Decision making in neurovascular disease 9781684200573, 1684200571

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Decision Making in Neurovascular Disease Leonardo Rangel-Castilla, MD Assistant Professor Department of Neurosurgery and Radiology Mayo Clinic Rochester, Minnesota

Robert F. Spetzler, MD Professor and Emeritus Chair Department of Neurosurgery Barrow Neurological Institute Phoenix, Arizona

Peter Nakaji, MD Professor of Neurosurgery Director of Minimally Invasive and Endoscopic Neurosurgery Program Director of the Neurosurgery Residency Program Department of Neurosurgery Barrow Neurological Institute Phoenix, Arizona

Elad I. Levy, MD, MBA, FACS, FAHA Professor and Chair L. Nelson Hopkins MD Professor Endowed Chair Department of Neurosurgery Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo Medical Director, Department of Neuroendovascular Services Co-Director, Gates Stroke Center Kaleida Health Buffalo, New York

Adnan H. Siddiqui, MD, PhD, FACS, FAHA, FAANS Professor and Vice Chair Director Neuroendovascular Fellowship Program Department of Neurosurgery and Radiology State University of New York Buffalo, New York

310 illustrations

Thieme New York • Stuttgart • Delhi • Rio de Janeiro

Executive Editor: Timothy Hiscock Managing Editor: Sarah Landis Assistant Managing Editor: Nikole Connors Director, Editorial Services: Mary Jo Casey Production Editor: Torsten Scheihagen International Production Director: Andreas Schabert Editorial Director: Sue Hodgson International Marketing Director: Fiona Henderson International Sales Director: Louisa Turrell Director of Institutional Sales: Adam Bernacki Senior Vice President and Chief Operating Officer: Sarah Vanderbilt President: Brian D. Scanlan Printer: King Printing Library of Congress Cataloging-in-Publication Data Names: Rangel-Castilla, Leonardo, editor. | Nakaji, Peter, editor. | Siddiqui, Adnan H., editor. | Spetzler, Robert F. (Robert Friedrich), 1944- editor. | Levy, Elad I., editor. Title: Decision making in neurovascular disease / [edited by] Leonardo Rangel-Castilla, Peter Nakaji, Adnan H. Siddiqui, Robert F. Spetzler, Elad I. Levy. Description: New York : Thieme, [2018] | Includes bibliographical references. Identifiers: LCCN 2018008649| ISBN 9781684200573 (print) | ISBN 9781626237780 (eISBN) Subjects: | MESH: Cerebrovascular Disorders—therapy | Vascular Neoplasms—therapy | Clinical Decision-Making Classification: LCC RC388.5 | NLM WL 355 | DDC 616.8/1—dc23 LC record available at https://lccn.loc.gov/2018008649

Important note: Medicine is an ever-changing science undergoing continual development. Research and clinical experience are continually expanding our knowledge, in particular our knowledge of proper treatment and drug therapy. Insofar as this book mentions any dosage or application, readers may rest assured that the authors, editors, and publishers have made every effort to ensure that such references are in accordance with the state of knowledge at the time of production of the book. Nevertheless, this does not involve, imply, or express any guarantee or responsibility on the part of the publishers in respect to any dosage instructions and forms of applications stated in the book. Every user is requested to examine carefully the manufacturers’ leaflets accompanying each drug and to check, if necessary in consultation with a physician or specialist, whether the dosage schedules mentioned therein or the contraindications stated by the manufacturers differ from the statements made in the present book. Such examination is particularly important with drugs that are either rarely used or have been newly released on the market. Every dosage schedule or every form of application used is entirely at the user’s own risk and responsibility. The authors and publishers request every user to report to the publishers any discrepancies or inaccuracies noticed. If errors in this work are found after publication, errata will be posted at www.thieme.com on the product description page. Some of the product names, patents, and registered designs referred to in this book are in fact registered trademarks or proprietary names even though specific reference to this fact is not always made in the text. Therefore, the appearance of a name without designation as proprietary is not to be construed as a representation by the publisher that it is in the public domain.

Copyright © 2018 by Thieme Medical Publishers, Inc. Thieme Publishers New York 333 Seventh Avenue, New York, NY 10001 USA +1 800 782 3488, [email protected] Thieme Publishers Stuttgart Rüdigerstrasse 14, 70469 Stuttgart, Germany +49 [0]711 8931 421, [email protected] Thieme Publishers Delhi A-12, Second Floor, Sector-2, Noida-201301 Uttar Pradesh, India +91 120 45 566 00, [email protected] Thieme Publishers Rio de Janeiro, Thieme Publicações Ltda. Edifício Rodolpho de Paoli, 25º andar Av. Nilo Peçanha, 50 – Sala 2508 Rio de Janeiro 20020-906 Brasil +55 21 3172-2297 / +55 21 3172-1896 Cover design: Thieme Publishing Group Cover art by Joshua Lai, MS, and cover art background design by Cindy Giljames Cover art (C) 2018 Barrow Neurological Institute Typesetting by DiTech Process Solutions Printed in the United States of America by King Printing ISBN 978-1-68420-057-3 Also available as an e-book: eISBN 978-1-62623-778-0

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This book, including all parts thereof, is legally protected by copyright. Any use, exploitation, or commercialization outside the narrow limits set by copyright legislation, without the publisher’s consent, is illegal and liable to prosecution. This applies in particular to photostat reproduction, copying, mimeographing, preparation of microfilms, and electronic data processing and storage.

I dedicate this book to the people who are always there for me: To my parents, Manuel and Estela. My mother Estela has always shown me that big accomplishments are the result of sacrifice, persistence, hard work, and determination. To my lovely sisters, Alicia and Karina, who have provided their unconditional support all the time. To my wife, Andrea, for her infinite care, tolerance, patience, and understanding of the life of a neurosurgeon in its good and bad moments. And last but not least, to my friend and mentor, Jaime Torres-Corzo, who has inspired me to become the neurosurgeon that I am today. —Leonardo Rangel-Castilla To the patients, whose care this book strives to improve, for we owe you much. To my residents, past and present, for all you have taught me. And to my family, for all you have given to neurosurgery. —Peter Nakaji My efforts are dedicated to my mentors to whom I owe everything. My parents, Nasim and Sarfaraz Siddiqui, who modulated my inclinations with a mix of encouragement and chagrin; Shirley Joseph, who gifted me with the power of scientific probity; Charlie Hodge, who made me a neurosurgeon; Robert Rosenwasser, who transformed me into a comprehensive vascular neurosurgeon; and Nick Hopkins, who made me what I am today. I am also eternally grateful to my wife Saint Josephine, whose tolerance and love know no bounds, and to my children Fatima, Gianni, and Hasan—may you exceed my highest aspirations. —Adnan H. Siddiqui To my residents and fellows from whom I have learned so much and who have liberally and vociferously discussed pertinent issues in neurosurgery which are a reflection of my contributions to this volume. —Robert F. Spetzler This book, like my career, is dedicated to the unyielding support, generosity, and love from my caring and benevolent wife, Cindy, and three children, Bennett, Hannon, and Lauren. And to my parents, who taught me by example that passion, grit, and sacrifice are the key components to everything worth accomplishing. —Elad I. Levy

Contents Foreword by L. Nelson Hopkins

xii

Foreword by Juha Hernesniemi

xiii

Preface

xiv

Acknowledgments

xv

Contributors I 1

xvi

Ischemic Stroke and Vascular Insufficiency Acute Ischemic Stroke: Small Vessel Disease

3

Haris Kamal and Robert N. Sawyer Jr.

2

Acute Ischemic Stroke: Large Vessel Occlusion

8

Maxim Mokin and Elad I. Levy

3

Acute Ischemic Stroke: Acute Internal Carotid Artery Occlusion and Tandem Lesions

14

Leonardo Rangel-Castilla, Adnan H. Siddiqui, and L. Nelson Hopkins

4

Acute Basilar Artery Occlusion

22

Visish M. Srinivasan, Rohini D. Samudralwar, Edward A.M. Duckworth, and Peter Kan

5

Intracranial Atherosclerotic Disease

29

Kunal Vakharia, Kenneth V. Snyder, and Adnan H. Siddiqui

6

Asymptomatic Extracranial Carotid Artery Stenosis

36

Daniel M. Heiferman, Michael P. Wemhoff, and Christopher M. Loftus

7

Symptomatic Extracranial Carotid Artery Stenosis

42

Andrew A. Fanous, Simon Morr, Gursant S. Atwal, Sabareesh K. Natarajan, and Kenneth V. Snyder

8

Vertebrobasilar Stenosis and Insufficiency

48

C. Benjamin Newman, Christian N. Ramsey, III, Curtis A. Given, II, and Gary B. Rajah

9

Vertebral Artery Ostium Stenosis

54

Leonardo Rangel-Castilla, Adnan H. Siddiqui, and Peter Nakaji

10

Pediatric Moyamoya Disease

60

Nadia Khan

11

Adult Moyamoya Disease

68

Mario K. Teo, Venkatesh S. Madhugiri, and Gary K. Steinberg

12

Traumatic and Iatrogenic Carotid Artery Injury

74

Jay U. Howington

13

Traumatic and Iatrogenic Vertebral Artery Injury

80

Hasan A. Zaidi, Alfred Pokmeng See, Leonardo Rangel-Castilla, and Peter Nakaji

14

Spontaneous Internal Carotid Artery Dissection

88

Joseph M. Zabramski

vii

Contents

15

Spontaneous Vertebral Arterial Dissection

95

J. Scott Pannell, Mihir Gupta, Jason Signorelli, and Alexander A. Khalessi

16

Chronic Internal Carotid Artery Occlusion

100

Nina Z. Moore, Andrew M. Bauer, and Peter A. Rasmussen

17

Cerebral Venous Thrombosis and Occlusion

106

Matthew R. Reynolds, Kimon Bekelis, Stavropoula I. Tjoumakaris, Pascal Jabbour, and Robert H. Rosenwasser

II 18

Aneurysms—Anterior Circulation Cervical Carotid Artery Aneurysms

115

Vernard S. Fennell, Peter Nakaji, and Robert F. Spetzler

19

Cavernous Carotid Artery Aneurysms

122

Karam Moon, Giovanni R. Malaty, Bradley A. Gross, and Felipe C. Albuquerque

20

Cave Carotid Artery Aneurysms

129

Laurent Pierot and Jean-Paul Lejeune

21

Superior Hypophyseal Artery Aneurysms

135

Oliver Bozinov, Jan-Karl Burkhardt, Anton Valavanis, and Luca Regli

22

Ophthalmic Artery Aneurysms

140

Stephan A. Munich and Demetrius Klee Lopes

23

Posterior Communicating Artery Aneurysms

147

Robert Asa Scranton and Gavin W. Britz

24

Anterior Choroidal Artery Aneurysms

156

Anna Štekláčová, Ondřej Bradáč, and Vladimír Beneš

25

Internal Carotid Artery Bifurcation Aneurysms

163

Biagia La Pira and Giuseppe Lanzino

26

Middle Cerebral Artery Aneurysms

171

Leonardo Rangel-Castilla, Peter Nakaji, and Adnan H. Siddiqui

27

Distal Middle Cerebral Artery Aneurysms

177

Wuyang Yang and Judy Huang

28

Anterior Cerebral Artery Aneurysms

183

Behnam Rezai Jahromi, Tarik F. Ibrahim, Joham Choque-Velasquez, Hugo Andrade-Barazarte, and Juha Hernesniemi

29

Anterior Communicating Artery Aneurysms

189

Mary In-Ping Huang Cobb, Ali R. Zomorodi, Tony P. Smith, Patrick A. Brown, and L. Fernando Gonzalez

30

Pericallosal Artery Aneurysms

197

John D. Nerva and Louis J. Kim

31

Giant Aneurysms of the Anterior Circulation

203

Matthew R. Reynolds, Joshua W. Osbun, C. Michael Cawley, and Daniel L. Barrow

32

Fusiform Aneurysms of the Anterior Circulation Leonardo B.C. Brasiliense, Pedro Aguilar-Salinas, Douglas Gonsales, Andrey Lima, Eric Sauvageau, and Ricardo A. Hanel

viii

212

Contents

33

Dissecting Intracranial Aneurysms of the Anterior Circulation

220

Stephen R. Lowe, Jan Vargas, Alejandro Spiotta, and Raymond D. Turner, IV

34

Traumatic Intracranial Aneurysms of the Anterior Circulation

227

Ben A. Strickland, Joshua Bakhsheshian, and Jonathan J. Russin

35

Previously Coiled Recurrent Aneurysms of the Anterior Circulation

232

Ethan A. Winkler, Brian P. Walcott, and Michael T. Lawton

36

Previously Clipped Recurrent Aneurysms of the Anterior Circulation

240

Naif M. Alotaibi, David Hasan, and R. Loch Macdonald

III 37

Aneurysms—Posterior Circulation Vertebral Artery Aneurysms

251

Jian Guan, Phil Taussky, and Min S. Park

38

Midbasilar Artery Aneurysms

257

Vikas Y. Rao, Mandy Binning, Daniel R. Felbaum, and Erol Veznedaroglu

39

Basilar Artery Apex Aneurysms

263

Rudy J. Rahme and Bernard R. Bendok

40

Posterior Cerebral Artery Aneurysms

270

Leonardo Rangel-Castilla and Robert F. Spetzler

41

Superior Cerebellar Artery Aneurysms

277

Jeremy Russell and Michael Tymianski

42

Anterior Inferior Cerebellar Artery Aneurysms

283

Michel W. Bojanowski, Ilyes Berania, and Thomas Robert

43

Posterior Inferior Cerebellar Artery Aneurysms

292

Visish M. Srinivasan, Jacob Cherian, Peter Kan, and Edward A.M. Duckworth

44

Giant Aneurysms of the Posterior Circulation

299

Adeel Ilyas, Dale Ding, Eric C. Peterson, and Robert M. Starke

45

Fusiform Aneurysms of the Posterior Circulation

306

Ahmed J. Awad, Justin R. Mascitelli, Joshua B. Bederson, and J Mocco

46

Dissecting Intracranial Aneurysms of the Posterior Circulation

312

Amit Singla and Brian L. Hoh

47

Traumatic Intracranial Aneurysms of the Posterior Circulation

320

Brian M. Snelling, Samir Sur, and Mohamed Samy Elhammady

48

Previously Coiled/Clipped Recurrent Aneurysms of the Posterior Circulation

326

Gerald W. Eckardt and Mandy Binning

IV 49

Aneurysms—Other Mycotic Intracranial Aneurysms

335

Kunal Vakharia, Marshall C. Cress, and Elad I. Levy

ix

Contents

50

Blood Blister–Like Aneurysms

344

Marcus D. Mazur, Phil Taussky, and Min S. Park

51

Pediatric Intracranial Aneurysms

350

Hosam Al-Jehani, Afnan Samman, and Abdulrahman Sabbagh

52

Spinal Aneurysms

355

Samuel Kalb and Peter Nakaji

V 53

Arteriovenous Malformations and Fistulas Spetzler–Martin Grade I and II Arteriovenous Malformations

363

Justin M. Moore, Christoph J. Griessenauer, Christopher S. Ogilvy, and Ajith Thomas

54

Spetzler–Martin Grade III Arteriovenous Malformations

373

Ethan A. Winkler, Brian P. Walcott, and Michael T. Lawton

55

Spetzler–Martin Grade IV and V Arteriovenous Malformations

386

Jason M. Davies and Michael T. Lawton

56

Brainstem Arteriovenous Malformations

395

Michael Kerin Morgan

57

Cerebellar Arteriovenous Malformations

407

João Paulo Almeida, Mateus Reghin Neto, Adailton Arcanjo dos Santos Jr., Feres Chaddad Neto, and Evandro de Oliveira

58

Spinal Arteriovenous Malformations

413

Hubert Lee, Brian Drake, Oliver Holmes, David Houlden, Daniela Iancu, Shawn Malone, and John Sinclair

59

Pial Arteriovenous Fistulas

420

Robert J. Darflinger, Daniel Cooke, and Steven W. Hetts

60

Dural Arteriovenous Fistulas

427

Christophe Cognard

61

Carotid-Cavernous Fistulas

437

Gary B. Rajah, Leonardo Rangel-Castilla, and Adnan H. Siddiqui

62

Spinal Arteriovenous Fistulas

444

Eduardo Martinez-del-Campo, Bradley A. Gross, Leonardo Rangel-Castilla, Peter Nakaji, and Robert F. Spetzler

63

Vein of Galen Malformations

453

Fabio Settecase, Vitor M. Pereira, Peter Dirks, and Timo Krings

VI 64

Cavernous Malformations Supratentorial Cavernous Malformations

465

Michael Lang, Ricky Medel, Aaron S. Dumont, and Peter S. Amenta

65

Thalamic and Basal Ganglia Cavernous Malformations

471

Leonardo Rangel-Castilla and Robert F. Spetzler

66

Brainstem Cavernous Malformations Jason M. Davies, Leonardo Rangel-Castilla, Peter Nakaji, Michael T. Lawton, and Robert F. Spetzler

x

477

Contents

67

Spinal Cord Cavernous Malformations

487

Gursant S. Atwal, Vernard S. Fennell, Leonardo Rangel-Castilla, and Peter Nakaji

VII 68

Hypervascular Tumors Intracranial Vascular Tumors

495

Keith Allen Kerr, Stephen Lee Katzen, Mark Danenbaum, and Yoshua Esquenazi

69

Skull Base Vascular Tumors

502

Amol Raheja and William T. Couldwell

70

Extracranial Vascular Tumors

509

Alfred Pokmeng See, Ramsey Ashour, and Mohammad Ali Aziz-Sultan

71

Spinal Vascular Tumors

515

Yoshua Esquenazi, Mark H. Bilsky, Ilya Laufer, and Athos Patsalides

Index

521

xi

Foreword This beautifully organized treatise on neurovascular disease addresses a long overdue need for recognizing and approaching vascular diseases in the nervous system holistically. Neurovascular diseases are challenging, high risk, and often present with minimal symptoms, resulting in significant ethical issues in decision making: to treat or not to treat (and how to treat) is the question. Given the very different disciplines making treatment decisions, personal preferences, background, and training all play into the eventual treatment choice and outcome. With their extensive multidisciplinary training background and experience, this group of leading experts have amalgamated diverse solutions and options for the treatment of neurovascular diseases for the benefit of the various neurovascular specialists and their patients. There are often many ways to successfully approach neurovascular diseases. However, herein is a major problem. “If all you have is a hammer, the whole world looks like a nail” is the underpinning

of one of the most troublesome aspects of neurovascular disease management; that is to say, if a patient goes to a practitioner who has only one background, the treatment decision may be significantly slanted one way or another, possibly missing a safer and more effective treatment alternative. Multidisciplinary teams may obviate this problem but often a single department or practitioner is the dominant decision maker and treater. Decision Making in Neurovascular Disease will help solve this problem and also provide valuable insights to multidisciplinary physicians and teams. Each disease entity is carefully examined from multiple clearly defined perspectives, allowing treatment alternatives to be thoroughly evaluated resulting in better decision making. Congratulations to Leonardo Rangel-Castilla and his co-editors and authors on creating a marvelous reference which will be invaluable to our patients and their treating physicians. L. Nelson Hopkins, MD SUNY Distinguished Professor, Neurosurgery and Radiology Founder and Chief Scientific Officer, Jacobs Institute Founder, Gates Vascular Institute Buffalo, New York

xii

Foreword There are four main milestones in the treatment of cerebrovascular diseases: 1) Antonio Egas Moniz published his experience on cerebral angiography in 1927; 2) Walter Dandy clipped a carotid aneurysm ten years later (even without angiography); 3) in the late 1960s, M. Gazi Yaşargil introduced microsurgery in all fields of neurosurgery including cerebrovascular diseases; and 4) Serbinenko in the early 1970s published his results on endovascular balloon treatment of cerebral aneurysms, followed by Schechlov and the French School, culminating in the development of endosaccular treatment with detachable coils of cerebral aneurysms by Guglielmi in 1991. Mark Twain wrote more than 100 years ago: “The arduous work of countless researchers has already thrown much darkness on the subject, and if they continue, we shall soon know nothing at all about it.” This is more the case by far nowadays, when publishing is common and made easier by telecommunication. In February 2018, a search in PubMed returned 34,632 publications on the term Cerebral aneurysm, 22,643 publications on Carotid stenosis, 3,621 publications on Cerebral AV fistula, and 3,046 publications on Cerebral AVM. It is clear that no one can read everything that

is published on these subjects, and we need special compendiums to remain informed about the latest developments in these fields. In the present book, Decision Making in Neurovascular Disease, authored by Leonardo Rangel-Castilla, Peter Nakaji, Adnan H. Siddiqui, Robert F. Spetzler, and Elad I. Levy, the concern articulated by Mark Twain is crushed down in a very nice way: the book holds what it promises in the beautiful cover showing all neurovascular diseases in one splendid drawing. The book is organized into seven sections, each covering widely its own topic of neurovascular disease. Just as the authors claim, this book is indeed “a must-have for residents and fellows in neurosurgery, neurology, endovascular, interventional neurology, interventional radiology, vascular neurology, and neurocritical care, as well as veteran clinicians in these specialties.” It is easy to agree with them. Going back centuries with Sir Francis Bacon (1561-1626), who said that “Every man owes it as a debt to his profession to put on record whatever he has done that might be of use to others,” I conclude that this book is an extremely useful diamond among the many books covering the wide field of neurovascular disease. Juha Hernesniemi, MD, PhD Professor and Head, Juha Hernesniemi International Center for Neurosurgery, Department of Neurosurgery, Henan Provincial People’s Hospital, Zhengzhou, PR China Emeritus Professor and Emeritus Chairman, Department of Neurosurgery, UH of Helsinki, Finland Adjunct Professor, Mayo Clinic, USA Professor, hc Burdenko Institute, Moscow, Russia

