as¬ trocyte proliferation, is the most evident pathological change found in resected epileptic brain cortex, along with neuronal loss or degeneration, loss of dendritic spines, and signs of synaptic reorganization.25-29-30 These are signs of neuronal deafferentation, which most authors think is the basic mecha¬ nism involved in epilepsy. Our experimental studies have shown a decrease of glial proliferation and an increase of neuropil branching and dendritic spines in irradiated and cured foci. Similar observations have been made by other au¬ thors, such as Malis and associates,31 who observed a great dendritic proliferation a few days after producing a deuteron laminar lesion in cortical layer IV of the rabbit brain. If synaptic deafferentation and loss of neuropil branching are due to gliosis, as glial cells are more sensitive to irradiation than neurons are, it is possible that a decrease of gliosis by irradiation may favor neurite outgrowth and synaptic plasticity.

FOCUS LOCALIZATION FOR RADIOSURGERY OF EPILEPSY The objective of focus localization in conventional epilepsy surgery is to determine a safely resectable area that contains the epileptogenic focus. In some cases, such as temporal lobe epilepsy, it is sufficient to decide which side is responsible for the origin of seizures. With the advent of more refined imaging techniques, there is a trend toward a lesser use of invasive recordings before surgery. Even when a more accurate location is needed, direct ECoG control can be made at the moment of resection.

The localization problem facing radiosurgery is quite differ¬ ent: It is necessary to stereotactically define a small volume in¬ side which the epileptogenic area is located. Two different methods have been used in radiosurgery for epilepsy: burr hole ECoG and MEG.

Burr Hole Electrocorticography Burr hole electrocorticography is the method used at the au¬ thors’ institution.32 Patients who are candidates for radiosurgical treatment enter a first noninvasive localization phase simi¬ lar to that performed in the majority of centers. The studies include clinical and psychological testing, standard scalp EEG, CT and MRI scans, single photon emission computed tomogra¬ phy (SPECT), and, when necessary, angiography. This leads to the determination of a suspect area of cerebral cortex from which seizures may originate. The patient is then subjected to burr hole ECoG. The proce¬ dure consists of introducing a flexible recording multiplecontact electrode probe into the subarachnoid space through a single burr hole and guiding it with the aid of radioscopic imaging to the areas previously selected during the noninvasive phase.19 In almost every case, a contralateral symmetrical set of electrodes is also introduced. The electrodes are left in place for a maximum of 7 days, and anticonvulsant drugs are progressively tapered off, starting from the day after implantation. ECoG recordings are done until the commencement of a clinical seizure is recorded. Continuous video monitoring is performed, and close relatives of the patient and the patient are interrogated to be sure that the seizures being recorded correspond to the usual ones. Once two to four seizures have been recorded, the electrode probes are removed. Electrode probe insertion is repeated in most cases until one of the contacts shows a tracing indicating close proximity to the focus in the interictal recording and evidence that it is clearly the origin of the seizures. The location of the electrodes is stereotactically calculated by x-ray films with the stereotactic frame in place.19 A com¬ puter program is used to recalculate the position of the elec¬ trodes, thus eliminating distortions from x-ray divergence. During this procedure, the determination of the cerebral area that is the most probable source of the epileptogenic activity is aided by a computer procedure that has been reported.33 The computer is fed the stereotactic coordinates of the electrodes and the value of the electric potential recorded by them and outputs the equivalent dipole source location in stereotactic co¬ ordinates. The same montage is used during the radiosurgical operation, thus avoiding unnecessary calculations, since the fi¬ nal locus position is obtained in the stereotactic frame coordi¬ nate reference system. When the epileptogenic area is clearly detected and there is reasonable evidence that it is small enough, a stereotactically directed deep electrode is introduced, guided by a rigid cannula to that point, and left in place until the recordings confirm that that point is the origin of the seizures. It is important to stress the need for accurate electrophysio¬ logical localization of the epileptogenic area. In our series, the patients who tailed to improve had difficulties in this localiz.a-

Chapter 198/The Role of Radiosurgery in the Treatment of Epilepsy

1931

tion process. An exhaustive ECoG study is thus essential in our opinion but may turn this preoperative procedure into a tedious aggressive localization method.

that the epileptogenic area is not located at the lesion but around it and stresses the importance of obtaining good electrophysiological localization.

Stereotactic

INDICATIONS FOR RADIOSURGERY OF EPILEPSY

Magnetoencephalography MEG consists of the detection from outside the scalp surface of the magnetic field originated by dipolar generators inside the brain.34 The advantages of MEG over EEG are that (1) the detected magnetic field depends only on the axial intra¬ cellular currents at the source, while the electric potential de¬ pends on other phenomena occurring inside a volume con¬ ductor such as the brain, (2) the media that modify the electric signal (especially the skull) are transparent to the magnetic fields, and (3) it is possible to obtain an absolute measure of the magnetic field, whereas the electric potential must be referred to a second electrode uptaking an undeter¬ mined potential. Interictal epileptic spikes recorded in the EEG also produce magnetic fields that can be recorded in the MEG.35 A source of a magnetic field can be calculated three dimensionally from the formula of the magnetic field pro¬ duced by a magnetic dipole generator,34 and so MEG may be a noninvasive alternative to cortical or depth electrode recording. Stereotactic MEG has been applied to epilepsy radio¬ surgery20 and is a promising ideal complement for that blood¬ less and apparently safe treatment method. Hellstrand and associates36 reported two patients with com¬ plex partial epilepsy who were evaluated before and after ra¬ diosurgery by multichannel MEG. The centers of epileptic di¬ pole activity that were found preoperatively disappeared after focal irradiation, as did the epileptic seizures. The combination of stereotactic MEG and radiosurgery is a completely noninva¬ sive alternative to conventional resective surgery for focal epilepsy.

The small number of cases reported to date is insufficient to draw definitive conclusions. However, some guidelines can be given for the possible indications for radiosurgery of epilepsy.

Idiopathic Seizures In the authors’ opinion, if an epileptic patient meets the criteria for both resective and radiosurgical treatment for epileptic seizures, resective or conventional surgery should be consid¬ ered first because of the limited experience accumulated so far with radiosurgical treatment. If there is any contraindication to conventional surgery, the following principles should be ob¬ served if radiosurgery is to be used: 1.

2.

3.

4.

The origin of the epilepsy should be focal, and a focus should be stereotactically located and included within a small area. Epilepsy is idiopathic or the lesion causing it needs no treatment, so that the primary concern is the seizures. When a treatable lesion is located at the focus, treatment should be directed to it first and the choice of treatment should depend on the nature of the lesion. Location near an eloquent area, bilateral or multiple foci, and failure of previous resective surgery are not contraindi¬ cations, as deduced from the limited clinical experience. In the published series, there has not been any patient re¬ ceiving a dose greater than 20 Gy at a normal brain area without incurring functional deficits, and so the maximal dose should not exceed this level.