xiii

Preface Cerebrovascular diseases, both ischemic and hemorrhagic, are leading causes of morbidity and mortality worldwide. Our understanding of these conditions and approaches to treating them has evolved tremendously in the last 20 years. In the early ’90s, early neuroendovascular techniques underwent an evolutionary leap forward. From a developing modality, they rapidly matured and dramatically expanded in capability to the point that they substantially changed the approach to most neurovascular diseases. As a result, for certain cerebrovascular diseases there has been a vigorous debate about when to use which therapy for which neurovascular condition. We are now realizing that there should not be debate between the two modalities, but a quest for synergism. Neuroendovascular techniques complement open cerebrovascular approaches; it is our job as vascular neurosurgeons, neurologists, neuroradiologists, and others treating these patients to select the appropriate modality(s) for each specific patient and disease. The goal of Decision Making in Neurovascular Disease is to integrate both modalities and assist the clinician navigating the complex decision-making process in selecting the most appropriate modality of treatment for a given condition. This book represents a compilation of what is currently known, to serve as reference for those already practicing and as a text for study for those entering the field. This book is designed to be both a comprehensive reference and a focused tool. It can serve as a text that one would read cover to cover or as a go-to resource for a specific patient. In both roles, the text is also designed to be beneficial to medical students, residents and fellows in need of a quick reference that can provide the pertinent must-know information in algorithmic form which is supported, wherever possible, by both expert opinion and updated clinical evidence. The text is organized in seven sections according to diagnosis, anatomical regions, or topic, and covers all cerebrovascular conditions. Section I includes ischemic stroke and vascular insufficiency, an area of equal interest to neurologists, neurocritical care physicians and neurosurgeons, and an area in

which management has dramatically changed since 2015. Section II covers all intracranial aneurysms of the anterior circulation, a chapter for every aneurysm anatomical location and variety, and every chapter integrates both cerebrovascular and endovascular disciplines. Section III contains all intracranial aneurysms of the posterior circulation in similar fashion to that of the anterior circulation section. Section IV covers other less common types of intracranial aneurysms, including mycotic, blood-blister, pediatric, and spinal aneurysms. Section V covers all intracranial and spinal arteriovenous malformations and fistulas, relatively uncommon but challenging lesions to manage. Section VI includes cranial and spinal cavernous malformations; we included a separate chapter for thalamic and for brainstem cavernous malformations. The last section, Section VII, covers intracranial, extracranial, and spinal hypervascular tumors. Surgical approaches to highly vascular tumors of the head, neck and spine have much in common with those pertinent to vascular malformations, and can be similarly addressed with embolization. Each chapter is organized concisely with an introduction, a “whether-to-treat-or-not” section based on most recent clinical trials, and subsections covering clinical work-up, open cerebrovascular treatment nuances, endovascular treatment nuances, complications avoidance, outcomes and durability, and follow-up. A unique aspect of this volume is a suggested treatment algorithm, presented in an easily accessible graphic format, that can be found at the beginning of each chapter summarizing and integrating information presented in the chapter. The algorithms contain numbers at the important decision-making steps, which are referenced within the chapter and refer to literature supporting the decision-making step. Each chapter is illustrated with open cerebrovascular and endovascular treatment options. Finally, a list of suggested further readings has been included for each chapter. We hope readers will find this volume both helpful and interesting, and that you will enjoy reading it as much as we enjoyed putting it together. Leonardo Rangel-Castilla, MD Peter Nakaji, MD Adnan H. Siddiqui, MD, PhD, FACS, FAHA, FAANS Robert F. Spetzler, MD Elad I. Levy, MD, MBA, FACS, FAHA

xiv

Acknowledgments We would like to thank all the enthusiastic neurosurgeons, interventional radiologists and neurologists, fellows, and residents for their contributions to this volume. Without their participation, this book would never have been possible. Our immense gratitude goes to the members of the Neuroscience Publications office of Barrow Neurological Institute, including Mark Schornak, medical illustrator and manager of Neuroscience Publications, Kristen Larson Keil, lead medical illustrator, Joshua Lai, medical animator and modeler, who created the exquisite cover art, Cindy Giljames, production assistant, who designed the layout of the cover art, and Cassie Todd, production editor. We also thank the editorial team of Neuroscience Publications, including Mary Ann Clifft, Paula Higginson, Dawn Mutchler, Lynda Orescanin, Samantha Soto, and Gena Lake. We also want to thank the personnel from the University at Buffalo–Neurosurgery: Debi Zimmer, senior author’s editor, for her skills in correcting and polishing our work ensuring accuracy

and consistency and Paul Dressel, medical illustrator, for his excellent work on algorithm design. Our dear friends from Thieme need to be recognized for their continued commitment to quality publishing: Tim Hiscock, leader of the team who enabled this whole endeavor; Sarah Landis, for her patience throughout the material compilation and editorial process and for always giving us the prodding we needed to see the project to completion; Nikole Connors, for helping to keep this project on track and well-organized. Lastly, we thank our patients, who allow us to serve them and inspire in us the obligation to labor on into the darkness, shedding what light we can; our colleagues, who strive alongside us every day in carrying out the patient care described in this book; our families, who with great love and patience support us in these endeavors and make it all possible; and you, the reader, who are the very reason we brought this volume into existence.

xv

Contributors Pedro Aguilar-Salinas, MD Cerebrovascular Research Fellow / Research Associate Lyerly Neurosurgery Baptist Neurological Institute Jacksonville, Florida, USA

Ramsey Ashour, MD Assistant Professor Department of Surgery and Perioperative Care University of Texas at Austin Dell Medical School Austin, Texas, USA

Felipe C. Albuquerque, MD Assistant Director Endovascular Surgery Professor of Neurosurgery Division of Neurological Surgery Barrow Neurological Institute Phoenix, Arizona, USA

Gursant S. Atwal, MD Neuroendovascular Fellow Department of Neurosurgery State University of New York, Buffalo Buffalo, New York, USA

Hosam Al-Jehani, MBBS, MSc, FRCSC Assistant Professor and Consultant Neurosurgery, Interventional Neuroradiology and Neurocritical Care KFHU, Imam Abdulrahman Bin Faisal University King Fahad Specialist Hospital-Dammam Dammam, Saudi Arabia Montreal Neurological Institute and Hospital McGill University Montreal, Quebec, Canada João Paulo Almeida, MD Division of Neurosurgery Toronto Western Hospital University of Toronto Toronto, Ontario, Canada Naif M. Alotaibi, MD, MSc Neurosurgery Resident Division of Neurosurgery, Department of Surgery University of Toronto Toronto, Ontario, Canada Peter S. Amenta, MD Assistant Professor Director, Cerebrovascular, Endovascular and Skull Base Surgery Department of Neurosurgery Tulane University New Orleans, Louisiana, USA Hugo Andrade-Barazarte, MD, PhD Department of Neurosurgery Helsinki University Hospital & University of Helsinki Helsinki, Finland Adailton Arcanjo dos Santos Jr., MD Assistant Professor Department of Surgery Univag School of Medicine Cuiaba, Mato Grosso, Brazil

xvi

Ahmed J. Awad, MD Neurosurgery Resident Department of Neurosurgery Medical College of Wisconsin Milwaukee, Wisconsin, USA Faculty of Medicine and Health Sciences An-Najah National University Palestine Mohammad Ali Aziz-Sultan, MD Chief, Divisions of Vascular and Endovascular Department of Neurosurgery Brigham & Women’s Hospital Associate Professor Harvard Medical School Boston, Massachusetts, USA Joshua Bakhsheshian, MD, MS Resident Physician Department of Neurosurgery Keck School of Medicine University of Southern California Los Angeles, California, USA Daniel L. Barrow, MD Pamela R. Rollins Professor and Chairman Director, Emory MBNA Stroke Center Emory University School of Medicine Atlanta, Georgia, USA Andrew M. Bauer, MD, MBA Vascular Neurosurgeon Boulder Neurosurgical and Spine Associates Boulder, Colorado, USA Joshua B. Bederson, MD Professor Department of Neurosurgery Mount Sinai Health System New York, New York, USA

Contributors Kimon Bekelis, MD Director, Stroke and Brain Aneurysm Center of Excellence at GSHMC Chairman, Neurointerventional Services at CHS Co-Director, Neuro ICU at GSHMC Long Island Neurosurgery and Pain Specialists West Islip, New York, USA Bernard R. Bendok, MD Professor and Chairman Department of Neurosurgery Mayo Clinic Phoenix, Arizona, USA Vladimír Beneš, MD, PhD Professor Department of Neurosurgery and Neurooncology Military University Hospital and First Medical Faculty Charles University Prague, Czech Republic Ilyes Berania, MD Resident Department of Otolaryngology - Head & Neck Surgery Centre Hospitalier de l’Universite de Montréal Montreal, Quebec, Canada Mark H. Bilsky, MD William E. Snee Endowed Professor Attending and Member Chief, Multidisciplinary Spine Tumor Center Memorial Sloan Kettering Cancer Center Professor of Neurosurgery Weill Medical College of Cornell University New York, New York, USA

Leonardo B.C. Brasiliense, MD Neurosurgery Resident Division of Neurosurgery University of Arizona Tucson, Arizona, USA Gavin W. Britz, MD Professor and Chairman Department of Neurosurgery The Methodist Neurological Institute Houston, Texas, USA Patrick A. Brown, MD Assistant Professor Department of Radiology University of Tennessee Knoxville, Tennessee, USA Jan-Karl Burkhardt, MD Neuroendovascular Fellow Departments of Neurosurgery and Neuroradiology NYU Langone Health New York, New York, USA C. Michael Cawley, MD Professor Departments of Neurosurgery and Radiology Emory University School of Medicine Atlanta, Georgia, USA Jacob Cherian, MD Resident Department of Neurosurgery Baylor College of Medicine Houston, Texas, USA

Mandy Binning, MD Assistant Professor Department of Neurosurgery Drexel Neurosciences Institute Philadelphia, Pennsylvania

Joham Choque-Velasquez, MD Department of Neurosurgery Helsinki University Hospital & University of Helsinki Helsinki, Finland

Michel W. Bojanowski, MD, FRCSC Professor Division of Neurosurgery Department of Surgery University of Montreal University of Montreal Hospital Center Montreal, Quebec, Canada

Mary In-Ping Huang Cobb, MD Chief Resident Department of Neurosurgery Duke University Hospitals Durham, North Carolina, USA

Oliver Bozinov, MD Vice Chairman Department of Neurosurgery University Hospital Zurich Zurich, Switzerland Ondřej Bradáč, MD, MSc, PhD Department of Neurosurgery and Neurooncology Military University Hospital and First Medical Faculty Charles University Prague, Czech Republic

Christophe Cognard, MD, PhD Professor of Radiology Chairman of the Department of Diagnostic and Therapeutic Neuroradiology University Hospital of Toulouse Purpan Toulouse, France Daniel Cooke, MD Assistant Professor in Residence Department of Radiology and Biomedical Imaging University of California San Francisco San Francisco, California, USA

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Contributors William T. Couldwell, MD, PhD Professor and Chairman Department of Neurosurgery University of Utah Salt Lake City, Utah, USA

Edward A.M. Duckworth, MD, MS Director, Cranial Neurosurgery Program Cerebrovascular and Endovascular Neurosurgery St. Luke’s Regional Medical Center Boise, Idaho, USA

Marshall C. Cress, MD Orlando Health Physicians Neurosurgery Group Director for Neurovascular Services Department of Neurosurgery Orlando Regional Medical Center Orlando Health Orlando, Florida, USA

Aaron S. Dumont, MD, MBA Charles B. Wilson Professor & Chair Department of Neurosurgery Director, Tulane Center for Clinical Neurosciences Tulane University New Orleans, Louisiana, USA

Mark Dannenbaum, MD Assistant Professor Department of Neurosurgery University of Texas Houston Health Science Center Memorial Hermann Hospital System Houston, Texas, USA Robert Darflinger, MD Clinical Fellow Interventional Neuroradiology, Department of Radiology and Biomedical Imaging University of California San Francisco San Francisco, California, USA Jason M. Davies, MD, PhD Cerebrovascular and Skullbase Neurosurgery Departments of Neurosurgery and Biomedical Informatics Director of Cerebrovascular Microsurgery Director of Endoscopy, Kaleida Health Research Director, Jacobs Institute State University of New York, Buffalo Buffalo, New York, USA

Mohamed Samy Elhammady, MD Associate Professor Department of Neurological Surgery University of Miami Miami, Florida, USA Yoshua Esquenazi, MD Assistant Professor and Director of Surgical Neuro-Oncology Vivian L. Smith Department of Neurosurgery The University of Texas Health Science Center at Houston Mischer Neuroscience Institute Houston, Texas, USA Andrew A. Fanous, MD Cerebrovascular Fellow Department of Neurosurgery University of Miami Miller School of Medicine Miami, Florida, USA

Evandro de Oliveira, MD, PhD Professor Department of Neurosurgery Instituto de Ciencias Neurologicas - ICNE Sao Paulo, SP, Brazil

Daniel R. Felbaum, MD Fellow Department of Neurosurgery Global Neurosciences Institute Philadelphia, Pennsylvania, USA

Dale Ding, MD Fellow in Endovascular Surgical Neuroradiology Department of Neurosurgery Barrow Neurological Institute Phoenix, Arizona, USA

Vernard S. Fennell, MD Neuroendovascular Fellow Department of Neurosurgery State University of New York, Buffalo Buffalo, New York, USA

Peter Dirks, MD, PhD, FRCSC Professor of Surgery and Molecular Genetics Hospital for Sick Children University of Toronto Toronto, Ontario, Canada

Curtis A. Given, II, MD Neurosurgical Associates Baptist Health Lexington Lexington, Kentucky, USA

Brian Drake, BESc, MB, BCh, BAO, MPH, FRCSC Neurosurgeon Division of Neurosurgery The Ottawa Hospital Ottawa, Ontario, Canada

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Gerald W. Eckardt, MD Neurosurgeon BayCare Medical Center Green Bay, Wisconsin, USA

Douglas Gonsales, MD Cerebrovascular Fellow Lyerly Neurosurgery Baptist Neurological Institute Jacksonville, Florida, USA

Contributors L. Fernando Gonzalez, MD Professor Department of Neurosurgery Duke University Durham, North Carolina, USA Christoph J. Griessenauer, MD Assistant Professor Department of Neurosurgery Geisinger Health Danville, Pennsylvania, USA Bradley A. Gross, MD Assistant Professor Department of Neurosurgery University of Pittsburg Medical Center Pittsburg, Pennsylvania, USA Jian Guan, MD Resident Department of Neurosurgery University of Utah Salt Lake City, Utah, USA Mihir Gupta, MD Resident Department of Neurosurgery University of California San Diego San Diego, California, USA Ricardo A. Hanel, MD, PhD Director of Baptist Neurological Institute Co-Director of Stroke & Cerebrovascular Surgery Endowed Chair of Stroke and Cerebrovascular Surgery Lyerly Neurosurgery Baptist Neurological Institute Jacksonville, Florida, USA David Hasan, MD Associate Professor Section Chief of Vascular Neurosurgery Department of Neurosurgery University of Iowa Hospitals and Clinics Iowa City, Iowa, USA Erik F. Hauck, MD Neurosurgeon Duke University Durham, North Carolina, USA Daniel M. Heiferman, MD Resident Physician Department of Neurological Surgery Loyola University Medical Center Maywood, Illinois, USA Juha Hernesniemi, MD, PhD Department of Neurosurgery Helsinki University Hospital & University of Helsinki Helsinki, Finland

Roberto C. Heros, MD, FACS Professor and co-chairman University of Miami International Health Center Miami, Florida, USA Steven W. Hetts, MD Professor in Residence of Radiology Chief of Interventional Neuroradiology, UCSF Mission Bay Hospitals Co-Director, UCSF Hereditary Hemorrhagic Telangiectasia Center of Excellence Co-Director, Interventional Radiology Research Laboratory Department of Radiology and Biomedical Imaging University of California, San Francisco San Francisco, California, USA Brian L. Hoh, MD Professor Department of Neurosurgery University of Florida Gainesville, Florida, USA David Houlden, PhD Neurophysiologist Department of Medical Imaging The Ottawa Hospital Ottawa, Ontario, Canada Oliver Holmes, MD, MSc, FRCPC Radiation Oncologist Eastern Health at Dr. H. Bliss Murphy Cancer Centre St. John’s, Newfoundland, Canada L. Nelson Hopkins, MD SUNY Distinguished Professor, Neurosurgery and Radiology; Founder, Gates Vascular Institute; Founder and Chief Scientific Officer, Jacobs Institute University at Buffalo Neurosurgery SUNY Buffalo, Kaleida Health Buffalo, New York, USA Jay U. Howington, MD, FACS Associate Professor Departments of Surgery and Radiology Mercer University School of Medicine Savannah, Georgia, USA Judy Huang, MD, FAANS Professor and Vice Chair Department of Neurosurgery Johns Hopkins University School of Medicine Baltimore, Maryland, USA Daniela Iancu, MD, MSc Associate Professor Department of Medical Imaging, Division of Neurosurgery The Ottawa Hospital Ottawa, Ontario, Canada

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Contributors Tarik F. Ibrahim, MD× Department of Neurosurgery Loyola University Medical Center Maywood, Illinois, USA × Deceased

Alexander A. Khalessi, MD, MS, FAANS Chairman Department of Neurological Surgery UC San Diego Health La Jolla, California, USA

Adeel Ilyas, MD Resident Physician Department of Neurosurgery University of Alabama at Birmingham Birmingham, Alabama, USA

Nadia Khan, MD Professor Head of Moyamoya Center Division of Pediatric Neurosurgery University Children’s Hospital Zurich, Switzerland Head of Adult Cerebral Revascularisation and Moyamoya Department of Neurosurgery University Tubingen Germany

Pascal Jabbour, MD Professor of Neurological Surgery Chief, Division of Neurovascular Surgery and Endovascular Neurosurgery Thomas Jefferson University Hospital Philadelphia, Pennsylvania, USA Behnam Rezai Jahromi, MD Department of Neurosurgery Helsinki University Hospital & University of Helsinki Helsinki, Finland Samuel Kalb, MD Neurosurgery Resident Department of Neurosurgery Barrow Neurological Institute Phoenix, Arizona, USA Haris Kamal, MD Stroke Director & Chief of Neurology LBJ Hospital/Smith Clinic Assistant Professor of Neurology Department of Neurology University of Texas Health Sciences Center at HoustonMcGovern Medical School Houston, Texas, USA Peter Kan, MD Associate Professor Department of Neurosurgery Baylor College of Medicine Houston, Texas, USA Stephen Lee Katzen, MD Resident Physician Department of Neurosurgery University of Texas Health Science Center at Houston Houston, Texas, USA Keith Allen Kerr, MD Resident Physician Department of Neurosurgery University of Texas Health Science Center at Houston Houston, Texas, USA Louis J. Kim, MD Professor & Vice Chairman Department of Neurological Surgery University of Washington School of Medicine Seattle, Washington, USA

xx

Timo Krings, MD, FRCP(C) Professor of Radiology and Neurosurgery Chair of Interventional Neuroradiology Joint Department of Medical Imaging Toronto Western Hospital University Health Network University of Toronto Toronto, Ontario, Canada Michael Lang, MD Chief Resident Department of Neurological Surgery Thomas Jefferson University Philadelphia, Pennsylvania, USA Giuseppe Lanzino, MD Professor Department of Neurosurgery Mayo Clinic Rochester, Minnesota, USA Biagia La Pira, MD Research Fellow Department of Neurosurgery Mayo Clinic Rochester, Minnesota, USA Ilya Laufer, MD, MS Associate Attending Department of Neurosurgery Memorial Sloan Kettering Cancer Center Associate Professor Department of Neurosurgery Weill Cornell Medical College New York, New York, USA Michael T. Lawton, MD Professor of Neurological Surgery, Barrow Neurological Institute President and Chief Executive Officer, Barrow Neurological Institute Chairman, Department of Neurological Surgery Chief of Vascular and Skull Base Neurosurgery Programs Robert F. Spetzler Endowed Chair in Neurosciences St. Joseph’s Hospital and Medical Center Phoenix, Arizona, USA

Contributors Hubert Lee, MD, MSc Division of Neurosurgery The Ottawa Hospital Ottawa, Ontario, Canada Jean-Paul Lejeune, MD Department of Neurosurgery CHRU Lille Université de Lille Lille, France Elad I. Levy, MD, MBA, FACS, FAHA Professor and Chair L. Nelson Hopkins Endowed Chair Department of Neurosurgery Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo Medical Director, Department of Neuroendovascular Services Co-Director, Gates Stroke Center Kaleida Health Buffalo, New York, USA Andrey Lima, MD Neuroendovascular Surgery Department of Neurology and Neurosurgery Memorial Healthcare System Hollywood, Florida, USA Christopher M. Loftus, MD Professor Department of Neurosurgery Temple University Lewis Katz School of Medicine Philadelphia, Pennsylvania, USA

Venkatesh S. Madhugiri, MCh Associate Professor Head of Neurosurgical Oncology Cancer Institute (WIA) Adyar, Chennai, India Giovanni R. Malaty, BS Department of Neurosurgery Barrow Neurological Institute St. Joseph’s Hospital and Medical Center Phoenix, Arizona, USA Shawn Malone, MD, FRCPC Radiation Oncologist Department of Radiation Oncology The Ottawa Hospital Ottawa, Ontario, Canada Eduardo Martinez-del-Campo, MD Neurosurgery Resident Department of Neurosurgery University of Wisconsin Madison, Wisconsin, USA Justin R. Mascitelli, MD Cerebrovascular Fellow Department of Neurosurgery Barrow Neurological Institute Phoenix, Arizona, USA Marcus D. Mazur, MD Neurosurgery Resident University of Utah Salt Lake City, Utah, USA