Functional Magnetic Resonance Imaging

Symptomatic Seizures

Functional magnetic resonance imaging (FMRI) is a subtrac¬ tion technique of fast-acquisition MRIs and can detect areas with changes in blood flow with better anatomic resolution than is possible with previous blood flow techniques.37 38 It is based on the decrease in the deoxyhemoglobin concentration in activated areas of the brain resulting from increased blood flow in that area in excess of that needed for metabolism. Mueller and colleagues39 reported the application of this technique in 3 patients with tumors and 10 patients with epilepsy, with a good correlation with awake stimulation cortical mapping in the same region. This can lead in the future to less costly noninva¬ sive stereotactic detection of epileptogenic foci for radio¬

The presence of epilepsy complicating a radiosurgically treat¬ able lesion may favor the use of radiosurgery. Kjellberg and coworkers3 recommended radiosurgical treatment for patients with cerebral AVMs and seizures as the only presenting symp¬ tom when anticonvulsant medication failed to control the seizures. Heikkinen and colleagues5 observed that relief of epilepsy by radiosurgery can favor choosing it as the treatment of choice in epileptogenic AVMs if one balances the risk asso¬ ciated with a delay of 6 months to 2 years to provide protection against rebleeding. Rogers and associates16 stated that radiation therapy should be considered when a hemispheric low-grade astrocytoma is unresectable and is complicated by medically

surgery.

intractable epilepsy.

Conventional Imaging Techniques

Recurrences

Selecting the target point for radiosurgery with MRI or CT has been unsuccessful in our experience. This reminds us of the fact

Seizures may recur after a more or less prolonged interval of complete cessation, often after a precipitating cause, as in

1932

Part 4/Functional Stereotaxis

the recorded cases. However, from the case reported by Heikkinen,6 we learn that previous radiosurgery does not pre¬ clude a good result with later conventional surgery. The reverse is also true, since six of our patients with good results had been previously operated on. This can lead one to think of radio¬ surgery as a complement, not only an alternative to conven¬ tional surgery, in the treatment of epilepsy.

20.

21.

22.

Steiner L, Lindquist C, Adler J, et al: Clinical outcome of radio¬ surgery for cerebral arteriovenous malformations. J Neurosurg 77:1-8, 1992.

2.

Lunsford L, Kondziolka D. Flickinger J, et al: Stereotactic radio¬ surgery for arteriovenous malformations of the brain. J Neurosurg 75:512-524, 1991.

3.

Kjellberg RN, Hanamura T, Davis KR, et al: Bragg peak proton beam therapy for arteriovenous malformation of the brain. N Engl J Med 309:269-274, 1983.

Alexander E III, Lindquist C: Special indications: Radiosurgery for functional neurosurgery and epilepsy, in Alexander E III, Loeffler J, Lundsford LD (eds): Stereotactic Radiosurgery. New York: McGrawHill. 1993, pp. 221-225. Heikkinen ER. Heikkinen MI. Sotanienii K: Stereotactic radiotherapy instead of conventional epilepsy surgery: A case report. Acta Neurochir (Wien) 119:159-160, 1992.

References 1.

pathic epilepsy: Report on the methods and results in a series of eleven cases. Stereotact Funct Neurosurg 63:271-279, 1994. Lindquist C, Kihlstrom L, Hellstrand E, Knutsson E: Stereotactic ra¬ diosurgery instead of conventional epilepsy surgery (abstract). Acta Neurochir (Wien) 122:179, 1993.

23.

24.

Barcia-Salorio JL, Vanaclocha V, Cerda M, et al: Response of experi¬ mental epileptic focus to focal ionizing radiation. Appl Neurophysiol 50:359-364. 1987. Vanaclocha V: Estudio experimental sobre la respuesta a las radiaciones ionizantes del foco epiieptico por oxido de cobalto en el gato. Ph.D. thesis, Universidad de Valencia, 1988.

25.

Westrum LE, White LE, Ward AA Jr: Morphology of the experimen¬ tal epileptic focus. J Neurosurg 21:1033-1046, 1964.

26.

Ronne-Engstrom E, Kihlstrom L, Flink R, et al: Gamma knife surgery in epilepsy: An experimental model in the rat (abstract). Acta Neurochir (Wien) 122:179, 1993.

4.

Kjellberg RN, Davis KR, Lyons S, et al: Bragg peak proton beam therapy for arteriovenous malformation of the brain. Clin Neurosurg 31:248-290,1984.

27.

5.

Heikkinen ER, Konnov B, Melnikov L, et al: Relief of epilepsy by ra¬ diosurgery of cerebral arteriovenous malformations. Stereotact Fund Neurosurg 53: 157-166, 1989.

Elomaa E: Focal irradiation of the brain: An alternative to temporal lobe resection in intractable focal epilepsy. Med Hypotheses 6:501-503. 1980.

28.

6.

Heikkinen ER: Personal communication, 1994.

7.

Heikkinen ER, Heikkinen MI: New diagnostic and therapeutic tools in stereotaxy. Appl Neurophysiol 50:136-142, 1987.

Kondziolka D, Claasen D, Linskey ME, et al: Cranial nerve sensitiv¬ ity and radiosurgery: Results with the rat optic chiasm model (ab¬ stract). Acta Neurochir (Wien) 122:147, 1993.

29.

8.

Lance JW, Smee RI: Partial seizures with visual disturbance treated by radiotherapy of cavernous angioma. Ann Neurol 26:782-785, 1989. Steinberg GK, Fabrikant JI, Marks MP, et al: Stereotactic heavy-

Babb T, Brown W: Pathological findings in epilepsy, in Engel J (ed): Surgical Treatment of the Epilepsies. New York: Raven Press, 1987, pp 511-540.

30.

Kallionen M, Heikkinen ER, Nystrom S: Histopathological and inmunohistochemical changes in neurosurgically resected epileptic foci. Acta Neurochir (Wien) 89:122-129, 1987. Malis L. Rose J, Kruger L. Baker C: Production of laminar lesions in the cerebral cortex by deuteron irradiation, in Haley T, Snider R (eds): Response of the Nervous System Ionizing Irradiation. New York: Academic Press, 1962, pp 359-368.

9.

10.

charged-particle Bragg-peak radiation for intracranial arteriovenous malformations. N Engl J Med 323:96-101, 1990. Steinberg GK, Fabrikant 11, Marks MP, et al: Stereotactic helium Bragg-peak radiosurgery for intracranial arteriovenous malforma¬ tions: Detailed clinical and neurorradiological outcome. Stereotact Funct Neurosurg 57:36-49, 1991.

31.

11.

Lindquist C, Kihlstrom L, Hellstrand E: Functional neurosurgery—a future for the gamma knife? Stereotact Funct Neurosurg 57:72-81 1991.

32.

12.

Sutcliffe JC, Forster DM, Walton L, et al: Untoward clinical effects after stereotactic radiosurgery for intracranial arteriovenous malfor¬ mations. Br J Neurosurg 6:177-185, 1992.

33.

13.

Rossi GF, Scerrati M. Roselli M: Epileptogenic cerebral low grade tu¬ mours: Effect of interstitial stereotactic irradiation on seizures. Appl Neurophysiol 48:127-132, 1985.

34.

Williamson S, Kaufman L: Biomagnetism. J Magn Mag Mat 22: 129-201, 1981.

35.

14.

DeRiu PL, Rocca A: Interstitial irradiation therapy of supratentorial gliomas by stereotaxic technique: Long-term results. Ital J Neurol Sci 9:243-248, 1988.

15.

Goldring S. Rich K. Picker S: Experience with gliomas in patients presenting with a chronic seizure disorder. Clin Neurosurg 33-15-42 1986.

Barth D, Sutherling W. Engel JJ. Beatty J: Neuromagnetic evidence of spatially distributed sources underlying epileptiform spikes in the human brain. Science 223:293-296. 1984. Hellstrand E, Abraham-Fuchs K. Jernberg B. et al: MEG localization of interictal epileptic focal activity and concomitant stereotactic ra¬ diosurgery: A non-invasive approach for patients with focal epilepsy. Physiol Meas 14:131-136, 1993.