Demetrius Klee Lopes, MD Professor Department of Neurosurgery Rush University Chicago, Illinois, USA

Ricky Medel, MD Neurosurgeon UC Health Neurosurgery Colorado Springs, Colorado, USA

Stephen R. Lowe, MD Resident Physician Department of Neurosurgery Medical University of South Carolina Charleston, South Carolina, USA

J Mocco, MD, MS Professor and Vice Chairman Department of Neurosurgery Mount Sinai Health System New York, New York, USA

R. Loch Macdonald, MD, PhD, FRCS(C), FAANS, FACS Professor of Surgery St. Michael’s Hospital Division of Neurosurgery and Department of Surgery University of Toronto Associate Scientist Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute Toronto, Ontario, Canada

Maxim Mokin, MD, PhD Assistant Professor Department of Neurosurgery and Brain Repair University of South Florida Tampa, Florida, USA Karam Moon, MD Neurosurgery Resident Department of Neurosurgery Barrow Neurological Institute Phoenix, Arizona, USA

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Contributors Justin M. Moore, MD, PhD, FRACS Assistant Professor Department of Neurosurgery Beth Israel Deaconess Medical Center Harvard Medical School Boston Medical Center Boston University Boston, Massachusetts, USA Nina Z. Moore, MD, MSE Neurosurgery Resident Department of Neurosurgery Cleveland Clinic Foundation Cleveland, Ohio, USA Michael Kerin Morgan, MD Professor of Cerebrovascular Neurosurgery Department of Clinical Medicine Macquarie University Sydney, Australia Simon Morr, MD Neurosurgery Resident Department of Neurosurgery State University of New York, Buffalo Buffalo, New York, USA Stephan A. Munich, MD Cerebrovascular Fellow Department of Neurosurgery University of Miami Miller School of Medicine Miami, Florida, USA Peter Nakaji, MD Professor of Neurosurgery Director of Minimally Invasive and Endoscopic Neurosurgery Program Director of the Neurosurgery Residency Program Department of Neurosurgery Barrow Neurological Institute Phoenix, Arizona, USA Sabareesh K. Natarajan, MD Neuroendovascular Fellow Department of Neurosurgery State University of New York, Buffalo Buffalo, New York, USA John D. Nerva, MD Resident Department of Neurological Surgery University of Washington Seattle, Washington, USA Feres Chaddad Neto, MD, PhD Professor Department of Neurosurgery Universidade Federal de Sao Paulo Sau Paulo, Brazil

xxii

Mateus Reghin Neto, MD Professor Department of Neurosurgery Universidade Federal de Sao Paulo Sau Paulo, Brazil C. Benjamin Newman, MD, FAANS Neurosurgical Associates Baptist Health Lexington Lexington, Kentucky, USA Christopher S. Ogilvy, MD Director, Endovascular and Operative Neurovascular Surgery BIDMC Brain Aneurysm Institute Professor of Neurosurgery Harvard Medical School Boston, Massachusetts, USA Joshua W. Osbun, MD Fellow, Cerebrovascular Surgery Department of Neurological Surgery Emory University School of Medicine Emory Clinic Atlanta, Georgia, USA J. Scott Pannell, MD Assistant Professor Department of Neurological Surgery UC San Diego Health La Jolla, California, USA Min S. Park, MD, FAANS Associate Professor Departments of Neurosurgery and Neurology University of Virginia Health System Charlottesville, Virginia, USA Athos Patsalides, MD, MPH Associate Professor Department of Neurosurgery New York Presbyterian Hospital/ Weill Cornell Medicine New York, New York, USA Vitor M. Pereira, MD Associate Professor Department of Radiology and Surgery University of Toronto Toronto, Ontario, Canada Eric C. Peterson, MD, FAANS Associate Professor Department of Neurological Surgery University of Miami Miller School of Medicine Miami, Florida, USA Laurent Pierot, MD, PhD Professor Head of the Department of Neuroradiology Université Reims-Champagne-Ardenne, CHU Reims Hôpital Maison-Blanche Reims, France

Contributors Amol Raheja, MBBS, MCH Assistant Professor Department of Neurosurgery All India Institute of Medical Sciences New Delhi, India Rudy J. Rahme, MD Resident Physician Department of Neurosurgery Northwestern University Feinberg School of Medicine and McGaw Medical Center Chicago, Illinois, USA Gary B. Rajah, MD Neurosurgical and Endovascular Resident Department of Neurosurgery Wayne State University Detroit Medical Center Detroit, Michigan, USA Christian N. Ramsey, III, MD, FAANS Neurosurgical Associates Baptist Health Lexington Lexington, Kentucky, USA Leonardo Rangel-Castilla, MD Assistant Professor Department of Neurosurgery and Radiology Mayo Clinic Rochester, Minnesota, USA Vikas Y. Rao, MD Orange County Neurosurgical Associates California, USA Peter A. Rasmussen, MD Associate Professor of Neurological Surgery Department of Neurological Surgery and Cerebrovascular Center Cleveland Clinic Cleveland, Ohio, USA Luca Regli, MD Professor and Chairman of Neurosurgery Department of Neurosurgery Clinical Neuroscience Center University Hospital Zurich Zurich, Switzerland Matthew R. Reynolds, MD, PhD Assistant Professor Department of Neurosurgery and Radiology Loyola University Medical Center Maywood, Illinois, USA Thomas Robert, MD Clinical Fellow in Neurovascular and Skull Base Surgery Department of Neurosurgery Hôpital Notre-Dame Centre Hospitalier de l’Université de Montréal Montreal, Quebec, Canada

Robert H. Rosenwasser, MD, MBA, FACS, FAHA Jewell L. Osterholm, MD Professor and Chair of Neurological Surgery Professor of Radiology, Neurovascular Surgery, Interventional Neuroradiology President, Vickie and Jack Farber Institute for Neuroscience Medical Director, Jefferson Neuroscience Network Thomas Jefferson Hospital Philadelphia, Pennsylvania, USA Jeremy Russell, MD Neurovascular Fellow Department of Neurosurgery Toronto Western Hospital Toronto, Ontario, Canada Jonathan J. Russin, MD Assistant Professor Department of Neurological Surgery University of Southern California Los Angeles, California, USA Abdulrahman Sabbagh, MD Assistant Professor and Consultant Neurosurgeon, Epilepsy Surgeon and Pediatric Neurosurgeon, Neurosurgery Section Assistant Chairman of Research and Higher Education Department of Surgery, College of Medicine Head of Research and Development, Clinical Skill and Simulation Center King Abdulaziz University Jeddah, Saudi Arabia Regional Director, Western and Southern Regions Committee of Neurosurgery Residency Training Programs Saudi Commission for Health Specialties, Saudi Arabia Afnan Samman, MD Resident, Neurological Surgery Department of Surgery Neurosurgery Division King Abdulaziz Medical City, National Guards Health Affaires Jeddah, Saudi Arabia Rohini D. Samudralwar, MD Fellow Department of Neurology Washington University St. Louis, Missouri , USA Eric Sauvageau, MD Director of Stroke & Cerebrovascular Surgery Endowed Chair of Stroke and Cerebrovascular Surgery Lyerly Neurosurgery Baptist Neurological Institute Jacksonville, Florida, USA Robert N. Sawyer Jr., MD Associate Professor Department of Neurology State University of New York at Buffalo Buffalo, New York, USA

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Contributors Robert Asa Scranton, MD Resident Physician Department of Neurological Surgery Houston Methodist Neurological Institute Houston, Texas, USA

Kenneth V. Snyder, MD, PhD Assistant Professor Department of Neurosurgery University at Buffalo Buffalo, New York, USA

Alfred Pokmeng See, MD Neurosurgery Resident Department of Neurosurgery Brigham and Women’s Hospital Harvard Medical School Boston, Massachusetts, USA

Robert F. Spetzler, MD Professor and Emeritus Chair Department of Neurosurgery Barrow Neurological Institute Phoenix, Arizona, USA

Fabio Settecase, MD, MSc, FRCPC Assistant Clinical Professor Department of Radiology and Biomedical Imaging University of California San Francisco San Francisco, California, USA Adnan H. Siddiqui, MD, PhD, FACS, FAHA, FAANS Professor and Vice Chair Director Neuroendovascular Fellowship Program Department of Neurosurgery and Radiology State University of New York Buffalo, New York, USA Jason Signorelli, MD Resident University of Utah School of Medicine Salt Lake City, Utah, USA John Sinclair, MD, FRCSC Assistant Professor Division of Neurosurgery The Ottawa Hospital Ottawa, Ontario, Canada Amit Singla, MD Neurosurgeon Department of Neurosurgery Covenant Medical Center Waterloo, Iowa, USA Tony P. Smith, MD Professor Department of Radiology, Division of Interventional Radiology Duke University Hospitals Durham, North Carolina, USA Brian M. Snelling, MD Chief Resident Department of Neurological Surgery University of Miami Miller School of Medicine Jackson Memorial Hospital Miami, Florida, USA

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Alejandro Spiotta, MD Professor Comprehensive Stroke and Cerebrovascular Center Medical University of South Carolina Charleston, South Carolina, USA Visish M. Srinivasan, MD Resident Department of Neurosurgery Baylor College of Medicine Houston, Texas, USA Robert M. Starke, MD, MSc Assistant Professor Department of Neurosurgery and Radiology University of Miami Miami, Florida, USA Gary K. Steinberg, MD, PhD Bernard and Ronni Lacroute-William Randolph Hearst Professor of Neurosurgery and the Neurosciences Chairman Department of Neurosurgery Stanford University School of Medicine Stanford, California, USA Anna Štekláčová, MD Department of Neurosurgery and Neurooncology Military University Hospital and First Medical Faculty Charles University Prague, Czech Republic Ben A. Strickland, MD Neurosurgery Resident Department of Neurosurgery University of Southern California Los Angeles, California, USA Samir Sur, MD Resident Department of Neurological Surgery University of Miami Miami, Florida, USA Phil Taussky, MD Associate Professor Department of Neurosurgery University of Utah Salt Lake City, Utah, USA

Contributors Mario K. Teo, MD, FRCS(SN) Consultant Neurosurgeon Department of Neurosurgery North Bristol University Hospital Bristol, United Kingdom Clinical Instructor Department of Neurosurgery Stanford University Medical Centre Stanford, California, USA Ajith Thomas, MD Associate Professor BIDMC Brain Aneurysm Institute Professor of Neurosurgery Harvard Medical School Boston, Massachusetts, USA Stavropoula I. Tjoumakaris, MD, FAANS Associate Professor of Neurosurgery Associate Residency Program Director Fellowship Director of Endovascular Surgery & Cerebrovascular Neurosurgery Director of Neurosurgery Clerkship Thomas Jefferson University Hospital Philadelphia, Pennsylvania, USA Raymond D. Turner, IV, MD Professor Comprehensive Stroke and Cerebrovascular Center Medical University of South Carolina Charleston, South Carolina, USA Michael Tymianski, MD, PhD, FRCSC Head, Division of Neurosurgery, UHN Professor, Department of Surgery, University of Toronto Harold and Esther Halpern Chair in Neurosurgical Stroke Research Canada Research Chair (Tier 1) in Translational Stroke Research Sr. Scientist, Krembil Research Institute Division of Neurosurgery, University Health Network Toronto, Ontario, Canada Kunal Vakharia, MD Fellow in Endovascular Neurosurgery Department of Neurosurgery University at Buffalo Buffalo, New York, USA Anton Valavanis, MD Professor Department of Neuroradiology, Clinical Neuroscience Center University Hospital Zurich Zurich, Switzerland

Jan Vargas, MD Resident Physician Department of Neurosurgery Medical University of South Carolina Charleston, South Carolina, USA Erol Veznedaroglu, MD, FACS, FAANS, FAHA Professor Director, Global Neurosciences Institute Department of Neurosurgery Philadelphia, Pennsylvania, USA Brian P. Walcott, MD Clinical Instructor Department of Neurological Surgery University of Southern California Los Angeles, California, USA Michael P. Wemhoff, MD Chief Resident Department of Neurosurgery Loyola University Medical Center Maywood, Illinois, USA Ethan A. Winkler, MD, PhD Resident Physician Department of Neurological Surgery University of California San Francisco San Francisco, California, USA Wuyang Yang, MD, MS Resident Department of Neurosurgery Johns Hopkins University School of Medicine Baltimore, Maryland, USA Joseph M. Zabramski, MD Professor Department of Neurosurgery Barrow Neurological Institute Phoenix, Arizona, USA Hasan A. Zaidi, MD Assistant Professor Department of Neurosurgery Harvard Medical School Brigham and Women’s Hospital Boston, Massachusetts, USA Ali R. Zomorodi, MD Associate Professor Department of Neurosurgery Duke University Hospitals Durham, North Carolina, USA

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Section I

1

Ischemic Stroke and ­Vascular­Insufficiency

2 3

Acute Ischemic Stroke: Small Vessel Disease

3

Acute Ischemic Stroke: Large Vessel Occlusion

8

Acute Ischemic Stroke: Acute Internal Carotid Artery Occlusion and Tandem Lesions

14

4

Acute Basilar Artery Occlusion

22

5

Intracranial Atherosclerotic Disease

29

6

Asymptomatic Extracranial Carotid Artery Stenosis

36

7

Symptomatic Extracranial Carotid Artery Stenosis

42

8

Vertebrobasilar Stenosis and Insufficiency 48

9

Vertebral Artery Ostium Stenosis

54

10 Pediatric Moyamoya Disease

60

11 Adult Moyamoya Disease

68

12 Traumatic and Iatrogenic Carotid Artery Injury

74

13 Traumatic and Iatrogenic Vertebral Artery Injury

80

14 Spontaneous Internal Carotid Artery Dissection

88

15 Spontaneous Vertebral Arterial Dissection

95

16 Chronic Internal Carotid Artery Occlusion

100

17 Cerebral Venous Thrombosis and Occlusion

106 1

1 Acute Ischemic Stroke: Small Vessel Disease Haris Kamal and Robert N. Sawyer Jr. Abstract Small vessel disease (SVD) is the result of several pathophysiological mechanisms including lipohyalinosis, microatheroma, small emboli, and failure of cerebral autoregulation. Risk factors include aging, hypertension, diabetes mellitus, smoking, and genetics. Differential diagnoses include CADASIL, Susac’s disease, intraventricular lymphoma, sarcoidosis, and amyloid angiopathy. It mostly affects the brainstem (pons), basal ganglia, and internal capsule. Clinical presentation is variable and usually discrete. Classic presentations include pure motor or sensory hemiparesis, ataxic hemiparesis, and dysarthria–clumsy hand syndrome. Magnetic resonance imaging (MRI) is key to identify and manage SVD, and classic MRI findings include subcortical infarcts, lacunes, white matter hyperintensities, microbleeds, and brain atrophy. Main treatment in the acute phase includes alteplase (for those eligible patients). Secondary management consists of hypertension and dyslipidemia control, lifestyle modifications (reduce obesity and smoking cessation), and antiplatelet agents. Endovascular management has no role in the management of stroke and SVD. Keywords: acute ischemic attack, lacunar infarction, small vessel disease, angiopathy, vasculitis, aspirin, clopidogrel

Introduction Small vessel disease (SVD) is responsible for approximately 20 to 30% of all strokes. They commonly occur in the basal ganglia, internal capsule, and pons. Recurrence is estimated to be relatively low at about 2% at 1 month and 3.4% at 3 months. The predominant cause of SVD is thought to be mostly lipohyalinosis secondary to fibrinoid necrosis. While advancing age is the most important risk factor, others include arterial hypertension, diabetes mellitus, and noncerebral vascular disease. Several mechanisms for SVD and lacunar infarction have been described, and they include (1) lipohyalinosis of the penetrating arteries, particularly of smaller infarcts (3–7 mm in length); (2) microatheroma of the origin of the penetrating arteries coming off the middle cerebral artery (MCA) stem, circle of Willis, or distal basilar or vertebral arteries; (3) small emboli, which can be the cause of small vessel stroke; and (4) failure of the cerebral arteriolar and capillary endothelium and the associated blood–brain barrier. Confluent SVD found on magnetic resonance imaging (MRI) shows faster progression than discrete lesions. Lacunar infarcts are small (0.2–15 mm in diameter), noncortical infarcts caused by occlusion of a single penetrating branch of a large cerebral artery. These branches arise at acute angles from the large arteries of the circle of Willis, stem of the MCA, or the basilar artery. Major controversies in decision making addressed in this chapter include: 1. Indications for tissue-type plasminogen activator and the best medical treatment. 2. Workup necessary for differential diagnosis. 3. Lifestyle modifications.

Whether to Treat Medical therapy is always indicated (1 in algorithm). Acute ischemic stroke (AIS) should be considered a true neurological emergency. The decision to treat is based on many factors. Stroke severity, based on the level of the National Institutes of Health Stroke Scale (NIHSS) score, can be used to estimate the likelihood of AIS and confirmed with a noninvasive study.

Pathophysiology/Classification SVD strokes are the result of two separate pathophysiologies that may occur separately or simultaneously. First, small penetrating arteries originate at right angles from large arteries to perforate the deep brain parenchyma. Hemodynamically, the structure of these perforating arteries undergoes great stress. The result is often called lipohyalinosis and results in gradual narrowing and occlusion of these arteries. Second, these small perforating arteries may be occluded by plaque forming in the large parent arteries and then occluding their origin. This is called intracranial branch atheromatous disease by Fisher and Caplan. Both lipohyalinotic and branch atheromatous diseases affect the deeper portions of the cerebral hemispheres to include the basal ganglia, thalamus, and brainstem. SVD can produce lacunar strokes in the superficial cortex/cerebellum. However, the pathophysiology of these strokes is more varied and includes hypertension, diabetes, CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy), Susac’s disease, intravascular lymphoma, cerebral amyloid angiopathy, and sarcoidosis (3 in algorithm).

Workup Workup for SVD should include a standard stroke workup: a complete physical and neurological examination, computed tomography (CT) of the head, CT angiogram, MRI including diffusion-weighted imaging, fluid-attenuated inversion recovery (FLAIR), apparent diffusion coefficient, gradient echo, carotid ultrasound, transthoracic echocardiogram with or without bubble study, lipid panel, and hemoglobin A1c.

Clinical Evaluation There are more than 20 clinical syndromes associated with lacunar strokes. Clinical examination should demonstrate discrete, focal neurological deficits such as unilateral weakness, sensory loss without cortical findings of aphasia, visual deficits, or cognitive deficits. Importantly, these clinical syndromes can be produced by small hemorrhages. The four most classic clinical lacunar syndromes are described: 1. Pure motor hemiparesis: Unilateral motor deficit of the face, arm, and leg without cortical or sensory signs. The leg weakness is often less pronounced and a dysarthria may result from the facial weakness. The lesions are in the internal capsule, corona radiata, or basis pontis. 2. Pure sensory stroke: Unilateral hemisensory deficit of the face, arm, trunk, and leg. The sensory deficit is often subjective. Affected areas are the ventroposterolateral nucleus of the thalamus, corona radiate, parietal cortex, or medial lemniscus of the pons. 3. Ataxic hemiparesis: Paresis involves the leg more than the arm and much more than the face. Incoordination on the same side in the arm and leg. The affected toes are upgoing. The contralateral lesions are classically in the posterior limb of the internal capsule or basis pontis, and also include thalamocapsular, red nucleus, and superficial anterior cerebral artery lacunes. 4. Dysarthria–clumsy hand syndrome: Facial weakness, tongue deviation, dysarthria, dysphagia, loss of fine motor control of the hand, and upgoing toes. Lacunes are located contralaterally, usually in the basis pontis, and also in the internal capsule.

Imaging MRI is key in identifying and managing SVD. Identifying features are subcortical infarcts, lacunes, white matter hyperintensities, microbleeds, and brain atrophy and may be coexistent with embolic strokes. About 30% of clinical lacunar syndromes are not accompanied by visible small

3

Ischemic­Stroke­and­Vascular­Insufficiency

Algorithm 1.1 Decision-making algorithm for acute ischemic stroke—small vessel disease.

4

1

Acute Ischemic Stroke: Small Vessel Disease

subcortical infarcts (►Fig. 1.1). Lacunar infarcts are defined as those 3 to 20 mm in maximum diameter on axial imaging. Larger infarcts are not lacunar and smaller ones are likely to be perivascular spaces. Recent infarcts are those less than 2 weeks old. White matter hyperintensities are supportive of SVD and are best seen in FLAIR sequences. Microbleeds are 2 to 5 mm-diameter areas of hypointensity on T2 sequences. Microbleeds can be up to 10 mm in size. Brain atrophy unrelated to a specific infarction or trauma is supportive of SVD. This atrophy specifically affects the corpus callosum, white matter (vacuolar) shrinkage, increased ventricular size, basal ganglia, hippocampus, and cortical regions connected with subcortical infarcts.

Differential Diagnosis 1. Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL): T2 hyperintensities involving the temporal poles differentiate this disease. This finding is associated with a sensitivity of 95% and specificity of 80%. CADASIL is associated with involvement of the external capsules (sensitivity of 93% and a specificity of 45%) and an age-related increased risk of intracerebral microbleeds. The age group for CADASIL is generally younger at 45 to 50 years and is caused by mutations in the NOTCH3 gene on chromosome 19. Vascular dementia is a frequent sequela in the fifth to seventh decades. 2. Cerebral amyloid angiopathy: Lobar microbleeds are more likely to represent cerebral amyloid angiopathy (►Fig. 1.2a, b). Mimics unrelated to SVD include subarachnoid hemorrhage, subdural hematoma, vascular malformations, large vessel ischemia, and intracerebral hemorrhage. 3. Susac’s disease: The cardinal clinical signs of bilateral hearing loss, encephalopathy, seizures, and myoclonus are the results of a microangiopathy of the brain, retina, and membranous labyrinth

Fig 1.1 Small vessel disease on MRI FLAIR imaging, showing subcortical infarcts and white matter hyperintensities.

Fig 1.2 (a,b) Amyloid angiopathy on GRE/ T2* imaging, showing microbleeds.

5

Ischemic­Stroke­and­Vascular­Insufficiency without systemic disorder. A brain biopsy is required for a diagnosis, but a 7-T MRI or diffusion tensor imaging is suggested by more recent literature. 4. Intravascular lymphoma: A rare non-Hodgkin’s disease–type lymphoproliferative disorder characterized by neoplastic growth of lymphoid cells in the arterioles of capillaries, and venules. The lymphoid cell line is devoid of adhesion molecules and cannot be taken into the tissues, but instead cause thrombosis and tissue infarction. The results are altered sensorium, dementia, seizures, ataxia, and vertigo. 5. Sarcoidosis: A central nervous system (CNS) sarcoidosis can affect venules causing lacunar infarctions. These tend to be cortical.

Treatment Hyperacute Management Alteplase (recombinant tissue-type plasminogen activator) improves functional outcome from AIS and that benefit outweighs the risks for eligible patients who receive treatment within 4.5 hours of symptom onset (or within 4.5 hours for patient who was last seen normal in cases when onset time is unknown). Subgroup analysis of trial data suggests that the benefit with thrombolysis is sustained in patients with lacunar stroke and should be offered to all patients eligible for treatment (supports algorithm step 1). There is a 6.4% chance of symptomatic intracranial hemorrhage in all patients treated with alteplase; however, the risk is dependent on multiple factors including age, size of infarct, and other parameters.

Secondary Stroke Management Hypertension In the case of lacunar stroke, AHA guidelines recommend a systolic blood pressure (BP) of less than 130 mm Hg after the first several days (Class II, Level of Evidence B). Best medical therapy to lower BP should be diuretics or diuretics and angiotensin-converting enzyme inhibitors in combination (Class I, Level of Evidence A) (supports algorithm step 4).

Dyslipidemia Statin therapy with intensive lipid lowering effects is recommended to reduce the risk of stroke and cardiovascular events among patients with ischemic stroke, an LDL-C level of less than 70 mg/dL with or without evidence for other clinical atherosclerotic cardiovascular disease (Class I, Level of Evidence C) (supports algorithm step 4).

Lifestyle Modifications Lifestyle modifications include salt restriction; a diet rich in fruits, vegetables, and low-fat dairy products; regular aerobic exercise; and limited alcohol consumption (Class IIA, Level of Evidence C). Sodium intake should be restricted to less than 2.4 g/day. Reduction to less than 1.5 g/ day is associated with a greater BP reduction. It is reasonable to counsel patients to adhere to a Mediterranean-type diet. The AHA recommends that adults participate in three to four sessions per week of moderate aerobic activity lasting an average of 40 minutes (Class IIa, Level of Evidence C). Alcohol consumption, if any, should be kept to no more than one drink per day for women and two drinks per day for men (Class IIb, Level of Evidence B). Smoking cessation is recommended (Class I, Level of Evidence C) (supports algorithm step 4).

Screening Testing of fasting HbA1C or an oral glucose tolerance test is recommended by the AHA (Class IIa, Level of Evidence C). Screening for obesity with a body mass index measurement is also recommended by the

AHA (Class I, Level of Evidence C) (supports algorithm step 4). A nutritional assessment for stroke patients is reasonable.

Antiplatelet Agents The effectiveness of aspirin for preventing ischemic stroke and cardiovascular events is supported by a meta-analysis from the Antithrombotic Trialists’ Collaboration (ATC) published in 2002 (supports algorithm step 4). The ATC analyzed 195 randomized controlled trials comparing antiplatelet therapy, primarily aspirin, with placebo in the prevention of stroke, myocardial infarction (MI), and vascular death among high-risk patients with some vascular disease or other condition implying an increased risk of occlusive vascular disease. Patients treated with an antiplatelet agent (primarily aspirin) had a 25% relative risk reduction in nonfatal stroke compared with placebo. The subgroup analysis of patients with prior cerebrovascular disease in an ATC analysis done in 2009 reduced the risk of secondary stroke by up to 22%. Given the risk of bleeding, a dose of 50 to 325 mg/day of aspirin has been recommended by many studies and guidelines. Clopidogrel, a thienopyridine that inhibits ADP-dependent platelet aggregation, compares well with aspirin, but has a greater incidence of diarrhea and rash, and lower incidence of gastrointestinal bleeding. Clopidogrel efficacy is reduced in the setting of proton pump inhibitors and carriers of CYP2C19 reduced function allele. The MATCH trial and CHARISMA trial compared combination therapy of aspirin and clopidogrel for patients with stroke or TIA and found no additional benefit over single antiplatelet therapy in the long-term outcomes; they did show an increased risk of life-threatening hemorrhages mainly intracranial and gastrointestinal. Certain stroke subtypes such as those due to symptomatic high-grade intracranial stenosis will benefit with dual therapy (SAMPRISS). Dipyridamole plus aspirin was evaluated in the ESPS-2 trial and the combination was found to be better than aspirin monotherapy alone. However, it is much less well tolerated by patients due to side effects like headache. PRoFESS trial evaluated clopidogrel monotherapy with aspirin-extended release dipyridamole therapy and found both the therapies to have comparable benefit in secondary stroke prevention. There is no role for anticoagulation therapy in SVD. Other agents such as ticlopidine, cilostazol, and triflusal have been studied but are rarely used in the United States commonly due to the side-effect profile.

Specific Syndromes CADASIL is best treated conservatively, minimizing use of antiplatelets and statins. Cerebral amyloid angiopathy is also treated conservatively, avoiding antiplatelets, anticoagulants, and statins. Susac’s syndrome is best treated with rapid and sustained immune suppression. CNS sarcoidosis is treated initially with steroids and failing that, with mycophenolate mofetil and infliximab. Intravascular lymphoma is rare, has a poor prognosis, and is treated with anthracycline-based chemotherapy or methotrexate.

Endovascular Management There is no evidence-based indication for endovascular management in SVD. However, cerebral diagnostic angiography is indicated to rule out diseases such as CNS or extracranial vessel vasculitis.

Complication Avoidance Outcomes Lacunar infarcts have a better short-term prognosis than infarcts due to other stroke mechanisms, at least up to 1 year after onset. Patients with lacunar infarction and more severe initial motor deficits have worse functional outcome. The MTHFR C677T genotype is associated with lacunar stroke and white matter hyperintensity volume and these strokes are associated with hypertensive individuals. The rate of recur-

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1 rence of lacunar strokes in a study was found to be around 12% in 1 year if not treated aggressively.

Risk of Bleeding There are some studies evaluating the risk of hemorrhagic conversion of all acute infarcts. The rates of asymptomatic hemorrhage in all infarcts are around 30% at 10 days. Asymptomatic petechial hemorrhage is actually a sign of recanalization and reperfusion. Rates of spontaneous hemorrhagic conversion of lacunar infarcts are unclear but appear to be very low. Hemorrhage is rarely detected unless repeated imaging is pursued in 10 to 15 days as all patients remain asymptomatic.

Clinical and Radiographic Follow-up Repeat imaging of a lacunar infarct is not indicated unless a change in the clinical condition is noted. The clinical exam should dictate the need for further imaging in short- as well as long-term follow-up.

Monitoring The patients should be followed up with a vascular neurologist who can manage the vascular risk factors and medical therapy as an outpatient to prevent recurrence of small vessel infarctions.

Vascular Dementia Vascular dementia was first described in the late 19th century by Binswanger and Alzheimer with the underlying pathologic mechanisms of multiple infarctions and chronic ischemia. The National Institute of Neurological Disorders and Stroke-Canadian Stroke Network Vascular Cognitive Impairment Harmonization Standards defines vascular dementia as cognitive impairment that is caused by or associated with vascular factors. Vascular dementia is the most common cause of dementia after Alzheimer’s in the United States, making up to 10 to 20% of all cases. No association has been found with diabetes mellitus, hypertension, insulin resistance, dyslipidemia, or heart disease. The etiology of vascular dementia is thought to be due to large artery infarctions, usually cortical, small artery lacunar infarcts and chronic subcortical ischemia occurring in the distribution of small arteries in the periventricular white matter. Commonly seen deficits are executive dysfunction, abulia, apathy, aphasia, apraxia, agnosia, as well as anterograde amnesia. Early gait disturbances (apraxic gait or magnetic gait), pseudobulbar palsy, and focal motor signs may also be seen. The Hachinski Ischemic Score (HIS) items highlight clinical features specific to vascular dementia, such as stepwise deterioration, fluctuating course, hypertension, history of stroke, and focal neurological symptoms and may be used as a tool for diagnosis. Neuropsychological testing is often helpful in determining domains and degree of cognitive impairment. One review found that patients with vascular dementia have similar deficits compared with Alzheimer's disease patients (on tests of language, construction, and memory registration) but are significantly less impaired on tests of recognition memory and are more impaired on measures of executive functioning.

Acute Ischemic Stroke: Small Vessel Disease

Intracranial Hemorrhage No discussion of SVD is complete without considering intracranial hemorrhage (ICH) especially due to longstanding hypertension. Hypertension is the most common cause of ICH in the territories of the penetrating arteries that branch off major intracerebral arteries. The blood vessels that give rise to hypertensive hemorrhage generally are the same as those affected by hypertensive occlusive disease and diabetic vasculopathy, causing lacunar strokes. Chronic hypertension causes intimal hyperplasia with hyalinosis in the vessel wall predisposing to focal necrosis. This leads to formation of pseudoaneurysms known as Charcot-Bouchard aneurysms. The areas for the hypertensive hemorrhages are the same as those for lacunar strokes, namely, in the basal ganglia, caudate, thalamus, pons, and cerebellum. Clinical features: Headache, vomiting, focal neurological deficits, as well as decreased level of consciousness are seen on initial presentation. Unlike ischemic infarcts, neurological deficits after ICH tend to worsen. Seizures in the first days after ICH occur in 4 to 29% of patients; they are more common in lobar hemorrhages (affecting cortical tissue) than in deep or cerebellar ICHs. Conservative management: Serial CT scans have shown that hemorrhages expand the most in the first 6 hours after presentation. Acute lowering of systolic BP to below 140 mm Hg was found to have reduction in expansion of hematoma volumes in the INTERACT study. Reversal of anticoagulation, withholding antiplatelets and statins, intracranial pressure management, and treatment of any seizures are among the other aspects of acute management.

Expert Commentary Pitfalls in the diagnosis and management of SVD include assuming that singular lacunes are not embolic, embolic and SVD strokes cannot coexist, and to underestimate the importance of lifestyle modification in the treatment of SVD. Specific syndromes such as CADASIL or CAA must be considered. Robert N. Sawyer Jr., MD University at Buffalo, Buffalo, NY

Suggested Reading Biller J, Ferro JM. Evidence Based Management of Stroke. Shrewsbury, UK: TFM Publishing Ltd.; 2011 Brazis PW, Masdeu JC, Biller J. Localization in Clinical Neurology 6th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2011 Caplan LR, van Gijn J. Stroke Syndromes 3rd ed. New York:Cambridge University Press; 2012 Grotta JC, Albers GW, Broderick JP, Kasner SE, Lo EH, Mendelow AD, Sacco RL, Kernan NW, et al. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association; 2014 Wong LA. Stroke: Pathophysiology, Diagnosis and Management 6th ed. New York: Elsevier; 2016

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2 Acute Ischemic Stroke: Large Vessel Occlusion Maxim Mokin and Elad I. Levy Abstract Acute ischemic stroke associated with a large vessel occlusion (LVO) has high morbidity and mortality. Tissue plasminogen activator (tPA) has limited efficacy in LVO-related strokes. In 2015, five randomized prospective clinical trials of endovascular therapy demonstrated the safety and efficacy of modern mechanical thrombectomy in achieving favorable clinical outcomes in patients with anterior circulation LVO in comparison to medical therapy. Patients with a National Institutes of Health Stroke Scale (NIHSS) score of 6 and above, within the first 6 hours of stroke symptom onset and a LVO, are candidates for mechanical thrombectomy, whether or not they have received tPA. The DAWN trial, published in 2017, included patients within 24 hours of stroke symptom onset to endovascular therapy and demonstrated good outcome in more than 50% of patients. In this trial, the patient selection was based on computed tomography perfusion criteria. Endovascular mechanical thrombectomy can be achieved by different techniques, including a direct aspiration first pass technique, stent retriever, or combination of both (the Solumbra technique). The use of balloon guide catheters is variable and depends mainly on the neurosurgeon’s or interventionist’s personal preference. Most endovascular stroke interventions can be performed under conscious sedation and do not require general anesthesia. Symptomatic intracerebral hemorrhage is the most dangerous complication of any stroke intervention; it is associated with high morbidity and mortality, and it can occur as a complication of the procedure or in a delayed fashion. Adequate patient selection and appropriate endovascular knowledge and experience are the two most important factors necessary to prevent this potential catastrophic complication. Keywords: stroke, large vessel occlusion, middle cerebral artery, internal carotid artery, tissue plasminogen activator, mechanical thrombectomy, aspiration, stent retriever

Introduction Acute ischemic stroke from large vessel occlusion (LVO) is associated with high morbidity and mortality, especially when internal carotid artery (ICA) terminus or basilar artery occlusion is involved. The clinical benefit of intravenous (IV) thrombolysis with tissue plasminogen activator (tPA) was demonstrated in the landmark 1995 National Institute of Neurological Disorders and Stroke (NINDS) study, and this therapy received Food and Drug Administration approval for the treatment of acute ischemic stroke in 1996. However, its efficacy for the treatment of stroke due to LVO is limited. Intra-arterial (IA) pharmacological thrombolysis with tPA and its analogs, clot destruction with microwire manipulation, and mechanical thrombectomy using the Merci retriever device are examples of initial attempts to design catheter-guided therapies as alternatives to IV tPA. In a series of randomized trials published in 2013, such therapies failed to demonstrate significant benefit over medical therapy alone. It should be mentioned that many neurointerventionists believe that other critical factors, such as poor selection of patients for randomization (e.g., lack of LVO) and delays to initiation of the procedure, also might have contributed to the lack of success from IA revascularization. In 2015, five trials of endovascular therapy were published (MR CLEAN, Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands; ESCAPE, Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion with Emphasis on Minimizing CT to Recanalization Times; SWIFT PRIME, Solitaire With the Intention For Thrombectomy as PRIMary Endovascular treatment; EXTEND-IA, Extending the Time for Thrombolysis in Emergency Neurological Deficits–Intra-arterial; and REVASCAT, Randomized Trial of Revascularization with Solitaire FR Device vs Best

Medical Therapy in the Treatment of Acute Stroke Due to Anterior Circulation Large Vessel Occlusion Presenting within Eight Hours of Symptom Onset), all demonstrating safety and efficacy of modern IA thrombectomy in achieving favorable clinical outcomes in patients with anterior circulation LVO, in comparison to medical therapy, including the use of IV tPA. The trials provided strong evidence for the treatment of patients with anterior circulation LVO using IA thrombectomy with retrievable stents (called stent retrievers), when this therapy is combined with prior administration of IV tPA and the thrombectomy is initiated within the first 6 hours of stroke symptom onset. However, subgroup analyses also showed evidence of benefit from IA thrombectomy in patients who were not eligible to receive IV tPA or in whom thrombectomy was initiated as long as 12 hours after stroke onset (1 in algorithm). Major controversies in decision making addressed in this chapter include: 1. Safety and efficacy of intracranial endovascular mechanical thrombectomy. 2. Indications for intracranial endovascular mechanical thrombectomy. 3. Role of endovascular mechanical thrombectomy in patients with more than 6 hours of time from onset (unknown or wake-up stroke). 4. Different mechanical thrombectomy techniques.

Whether to Treat Several studies have shown that the efficacy of IA thrombectomy is time dependent. Therefore, acute stroke should be considered a true neurological emergency; and in qualified patients, such treatment should be initiated without delay. The decision to treat is based on many factors. Stroke severity, which is typically based on the level of the National Institutes of Health Stroke Scale (NIHSS) score, can be used to estimate the likelihood of LVO but should be confirmed with a noninvasive study, such as computed tomographic angiography (CTA) or magnetic resonance angiography (MRA). On the basis of the American Health Association (AHA)/America Stroke Association (ASA) guidelines on the acute management of ischemic stroke that were updated in 2015 to reflect the findings of the 2015 endovascular trials, patients with an NIHSS score of 6 and above should be considered candidates for stroke thrombectomy (2 in algorithm). Among the 2015 trials, subgroup analyses showed that patients with advanced age do show benefit from endovascular therapy. Also, previous administration of IV tPA does not increase the risk of adverse events, such as intracranial hemorrhage (ICH). It is still unknown at which time point endovascular interventions for acute stroke become futile or harmful—in other words, when it is too late to perform IA revascularization. As mentioned, the 2015 trials provided strong evidence for thrombectomy when that treatment was initiated within the first 6 hours from the onset of stroke symptoms. The ESCAPE trial included patients in whom thrombectomy was initiated in up to 12 hours, and there was a trend toward benefit from thrombectomy, although it did not reach statistical significance, possibly due to the limited sample size (n = 49) of this subgroup of patients. Currently, many endovascular centers utilize CT- or MR-based perfusion imaging as a tool to determine the extent of irreversible ischemic damage versus salvageable tissue (penumbra) when selecting patients for interventions beyond the 6-hour therapeutic window or in patients with unknown time of stroke onset. Studies from these centers demonstrate that such a selection approach achieves clinical results that are comparable to those achieved in the 2015 trials, supporting the use of endovascular therapy at later time points in carefully selected patients (3 in algorithm).

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Acute Ischemic Stroke: Large Vessel Occlusion

Algorithm 2.1 Decision-making algorithm for acute ischemic stroke—large vessel occlusion.

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Ischemic Stroke and Vascular Insufficiency

Anatomical Considerations Anterior circulation strokes account for the majority of all strokes from LVO, with the M1 middle cerebral artery (MCA) segment being the most common location affected (►Fig. 2.1a–c). Stent retrievers were considered the first-line treatment strategy; nowadays high recanalization rates are achieved with aspiration thrombectomy alone. Severe carotid artery stenosis or acute occlusion makes endovascular stroke intervention more challenging, as these conditions require the performance of an angioplasty or a stenting procedure before access to the intracranial circulation can be established (►Fig. 2.1a–e). Transfemoral access is most commonly utilized for stroke intervention. However, rarely, alternative access such as via a transradial or a transbrachial approach or even via a direct carotid artery puncture is required, such as in cases of type III arch, extreme tortuosity, severe angulation, or loops of the common carotid artery, and ostial stenosis of the common carotid artery where the classic transfemoral approach is likely to cause significant delay or such access cannot be established. Cases of posterior circulation strokes can be complicated by the presence of severe vertebral artery origin stenosis, which can also be treated via balloon angioplasty or stenting.

Workup Clinical Evaluation The NIHSS score is considered the standard bedside clinical tool when evaluating patients with a suspected stroke. The score ranges from 0 to 42 and measures multiple functions, including level of consciousness, speech, motor and sensory function, vision, neglect, and extinction. According to the current AHA/ASA guidelines, patients with an NIHSS score of ≥6 should be considered for endovascular stroke revascularization. Based on a specific clinical scenario, thrombectomy could be indicated even with an NIHSS score of less than 6 if the neurological deficit is severe and likely to result in long-term morbidity and loss of neurological function (2 in algorithm). Of note, for IV thrombolysis, the currently recommended lower NIHSS score threshold is set at 4 (1, 2 in algorithm). Neurointerventionists should be familiar with other screening tools such as the Los Angeles Motor Scale (LAMS), Rapid Arterial oCclusion Evaluation (RACE) scale, and Cincinnati Prehospital Stroke Severity Scale (CPSSS). These scales are simpler to administer than the NIHSS and can be used by emergency medical services and emergency room personnel to quickly screen patients with stroke for LVO to identify potential candidates for thrombectomy.

Imaging Multiple imaging protocols exist currently. At a minimum, every patient with a suspected LVO based on clinical examination findings should undergo emergent noncontrast head CT scanning and head CTA to confirm the presence of LVO (►Fig. 2.1a, b, f, g). A few institutions rely on the use of magnetic resonance imaging (MRI) and MRA; however, these tests often require additional information that stroke patients are not able to provide (such as whether metal-containing implants are present), making the use of CT more practical. A noncontrast head CT study not only rules out ICH to differentiate an ischemic stroke from a hemorrhagic stroke but also helps determine the extent of early ischemic changes using the Alberta Stroke Program Early CT Score (ASPECTS). This is a 10-point score that assigns points to areas of the brain that are free of ischemic changes on the CT scan, and it can be accessed at www.aspectsinstroke.com. Patients with low ASPECTS are less likely to demonstrate clinical improvement even if successful recanalization is established and also are at higher risk for reperfusion ICH. The updated AHA/ASA guidelines do not recommend thrombectomy in patients with ASPECTS less than 6. ASPECTS was orig-

inally designed for anterior circulation strokes, but can also be applied to posterior circulation strokes (those involving the vertebral, basilar, or posterior cerebral arteries; 3 in algorithm). CTA reliably confirms or excludes the presence of LVO and also provides critical information about the anatomy of the aortic arch and cervical vasculature. It helps identify areas of critical stenosis, dissection, or occlusion that might require angioplasty or stenting before intracranial thrombectomy can be executed (►Fig. 2.1). A variation of head CTA, called multiphase CTA, provides more detailed information about the status and extent of collateral circulation. This approach was tested in the ESCAPE trial, and is described in detail in the supplemental portion of the publication of that trial (3 in algorithm). The role and value of CT- or MR-based perfusion imaging in selecting patients for endovascular therapy is the focus of extensive research nowadays. At several Comprehensive Stroke Centers, CT perfusion imaging is routinely used for the evaluation of patients with strokes of unknown time of onset (including the so-called wake-up strokes) and in those patients who arrive at the emergency department beyond the 6-hour therapeutic window (►Fig. 2.2). Patients with a greater ischemic penumbra–core mismatch have been found to have the best clinical outcomes following IA thrombectomy (3 in algorithm; ►Fig. 2.1c).