16.

Rogers L. Morris H. Lupica K: Effect of cranial irradiation on seizure frequency in adults with low-grade astrocytoma and medically in¬ tractable epilepsy. Neurology 43:1599-1601, 1993. Barcia-Salorio JL, Rolddn P. Herndndez G, Lopez-Gdmez L: Radiosurgical treatment of epilepsy. Appl Neurophysiol 48-400-403 1985.

17.

18. 19.

Barcia-Salorio JL, Barcia JA, Roldiin P. et al: Radiosurgery of Epilepsy. Acta Neurochir Suppl (Wien) 58:195-197, 1993. Barcia JA, Barcia-Salorio JL, Ldpez-Gdmez L, Hernandez G: Stereotactic radiosurgery may be effective in the treatment of idio¬

36.

Barcia-Salorio JL, Roldan P, Ramos S, et al: Chronic burr-hole ECoG and SEEF in the assessment of surgical treatment of epilepsy. Acta Neurochir Suppl (Wien) 33:79-83. 1984. Barcia-Salorio JL. Barcia JA, Ciudad J, Such V: Automatic calcula¬ tion of epileptogenic focus location within the brain. Appl Neuro¬ physiol 50:600-603, 1987.

37.

Hinke R, Hu X. Stillman A. et al: Functional magnetic resonance imaging of Broca’s area during internal speech. Neuroreport 4: 675-678. 1993.

38.

Bandettini P. Jesmanowicz A. Wong E, Hyde J: Processing strategies tor time-course data sets in functional MR1 of the human brain. Magn Resort Med 30:161-173, 1993. Mueller W. Morris G. Samantha-Roy R, et al: Cortical localization with magnetic resonance imaging compared to direct stimulation mapping (abstract). XI Meeting of the World Society of Stereotactic and Functional Neurosurgery, ixtapa. Mexico, 1993.

39.

CHAPTER

1 99

THE ROLE OF THALAMIC ELECTRICAL STIMULATION IN THE CONTROL OF SEIZURES

Francisco Velasco, Marcos Velasco, Fiacro Jiminez, Ana Luisa Velasco, Francisco Brito, and Mark Rise

The rapid generalization of cortical electroencephalographic (EEG) discharges during the onset of a generalized seizure sug¬ gested that convulsive activity propagates through a nervous structure with widespread anatomical and functional connec¬ tions.1 Widespread cortical recruiting responses elicited by stimulation of nonspecific thalamic nuclei,2 and anatomic stud¬ ies demonstrating the extensive connections of intralaminar and midline thalamic nuclei with cortical areas3 6 give support to the theory of a central pacemaker of cortical synchronization that might serve in the propagation of convulsive activity. Thalamic structures were also suspected to participate in the genesis of some forms of generalized seizures, 3 cps spike-andwave discharges on EEG and behavioral changes have been in¬ duced by thalamic stimulation, resembling typical absences.7,8 Also, lesions in the thalamus prevented the propagation of ex¬ perimental models of acute epileptic foci,9,10 while thalamic le¬ sions in the “lateral” and “subventral lateral” thalamus de¬ creased the frequency and severity of seizures in patients with

poses—pain control, for example13—and more recently tremor control;14 (2) to use surgical tools approved for clinical use; and (3) to select cases that were not candidates for other wellestablished surgical procedures for seizure control. We chose CM as target because it is a large, rounded nu¬ cleus, close to easily identified landmarks [posterior commis¬ sure and anterior commissure-posterior commissure (AC-PC) line] and the fact that, when CM is stimulated with the parame¬ ters used in chronic thalamic and brain-stem stimulation, sub¬ jects do not experience unpleasant sensations. At the same time, CM is close to the thalamic sensory nucleus which, when activated, gives rise to the sense of paresthesia readily identi¬ fied by the patient. This allows detection of the spreading of electrical current beyond the limits of CM.15 Others have at¬ tempted to interfere with thalamic propagation of seizures us¬ ing electrical stimulation of the ventralis anterior nucleus, which is also an intralaminar nonspecific nucleus.16,17

intractable epilepsy.11 Studies in animals testing the control of seizures by interfer¬ ing with thalamic propagation are limited because of the lack of good experimental models of chronic epilepsy that resemble the variety of clinical and EEG patterns seen in patients.12 Consequently, new procedures must be explored directly in pa¬ tients. On the other hand, lesioning of thalamic structures is not without risks. This fact, taken in conjunction with the uncertain indications and the irreversible effects induced by lesioning, makes this approach questionable. Electrical stimulation, in contrast with lesioning, induces reversible changes, and its application may be graded through the stimulation parameters to the point of maximal response and minimal side effects. For these reasons, we decided to explore the possibility of seizure control by interfering with the thalamic propagation of epilep¬ tic discharges through electrical stimulation (ES) of the centromedian nucleus (CM), and intralaminar nucleus that is part of the “diffuse thalamic (or reticular) projection system.” The use of this new approach was necessarily guided by ethical considerations: (1) To restrict the amount and mode of stimulation to those parameters found to be safe when used previously in humans to stimulate deep structures for other pur¬

SELECTION OF CASES FOR ELECTRICAL STIMULATION OF THE CENTROMEDIAN NUCLEUS Candidates have been selected from among those patients with seizures found difficult to control, with stable or nonprogres¬ sive diseases, such as birth trauma and postencephalitic seque¬ lae, cortical dysplasia, chronic nonevolving cysticercosis (cal¬ cified granulomas), stable tuberous sclerosis, or cases of unknown etiology that have had chronic (several years) epilep¬ tic attacks. All cases have been observed over months to years in the Epilepsy Clinics at the General and Children’s Hospitals of Mexico City. During those periods, they have received max¬ imal doses of specific anticonvulsants for their seizure types. While the adequacy of medication dosage was monitored through repeated determinations of anti-convulsant blood lev¬ els, the patients did not obtain adequate seizure control. The subject’s epileptic patterns as manifest clinically and by EEG have been followed through monthly visits and EEG recordings (average six). They were imaged by computed to¬ mography (CT) and magnetic resonance imaging (MRI) to

1933

1934

Part 4/Functional Stereotaxis

identify possible etiology. Their seizure frequency was estab¬ lished by careful recordings kept by the relatives and physi¬ cians for at least 3 months prior to their selection for the proce¬ dure. All patients included thus far have had more than one seizure type but may be grouped in four categories according to their more frequent seizure pattern: (1) generalized tonic-clonic seizures (GTC) with EEG evidence of bilateral involvement of cerebral hemispheres from the start; (2) focal motor seizures (epilepsia partialis continua) either idiopathic or postenceph¬ alitic in origin (Rasmussen type) with secondary GTC; (3) par¬ tial complex seizures with bilateral temporal foci or evidence that the remaining temporal lobe would not sustain memory following unilateral lobectomy; (4) Lennox Gastaut syndrome with tonic, atonic, myoclonic, or propulsive spasms and occa¬ sional GTC.