Differential Diagnosis CTA is critical in differentiating strokes from LVO that are secondary to occlusion of very distal branches or lacunar strokes, in which thrombectomy is not indicated. A variety of stroke mimics (such as hemiplegic migraine, post-ictal state following a seizure, a brain tumor, or psychogenic disorders) can cause patients to present with symptoms suspicious for a stroke, but normal CTA will help exclude those patients as candidates for thrombectomy.

Treatment Choice of Treatment Conservative management of patients with strokes from LVO is reserved for cases where endovascular therapy is likely to be futile or contraindicated, which commonly involve patients with evidence of extensive ischemic damage on noncontrast CT imaging (low ASPECTS) or poor penumbra–core mismatch on perfusion imaging. Also, patients with poor functional status (such as those with high modified Rankin’s scale [mRS] scores, typically within the 3–5 range) are unlikely to demonstrate clinical benefit from endovascular therapy. For those patients who are likely to benefit from IA thrombectomy, such therapy should be initiated as soon as possible. The 2015 studies demonstrated that one in three to four patients (the number needed to treat [NNT]) will show clinical benefit from endovascular therapy of stroke. Very few currently available surgical interventions can demonstrate such a remarkably low NNT. For comparison, the NNT for IV thrombolysis ranges from 4 to 19, depending on the timing of tPA administration.

Conservative Management Conservative medical management involves the use of antiplatelet agents, aggressive IV hydration, and blood pressure control. Permissive hypertension during the acute phase of stroke is advised. In patients with large strokes (such as infarction affecting one-half of the MCA), the benefit of antiplatelet therapy should be weighed against the risk of spontaneous hemorrhagic transformation, which is especially high in patients with large embolic strokes. There is no evidence to support the use of an IV heparin drip for patients with acute stroke. Exceptions are patients with evidence of cardiac thrombus and also sometimes patients with intraluminal thrombus of carotid or vertebral arteries.

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Acute Ischemic Stroke: Large Vessel Occlusion

Fig 2.1 A case of acute ischemic stroke in a patient with history of smoking and hypertension. The patient presented outside the therapeutic window for intravenous thrombolysis, and noninvasive imaging showed (a) near-complete occlusion of the right internal carotid artery origin (arrow) and (b) a tandem right middle cerebral artery (MCA) occlusion (arrow). (c) Computed tomographic perfusion imaging demonstrated ischemic penumbra within the right MCA territory (cerebral blood volume loss is labeled in red, cerebral blood flow reduction is shown in green). To minimize the risk of hemorrhagic transformation, balloon angioplasty rather than stenting was performed to establish intracranial access, because the latter would require the administration of dual antiplatelet therapy. (d) Catheter angiography, lateral view, confirmed critical right internal carotid artery origin stenosis (arrow), which was treated with balloon angioplasty (e; arrows point to the angioplasty balloon). This allowed immediate access into the internal carotid artery, which demonstrated persistent occlusion of the proximal right MCA at its M1 segment (f, arrow). Following stent retriever thrombectomy, full recanalization of the right MCA was established (g). Carotid endarterectomy was performed in this patient 4 days later, after a follow-up head CT study confirmed no hemorrhagic transformation. The patient demonstrated a remarkable clinical recovery.

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Ischemic Stroke and Vascular Insufficiency usually caused by LVO due to an atherosclerotic plaque rather than an embolus. Most endovascular stroke interventions can be performed under conscious sedation and do not require the use of general anesthesia. On the basis of multiple studies comparing safety, technical aspects, and outcomes of the two approaches, conscious sedation is safer and associated with a higher rate of good clinical outcomes than general anesthesia.

Complication Avoidance Outcome

Fig 2.2 CT perfusion in a patient with acute right MCA occlusion who presented after 6 hours of onset of symptoms: it demonstrates increased time-to-peak (upper right) with preserved volume (upper middle). Even though, the patient is beyond the 6 hours therapeutic window, the CT perfusion information indicates that the patient is a good candidate for mechanical thrombectomy.

Cerebrovascular Management—Operative Nuances Decompressive craniectomy for malignant anterior circulation strokes was evaluated in three randomized trials (Decompressive Surgery for the Treatment of Malignant Infarction of the Middle Cerebral Artery [DESTINY], Decompressive Craniectomy in Malignant Middle Cerebral Artery Infarction [DECIMAL], and Hemicraniectomy After Middle Cerebral Artery Infarction with Life-threatening Edema Trial [HAMLET]). The AHA/ASA recommends decompressive craniectomy in patients with malignant MCA strokes who deteriorate clinically despite medical therapy, such as the use of osmotic agents. Also, suboccipital craniectomy is recommended for patients with large cerebellar infarctions (such as those involving the posterior inferior cerebellar artery) who fail medical therapy.

Endovascular Management—Operative Nuances Most operators considered the use of stent retrievers as their first-line treatment strategy for IA thrombectomy (►Fig. 2.1d–g). The choice of stent retriever depends on the diameter of the affected vessel and the extent of the clot. Undersizing the device will reduce the chance of successfully engaging the clot, whereas a significantly oversized device can potentially increase the risk of vessel damage by causing a dissection or intraprocedural rupture. There are conflicting data regarding the efficacy of the use of balloon-guided catheters versus the use of distal aspiration catheters when performing stent-retriever thrombectomy. Both approaches seem to decrease the rate of distal embolic events and reduce the number of retrieval attempts required to achieve successful recanalization. Because of the great variability in how different operators perform thrombectomy, direct comparison of both approaches has not been successful. The use of distal aspiration catheters offers an additional advantage in that aspiration thrombectomy without the use of stent retrievers can be attempted first, which can potentially make the procedure faster. This approach is called ADAPT FAST (a direct aspiration first pass technique for acute stroke thrombectomy). Publications of real-world experience show that in approximately 10 to 15% of endovascular stroke interventions with stent retrievers, additional techniques are utilized. The IA administration of IIb/IIIa inhibitors and tPA is reserved for cases with more distally located occlusions that are too far to be safely reached with stent retrievers. Intracranial angioplasty with stenting is sometimes required in cases where persistent occlusion is seen despite multiple thrombectomy attempts; this is

Endovascular therapy for LVO stroke with modern approaches (thrombectomy with stent retrievers and distal aspiration catheters) has made stroke intervention much safer, when compared to the rates of adverse events reported in studies of IA pharmacological thrombolysis and early-generation thrombectomy devices (supports algorithm step 3), such as the Merci retriever (Stryker, Kalamazoo, MI; used in the Mechanical Embolus Removal in Cerebral Ischemia [MERCI] and Multi MERCI trials) or the Penumbra aspiration system (Penumbra Inc., Alameda, CA; used in the Penumbra Pivotal trial). Symptomatic ICH (sICH) is considered the most dangerous complication of any stroke intervention, including the use of IV thrombolysis alone. It is associated with high morbidity and mortality. In cases of IA thrombectomy, sICH can result from intraprocedural vessel rupture, which commonly manifests as a rapid change in vital signs during the procedure. sICH can also occur in a delayed fashion, 24 to 48 hours postprocedure, as a result of reperfusion hemorrhage. Proper selection of patients for thrombectomy, using CT ASPECTS, CT perfusion imaging, and/or MRI diffusion-weighted or perfusion imaging, helps identify patients who are at high risk for reperfusion hemorrhage and should be managed conservatively (supports algorithm step 3). The 2015 trials showed no increased risk for sICH among patients treated with endovascular therapy, in comparison to those treated with medical therapy alone (including the use of IV tPA). Vasospasm of the intracranial or cervical vasculature can occur during the procedure, especially with the use of multiple devices. This is often successfully treated with local IA administration of calcium channel blockers.

Durability and Rate of Recurrence IA thrombectomy is a highly effective procedure. Stroke recurrence occurs as a result of a deficiency in secondary stroke prevention. To minimize the rate of stroke recurrence, timely administration of antiplatelet or anticoagulant therapy is very important; however, it should be weighed against the risks of hemorrhagic transformation, which is increased in cases with large strokes. In the REVASCAT, the rate of recurrent stroke was 3.9% in the thrombectomy group versus 2.9% in the control (medical therapy with IV tPA alone) group.

Clinical and Radiographic Follow-up All patients undergoing IA thrombectomy should be monitored in a neurointensive care unit, with special protocols, similar to those developed for IV thrombolysis. With an increased number of endovascular stroke interventions performed at many hospitals, it is critical that hospitals evaluate their performance to identify areas of improvement. This can be done by participating in the national Get With The Guidelines-Stroke database sponsored by the AHA. The sICH rates, discharge NIHSS scores, and 3-month mRS scores are well-established metrics used in both clinical research and hospital practice, and these data can be compared with the national average for each year. Radiographic follow-up typically involves a repeat noncontrast CT scan of the head obtained at 24 hours postthrombectomy. For those cases in which the suspicion for ICH is high, an immediate postprocedure CT scan or a series of CT scans may be required.

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Expert Commentary A few years ago, the future of endovascular stroke interventions was very bleak. Currently, we are witnessing a paradigm shift in the treatment of stroke, moving from an era of rehabilitation into an era of active intervention. The announcement of the 2015 endovascular stroke trials has been, by far, the most exciting news not only in the neurointerventional community but also for all clinicians caring for stroke patients. Stroke remains the number one cause of long-term disability in the United States. Despite all of the enthusiasm surrounding the recent stroke trials, we need to realize that currently only 1 to 2% of all stroke patients are treated with endovascular therapy. Considering that an estimated 30 to 40% of ischemic strokes are caused by LVO, which is potentially amenable to endovascular therapy; this means that the majority of patients do not receive this life-saving procedure. The reasons for such a disconnect are that patients who qualify for such therapies are not identified properly and there is a significant delay in triaging them to centers that are capable of performing emergent stroke interventions. In the next few years, we will witness a series of changes in how patients with strokes are being evaluated and triaged so that the most efficient ways of delivering endovascular stroke therapy can be achieved. Elad I. Levy, MD, MBA University at Buffalo, Buffalo, NY

Editor Commentary Over the last few years, and especially after the publications of several stroke trials in the New England Journal of Medicine in 2015, LVO-related stroke has become a neurosurgical or neurointerventional disease. Adequate patient selection is key to achieve good outcomes. In general, all patients presenting with acute stroke symptoms with an NIHSS score of 6 or more with less than 6 hours of evolution and a negative CT scan for ICH are potential candidates for endovascular intervention. A subgroup of patients who do not meet these criteria require further evaluation (e.g., CT perfusion). The results of the DAWN trial demonstrated that a subgroup of patients presenting within 24 hours after symptoms onset are still candidates for an endovascular procedure. Endovascular technology (e.g., stent retrievers, large bore aspiration catheters) has

Acute Ischemic Stroke: Large Vessel Occlusion

improved significantly and has contributed to the achievement of good radiological and clinical results. I personally have moved from the stent retriever technique to ADAPT and have observed less thrombus fragmentation and vessel perforation. Leonardo Rangel-Castilla, MD Mayo Clinic, Rochester, MN

Suggested Reading Berkhemer OA, Fransen PS, Beumer D, et al; MR CLEAN Investigators. A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med 2015;372(1):11–20 Campbell BC, Mitchell PJ, Kleinig TJ, et al; EXTEND-IA Investigators. Endovascular therapy for ischemic stroke with perfusion-imaging selection. N Engl J Med 2015;372(11):1009–1018 Goyal M, Demchuk AM, Menon BK, et al; ESCAPE Trial Investigators. Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med 2015;372(11):1019–1030 Jovin TG, Chamorro A, Cobo E, et al; REVASCAT Trial Investigators. Thrombectomy within 8 hours after symptom onset in ischemic stroke. N Engl J Med 2015;372(24):2296–2306 Mokin M, Kan P, Kass-Hout T, et al. Intracerebral hemorrhage secondary to intravenous and endovascular intraarterial revascularization therapies in acute ischemic stroke: an update on risk factors, predictors, and management. Neurosurg Focus 2012;32(4):E2 Powers WJ, Derdeyn CP, Biller J, et al; American Heart Association Stroke Council. 2015 American Heart Association/American Stroke Association Focused Update of the 2013 Guidelines for the Early Management of Patients With Acute Ischemic Stroke Regarding Endovascular Treatment: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke 2015;46(10):3020–3035 Saver JL, Goyal M, Bonafe A, et al; SWIFT PRIME Investigators. Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke. N Engl J Med 2015;372(24):2285–2295 Turk AS, Frei D, Fiorella D, et al. ADAPT FAST study: a direct aspiration first pass technique for acute stroke thrombectomy. J Neurointerv Surg 2014;6(4):260–264 Wijdicks EF, Sheth KN, Carter BS, et al; American Heart Association Stroke Council. Recommendations for the management of cerebral and cerebellar infarction with swelling: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2014;45(4):1222–1238

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3 Acute Ischemic Stroke: Acute Internal Carotid Artery

Occlusion and Tandem Lesions Leonardo Rangel-Castilla, Adnan H. Siddiqui, and L. Nelson Hopkins

Abstract Internal carotid artery (ICA) occlusion has a mortality of more than 50%. Tissue plasminogen activator has minimal to no beneficial effect. Intracranial ICA terminus occlusions have the worst functional outcome and are usually secondary to cardiac embolism. Extracranial ICA occlusion can be caused by atherosclerosis, dissection, and rarely by cardiac embolism; most cases are associated with sudden occlusion of a previously preexisting ICA stenosis or plaque rupture. Tandem occlusions (extracranial ICA occlusion and intracranial ICA or middle cerebral artery [MCA] occlusion) involve the complexity of different stroke mechanisms and endovascular treatment is challenging. Computed tomography angiography of the neck and head is the best imaging study to diagnose ICA occlusion. Endovascular management strategy varies depending on the site of occlusion. Treatment includes mechanical thrombectomy with or without intracranial or extracranial carotid artery stenting (CAS). After an ICA occlusion is confirmed with cerebral angiography, the extracranial occlusion/stenosis is usually resolved first with aspiration thrombectomy or CAS. Once the extracranial ICA has been revascularized, better visualization of the intracranial ICA or MCA occlusion is possible. Intracranial mechanical thrombectomy is performed with direct aspiration using a large bore catheter or with a stent retriever. Balloon guide catheters are frequently used in ICA occlusions allowing endovascular mechanical thrombectomies and CAS to be performed under flow arrest to decrease the risk of iatrogenic intracranial thrombus embolism. Other potential risks include injury to the ICA resulting in dissection and/or occlusion. Extracranial–intracranial bypass is usually not indicated in the acute ICA occlusion management, but it can be considered once patient is stable and adequate revascularization was not achieved by endovascular means. Keywords: stroke, large vessel occlusion, internal carotid artery, tandem occlusion, mechanical thrombectomy, aspiration, stent retriever, carotid stenting

Introduction Acute ischemic stroke (AIS) caused by intracranial internal carotid artery (ICA) occlusion has a dismal natural history, with neurological morbidity and mortality rates of 70 and 55%, respectively. Recanalization rates after intravenous (IV) tissue plasminogen activator (tPA) in patients with intracranial ICA are exceptionally poor (4.4–12.5%). Recanalization rates after intra-arterial (IA) therapy in patients with extra- and/or intracranial ICA occlusion are 62 to 63%. Extracranial ICA occlusion has a better prognosis than intracranial ICA occlusion due to collateral supply from the external carotid artery (ECA) and the circle of Willis. Major controversies in decision making addressed in this chapter include: 1. Should acute symptomatic ICA occlusion be treated medically, endovascularly, or with both therapies? 2. Whether the benefit of improved recanalization associated with therapy is outweighed by time delays and complications, such as embolization of thrombotic material into more distal territories. 3. The precedence of endovascular recanalization—which one should be considered first, extracranial or intracranial occlusive lesion? 4. The role of open cerebrovascular techniques in the management of ICA occlusion.

Whether to Treat In individuals with extracranial ICA occlusion and poor collateral circulation or simultaneous intracranial ICA occlusion, the treatment goal is

to achieve rapid and complete recanalization of the artery (1 and 2 in algorithm). For patients with tandem lesions, revascularization of both lesions is warranted to achieve a good outcome. The natural history of patients with acute symptomatic ICA occlusion is poor. Historically, due to the poor prognosis, many clinicians used to hesitate, wondering if outcome could be improved with therapy. A Dutch study, the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN), changed that misperception; in fact, of all the cohorts in that trial, the group most likely to benefit from revascularization was the group with cervical and intracranial occlusion presenting with AIS. Unfortunately, the Food and Drug Administration did not allow patients who presented with tandem cervical and intracranial ICA occlusion in U.S.-based trials (e.g., Solitaire With the Intention For Thrombectomy as PRIMary Endovascular treatment [SWIFT PRIME], Assess the Penumbra System in the Treatment of Acute Stroke [THERAPY], and Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion with Emphasis on Minimizing CT to Recanalization Times [ESCAPE]) because of concern about safety of acute extracranial ICA angioplasty and/or stenting. Patients with complete recanalization of the occluded ICA have the best chance of regaining independence. There was a major concern that aggressive endovascular therapy resulted in symptomatic intracranial hemorrhage (ICH) and decreased survival. However, MR CLEAN demonstrated that the rate of symptomatic ICH is similar in patients treated with IV tPA (medical therapy) alone or with endovascular therapy (1, 2 in algorithm).

Anatomical Considerations For endovascular procedures, anatomical relevance starts with arterial access. Transfemoral access is most commonly used for stroke interventions. Other alternatives include transradial or transbrachial access (especially for the posterior circulation) and even direct carotid artery access in cases of a type III arch, extreme tortuosity, or ostial stenosis of the common carotid artery (CCA). A computed tomography angiography (CTA) of the aortic arch extending up to the vertex (therefore including the entire intracranial circulation) should be obtained and evaluated before the procedure to assess for difficult anatomy and assist with planning. A heavily calcified cervical ICA (seen on CTA) suggests extracranial ICA occlusion with possible intracranial occlusion. An intracranial ICA bifurcation occlusion could have the radiographic appearance of an extracranial ICA occlusion. Here, a four-dimensional (4D) CTA can be very useful to distinguish an intracranial from an extracranial occlusion. This noninvasive study reciprocates a diagnostic angiogram revealing the extension of contrast material intracranially during the venous phase for pure intracranial ICA occlusions. Alternatively, contrast material can be noted to head downward from the circle of Willis toward the occluded carotid artery during extracranial occlusion. This is a key distinction because if there is complete extracranial occlusion, it is likely that stent-assisted revascularization and a loading dose of dual-antiplatelet therapy are needed emergently en route to the interventional suite; although if the lesion is solely intracranial, one can forgo the additional anticoagulation therapy. Once endovascular access into the CCA has been established, the anatomy and site(s) of occlusion should be assessed. The following anatomical characteristics should be addressed: 1. Flame-shaped occlusion at the cervical ICA bifurcation indicating possible dissection or intracranial ICA terminus occlusion (►Fig. 3.1). 2. Collateral flow from the ECA into the intracranial ICA, most commonly through an anastomosis or anastomoses with the ophthalmic artery.

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3

Acute Ischemic Stroke: Acute Internal Carotid Artery Occlusion and Tandem Lesions

Algorithm 3.1 Decision-making algorithm for acute ischemic stroke—acute internal carotid artery occlusion and tandem lesions.

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Ischemic Stroke and Vascular Insufficiency 3. Presence of retrograde filling of the ICA to the level of the skull base. This is a good marker for the absence of thrombus in the petrocavernous segment. 4. Contralateral ICA and vertebral artery injections to evaluate collateral flow through the anterior and posterior communicating arteries are typically not recommended if the patient has a high National Institutes of Health Stroke Scale (NIHSS) score and CT or magnetic resonance (MR) perfusion imaging suggests salvageable penumbra. This is because the presence of collaterals may erroneously suggest adequacy, when the clinical picture suggests otherwise. Conversely, a low NIHSS score may be explained by excellent intracranial collaterals, which obviates the need for revascularization and subsequent exposure of the patient to distal and more consequential embolization.

Pathophysiology/Classification Intracranial Internal Carotid Artery Occlusion The outcome depends on the site of vessel occlusion. Occlusion of the ICA terminus has the worst functional outcome. Most of these cases are caused by cardiogenic embolism; however, other etiologies, such as atherosclerosis and dissection, should be considered. Functional ICA terminus occlusions are prone to impaired collateral circulation because they cut off the circle of Willis.

Extracranial Internal Carotid Artery Occlusion Various mechanisms have been proposed to cause extracranial ICA occlusion, including atherosclerosis, dissection, and in rare cases cardiac embolism. Most cases of extracranial ICA occlusion are associated with sudden occlusion of a previously preexistent ICA stenosis, plaque rupture with hemorrhage, or cardioembolic thrombus on a preexistent ICA stenosis.

Tandem Lesions Some cases of ICA terminus occlusion are due to cervical ICA plaque rupture and secondary artery-to-artery large embolus with resultant tandem occlusion of the extracranial ICA and intracranial ICA terminus. In these cases, total blockage of anterograde ICA flow and the major collateral pathways of the circle of Willis results in a severe perfusion deficit and acute dense neurological symptoms. Tandem occlusions involve the complexity of different stroke mechanisms. Some patients have clinical symptoms caused by a focal thrombus at the site of the intracranial occlusion. Other patients have symptoms caused by an entire hemispheric ischemia due to cervical occlusion. Treatment strategies are challenging because of the coexistence of hard, though fragile, ruptured plaque and the secondary very large thrombus extending from the cervical ICA up to the ICA terminus (►Fig. 3.2).

Workup

Imaging All patients with an LVO that is suspected on the basis of clinical examination findings should undergo a noncontrast head CT scan and an archto-vertex CTA to confirm the presence of LVO (►Fig. 3.2). The CT scan of the head rules out ICH and helps determine the extent of early ischemic changes using the Alberta Stroke Program Early CT Score (ASPECTS). Patients with a low ASPECTS are less likely to demonstrate clinical improvement even if successful recanalization is established and also are at higher risk for reperfusion ICH. CTA confirms the presence of LVO and provides information about the anatomy of the aortic arch and cervical vasculature. It helps identify areas of critical stenosis, dissection, or occlusion that might require angioplasty or stenting before intracranial IA thrombectomy. At some centers, CT perfusion imaging (►Fig. 3.1, ►Fig. 3.2) is routinely used for the evaluation of patients with strokes of unknown time of onset and in those patients who arrive at the emergency department beyond the 6-hour therapeutic window. Patients with a greater ischemic penumbra–core mismatch have been found to have the best clinical outcomes following endovascular treatment. CT perfusion imaging remains a tool under development. What we are trying to assess with this imaging, in addition to the clinical presentation, is whether there is salvageable penumbra or is the entire infarct already completed. Three main image sets are evaluated using the contralateral hemisphere as a control. The first is a measure of the time of contrast appearance in various regions of the brain. This is the ideal study to demonstrate potential area at risk. The second is cerebral blood flow (CBF), which is typically decreased in the ischemic territory. The final key image set is cerebral blood volume (CBV), which can be increased, normal, or decreased. An increase suggests preserved autoregulation with maximal vasodilation; this is the scenario where even with a low NIHSS score one should consider revascularization, especially when associated with decreased CBF. Alternatively, patients with a normal CBF and CBV with purely extracranial occlusion and a low NIHSS score are typically not candidates for interventions. Similarly, almost no preserved CBF and CBV indicates a completed infarct. It should be noted that at the earliest time points, CT perfusion imaging can be misleading but becomes increasingly reliable beyond 6 hours of onset. A few institutions rely on the use of MR imaging and MR angiography; however, these tests often require additional screening that may not be possible unless the patient is well known or the family accompanies the patient, making the use of CT more practical.

Treatment Conservative Management Medical management includes antiplatelet agents, aggressive IV hydration, and blood pressure control. Permissive hypertension during the acute phase of stroke is advised. Intravenous heparin has been used in patients with ICA occlusion. In patients with large strokes, the benefit of antiplatelet therapy and/or heparin should be weighed against the risk of spontaneous hemorrhagic transformation.

Clinical Evaluation

Cerebrovascular Management—Operative Nuances

The NIHSS score is the standard bedside clinical evaluation for patients with stroke. It measures multiple functions, such as level of consciousness, speech, motor and sensory function, vision, neglect, and extinction. Patients with an NIHSS score of ≥6 should be considered for endovascular stroke revascularization associated with large vessel occlusion (LVO) (3 in algorithm). Endovascular mechanical thrombectomy could be indicated even with an NIHSS score of less than 6 if the neurological deficit is severe (e.g., severe aphasia) or perfusion imaging suggests severe hemodynamic susceptibility (see below) and is likely to result in long-term morbidity (1, 2 in algorithm).

Emergent surgery is usually confined to the cervical ICA region (cervical endarterectomy [CEA]) because of the time involved in preparing for a craniotomy/craniectomy to reach the intracranial ICA. Urgent CEA for acute ICA occlusion (60% stenosis) or ultrasonography (>70% stenosis) is recommended for “asymptomatic” patients (who have not had an ipsilateral ischemic infarct or transient attack within the past 6 months) and these patients have a low risk for surgery. For patients with high-risk features (age older than 80 years, severe medical comorbidities, previous neck surgery or radiation, carotid bifurcation or stenotic plaque at or above C2 or into the common carotid artery into the intrathoracic segment, or “twisted carotid”) carotid artery stenting or angioplasty is an excellent alternative. Keywords: transient ischemic attack, stroke, carotid artery disease, carotid artery stenosis, ACST, ACST-2, CREST, CREST-2, carotid endarterectomy, carotid artery stenting

Introduction Extracranial carotid artery stenosis is a common cause of ischemic stroke, noted to be responsible for 20% of cases. Epidemiological studies report a prevalence estimated between 0.1 and 9% among the general population, but in those older than 65 years and/or with risk factors including smoking, hypertension, coronary artery disease, and recent strokes, the prevalence may be as high as 60%. Carotid artery disease has been the source of significant debate among the neurological and cardiovascular medicine communities, including the propriety of surgical reconstruction and/or the use of novel endovascular remedies. While all carotid artery stenosis treatment is prophylactic by nature to prevent cerebral embolic events, a challenging area of management is the indications for treatment of lesions that have not demonstrated the propensity to embolize by causing a previous stroke, hence deemed asymptomatic stenosis. Major controversies in decision making addressed in this chapter include: 1. Whether or not treatment is indicated. 2. Endarterectomy versus stenting for asymptomatic carotid artery stenosis. 3. Complications, outcome, and durability of the treatment.

Whether to Treat Throughout the 1990s and early 2000s, many large, multicenter, randomized trials were conducted to shed light on the appropriate indications for surgical reconstruction of asymptomatic carotid disease. CASANOVA, published in 1991, compared carotid endarterectomy (CEA) to medical therapy alone in patients with asymptomatic carotid stenosis measuring 50 to 90%, as seen on angiography. Due to an unacceptably high surgical complication rate, very complicated study protocols, and exclusion of patients with greater than 90% stenosis, no difference was seen in the number of strokes or deaths between the two study arms. Published in 1992, the MACE study was a single-center study that com-

pared CEA alone with aspirin therapy, and reinforced the importance of use of aspirin peri- and postoperatively. Given the significantly higher number of myocardial infarctions (MIs) and transient cerebral ischemic events in the surgical group, the study was terminated early, after only 71 patients had been randomized. The consensus was that these complications were attributable to the lack of aspirin use in the surgical arm, which was further supported in subsequent studies. The Veterans Affairs Cooperative Study Group in 1993 published a multicenter prospective randomized study with two treatment arms, CEA plus aspirin–antiplatelet therapy and antiplatelet therapy alone. The surgical arm demonstrated a reduction of ipsilateral neurological events (8 vs. 20.6%), although the study was not statistically powered and failed to show a reduction of ipsilateral strokes or death. Nevertheless, after a long-term 4-year follow-up period, the ipsilateral stroke rate in the surgical group was 4.7% compared to 9.4% in the medical group (1, 2, 3, 4, 5 in algorithm). The Asymptomatic Carotid Surgery Trial (ACST), published in 2004, is the largest trial on this topic to date, consisting of more than 3,000 patients with greater than 60% asymptomatic stenosis diagnosed by duplex ultrasound, who were randomized to CEA with medical management versus medical management alone. Exclusion criteria included poor surgical risk, prior ipsilateral CEA, and probable cardiac emboli. Surgeons were required to have demonstrated a perioperative morbidity and mortality rate of less than 6% to be involved in the trial, and this rate was just over 3% in the study. The mean follow-up was 3.4 years. The overall 5-year risk of all strokes and deaths, including perioperative stroke and death, was 6.4 and 11.8% in the surgical and medical groups, respectively. Fatal or disabling stroke rates were 3.5 versus 6.1%. Fatal stroke rates alone were 2.1 versus 4.2%. So, in consideration of “asymptomatic” carotid patients (who have not had an ipsilateral ischemic infarct or transient ischemic attacks (TIAs) within the past 6 months), we recommend consideration of surgery (CEA) for otherwise low-risk patients with higher than 60% stenosis by angiography or for those with higher than 70% stenosis by ultrasonography (5 in algorithm). We note that all of the studies cited earlier were completed in the pre-statin therapy era. There is evidence that statin therapy, in concert with routine antiplatelet therapy, affords a greater measure of protection in the medical management of asymptomatic carotid stenosis. To evaluate this, three new randomized controlled trials are in progress, the SPACE 2, ACST-2, and CREST-2. All of these will evaluate the role of prophylactic CEA for asymptomatic disease in the era of modern pharmacotherapy (1, 2, 3 in algorithm).

Anatomical Considerations It is important to note anatomical parameters that may increase the degree of surgical difficulty. On preoperative imaging, the features we look for include the presence of a high carotid bifurcation or stenotic internal carotid artery (ICA) plaque distal to the second cervical vertebra or above the angle of the mandible, or common carotid artery (CCA) plaque extending proximal into the intrathoracic segment. In the era of carotid stenting, transmandibular extended approaches or dislocation of the temporomandibular joint that might have been necessary to access the high distal ICA are no longer appropriate. We also look for the “twisted carotid” variant where the ICA is medially rotated under the external carotid artery (ECA), which renders adequate distal ICA exposure more difficult; this relationship is easy to predict preoperatively by studying the anteroposterior and lateral angiograms (4, 5 in algorithm). Other anatomical factors that add significant perioperative risk of a CEA and should be taken in consideration in the decision-making process are previous ipsilateral neck surgery including CEA, radial neck dissection, and open tracheostomy. Nonanatomical factors include age older than 80 years, previous radiation, contralateral vocal cord paralysis, and severe neck stiffness (4, 5, 6 in algorithm).

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6

Asymptomatic Extracranial Carotid Artery Stenosis

Algorithm 6.1 Decision-making algorithm for asymptomatic extracranial carotid artery stenosis.

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Ischemic Stroke and Vascular Insufficiency

Workup Clinical Evaluation Many patients with carotid artery stenosis will present without any threatening neurological complaints. These lesions often reach the attention of clinicians after careful physical examination and the detection of a carotid bruit. While physical exam findings are valuable tools, the absence of a cervical bruit does not rule out carotid disease, and between a quarter and a third of patients with high-grade stenosis will have no auscultatable carotid bruit. A careful history-taking is essential, focusing on specific symptomatology of cerebral embolic disease, including visual changes, language difficulty, facial paresis, dysarthria, numbness, or weakness. Although this chapter addresses the appropriate clinical rationale for reconstruction of “asymptomatic” carotid disease, “symptomatic” carotid stenosis with concomitant ipsilateral ischemic disease is a much more compelling trigger for fast-track surgery, as the 2-year risk of stroke in untreated symptomatic and asymptomatic carotid artery disease is 26 and 6%, respectively.

Imaging Rational choice of imaging facilitates confirmation of the presence and degree of carotid artery stenosis. Carotid ultrasound is used as a tool to screen patients, or to follow patients either on medical management or postoperatively. Computed tomography angiography (CTA) and magnetic resonance angiography (MRA) have become increasingly useful in noninvasive screening of carotid artery disease. In many cases, CTA can be substituted for digital subtraction angiography (DSA) in planning surgery. MRA can be insensitive to resolve the difference between high-grade stenosis and/or complete occlusion, and also it does not sufficiently show the extent of distal ICA disease, which is necessary information to plan a safe and effective surgery. CTA is much better at resolving these questions, but can underestimate the degree of stenosis in the presence of calcium at the carotid bulb (this is critically important), which is often seen in carotid atheroma cases. Therefore, we create a surgical plan based on CTA alone, but we have a low threshold for the addition of formal DSA imaging (the majority of our patients do have bulb calcification on the CTA), and both studies can give us anatomical clues (4 in algorithm).

Treatment Conservative Management Initial conservative management of carotid artery disease should attempt to avoid progression or development of concurrent cardiovascular disease. The mainstays of risk modification include glycemic control, blood pressure control, serum lipid monitoring, and smoking cessation. All patients presenting with carotid artery disease should be started on aspirin. There is Level A evidence and a Class I recommendation that low-dose aspirin (75–325 mg) reduces the risk of stroke in this patient population (1 in algorithm). Medical treatments for carotid artery stenosis have evolved, thanks to a series of clinical trials over the last 40 years, most notably with the addition of statins and dual-antiplatelet regimens. The ESPS-2 and ESPRIT studies both have shown notable relative risk reduction for stroke when patients received dual-antiplatelet therapy compared to either medication individually (aspirin + clopidogrel: 37% vs. aspirin alone: 18%), although the literature has shown an increase in hemorrhagic complications. Thus, routine dual-antiplatelet therapy is not our standard treatment for carotid disease. The data for statin use in carotid stenosis patients are more impressive, with SPARCL trial showing subgroup analysis of over a thousand patients with carotid stenosis and no clinical coronary disease demonstrating a significant 33% stroke risk reduction for patients randomized to high-dose atorvastatin compared to placebo (1 in algorithm). The literature suggests that maximal conservative therapy may be lowering stroke rates across all

treatment modalities. We must look for novel data from SPACE 2, ACST-2, and CREST-2 for guidance in the next several years. Additionally, regardless of whether or not a patient with carotid artery stenosis requires surgical treatment, their comorbid risk of future MIs, strokes, or peripheral vascular syndromes over 5 years exceeds 20%, compelling reason for medication therapy and counseling on cardiovascular monitoring, and for sophisticated primary care.

Cerebrovascular Management—Carotid Endarterectomy We have Level A evidence in favor of CEA for asymptomatic carotid stenosis greater than 60% by angiography, so long as comorbid risks remain low and surgical anatomy is favorable (5 in algorithm). We carefully select and screen patients appropriate for surgical intervention, necessitating appropriate medical clearance. Factors and comorbidities associated with increased surgical risk include age more than 80 years, left ventricular ejection fraction less than 30%, New York Heart Association class III or IV heart failure, left main or multilevel coronary artery disease, MI within 4 weeks, need for cardiac surgery within 30 days, and severe chronic lung disease (3 in algorithm). Prior to surgery, patients must be on aspirin and statin medication, and blood pressure should be controlled. There are multiple anatomical criteria that must be acknowledged before choosing to pursue surgical intervention that would increase the risk of a CEA, including stenotic plaque distal to the second cervical vertebra or above the angle of the mandible, intrathoracic carotid stenosis, previous ipsilateral neck surgery, contralateral vocal cord paralysis, and/or previous radiation at the operative site (4, 5, 6 in algorithm). As with the indications for CEA, the intricacies of many aspects of the surgical procedure have been studied and scrutinized. The surgeon has technique choices to make, such as local or general anesthesia, intraprocedural neuroprotectant agents, intraoperative monitoring and the linked need for intraoperative carotid shunting, and endarterectomy type, whether linear or eversion, primary repair, microscopic repair, or with carotid patch grafting. As we perform and teach carotid surgery, the patient is positioned supine with the head turned variably to the contralateral side, and with the neck slightly extended by placement of an interscapular roll. We utilize concomitant electroencephalograph (EEG) and somatosensory-evoked potential (SSEP) monitoring. A linear skin incision is made along the anterior border of the sternocleidomastoid muscle extending two fingerbreadths above the clavicle to two fingerbreadths below the angle of the mandible. The platysma is then incised sharply and blunt self-retaining retractors are placed, staying superficial on the medial side to prevent injury to the laryngeal nerves. (Once deep to the platysma, we use only blunt fish-hook type [LoneStar] retraction to prevent nerve injury). The dissection is then carried along the anterior aspect of the sternocleidomastoid muscle. The carotid sheath is entered, and the internal jugular vein and ansa cervicalis nerve are identified and mobilized laterally and medially, respectively. The common facial vein is then identified and ligated to further facilitate lateral mobilization of the internal jugular. The surgeon should carefully dissect the CCA while avoiding injury to the vagus nerve, which typically lies along the posterior aspect of the carotid vessels. Then the dissection is carried cephalad to expose the origins of the ICA, ECA, superior thyroid artery, and occasionally some anomalous ECA branches. As the dissection continues rostrally, the hypoglossal nerve should be identified and should be carefully mobilized medially. Once the ICA distal to the plaque has been exposed, 0 silk ties are passed around the CCA, ICA, and ECA, with a rubber Rummel tourniquet to the CCA, in preparation for possible shunting. At the first visualization of the CCA, before the real arterial dissection begins, the patient is given an intravenous dose of 5,000 IU heparin, so that intravascular thrombosis does not occur during the period of temporary carotid occlusion. (We do not routinely re-dose heparin, we do not routinely check activated clotting time [ACT] levels, and we never use protamine for heparin reversal.)

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6 Atraumatic vascular clamps are then applied as follows: first on the ICA, then on the CCA, and finally on the ECA. Note that the ICA is occluded first, and never declamped until the repair is complete (unless a shunt is placed). This sequence affords maximal brain protection from embolized plaque or thrombus. An arteriotomy is done and extended into the ICA distal to the plaque using Potts scissors. The proximal end of the plaque is circumferentially separated from the wall of the artery. The plaque is then elevated and carefully separated from the wall of the artery at the origin of the ECA through a wall inversion technique, and the stump is sharply divided. This is followed by a similar, but more delicate feathering technique, for the ICA plaque to prevent flap formation. During cross-clamping, the senior author places a shunt in situations of significant change in the EEG or SSEP or both after cross-clamping. Our threshold is low; we shunt immediately and without hesitation for any perceived monitoring change. Additionally, in our practice, the arteriotomy is always closed with a patch graft, which has reduced our rates of acute postoperative occlusion and longterm restenosis to zero. This is sutured with two limbs, first from distal to proximal on the medial side with the use of a running 6–0 Prolene suture, then two suture lines on the lateral side that meet in the middle and are tied together at their meeting point after backbleeding and evacuation of all air and debris from the lumen. After the final knot is secured, we complete the declamping first by unclamping the ECA, then the CCA, waiting 10 seconds, and finally opening the ICA. In this way any potential residual air or debris passes harmlessly into the ECA circulation, and not to the brain (►Fig. 6.1).

Endovascular Management—Carotid Artery Stenting In the decades since the publications of the asymptomatic carotid stenosis trials, novel technologies in the form of endovascular carotid artery stents have presented other potential treatment options. To date, the merit of open surgical repair as compared to endovascular intervention of carotid artery stenosis continues to be debated, and there is no Level A evidence to recommend carotid stenting in the setting of asymptomatic stenosis. In the SAPPHIRE and CREST trials, approximately half of the patients enrolled had not had cerebral embolic events. The SAPPHIRE trial, released in 2004, stands as the lone exception among the CEA versus CAS trials in favor of carotid stenting. However, it is to be noted that there were a large number of patients treated with carotid stenting outside of the trial, which had the potential to introduce a tremendous selection bias against surgery. The Carotid Revascularization Endarterectomy versus Stenting Trial (CREST), published in 2010, is the largest and most comprehensive randomized control trial to date and with the inclusion of asymptomatic patients, it is one of the best points of data currently to evaluate the indication for carotid stenting in this setting. The results of this trial show

Asymptomatic Extracranial Carotid Artery Stenosis

that in both the asymptomatic and symptomatic carotid stenosis populations, stenting bears a higher risk of perioperative stroke than CEA, while CEA was shown to carry a higher periprocedural cardiac risk (supports algorithm steps 5 and 6). To further address this point, it was identified by patient questionnaire that stroke imparts a more dramatic impact on quality of life than MI. Advocates of carotid stenting, on the other hand, cite continuous rapid advancement in the field of endovascular intervention. These technologies include new distal protection devices and proximal protection systems, for example, the application of suction. Equipoise, if it exists, remains to be demonstrated. As mentioned, these studies are coming in the form of SPACE 2, CREST-2, and ACST-2. With these data in mind, the U.S. Food and Drug Administration has granted approval for carotid stenting in high-risk patients with symptomatic disease only. The CMS draft decision for Medicare reimbursement excludes payment for CAS in asymptomatic patients. The American Heart Association published 2011 guidelines with slightly more liberal application of carotid stenting, with class IIb recommendation that “prophylactic CAS might be considered in highly selected patients with asymptomatic carotid stenosis,” while they note that the effectiveness has not been well established (supports algorithm step 6) (►Fig. 6.2).

Complication Avoidance Outcome CEA complications can be acute or delayed, and can be wound-related, systemic, or neurological. Wound-related complications include hoarseness, nerve injury, hematoma, arterial disintegrity, and infection. Systemic complications are primarily cardiac, including MI. Neurological complications include TIA and stroke. In the hands of experienced surgeons, anesthesiologists, and neurocritical care intensivists, patients undergoing CEA experience a low incidence of complications, with common complications tending to be transient. But despite the rare incidence of devastating complications, their clinical course can evolve rapidly and patients may deteriorate unless there is immediate recognition of untoward events and quick intervention to reverse them. Arterial leak or disruption is, fortunately, an exceedingly rare complication of CEA. (We have actually never experienced an acute arterial leak, nor have we ever had to reexplore a fresh CEA patient for hematoma or airway compromise, and we attribute this good fortune to meticulous hemostasis and assiduous attention to the details of the arterial closure). If there is an acute arterial leak, patients will demonstrate signs of airway compromise such as dyspnea, dysphagia, and also demonstrate symptoms of cerebral ischemia. In a delayed loss of arterial integrity, patients may present days to weeks after a CEA with a pseudoaneurysm. Fevers and cellulitis often present at this time, as the etiology of pseudoaneurysms is often linked to postoperative wound infections. The Texas Heart Institute’s series of 4,991

Fig. 6.1 Asymptomatic severe internal carotid ar tery (ICA) stenosis. Patient is a 68-year-old male with lesion at C2 level (high risk for cervical endarterectomy); therefore, he is considered a good candidate for endovascular carotid stenting and angioplasty. (a) Lateral view of a left CCA angiography demonstrating severe ICA stenosis of more than 85%. (b) Roadmap and lateral view of the proximal protection device (double-balloon guide catheter). Both balloons (common carotid and external carotid) are inflated and the stent is deployed under flow arrest. (c) Intraoperative image of the double-balloon guide catheter. (d) Immediate postoperative angiography demonstrating significant improvement of the cervical stenosis. Patient remained neurologically intact and was discharged the following day. (Images provided courtesy of Leonardo Rangel-Castilla, MD, Mayo Clinic, Rochester, MN.)