SURGICAL TECHNIQUE Under general anesthesia, electrodes are stereotactically placed in both left and right CM nuclei through a coronal incision and

bifrontal burr holes. Target localization is accomplished by air ventriculography in which the anterior (AC) and posterior (PC) commissures of the third ventricle are demonstrated. The AC-PC line is drawn and CM is considered to lie at the level of PC, with its inferior border 2 or 3 mm above the AC-PC line in the lateral radiogram (Fig. 199-1 A) and extending between points 6 mm and 15 mm lateral to the midsagittal plane in the anteroposterior (AP) radiograms (Fig. 199-lfi). The tip of the lead is directed toward the PC at an angle of 50 to 70° to the AC-PC line and with its tip left at 1/10 the AC-PC distance above the AC-PC plane and 5/10 lateral to the midline, accord¬ ing to the system of standardization for target localization de¬ scribed elsewhere. 18,19 The lead consists of four isolated platinum electrodes sepa¬ rated by 1 to 3 mm. Initially, the leads were home-made, but more recently we have used “depth brain stimulation leads” (Model 3380, Medtronic Inc., Minneapolis, Minnesota). The electrodes are held in place by means of a plastic ring inserted in the burr hole and a silastic cap that presses the electrode against a slot in the ring wall. A percutaneous wire provided in the lead kit is tunneled subcutaneously to a skin incision on top

Figure 199-1. A and B: Stereotactic placement of stimulating electrodes using as reference the AC-PC line. 1 he tip of the electrode is aimed at the posterior commissure with tip 2 to 3 mm above the AC-PC level in the lateral radiogram A and 10 mm lateral to the midline in the AP radiogram B. C: Two ltrel systems implanted subcutaneously 5 mm below the clavicle in the anterior chest wall and connected to the intracranial electrodes through extension wires (arrows).

Chapter 199/The Role of Thalamic Electrical Stimulation in the Control of Seizures

of the mastoid bone on each side and there externalized. The extension cable is then connected to the electrode by a connec¬ tor that will be left in place subcutaneously until the time of internalization of the entire stimulation system. The extra length of the electrode is gently looped around the skull cap to avoid damage to the electrode by accidental pulling on the externalized wires. The incisions are closed in planes. Once connected, each one of the leads’ electrodes is readily identified by the length of the externalized wires: the shortest corre¬ sponds to the deepest contact. The percutaneous wires are left externalized for a period of time to carry out electrophysiological tests. These tests confirm that the electrode’s placement is correct, establish the stimulation parameters to be used, and test the effectiveness of ES for seizure control (see below).

ELECTROPHY SIOLOGIC AL CONFIRMATION OF CORRECT ELECTRODE PLACEMENT In the cat, low-frequency (6 to 8 Hz) ES of intralaminar and midline thalamic nuclei induces long-latency, waxing and wan¬ ing, widespread cortical EEG potentials known as recruiting re¬ sponses,2'20 while high-frequency (60 to 100 Hz) stimulation induces cortical desynchronization.21 These EEG responses are better obtained when the animal is kept in a quiet, drowsy ex¬ perimental condition. In humans, similar responses are observed with low- and high-frequency CM stimulation and are better demonstrated when the patient rests quietly with the eyes closed and when the EEG shows a well-organized background activity. Bipolar (negative electrode deep) stimulation at 6 Hz, 1.0 ms duration, biphasic square pulses and 800 to 1200 |xA induces incremen¬ tal responses recorded at the scalp leads. These responses are of three different types, (1) Stimulation of ventral CM and upper mesencephalon (probably the mesencephalic lemniscus) in¬ duces monophasic, negative potentials with widespread distri¬ bution in the scalp recordings but with emphasis on the ipsilateral frontal region; (2) stimulation of the central part of CM induces biphasic (positive-negative) potentials of widespread distribution, with emphasis in the ipsilateral central region; (3) stimulation of dorsal CM induces monophasic positive po¬ tentials circumscribed to the parietal region similar to the pri¬ mary somatosensory potentials. No objective or subjective clinical responses were obtained with this mode of stimulation (Fig. 199-2). High-frequency (60-Hz) stimulation of CM at intensities ranging from 400 to 1250 |iA induces desynchronization of scalp EEG and blocks or suppresses spontaneous paroxysmal activities (Fig. 199-3A). This regimen, when high intensity was used, was occasionally accompanied by paresthesias and dysesthesia in the contralateral arm and face or strabismus and diplopia, presumably due to spreading of stimulation to adja¬ cent ventromedial and lateral thalamic nuclei or upper mesen¬ cephalon. Should those responses be obtained below 800 p,A, it is likely that the lead and the stimulated electrodes are placed too far laterally, or below the thalamus. Occasionally, simultaneous bilateral stimulation of CM at 3 cps and intensities from 1000 to 2000 p.A induces scalp recorded 3 cps spike and wave complexes accompanied by

1935

behavioral arrest and blinking resembling a typical absence in patients not normally exhibiting this type of seizure spontane¬ ously (Fig. 199-36).22

STIMULATION TECHNIQUES AND EVALUATION OF RESULTS Short-Term Electrical Stimulation Plotting the locations of leads from the radiographs with refer¬ ence to anatomic sections from Schaltenbrand and Bailey’s at¬ las23 confirmed that most electrode contacts were located within CM, particularly in its ventrobasal and central parts. A pair of electrodes from which ES at 6 Hz induced recruiting re¬ sponses of types A or B were then selected to be used for thera¬ peutic ES. The stimulation program in all cases studied so far consisted of daily 2-h sessions alternating between the right and left sides with 4-min intervals, using l-min trains for stimulation at 60 Hz, 1.0-ms pulse width, biphasic (Lilly type) pulses. The intensity was adjusted in each case subthreshold for any clini¬ cal responses of the type described before (paresthesia, dyses¬ thesia, or diplopia). The intensity level usually ranged from 450 to 800 |xA with the maximum being 1250 p,A. Stimulation parameters were fixed by the medical staff while the patients were still hospitalized, using a Grass S8 stimulator (Grass Instruments, Quincy, Massachusetts) and isolation unit. There¬ after, a portable stimulator (Almanza Mod IA Ibifax Mexico) was used that the relatives or nurses continued to manage at home. Current flow and electrode impedance were periodically checked through the externalized wires, using a method de¬ scribed elsewhere,24 and both were found to remain stable for periods up to 6 months.25 Patients continued their ES at home for 3 months with monthly visits to the epilepsy clinic and EEG laboratory for followup. Evaluation of the effects of ES on seizure frequency and severity was accomplished through the use of charts on which seizure type and time of occurrence were carefully recorded. Quantitative evaluation of EEG changes was obtained by selecting 10/s samples of maximal abnormalities from each monthly recording and counting the number of spikes or spike-wave complexes. Neuropsycho¬ metric tests were performed through a scale of abilities sepa¬ rately designed by the neuropsychologist to test children and adults and applied before and after this 3-month ES period.26 At the end, those cases that showed significant improvement were selected for internalization of the stimulation system. The response to ES depended on the seizure type presented by the patient; in general, better results were observed in pa¬ tients with GTC and partial motor seizures while partial com¬ plex and generalized seizures associated with Lennox-Gastaut syndrome were not significantly improved (Fig. 199-4).

Long-Term Electrical Stimulation Those cases selected for internalization of the stimulation sys¬ tem are readmitted to hospital. Under general anesthesia the scalp incision is reopened and the electrodes disconnected from the externalized percutaneous wires, which are then removed. Bilateral subclavicular, subcutaneous pockets are made to host

1936

Part 4/Functional Stereotaxis

A

B

C

FP2 F4 C4 P4 02

C3 VvVw% P3

Hvv^w^

oi V^yA^v F7 T3 Vcpci

Ce

the internalized pulse generator (Itrel, Model 7420, Medtronic Inc.). An extension cable (Medtronic, Model 7492) is tunnelled subcutaneously from the scalp to the subclavicular incisions and connected through the extension cable to the pair of con¬ tacts previously selected. Incisions are closed in layers. The next day, the ES parameters are set transcutaneously with the use of a programmer (Model 7432 Programmer, Medtronic. Inc.). The parameters of the available models of fully internalized systems for ES do not match exactly those of the portable stimulator used for stimulation through external¬ ized electrodes. The pulse duration of the implanted stimulator is limited to 0.09 ms, which is one-tenth the duration of the pulse delivered with the portable stimulator. The stimulus in¬

Li Por

J200/O

Figure 199-2. Low-frequency stimulation of CM. Types of incremental responses at surface cortical regions induced by lowfrequency stimulation of the right CM in patient K20 (8/s, 1.0 ms, 800 p,A). A. Recruiting like responses. Induced by stimulation of the ventral portion of CM. Monophasic surface negative potentials with a widespread distribution are seen bilaterally especially in both frontal regions (FP2, F4, FP1, F3). B. Augmentinglike responses. Induced by stimulation of the central portion of CM. Biphasic positive potentials, with a distribution prominent in the ipsilateral parietal region (P4 or P3). C. Primarylike responses. Induced by stimulation of the dorsal portion of CM. Monophasic positive potentials, with a circumscribed distribution in the ipsilateral parietal region (P4 or P3). (From Velasco et al.,22 with permission.)

tensity of the implanted IPG is established by programming volt¬ age. A setting of 4.5 V is calculated to correspond approximately to 400 |j.A, while 7.5 V corresponds to 600 p.A. One problem we have faced with the use of two internalized systems is that the magnet used to activate and deactivate the IPG frequently acti¬ vates the right and left systems simultaneously. When this hap¬ pens, it is difficult to determine, without the use of the program¬ mer, when the systems are on or off. To avoid this problem, we have made use of the cycling features of the IPG to fix a 24-h program of stimulation of 1 min on and 9 min off for each side, leaving an interval of 4 min between the onset of stimulation on the right and left sides. The batteries of the internalized IPGs are expected to last 2 to 3 years with this program.

Chapter 199/The Role of Thalamic Electrical Stimulation in the Control of Seizures

1937

FPI - F7

i »«c

m B

—^vrvvyYVyVVVWSvYyyW^

,response1 flash

■

-*-•-**r

Figure 199-3. A. High-frequency stimulation of CM. Desynchronization of the background, partial blocking of the ongoing paroxysmal EEG activities induced by high-frequency (60/s) stimulation of CM, indicated by horizontal bars. B. Low-frequency suprathreshold stimulation of CM. EEG and clinical features of a typical absencelike attack elicited by simultaneous low frequency (three per second) suprathreshold (2400-p.A) stimulation of the right central and left ventral portions of CM. “ON” and “OFF” indicate the duration of CM stimulation. Notice that the response to flash (bottom) is blocked during the acute CM stimulation. (Modified from Velasco et al.,22 with permission.)

The results obtained up to 33 months of follow-up indicate that the beneficial effects on seizure control obtained in the first 3 months of stimulation are sustained in spite of the fact that the stimulation parameters are not the same as those used in the acute phase. Furthermore, evidence that the improvement is the result of ES and not of spontaneous fluctuation of seizure fre¬ quency comes from the fact that seizure frequency returns to baseline values when ES is interrupted due to IPG battery de¬ pletion. This improvement in seizure frequency is observed in

spite of the fact that paroxysmal, interictal abnormalities may not be significantly improved by long-term ES with totally im¬ planted devices 27

ANCILLARY FINDINGS With electrodes placed in CM and left externalized for periods of 3 to 6 months, we had the opportunity of carrying out a num-

1938

Part 4/Functional Stereotaxis

■ K 21 J SA

K 20 Z L

I00-|

100-1

10,000-1

lOO-i

‘ K24 PA

lOpOO-i

K 25 AM

TOTAL

- NUM SEIZURES/MO

50-

5000

BL ESCM POST LT

50-

50-

BL ESCM POST LT

BL ESCM POST LT

BL ESCM POST LT

BL ESCM POST LT ESCM

5000

BL ESCM POST LT

BL ESCM POST LT

BL ESCM POST LT

BL ESCM POST LT

BL ESCM POST LT

NUM PAROXYSMAL 50-|EEG WAVES /10 S

BL ESCM POST LT ESCM

NUM BACKGROUND ,OO-i^eg waves/ios

ESCM

ESCM

ESCM

K24

50-

BL ESCM ROST LT

BL ESCM POST LT

ESCM

ESCM

BL ESCM POST LT ESCM

Figure 199-4. Statistical analysis of the effects of chronic electrical stimulation of CM in five patients (K20, 21, 24, 25, 28) with severe intractable epileptic attacks. The upper graphs indicate the occurrence of clinical seizures: filled bars = generalized tonic-clonic seizures: dashed bars = atypical absences; clear bars = partial complex seizures. Seizures occurred at a frequency of from 12 to over 5000 per month during the baseline (BL) period and were significantly decreased by ESCM through externalized electrodes for 3 months (ESCM), continued to be decreased in the poststimulation period of 3 months (POST), and throughout the long-term ESCM, which varied from 7 to 33 months (LT). The analysis for the group (total) presented in the left-side graphs shows a significant decrease of seizures (p < 0.001), particularly the generalized tonic clonic seizures. This is accompanied by a significant decrease in the number of paroxysmal EEG discharges (p < 0.01) (middle graphs) and an increase of background EEG frequency (p < 0.05) (lower graphs). (From Velasco et al.,25 with permission.)

ber of observations pertinent to the physiopathology of the epilepsies and the effect of chronic ES on the thalamus.

Recording Simultaneous EEG recordings from CM, scalp, and mesial temporal lobe (through implanted electrodes in cases of tem¬

poral lobe seizures) allowed the study of the time relationships between cortical and thalamic epileptic discharges in a large variety of epileptic attacks. It was observed that ictal activity in cases of partial complex seizures originating from the amyg¬ dala were not accompanied by CM epileptic activity, as re¬ ported by others for the ventrobasal thalamus,28 except when the seizure evolved into a secondary generalized attack. This was also the case with focal motor seizures that originated in the

Chapter 199/The Role of Thalamic Electrical Stimulation in the Control of Seizures

primary motor cortex. In cases of primary GTC seizures, corti¬ cal and thalamic paroxysmal discharges started simultaneously. This was also true for atypical absences in cases of LennoxGastaut syndrome. In cases of typical absences, paroxysmal discharges increased in CM several seconds before the clinical and cortical EEG manifestations. Finally, we observed clinical seizures, such as brief tonic attacks in children, without seeing concomitant CM or cortical EEG paroxysms.22 On the other hand, prominent interictal spikes in CM, in the absence of concomitant scalp or temporal lobe paroxysmal ac¬ tivity, were observed in practically all cases, including those with temporal lobe seizures.29,30 These observations suggest that thalamic neurons become hyperexcitable in cortically and subcortically initiated seizures and behave as epileptic neurons. It also indicates that CM participates in the propagation of cor¬ tically initiated GTC seizures in the “primary” GTC seizures and atypical absences. CM may be the place of onset of typical absences, but it does not participate in the onset and propaga¬ tion of some other seizure types such as brief tonic jerks.