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Ischemic Stroke and Vascular Insufficiency

Fig. 6.2 Carotid endarterectomy intraoperative images of a 65-year-old woman with asymptomatic severe internal carotid artery (ICA) stenosis. (a) Once the carotid artery is exposed, the three arteries (common, internal, and external carotid) are clamped and the arteriotomy incision is marked. (b) The arteriotomy is performed and the plaque is removed en bloc. (c) Final result after endarterectomy and artery closure with running (6–0) sutures under the microscope. (Images provided courtesy of Leonardo Rangel-Castilla, MD, Mayo Clinic, Rochester, MN.)

CEAs found that 35% of postoperative pseudoaneurysms could be directly linked to staphylococcus or streptococci wound infections. The arteriotomy site should be examined, and direct repair should be carried out if possible, otherwise other vascular strategies, like bypass of the diseased segment, may be needed. Realistically, in the present era, we would look first at an endovascular strategy as the low-risk option for arterial disruption, with or without infection, when the presentation is delayed. Cerebral ischemia that follows CEA may or may not be symptomatic, but has been reported in approximately 5% of CEA patients. Neurological symptoms in the immediate postoperative period must always be evaluated promptly with imaging of the arterial repair. Minor episodes, such as TIAs, or major stroke, such as hemiparesis, may reflect embolic phenomena from a denuded arteriotomy bed or may signal a complete occlusion of the carotid. In the rare case where a patient shows neurological changes postoperatively, we evaluate the repair immediately with the fastest available method, usually CTA, or if not, duplex ultrasound. Most cases prove to be widely patent repairs, and will resolve spontaneously. For this reason, we do not rush back to surgery without imaging; it is almost never necessary and for the most part the problem resolves on its own. If the vessel is occluded, of course, an immediate exploration and reconstruction is the best option. In our practice, acute occlusion has been essentially eliminated by the use of universal Hemashield patch grafting. This has been confirmed by others. In a series by Sundt et al, patients treated with patch grafts had a 0.8% rate of occlusion versus a 4% rate among patients treated with primary closure, an improved outcome in patients with patch closure. A severe cerebral hyperperfusion state may occur in less than 1 to 3% of CEA patients. The exact etiology is unknown, but chronic ischemia may disrupt the normal autoregulation of cerebral arteries, which may not be able to handle the correction of cerebral blood flow. Several studies have evaluated postoperative cerebral perfusion and found transient elevations in cerebral blood flow of 20 to 40% for several days following CEA. In a hyperperfusion state caused by flow dysregulation, however, cerebral blood flow may increase 100 to 200% above baseline. Typically, these pathologic elevations begin 3 to 4 days following a CEA, but they may even occur up to 1 month from the time of surgery. Patients suffering from hyperperfusion syndrome may show signs of headache, ipsilateral eye pain, face pain, vomiting, confusion, visual disturbances, focal motor seizures, or focal neurological deficits. If hyperperfusion syndrome is suspected, immediate steps should be taken to lower blood pressure to a normal range, usually with labetalol or clonidine. Antihypertensive therapy with strict normotensive goals is necessary for at least 6 months while cerebral autoregulation is reestablished. A CT scan has been recommended as the first-line imaging study of choice, and may demonstrate ipsilateral hemispheric petechial hemorrhages, ipsilateral basal ganglia hemorrhage, and parietooccipital white mater edema, all of which may be indicative of hyperperfusion syndrome. While acute hemorrhagic and ischemic complications are worrisome, the most common issue seen is transient cranial nerve injury, which

occurs with low, but predictable regularity following CEA. In the NASCET trial, cranial nerve injury was found to occur in 8.6% of patients. Studies carried out more recently have demonstrated lower (~5%) rates (supports algorithm step 5). Most nerve deficits will result from traction injury of the hypoglossal nerve or the marginal mandibular branch of the facial nerve. Preoperative nerve evaluation is important, particularly in the case of hypoglossal or recurrent laryngeal nerve palsies contralateral to the proposed CEA. When there are contralateral nerve palsies, we prefer an endovascular strategy to avoid the devastating possibility of a bilateral laryngeal or hypoglossal injury (supports algorithm step 6). Postoperative cranial nerve palsy incidence is best predicted by the length and anatomical difficulty of the CEA. In our practice, as mentioned earlier, we have moved away from fixed retractors to a fish-hook LoneStar retraction system, and this change has markedly reduced our incidence of nerve injury, to almost zero.

Durability and Rate of Recurrence Recurrent carotid stenosis after CEA can occur as a result of neointimal hyperplasia (for stenosis recurring within 24 months of surgery) and from recurrent atherosclerosis (after 24 months). A small but finite incidence of recurrent carotid stenosis can occur after a CEA. Most studies quote a symptomatic recurrence rate of approximately 4 to 5%. In one study of noninvasive follow-up after CEA, a 4.8% recurrence rate of symptomatic carotid restenosis was found, with an additional 6.6% asymptomatic restenosis. Some authors have reported lower numbers with their use of a patch graft repair (1% symptomatic, 4–5% total at 2 years of follow-up) (supports algorithm step 5). Redo CEA can be performed for restenosis, although, in general, it should be regarded as a high-risk procedure, as reoperation can lead to more cranial nerve injuries and local complications. There has also been an increased incidence of stroke reported in patients undergoing redo CEA. We recommend CAS for recurrent symptomatic carotid disease (supports algorithm step 6).

Clinical and Radiographic Follow-up Despite the rigorous clinical trials that have been designed to evaluate the indications and outcomes of CEA and CAS for asymptomatic carotid stenosis, there is a paucity of data on appropriate clinical and radiographic follow-up, and at the time of this publication there are no guidelines for clinicians to follow. We elect to perform an ultrasound on the patient the day after treatment to verify patency and establish a baseline. Thereafter, routine clinical care is provided to the patient, including aforementioned blood pressure control, and the patient will be seen in the outpatient setting. At that time, we typically obtain a repeat Doppler ultrasound at 3 months, and then annually. Once stability has been established over an extended period, surveillance at longer intervals may be appropriate. Termination of surveillance is reasonable when the patient is no longer a candidate for intervention.

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6

Editor Commentary Treatment of asymptomatic carotid stenosis remains in evolution. Better medical care continues to lower the previously established natural history requiring reassessment of our risk–benefit calculations when considering surgical or endovascular intervention. Currently, patients who were previously offered surgery are now being managed medically. However, for high-grade asymptomatic stenosis, the benefit for intervention remains reasonable. Patients with high-grade stenosis with good life expectancy and low surgical risk should be offered surgery, or should be enrolled in prospective clinical trials. Open carotid endarterectomy is the most rigorously studied operation in surgery, and its benefit holds up very well. For a minority of patients, endovascular treatment is reasonable, such as for high riding lesions or lesions secondary to radiation. While some have argued that there are “two good treatments” referring to open and endovascular, there is little question that endarterectomy continues to be the better of the two. Peter Nakaji, MD Barrow Neurological Institute, Phoenix, AZ Asymptomatic patients with high-grade carotid artery stenosis benefit from carotid intervention. CAS and CEA are equally effective and safe in decreasing the stroke risk of carotid artery stenosis. As a neurosurgeon who performs both procedures, I think that they are complementary, and high-risk patients for CEA are good candidates for CAS and vice versa. Our job is to select the appropriate procedure with less risk for that particular patient. Besides the variables discussed in this chapter, I take into consideration patient’s overall medical condition, anatomy of the common, internal, and external carotid artery, aortic arch type, previous neck procedures, and possible side effects of dual-antiplatelet drugs (e.g., history of gastrointestinal bleed). Leonardo Rangel-Castilla, MD Mayo Clinic, Rochester, MN

Asymptomatic Extracranial Carotid Artery Stenosis

Brott TG, Halperin JL, Abbara S, et al; American College of Cardiology Foundation/ American Heart Association Task Force on Practice Guidelines. American Stroke Association. American Association of Neuroscience Nurses. American Association of Neurological Surgeons. American College of Radiology. American Society of Neuroradiology. Congress of Neurological Surgeons. Society of Atherosclerosis Imaging and Prevention. Society for Cardiovascular Angiography and Interventions. Society of Interventional Radiology. Society of NeuroInterventional Surgery. Society for Vascular Medicine. Society for Vascular Surgery. American Academy of Neurology and Society of Cardiovascular Computed Tomography. 2011 ASA/ACCF/AHA/AANN/AANS/ACR/ASNR/CNS/SAIP/ SCAI/SIR/SNIS/SVM/SVS guideline on the management of patients with extracranial carotid and vertebral artery disease. Stroke 2011;42(8):e464–e540 Brott TG, Hobson RW II, Howard G, et al; CREST Investigators. Stenting versus endarterectomy for treatment of carotid-artery stenosis. N Engl J Med 2010;363(1):11–23 The CASANOVA Study Group. Carotid surgery versus medical therapy in asymptomatic carotid stenosis. Stroke 1991;22(10):1229–1235 Duncan JM, Reul GJ, Ott DA, Kincade RC, Davis JW. Outcomes and risk factors in 1,609 carotid endarterectomies. Tex Heart Inst J 2008;35(2):104–110 Endarterectomy for asymptomatic carotid artery stenosis. Executive Committee for the Asymptomatic Carotid Atherosclerosis Study. JAMA 1995;273(18):1421–1428 Gurm HS, Yadav JS, Fayad P, et al; SAPPHIRE Investigators. Long-term results of carotid stenting versus endarterectomy in high-risk patients. N Engl J Med 2008;358(15):1572–1579 Hobson RW II, Weiss DG, Fields WS, et al; The Veterans Affairs Cooperative Study Group. Efficacy of carotid endarterectomy for asymptomatic carotid stenosis. N Engl J Med 1993;328(4):221–227 Loftus CM. Carotid Endarterectomy: Principles and Technique. New York: Informa Healthcare;2007 Loftus CM, Kresowik TF, eds. Carotid Artery Surgery. New York: Thieme Medical Publishers; 2000 Mayo Asymptomatic Carotid Endarterectomy Study Group. Results of a randomized controlled trial of carotid endarterectomy for asymptomatic carotid stenosis. Mayo Clin Proc 1992;67(6):513–518 Sundt TM Jr, Houser OW, Fode NC, Whisnant JP. Correlation of postoperative and two-year follow-up angiography with neurological function in 99 carotid endarterectomies in 86 consecutive patients. Ann Surg. 1986;203(1):90–100

Suggested Reading Barnett HJM, Taylor DW, Haynes RB, et al; North American Symptomatic Carotid Endarterectomy Trial Collaborators. Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. N Engl J Med 1991;325(7):445–453

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7 Symptomatic Extracranial Carotid Artery Stenosis Andrew A. Fanous, Simon Morr, Gursant S. Atwal, Sabareesh K. Natarajan, and Kenneth V. Snyder

Abstract Stroke is the fourth most common cause of death and leading cause of disability in the United States; therefore, treatment of internal carotid artery (ICA) stenosis is of paramount importance. All patients should receive best medical treatment including glycemic control and blood pressure control, smoking cessation, and antiplatelet therapy. Symptomatic patients with ≥50% extracranial ICA stenosis should be considered for intervention. In asymptomatic patients with ICA stenosis, intervention should be reserved for those harboring ≥70% stenosis. Carotid revascularization in symptomatic patients should not be delayed and should be viewed as an urgent procedure. Early revascularization has been shown to prevent more strokes than delaying the procedure until it can be performed with negligible risks. The choice of revascularization treatment in patients with extracranial ICA stenosis has been a topic of debate. Carotid endarterectomy should be avoided in patients considered high risk for open surgical intervention and in those high risk for undergoing anesthesia. Carotid artery stenting (CAS) should be avoided in severe ICA tortuosity, concentric calcifications, carotid pseudoocclusion, and difficult distal landing zone for distal protection devices. Proximal protection devices such as balloon guide catheters and flow-reversal devices occlude forward flow from the heart and common carotid artery creating a gradient that reverses flow away from the ICA toward the bifurcations. The Safety and Efficacy Study for Reverse Flow Used During Carotid Artery Stenting Procedure (ROADSTER) multicenter trial of transcarotid stenting has the lowest stroke risk of any CAS trials reported to date. Hyperperfusion syndrome is a well-recognized phenomenon following CAS, caused by altered cerebral autoregulation secondary to long-standing stenosis. In order to prevent this complication, it is important to maintain relative hypotension in the immediate period following CAS.

medical management, depends on the patient’s overall health and the existence of comorbidities. Symptomatic patients with ≥50% extracranial carotid artery stenosis should be considered for intervention (1 in algorithm). According to the North American Symptomatic Carotid Endarterectomy Trial (NASCET), CEA in these patients reduces the 2-year risk of stroke from 26 to 9% when compared to best medical management (1 in algorithm). Similarly, the European Carotid Surgery Trial (ECST) reported a stroke-risk reduction from 27 to 15% in patients with ≥80% symptomatic carotid disease following CEA compared to the best medical management (1 in algorithm). Very few strokes involve patients with previously asymptomatic carotid disease. Therefore, the degree of carotid stenosis in this patient population must be higher than that in symptomatic patients for the treatment to be warranted and beneficial. Thus, in asymptomatic patients with carotid occlusive disease, intervention should be reserved for those harboring ≥70% stenosis. In these patients, the Asymptomatic Carotid Atherosclerosis Study (ACAS) and the Asymptomatic Carotid Surgery Trial (ACST) demonstrated a 5-year reduction in stroke risk from 11 to 6% following CEA compared to the best medical management. Age has been a point of contention in the treatment of patients with extracranial carotid disease. Patients older than 70 years were shown to have a significantly higher risk of stroke or death following CAS compared to younger patients. However, we maintain that age is not a risk factor for CAS and that the higher risk of complications in older patients is a product of this population’s anatomical features, rather than age itself. As discussed later, unfavorable anatomical features for stenting are more prevalent in older patients. Therefore, patients should be stratified for treatment based on their anatomical high-risk features rather than their age (2, 3 in algorithm).

Keywords: transient ischemic attack, stroke, carotid artery disease, carotid artery stenosis, CREST, carotid endarterectomy, carotid artery stenting, angioplasty, ROADSTER, SAPPHIRE

Conservative Management

Stenosis at the bifurcation of the carotid artery is the most common site of stenosis among all blood vessels supplying the brain. Extracranial carotid artery stenosis is responsible for up to one-third of all strokes, amounting to 750,000 strokes per year in the United States. These strokes are most commonly the result of atherosclerotic emboli from plaque rupture rather than from vessel occlusion. The risk of stroke is proportional to the degree of ipsilateral internal carotid artery (ICA) stenosis. Although the management of carotid artery disease has been investigated in many clinical trials, it remains a topic of strong contention between various medical and surgical practitioners. Major controversies in decision making addressed in this chapter include: 1. Whether or not treatment is indicated. 2. Endarterectomy versus stenting for symptomatic carotid artery stenosis. 3. Complications, outcome, and durability of the treatment. 4. Current trials and controversies in management.

Treatment of extracranial ICA stenosis, either via open or endovascular means, is beneficial only under the condition that surgical complication rates are kept below a certain threshold. For instance, the superiority of CEA in the NASCET trial assumes a 30-day risk of perioperative complications (stroke, myocardial infarction, or death) of ≤6%. In the ACAS trial, this superiority assumes an even lower perioperative complications risk of ≤3%. At centers where such rates are higher, conservative management should be considered until patients are referred to facilities with more expertise and acceptable complication risks. Current medical management comprises the use of statins, antiplatelet agents, and blood pressure control. Such conservative medical therapy is a reasonable treatment choice, particularly in patients with asymptomatic carotid disease. In fact, studies have demonstrated a progressive and sustained decrease in stroke rates in asymptomatic patients with carotid disease treated conservatively over the past 30 years. Currently, in asymptomatic patients with ≥50% carotid artery stenosis treated with best medical therapy, the average annual rate of any ipsilateral ischemic stroke is less than 0.5% and the average annual rate of any ipsilateral transient ischemic attack (TIA) is less than 2%. For symptomatic patients who have less than 50% stenosis, best medical treatment alone is indicated (4 in algorithm).

Whether to Treat

Timing of Treatment

Because stroke is the fourth most common cause of death and the leading cause of disability in the United States, treatment of carotid artery stenosis is of paramount importance. However, the decision to treat relies profoundly on the degree of stenosis and the presence of symptomatology. Furthermore, the choice of treatment, whether by open carotid endarterectomy (CEA), endovascular carotid artery stenting (CAS), or

Following an initial ischemic event, the risk of stroke is 1 to 2% in the first 7 days and 2 to 4% in the first 30 days. Therefore, carotid revascularization in symptomatic patients should not be delayed and should be viewed as an urgent procedure. For these patients, delaying treatment significantly reduces the treatment benefit, even though performing CEA or CAS in an urgent fashion may increase the periprocedural risks of

Introduction

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7 Symptomatic Extracranial Carotid Artery Stenosis

Algorithm 7.1 Decision-making algorithm for symptomatic extracranial carotid artery stenosis.

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Ischemic Stroke and Vascular Insufficiency complication. Early revascularization has been shown to prevent more strokes than delaying the procedure until it can be performed with negligible risks.

Anatomical Considerations Throughout the development of the CAS procedure, several anatomical features have been recognized as high risk for stenting. Such features include carotid artery tortuosity, difficult distal landing zone for the deployment of distal protection devices, concentric calcification, carotid pseudoocclusion, aortic arch type III, and difficult peripheral femoral access. Such features considerably increase the technical difficulty and duration of the CAS procedure, thus putting patients at increased risk. CAS should be avoided in such patients (2, 5 in algorithm). A new scoring system known as the Buffalo Risk Assessment Scale (BRASS) has been developed to predict the safety of performing CAS in symptomatic patients with carotid artery disease with such unfavorable anatomy. Conversely, CEA should be avoided in patients with anatomical high-risk features for surgery, including tandem stenosis and surgically inaccessible high or low cervical lesions. Endovascular treatment of ICA stenosis is a more suitable option for these patients (2, 6 in algorithm) (►Fig. 7.1).

Workup Clinical Evaluation The carotid arteries supply most of the cerebral hemispheres and are responsible for providing oxygenated blood to areas of the brain that control strength, sensation, and speech, among other functions. Thus, strokes or TIAs involving the carotid arteries are expected to produce

Fig 7.1 A 56-year-old woman who presented with recurrent left side weakness secondary to internal carotid artery (ICA) stenosis. (a) Diffusion-weighted imaging demonstrated right hemisphere acute ischemic strokes (arrows). (b) Digital substraction angiography (DSA) lateral cervical view demonstrating severe stenosis of the right ICA. (c) DSA intracranial view of the right common carotid artery injection demonstrating slow and diminished intracranial blood flow. (d–f) Stenting and balloon angioplasty with proximal protection. (d) Road map angiography showing a dual-balloon guide catheter (one balloon at the proximal external carotid artery and the other balloon at the common carotid artery) causing complete flow arrest and stent being deployed. (e) Balloon angioplasty after stent deployment. (f) Post-stenting DSA lateral cervical view demonstrating significant improvement of the stenosis. (g) Post-stenting DSA intracranial view of the right common carotid artery injection demonstrating significant improvement on intracranial blood flow; branches of the middle and anterior cerebral artery are now visible. (Images provided courtesy of Leonardo Rangel-Castilla, MD, Mayo Clinic, Rochester, MN.)

symptoms such as contralateral weakness, contralateral numbness, inability to produce speech, or lack of speech understanding. Another symptom is amaurosis fugax, which is caused by embolization into the ophthalmic artery. The presentation of such symptoms in an acute setting in any patient should prompt an emergent workup for stroke, including a detailed history focused on the time of symptom onset and the presence of renal disease, a thorough physical examination to document a National Institute of Health Stroke Scale (NIHSS) score, as well as diagnostic imaging (including diffusion-weighted magnetic resonance imaging [MRI] [►Fig. 7.2]; and computed tomographic [CT] perfusion imaging studies [►Fig. 7.1]).