Low-Frequency Stimulation As described above, 6- to 8-Elz stimulation of CM induces re¬ cruiting responses in the cortex with similar characteristics and distribution to those obtained in the cat. This suggests that in humans, CM is also part of the diffuse thalamic projection system. Bilateral stimulation (3 Hz) of CM at high intensity (2000 p,A) induces typical EEG and clinical absences in pa¬ tients without a history of spontaneous typical absences. This indicates that typical absences can be elicited by thalamic stim¬ ulation regardless of the spontaneous cortical seizure pattern and that in order to obtain such responses, abnormal highintensity thalamic output to the cortex is required. This is dif¬ ferent to the typical absences obtained experimentally by systemic administration of penicillin, where a cortical hyperex¬ citable response to normal thalamic impulses has been pro¬ posed as the mechanism.31

term studies, improvement of seizure frequency and intensity continue to depend on the adequacy of stimulation. When stim¬ ulation is discontinued after 33 months, seizures tend to return to their baseline frequency. This indicates that CM stimulation is a safe and effective procedure.27 During the preliminary ob¬ servations, the stimulation regimen has been limited to the use of certain parameters and patterns of stimulation. Of course, it is desirable to explore the effect of different stimulation regi¬ mens (higher frequency, continuous stimulation, etc.) that have been used safely for other purposes such as tremor or pain con¬ trol.14 At the present the technique may be recommended to treat GTC seizures and partial motor seizures.

Improvement in Background

One of the most intriguing observations made after stimulation of CM is the increased background EEG frequency that is ac¬ companied by a better performance of daily activities. Relationship between EEG frequency and psychological per¬ formance has been described.34,35 In the case of epileptic pa¬ tients, improvement in neuropsychological performance seems to be independent of improvement in seizure frequency.26

References 1. 2. 3.

4. 5.

High-Frequency Stimulation 7.

8. 9. 10.

11. 12. 13.

14.

Chronic Electrical Stimulation The impedance of the electrodes remains relatively stable for periods of up to 6 months, indicating that no lesioning or scar¬ ring of tissue around the electrode has occurred. In the long¬

EEG

Frequency and Neurometric Scores

6.

Stimulation (60 Hz) of CM induces cortical EEG desynchro¬ nization as described in animals for the stimulation of the as¬ cending reticular system,21 suggesting that in humans, as in other species, CM is part of the reticular thalamic system. On the other hand, repeated high-frequency CM stimulation is often followed by EEG 2- to 3-Hz afterdischarges that re¬ semble some forms of afterdischarge seen in sensitization pro¬ cedures like the kindling phenomenon.30 This may explain the fact that seizures remain improved for variable periods of time after the stimulation is discontinued.22,25,29 For that reason, a pro¬ gram of double-blind controlled studies may be unsatisfactory forjudging the effect of CM stimulation, as a placebo response period following a stimulation period may give the false im¬ pression of similar effects.32,33

1939

15.

Jasper HH, Kershman J: Electroencephalographic classification of the epilepsies. Arch Neurol Psychiatry 45:903-945, 1941. Dempsey EW, Morrison RS: The mechanism of thalamocortical aug¬ mentation and repetition. Am J Physiol 138:297-308, 1942. Nauta WJH, Whitlock DG: An anatomic analysis of the nonspecific thalamic projection system, in Adrian ED (ed): Brain Mechanisms and Consciousness. Oxford, England: Blackwell, 1954, pp 81-116. Jones EG: The Thalamus. New York: Plenum Press, 1985, pp 22-26. Royce GJ, Mourey RJ: Efferent connections of the centromedian and parafascicular nuclei: An autoradiographic investigation in the cat. J Comp Neurol 235:277-300, 1985. Sadikot AF, Parent A, Frangois C: The centromedian and parafascicu¬ lar thalamic nuclei project respectively to the sensorimotor and asso¬ ciative limbic striatal territories in the squirrel monkey. Brain Res 510:161-165, 1990. Jasper HH, Droogleever-Fortuyn J: Experimental studies of the func¬ tional anatomy of petit mal epilepsy. Res Publ Assoc Nerv Ment Dis 26:272-298, 1947. Hunter J, Jasper HH: Effects of thalamic stimulation in unanesthetized animals. Electroencephalogr Clin Neurophysiol 1:305-324, 1949. Kusskee JA: Interactions between thalamus and cortex in experimen¬ tal epilepsy in the cat. Exp Neurol 50:568-578, 1976. Van Straaten JJ: Abolition of electrically induced cortical seizures by stereotaxic thalamic lesions: Evidence for descending thalamopontine medullar spinal connections in the centroencephalic epileptic system of the cat. Neurology (Minneapolis) 25:141-149, 1975. Mullan S, Veilati G, Karasick J, Malis M: Thalamic lesions for the con¬ trol of epilepsy: A study of nine cases. Arch Neurol 16:277-285, 1967. Fisher RS: Animal models of the epilepsies. Brain Res Rev 14: 245-278, 1989. Andy JO: Parafascicular centromedian nuclei stimulation for in¬ tractable pain and dyskinesia (painful-dyskinesia). Appl Neurophysiol 43:133-144, 1980. Benabid AL, Pollack P, Gervason C, et al: Long term suppression of tremor by chronic stimulation of ventral intermediate thalamic nucleus. Lancet 337:403-406, 1991. Velasco F, Velasco M, Alcala H: The electrical stimulation of the thal¬ amus, in: Kautt H, Resor SR (ed): Advances in Neurology. New York: Marcel Dekker, 1989, pp 236-239.

1940

16.

17.

18.

19. 20. 21. 22.

23. 24.

Part 4/Functional Stereotaxis

Sussman NM, Goldman, HW, Jackel RA, et al: Anterior thalamic stimulation in medically intractable epilepsy: Part II. Preliminary clinical results. Epilepsia 29:677, 1988. Goldman HW, Sussman NM, Callahan M, et al: Anterior thalamic stimulation for medically intractable epilepsy: Part I. Implantation and stimulation. Epilepsia 29:677, 1988. Velasco F, Molina Negro P, Bertrand C, et al: Further definition of the subthalamic target for the arrest of tremor. J Neurosurg 36:184-191, 1972. Velasco F, Velasco M, Machado J: Statistical outline of the subthalamic target for the arrest of tremor. Appl Neurophysiol 38:38-46, 1975. Velasco M, Lindsley DB: Role of orbital cortex in regulation of thala¬ mocortical electrical activity. Science 149:1375-1377, 1965. Moruzzi G, Magoun HW: Brain stem reticular formation and activation of the EEG. Electroencephalogr Clin Neurophysiol 1:455-473, 1949. Velasco F, Velasco M, Velasco AL, et al: Role of the centromedian thalamic nuclei in the onset, propagation and arrest of epileptic seizures: An electrophysiological study in man. Acta Neurochirurg (Wien) 58:201-204, 1993. Schaltenbrand G, Bailey P: Introduction to stereotaxis with an atlas of the human brain. Stuttgart: Thieme, 1959, vol IV. Becker HC, Peacock SM, Heath RG, et al: Methods of stimulation control and concurrent electroencephalographic recording, in Scheer, DE (ed): Electrical Stimulation of the Brain. Dallas: University of Texas, 1961, pp 74-90.

25.

Velasco F, Velasco M, Velasco AL, Jimenez F: Effect of chronic elec¬ trical stimulation of the centromedian thalamic nuclei on various in¬ tractable seizure patterns: I. Clinical seizures and paroxysmal EEG activity. Epilepsia 34:1052-1064, 1993.

26.

Velasco M, Velasco F, Velasco AL, et al: Effect of chronic electrical stimulation of the centromedian thalamic nuclei on various in¬

tractable seizure patterns: II. Psychological performance and back¬ ground EEG activity. Epilepsia 34:1065-1074, 1993. 27.

Velasco F, Velasco M, Velasco AL, et al: Electrical stimulation of the centromedian thalamic nucleus in the control of seizures: Long term studies. Epilepsia 36:63-71, 1995.

28.

Rossi GF, Walter RD, Crandall PH: Generalized spike and wave dis¬ charges and nonspecific thalamic nuclei. Arch Neurol 19:174-183, 1968.

29.

Velasco F, Velasco M, Ogarrio C, Fanghanel G: Electrical stimulation of the centromedian thalamic nucleus in the treatment of convulsive seizures: A preliminary report. Epilepsia 28:421-430, 1987. Velasco F, Velasco M, Velasco G: Kindling en el tdlamo? Postdescarga local inducida por estimulacion electrica crdnica en el tdlamo del hombre. Gaceta Medica (Mexico) 125:264-269, 1989.

30.

31.

Gloor P: Generalized epilepsy with spike and wave discharge: A rein¬ terpretation of its electrographic and clinical manifestations. Epi¬ lepsia 20:571-588, 1979.

32.

Fisher RS, Uematsu S, Krauss GL: A placebo controlled pilot study of centromedian thalamic stimulation in the treatment of intractable seizures. Epilepsia 33:841-851, 1992.

33.

Fisher RS, Uthman BM, Ramsay E, et al: Alternative surgical tech¬ niques for epilepsy, in Engel J (ed): Surgical Treatment of the Epi¬ lepsies. New York: Raven Press, 1993, pp 549-564. Creutzfeld O, Griinewald G, Simonova O, Schmitz H: Changes of basic rhythms of the EEG during performance of mental and visualmotor-tasks, in Evans CR, Mulholland TB (eds): Attention in Neurophysiology. London: Butterworth, 1969, pp 148-168. Mulholland, TB: The concept of attention and the electroencephalo¬ graphic alpha rhythm, in Evans CR, Mulholland TB (eds): Attention in Neurophysiology. London: Butterworth, 1969, pp 100-127.

34

35.

CHAPTER 200

VAGAL NERVE STIMULATION FOR THE TREATMENT OF REFRACTORY SEIZURES

Lars-Erik Augustinsson and Elinor Ben-Menachem

Currently about 30 percent of patients with epilepsy do not achieve satisfactory seizure control from available antiepileptic drug (AED) therapy despite the benefits of new AEDs for many patients. For a specific group of patients, resective brain surgery can be highly effective, but this still leaves a large group of patients without a therapeutic alternative. Vagal nerve stimulation (VNS) is a new treatment for pa¬ tients with refractory partial seizures. Chronic intermittent stim¬ ulation of the left vagal nerve has been studied in animals over the last few decades and in humans since 1987. Vagal nerve stimulation has a demonstrated anticonvulsant effect in a num¬ ber of animal seizure models, which has led to the undertaking of two single-blind human pilot studies.1 Based on the anti¬ convulsant effect demonstrated in these studies, a 114-patient, 17-center, double-blind placebo-controlled study of patients with refractory partial seizures was conducted. Both at shortand long-term follow-up, VNS demonstrated statistically sig¬ nificant anticonvulsant effects.

ANIMAL STUDIES A wide body of literature exists covering the use of anticonvul¬ sant VNS in seizure models. Zabara2 first demonstrated that va¬ gal stimulation could stop strychnine-induced seizures in dogs. In this study, strychnine was injected until seizure activity was observed on the electromyogram (EMG), and the stimulation was started 1 to 3 min later. Repetitive VNS was reported to ei¬ ther interrupt or terminate the seizure process, often within sec¬ onds of initiation. Stimulation also appeared to prevent the re¬ turn of seizure activity. Transection of the vagal nerve distal to the electrode site did not change the ability of VNS to suppress the seizures. In another experiment,2 pentelenetetrazol (PTZ) was injected into two dogs until tremor was observed on the EMG. Vagal nerve stimulation terminated the tremor, which then was delayed in its reappearance. The level of voltage needed to control the tremor was less than that needed to con¬ trol seizures. Heart and respiratory functions were not impaired during VNS in these experiments. Woodbury and Woodbury3 showed VNS to be effective against maximal electroshock seizures (MES) in rats, a model that predicts efficacy against tonic-clonic seizures. The stimu¬ lation parameters used were those capable of stimulating C fibers, and therefore a slight slowing of respiration as well

1941

as bradycardia were seen in the study animals. In PTZ and 3-mercaptoproprionate (3-MP)-induced seizures, which pre¬ dict efficacy against absence seizures,3 an intraperitoneal (IP) injection of PTZ (50 mg/kg) was given to produce a mild and steady status epilepticus. Vagal nerve stimulation consistently abolished EMG activity caused by the status state. When a sin¬ gle dose of PTZ was given to produce a fully developed seizure, VNS commenced after the initiation of the seizure was unable to terminate it, although it may have shortened its duration. Vagal nerve stimulation had no effect on the electrocorticogram (ECoG) but did have a slight effect on the EMG. However, VNS applied at the end of a seizure was able to pre¬ vent the initiation of additional seizures. The effects of vagal nerve stimulation on 3-MP-induced seizures were comparable to those with PTZ.3 Penicillin-induced seizures in rats4 could also be aborted by VNS. In this study, 15 rats were treated with either penicillin (PCN) applied to the cortex to induce focal spike activity or with IP PTZ to induce recurrent seizures. The animals then re¬ ceived VNS or had their tails heated as a control stimulation with or without cooling of the vagus nerve proximal to the stimulation location to simulate a nerve conduction block. After application of PCN, VNS reduced and occasionally ter¬ minated interictal spike activity 1 to 2 s after stimulation began (mean spike frequency decreased 33 percent). This effect was observed thoughout the stimulation period and persisted even after VNS was discontinued. The amplitude of residual spikes was also reduced during the stimulation and after it was discon¬ tinued. After injection of PTZ, VNS was applied >4 s after the start of seizures and did not have any effect. However, VNS ap¬ plied £

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Dostrovsky J, Sher G, Davis K, et al: Microinjection of lidocaine into human thalamus: A useful tool in stereotactic surgery. Stereotact Fund Neurosurg 60:168-174, 1993.

16.

7.

Sendelbeck S, Urquhart J: Spatial distribution of dopamine, methotrexate and antipyrine during continuous intracerebral micro¬ perfusion. Brain Res 328:251-258, 1985.

17.

8.

Bouvier G, Penn RD, Kroin JS. et al: Direct delivery of medication into a brain tumor through multiple chfonic catheters. Neurosurgery 20:286-291, 1987.

Bergman H. Wichmann T, DeLong M: Reversal of experimental parkinsonism by lesions of the subthalamic nucleus. Science 249:1436-1438, 1990. Seiger A, Nordberg A, Holst HV. et al: Intracranial infusion of puri¬ fied nerve growth factor to an Alzheimer patient: The first attempt of a possible future treatment strategy. Behav Brain Res 57:255-261, 1993.

CHAPTER

219

NEURO-ONCOLOGY ADVANCES IN THE MANAGEMENT OF BRAIN TUMORS: TODAY AND TOMORROW

Raymond Sawaya and B. Lee Ligon

Brain tumors are the third leading cause of death from cancer in persons 15 to 34 years of age,1 and according to recent stud¬ ies, the prevalence of primary brain tumors is increasing, espe¬ cially among the elderly.2 Despite the advances in medical technology that have occurred over the last several decades, brain cancer remains a debilitating disease that often is rapidly fatal. These research and clinical advances have also, however, resulted in an increase in the number of researchers and clini¬ cians involved in molecular, genetic, and technological studies that will offer more efficacious treatment modalities. As we en¬ ter the mid-1990s, designated “the decade of the brain,” and approach the turn of the century, we have a wealth of biological information and technical advances that portend unprecedented clinical approaches to brain tumors. To date, the most dramatic and tangible advances in neuro¬ oncology have occurred in the field of neuroimaging with the introduction of computed tomography (CT) and magnetic res¬ onance imaging (MRI). MRI includes phase-contrast angi¬ ography, which has the potential to quantitate blood flow; phased-array coils, which allow an increased field of view that improves the image quality and reduces examination time; and tissue spectroscopy, which, by advancing studies in the bio¬ chemical makeup of tissue, aids physicians in making diag¬ noses. In addition, a new field of computer-guided intracranial navigation that combines modern imaging tools with stereo¬ tactic three-dimensional localization and standard neurosurgi¬ cal techniques should lead to better selection of candidates, more radical resection of tumors, and safer surgical proce¬ dures. This chapter reviews two areas of neuro-oncology: cur¬ rent treatment modalities based on these advances and futuris¬ tic therapies that are emerging from biological and technical advancements, including robotics, gene therapy, and computer¬ generated virtual reality.

CURRENT TREATMENT MODALITIES FOR BRAIN TUMORS Regardless of their etiology, brain tumors have different impli¬ cations for the individual patient, requiring specific diagnoses and individualized decisions regarding the most efficacious

treatment. Currently, malignant brain tumors are treated with surgery, stereotactic radiosurgery, radiation therapy, chemother¬ apy, and combinations of those therapies; benign tumors usu¬ ally are treated with surgery or radiosurgery. The information presented in this chapter provides a brief overview of the his¬ torical background and current applications of these modalities.

Surgery The advent of modern diagnostic procedures and the introduc¬ tion of surgical advances have enhanced the safety of intracra¬ nial surgeiy significantly, with the result that neurosurgery has assumed an increasingly critical role in the management of brain tumors. Today most patients can tolerate brain tumor re¬ section3 and, with the appropriate neurosurgical intervention, expect an improved quality of life and prolonged survival even when the tumor is extremely aggressive. Tremendous strides in technology have occurred in the last two decades, including the surgical microscope, which provides a wide range of magnifi¬ cation and enhanced illumination. Also, the development of long, bayonet-shaped microsurgical instruments allows sur¬ geons to approach lesions in any intracranial location and maintain good visualization of the vascular supply and critical areas of the central nervous system. The addition of the laser allows surgeons to perform intricate and delicate cutting, evap¬ orating, and coagulating. With this technique, a light is ampli¬ fied in a resonator and energy is directed by reflective mirrors into the operative field, where the surgeon manipulates a beam by adjusting the power intensity of the laser source and the fo¬ cal point of the beam. The laser then is used to vaporize cells by overheating them, inflicting only minimal injury on the sur¬ rounding tissue, or, at a lower power density, to coagulate blood vessels. Other advances include bipolar coagulators, which provide efficacious hemostasis and eliminate the danger of spreading current (a difficulty encountered with older monopolar coagu¬ lators), and self-retaining brain retractors, which simultane¬ ously improve the surgical exposure, maintain a constant pres¬ sure force on the brain, and free the surgeon’s hands. Modem neuroanesthesia, improved methods of managing increased in-

2077

2078

Part 5/Future Technological Advances

tracranial pressure, and improved control of fluids and elec¬ trolyte balance also have advanced the field of neurosurgery.

Stereotactic Neurosurgery Stereotactic neurosurgery is a term that refers to a minimally invasive technique that allows a surgeon to navigate to any point in the brain to obtain tissue samples and/or destroy in¬ tracranial tissues or lesions that might otherwise be inoperable. Derived from the Greek word stereo, meaning “three dimen¬ sions,” and the Latin tactus for “touch,” the term reinforces the concept of using a three-dimensional surgical system to reach and touch a structure deep in the brain.4 The technique involves directing an electrode or probe to an intracerebral target with minimal damage to the overlying structures. In the late 1970s, the advent of CT scanning greatly enhanced the efficacy of stereotactic neurosurgery. At that time, Memorial Medical Center of Long Beach developed a CT-guided stereotactic ap¬ paratus (Fig. 219-1) that allowed the patient to lie on the CT scanner couch with the head affixed to the frame by four screws inserted by the surgeon with the patient under local anesthesia. Three N-shaped locators localize the scan plane with respect to the frame. The target tumor can be identified on the CT picture and can be localized in three dimensions in the frame coordinate system. Once the coordinates (x, y, z) of the tumor are computed, the biopsy instrument, which is located and positioned according to reference marks along the axes, is passed through a single burr hole or a small craniotomy to the predetermined point; it is then used to alter the function of deep structures in the brain, treat various lesions, or obtain tissue biopsy for study.5 With the increased use of computers, computer workstations have been designed that, combined with stereotactic systems, improve surgical planning and implementation. These systems provide for simple and rapid calculations of localizer fiducial

points, target coordinates, and arc settings, with the data acqui¬ sition usually transferred from CT or MRI images that are stored on magnetic tape to the hard disk of the workstation. Stereotactic craniotomies can reduce the morbidity of tumor surgery because they (1) require a smaller scalp incision and skull opening, reducing the potential for postoperative intracra¬ nial hematomas, (2) provide the ability to follow a precisely planned trajectory through noneloquent brain to a target lesion, and (3) reduce the risk of resection of “normal” brain surround¬ ing the tumor. In addition to being particularly beneficial in cases of mass lesions of the midbrain and pons and for deep and small tumors, stereotactic craniotomies are especially use¬ ful in treating multiple brain metastases, which can be resected during one sitting under local anesthesia.4 Of particular importance is the diagnostic advantage of stereotactic biopsy. The tendency to treat patients with brain le¬ sions solely on the basis of the neuroimaging diagnosis (CT or MRI) is unwise and can result in unnecessary therapy or mis¬ treatment. Current studies indicate that 10 to 15 percent of pa¬ tients who are referred for a diagnostic biopsy with a prebiopsy diagnosis of tumor are found to have nonneoplastic lesions, and one report revealed that patients were treated with radia¬ tion for tumors that were thought to be malignant but that were found at stereotactic biopsy to be nonneoplastic.6 Stereotactic neurosurgery also has been reported to be especially efficacious (96 percent) in diagnosing intracranial lesions in patients with acquired immune deficiency syndrome,7 although the proce¬ dure poses risks for both the patient and the surgeon.8

Radiosurgery 1 he term stereotactic radiosurgery refers to a procedure that uses small, well-collimated beams of ionizing radiation to ab¬ late intracranial lesions.4 Lars Leksell9 coined the term in 1951, specifically intending that it be used to “stress the fact that this

Figure 219-1. The Memorial

N-SHAPED LOCATOR

Hospital CT-guided stereotactic head frame that was a precursor to the high-precision, computercontrolled latest-generation robot. (Kwoh YS: Special stereotactic techniques: Robotic methods applied to stereotactic surgery, in Heilbrun MP (ed): Stereotactic Neurosurgery, vol 2, p 220: Concepts in Neurosurgery. Baltimore: Williams