Imaging Doppler ultrasonography is the most common screening tool for diagnosing carotid artery stenosis in a nonemergent setting, usually in asymptomatic patients. In patients with significant stenosis, Doppler ultrasonography demonstrates elevated blood flow velocities within the arterial lumen. The most common imaging modalities for the diagnosis of carotid stenosis in an emergent setting, typically in symptomatic patients who present with stroke or TIA, are CT angiograms and CT perfusion studies. Digital subtraction angiography (DSA) is the gold standard imaging modality for patients with carotid disease and the most accurate tool for calculating the degree of carotid artery stenosis. Because atherosclerosis is a systemic disease (►Figs. 7.1 and 7.2), DSA should include studies of the bilateral carotid systems as well as both vertebral arteries. MRI can be useful in the diagnosis of carotid artery disease in patients with symptoms of stroke or TIAs. MRI can help determine whether a certain carotid plaque presents features of intraplaque hemorrhage, inflammation, large lipid core, and/or ulcerations. Such features are usually associated with a high risk of embolization. Undoubtedly, MRI provides more information regarding the nature and morphology of the carotid plaque than Doppler ultrasonography. However, the latter

Fig. 7.2 An 82-year-old man with a previous history of an anterior cervical discectomy and fusion presented with the acute onset of word-finding difficulty. CT perfusion imaging (a) demonstrated mildly increased time to peak on the left side. CT angiography (b) showed a soft plaque in the left carotid bifurcation that extended to the C2 level. The patient subsequently underwent a diagnostic cerebral angiogram (c) which confirmed the level of the carotid bifurcation at C2. Given the patient’s previous anterior cervical discectomy and fusion and his high risk for CEA because of the high level of the bifurcation, a decision was made to proceed with CAS for symptomatic carotid stenosis with high-risk features. The patient underwent balloon angioplasty followed by stenting of the left carotid artery (d). (e) The final result in lateral (left) and anteroposterior (right) views showed resolution of the stenosis and patency of the left carotid artery with restoration of normal blood flow.

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7 Symptomatic Extracranial Carotid Artery Stenosis is much quicker and considerably less costly, making the use of MRI an uncommon practice as a diagnostic modality in patients who are evaluated for carotid revascularization.

Treatment The choice of revascularization treatment in patients with extracranial ICA stenosis has been a topic of debate since the advent of endovascular techniques in the second half of the 20th century. CEA should be avoided in patients considered high risk for open surgical intervention and in those at high risk for undergoing anesthesia, such as individuals with significant cardiac and/or pulmonary comorbidities (6 in algorithm). CEA should also be avoided in patients with contralateral carotid artery occlusion, contralateral recurrent laryngeal palsy, and in those with anatomical high-risk features for surgery as discussed earlier in the Anatomical Considerations section (6 in algorithm). Furthermore, CEA should be avoided in patients with previous ipsilateral CEA, radical neck dissection, or radiation to the neck. In such patients, the atherosclerotic plaque tends to be more fibrous and less prone to embolize. Such patients are also at higher risk than average individuals for cranial nerve injury. For these patients, endovascular treatment is certainly more suitable (6 in algorithm). Conversely, CAS should be avoided in patients with anatomical high-risk features for stenting as discussed earlier in the Anatomical Considerations section. Furthermore, patients who cannot tolerate dual-antiplatelet therapy, such as patients at high risk for or with recent intracranial or gastrointestinal hemorrhage, should not undergo CAS (5 in algorithm).

Cerebrovascular Management—Operative Nuances The technique for CEA varies among different centers. In general, CEA is performed under general anesthesia. Neuromonitoring (electroencephalography and/or cranial nerve monitoring) is almost always used. Patients who present electively for the procedure are usually placed on aspirin (81 mg daily) 4 days prior to surgery and for 6 weeks thereafter. Patients who present on an emergent basis for the procedure are given a loading dose of aspirin (325 mg). Certain centers also elect to place patients undergoing CEA on clopidogrel bisulfate (75 mg daily) 4 days before and for 6 weeks after surgery or administer a loading dose (300 mg) of the drug in emergent cases. However, this is not a common practice for all surgeons. The patient is positioned supine on the operating table, with the head turned approximately 30 degrees toward the contralateral side with the neck slightly extended. A transverse incision is performed approximately 4 cm below the mandible but may vary slightly depending on the level of the carotid bifurcation. The dissection is carried downward medial to the anterior border of the sternocleidomastoid muscle until the carotid sheath is encountered. Dissection continues between the internal jugular vein and the common carotid artery (CCA) and rostrally along the CCA past the bifurcation until the external carotid artery (ECA) and the superior thyroid artery are clearly identified. The ICA is also identified and dissected circumferentially. The patient is given 5,000 units of heparin a few minutes prior to clamping of the carotid artery. Temporary clamps or aneurysm clips are subsequently used to occlude the superior thyroid artery, ICA, CCA, and ECA, in that particular order. Arteriotomy is performed in the CCA with a no. 11 blade and subsequently carried with Potts scissors distally into the ICA, past the most distal edge of the plaque. Persistent backbleeding at this point is almost always caused by an ascending pharyngeal artery with an aberrant location, which must be identified and occluded. The plaque is first transected proximally at the proximal-most end of the CCA arteriotomy, then at the ECA. The plaque is then carefully dissected distally at the ICA. The lumen is subsequently flooded with heparinized saline solution to float and remove any remaining debris. The arteriotomy is then closed with a running monofilament 5–0 or 6–0 suture. Immediately prior to completion of the arteriotomy closure, the ICA clamp is opened temporarily for

approximately 10 seconds to allow for backbleeding and further flushing out of any debris. The clamp is then reapplied and the arteriotomy closure is completed. The ECA and CCA clamps are subsequently removed to allow for flushing of any debris into the external circulation. The ICA clamp is removed last. After ensuring absolute hemostasis, the wound is irrigated with copious antibiotic irrigation before the platysma, subcutaneous tissue, and skin are closed.

Endovascular Management—Operative Nuances Carotid artery stenting is the mainstay of endovascular treatment. Stents are available in balloon-expandable and self-expanding varieties, although the use of the former has fallen out of favor and is currently an uncommon practice. Given the difference in diameter between the CCA and the ICA and the irregular bends commonly seen in this region, self-expanding stents are well suited for conforming to lesions of the carotid bifurcation. Self-expanding stents have a predetermined springlike force that is compressed by a sheath in the manufactured form. After insertion into the carotid bifurcation, the stent is held in place and the sheath is removed, thus allowing for expansion of the stent by removal of the compressive external force (►Fig. 7.2). The expansile force is determined by the various inherent material and structural qualities of the stent. The most common alloys used in the manufacturing of carotid stents are nickel-titanium, commonly known as nitinol, and cobalt-chromium. Carotid stents are either open-or closed-cell, depending on the amount of space between the thin metal meshworks comprising the stent. Open-cell stents allow for larger uncovered gaps and are usually more malleable, thus preferred by many for tortuous vasculature and for complex and angulated lesions. Closed-cell stents are stiffer and require greater manipulation to deploy. They offer more complete surface coverage and are preferred in straight, noncomplex lesions. The choice of stent does not appear to affect outcome in patients undergoing CAS. Although certain authors have suggested that open-cell stents may be associated with higher rates of CAS complications, particularly in symptomatic patients and in those with echolucent plaques, large series have failed to confirm this relationship. Newer stent technologies have introduced regional stent diameter variability along the length of the stent, referred to as “hybrid” stent technology. Though these stents can be designed with an abrupt change in diameter, tapered options are also available. Given that the CCA is in most cases substantially larger than the ICA, a built-in, gradual decrease in diameter is available. Studies are inconclusive regarding the benefits of hybrid stents. Hybrid stents are also available that allow for a combination of open- and closed-cell constructs. The most dreaded complications associated with CAS relate to distal perioperative plaque embolization. Understandably, the use of embolic protection devices is currently mandatory in all patients undergoing CAS. Three categories of embolization protection devices predominate on the market, namely, distal nonocclusive systems, distal occlusive systems (►Fig. 7.1), and proximal protection devices (►Fig. 7.2) that establish flow reversal. Distal nonocclusive devices are intended to prevent distal embolization while preserving distal flow. Distal occlusive devices provide complete flow arrest to the brain, thus resembling clamping techniques in CEA. Proximal protection devices (►Fig. 7.2), also known as flow-reversal devices, occlude forward flow from the heart through the CCA proximal to the carotid bifurcation while simultaneously occluding the ECA. This preferentially creates a gradient that reverses flow away from the ICA toward the bifurcation. The advantage of proximal protection is that it avoids crossing an unprotected lesion. CAS is usually performed under mild sedation to permit continuous assessment of the patient’s neurological status during the procedure. Heparin, with an activated coagulation time goal of >250 seconds, is infused throughout the procedure. In patients who undergo CAS electively, a dual-antiplatelet regimen is started 5 to 7 days prior to the

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Ischemic Stroke and Vascular Insufficiency procedure. In patients undergoing revascularization in an acute setting, a loading dose of clopidogrel (600 mg) is administered. The technique for CAS consists of three major portions: access, guide catheter (shuttle) placement, and stent delivery. The most commonly cannulated artery for access is the common femoral artery; an 8 French (8F) sheath accommodates most of the guiding (shuttle) catheter except for certain balloon guide catheters that require a 9F sheath. The choice of the shuttle depends on the surgeon’s preference. The shuttle is advanced to the CCA, just proximal to the bifurcation. A distal or proximal protection device is subsequently deployed, as previously discussed. The final stage of the procedure is stent deployment, and the proximal end of the stent is usually placed in the distal CCA, while the distal end is positioned in the proximal ICA. In rare cases where the clot burden is extensive, multiple stents are stacked in a telescopic fashion. If there is sufficient concern for in-stent thrombus following stent deployment, an intravascular ultrasound (IVUS) device can be used to visualize the internal lumen of the stent. Following completion of the procedure, all protection devices, stent deployment catheters, and sheaths are withdrawn. The groin access site is then closed with a closure device or the use of direct pressure.

Outcome and Evidence-Based Decision Making

During dissection of the carotid sheath, care must be taken to avoid injury to the hypoglossal nerve, which is occasionally adherent to the posterior wall of the common facial vein. Also, when jugular chain lymph nodes are encountered, the best practice is to perform the dissection medial to them and retract them laterally, along with the internal jugular vein. Care must be taken to identify and avoid injury to the vagus nerve, which runs between the jugular vein and the carotid artery.

Many clinical trials have compared CEA to CAS, yielding various results. In 2001, the Carotid and Vertebral Transluminal Angioplasty Study (CAVATAS) demonstrated no significant difference between the two procedures with regard to the risk of perioperative complications and during a 3-year follow-up period. In 2004, the Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy (SAPPHIRE) trial demonstrated the noninferiority of CAS in comparison to CEA in highrisk surgical patients (supports algorithm steps 5 and 6). In 2006, the Endarterectomy vs. Stenting in Patients with Symptomatic Severe Carotid Stenosis (EVA-3S) trial was prematurely terminated because of concerns regarding the high incidence of complications in the stenting arm. In the same year, the Stent-supported Percutaneous Angioplasty of the Carotid artery vs. Endarterectomy (SPACE) was also terminated early for similar reasons. Similarly, in 2010, the International Carotid Stenting Study (ICSS) failed to demonstrate the noninferiority of CAS compared to CEA. The lack of required use of embolic devices in these three trials was cited as the main criticism for their design and results. The Carotid Revascularization Endarterectomy vs. Stenting Trial (CREST), published in 2010, is the largest study to date comparing CEA to CAS. It comprised both symptomatic and asymptomatic patients with ICA stenosis who were randomly assigned to one of the two interventions. Unlike the case of the three aforementioned trials, CREST comprised a requirement of using embolic protection devices in all patients undergoing CAS. CREST reported no significant difference in all complications between CAS and CEA, neither during the perioperative period nor at the 4-year follow-up point. Nevertheless, minor strokes were more common after CAS, whereas myocardial infarction and cranial nerve injury were more common after CEA (supports algorithm steps 5 and 6).

Carotid Artery Stenting/Angioplasty

Clinical and Radiographic Follow-up

During femoral artery access, the puncture should be below the level of the inguinal ligament. A puncture above that level risks injuring the external iliac artery, which places the patient at risk for retroperitoneal hematoma when the sheath is removed. Conversely, a very low puncture risks cannulating the superficial femoral artery or the profunda femoral artery, which can result in the formation of a pseudoaneurysm or an arteriovenous fistula. Navigating a guide catheter through a type III or bovine arch or a very tortuous CCA can be difficult. An intermediate sliding catheter such as a VTK (Cook) and an exchange 0.038 Glidewire can overcome this technical difficulty. When crossing the lesion (carotid stenosis) with the distal wire for filter deployment, a well-controlled and delicate maneuver should be performed to avoid plaque rupture and debris embolization. The filter should be deployed in a straight segment of the ICA, usually at the level of C1, to prevent filter motion and potential artery vasospasm. If vasospasm occurs, it usually responds to 10 to 20 mg of verapamil slow infusion. The differential diagnosis between vasospasm and arterial dissection has to be made. After the stent is deployed, the filter capture device can get caught at the proximal end of the stent, slightly pull/ push on the wire or ask the patient to rotate the head: one of these two maneuvers will let the capture device pass through the stent. After completing the stenting procedure, perform intracranial angiography to rule out any intracranial vessel occlusion as a consequence of the procedure. Hyperperfusion syndrome is a well-recognized phenomenon following CEA or CAS. It is thought to be caused by altered cerebral autoregulation secondary to long-standing stenosis. Risk factors for hyperperfusion include hypertension and severe contralateral stenosis. In order to prevent this complication, it is important to maintain relative hypotension in the immediate period following the procedure. A systolic blood pressure of less than 120 mm Hg is recommended for the first 24 hours following the procedure.

In patients who undergo CAS, immediate radiographic follow-up can be achieved with the help of IVUS. The use of IVUS immediately after stent deployment has been a major advancement in the prevention of procedure-associated thromboembolism. In that respect, IVUS is used to ensure the absence of any residual stenosis or intrastent thrombosis following stent deployment. This allows for real-time intervention before termination of the procedure. This technology is of particular practicality in cases of flow reversal, wherein antegrade angiographic runs cannot be performed until the flow reversal is discontinued. The follow-up algorithm for patients who undergo either CEA or CAS is identical. In addition to monitoring the patient clinically, Doppler ultrasound is performed at 1, 6, and 12 months following the procedure. As long as the patient remains asymptomatic relative to the treated carotid artery and provided the Doppler velocities remain reasonably slow, the follow-up examination is then extended to yearly Doppler ultrasonography on an indefinite basis.

Complication Avoidance Carotid Endarterectomy

Expert Commentary CREST has shown that CAS and CEA could be equally effective and safe in decreasing stroke risk for atherosclerotic carotid diseases. It has improved the ability to offer CAS in patients without high risk for CEA, as private insurance companies now reimburse CAS in patients without high risk for CEA. CEA and CAS are complementary. Individuals who are high risk for CAS technique are likely good candidates for CEA. One of the most common reasons for increased risk of CAS is aortic arch disease, manipulation through type III aortic arches and aortic ostial disease. Transradial/transbrachial approaches to the right carotid circulation or to the left carotid circulation in bovine arch types bypass the aortic arch/ostia and could significantly decrease the risk of CAS in these patients. Patients with a left carotid disease with a nonbovine origin with arch/ostial disease may benefit from direct transcarotid stent-

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7 Symptomatic Extracranial Carotid Artery Stenosis ing with proximal protection and flow reversal to bypass the arch. The ROADSTER transcarotid stenting trial has the lowest stroke risk of any CAS trials reported to date. The minor stroke rate was higher with CAS patients in the CREST trial and the majority of these happened within 24 hours of CAS. This could be due to inadequacy of stent scaffolding with plaque protrusion through the stent tines. Preplasty with proximal or distal protection avoids stent expansion against a narrow lumen and may decrease the chances of plaque protrusion. An oversized closed-cell stent decreases the stent porosity and improves its ability to trap the plaque. Plaque protrusion could be visualized with an IVUS. We use IVUS after every CAS for symptomatic disease, especially in cases performed with proximal protection and flow reversal before flow restoration. New stent technology that uses much smaller cell sizes to try and trap active or hot plaques such as the Roadsaver stent is currently in trial and shows great promise. Although these stents may do a very good job of limiting plaque protrusion, they act as flow diverters because of their low porosity and may cause endoleak directing flow along the outside of the stent if wall apposition is not perfect. The ongoing CONFIDENCE trial testing the Roadsaver stent may shed light on this topic. Kenneth V. Snyder, MD, PhD University at Buffalo, Buffalo, NY

Editor Commentary Approximately 20% of strokes are related to extracranial atherosclerotic disease. Early trials have found better outcomes after CEA compared with best medical therapy. Recent randomized trials comparing CEA with CAS for symptomatic carotid stenosis found that CEA was associated with higher rates of myocardial infarction, access site hematoma, and cranial nerve palsy but less risk of stroke. Preliminary evidence demonstrated no significant differences in terms of overall composite primary outcomes. CREST evaluated patients with severe carotid stenosis and demonstrated no significant differences between CAS and CEA in the 4-year rates of stroke, myocardial infarction, or death. Rates of myocardial infarction were higher in patients who underwent CEA, and higher rates of stroke in patients receiving CAS. The ICSS found no differences in fatal or disabling stroke or overall functional outcomes. The 10-year outcomes of CREST were reported; there was no significant difference in the rate of the primary composite outcome of stroke, myocardial infarction, or death between the CAS group (11.8%) and the CEA cohort (9.9%). On long-term follow-up, there were again slightly higher rates of stroke in stented patients, but this did not reach statistical significance. We have to realize that in CREST and ACT surgeons required stringent certification for investigators. In the real-world setting outside of randomized trials, complication rates might be higher. Aside from

symptomatic status, further stratification by disease and patient characteristics may allow improved outcomes. CREST-2 will assess this further through determination of outcomes based on optimal therapeutic strategies by each enrolling institution. Additional trials may identify specific patient or disease characteristics that make one treatment more beneficial over another for specific patients and may allow further decreases in complications. We are anxiously awaiting the results of current trials including Stent-Protected Angioplasty in Asymptomatic Carotid Artery Stenosis Versus Endarterectomy, and ACT-2 and the ECST-2, which we hope can clarify the optimal treatment in select patients. Leonardo Rangel-Castilla, MD Mayo Clinic, Rochester, MN

Suggested Reading Bersin RM, Stabile E, Ansel GM, et al. A meta-analysis of proximal occlusion device outcomes in carotid artery stenting. Catheter Cardiovasc Interv 2012;80(7):1072–1078 Brott TG, Howard G, Roubin GS, et al; CREST Investigators. Long-term results of stenting versus endarterectomy for carotid-artery stenosis. N Engl J Med 2016;374(11):1021–1031 Eckstein HH, Kühnl A, Dörfler A, Kopp IB, Lawall H, Ringleb PA; Multidisciplinary German-Austrian Guideline Based on Evidence and Consensus. The diagnosis, treatment and follow-up of extracranial carotid stenosis. Dtsch Arztebl Int 2013;110(27-28):468–476 Eller JL, Dumont TM, Sorkin GC, et al. Endovascular advances for extracranial carotid stenosis. Neurosurgery 2014;74(Suppl 1):S92–S101 Fanous AA, Natarajan SK, Jowdy PK, et al. High-risk factors in symptomatic patients undergoing carotid artery stenting with distal protection: Buffalo Risk Assessment Scale (BRASS). Neurosurgery 2015;77(4):531–542, discussion 542–543 Harbaugh RE, Patel A. Surgical advances for extracranial carotid stenosis. Neurosurgery 2014;74(Suppl 1):S83–S91 Kwolek CJ, Jaff MR, Leal JI, et al. Results of the ROADSTER multicenter trial of transcarotid stenting with dynamic flow reversal. J Vasc Surg 2015;62(5):1227–1234 Montorsi P, Galli S, Ravagnani PM, et al. Carotid artery stenting with proximal embolic protection via a transradial or transbrachial approach: pushing the boundaries of the technique while maintaining safety and efficacy. J Endovasc Ther 2016;23(4):549–560 Morr S, Lin N, Siddiqui AH. Carotid artery stenting: current and emerging options. Med Devices (Auckl) 2014;7:343–355 Nerla R, Castriota F, Micari A, et al. Carotid artery stenting with a new-generation double-mesh stent in three high-volume Italian centres: clinical results of a multidisciplinary approach. EuroIntervention 2016;12(5):e677–e683 Setacci C, Argenteri A, Cremonesi A, et al; Italian Society for Vascular and Endovascular Surgery. Guidelines on the diagnosis and treatment of extracranial carotid artery stenosis from the Italian Society for Vascular and Endovascular Surgery. J Cardiovasc Surg (Torino) 2014;55(1):119–131 White CJ. Carotid artery stenting. J Am Coll Cardiol 2014;64(7):722–731

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8 Vertebrobasilar Stenosis and Insufficiency C. Benjamin Newman, Christian N. Ramsey, III, Curtis A. Given, II, and Gary B. Rajah

Abstract Symptomatic basilar and vertebral artery stenosis is a particularly morbid disease with an extremely poor natural history. Posterior circulation ischemia (PCI) accounts for 25 to 30% of all ischemic infarctions. Symptoms of vertebrobasilar insufficiency (VBI) can be nonspecific or nonfocal and diagnosis could be difficult to make. PCI symptoms or VBI should undergo a complete stroke workup, including MRI of the brain and CTA of the neck and head. Diagnostic cerebral angiography should also be obtained to document the degree and location of the stenosis, collateral circulation, and proximal endovascular access if an intervention is planned. The first line of treatment is optimal medical therapy including antiplatelet agents. Additional treatments should be considered if medical management fails as documented with progressive clinical strokes, silent ischemia, or hemodynamic failures. Endovascular submaximal balloon angioplasty (SBA) consists of progressive dilation of the intracranial stenosis with a semicompliant intracranial balloon. If the intracranial stenosis is recurrent, one should consider intracranial stenting. SBA is a relatively safe procedure; however, it is not free from complications that usually occur secondary to a poor understanding of the lesion anatomy, technical mishaps during navigation of the lesion or during angioplasty, inadequate platelet aggregation or anticoagulation, or residual flow issues due to stenosis or dissection. Bypass revascularization is not a common practice for VBI and it is limited to tertiary centers. These strategies should not be ignored and should take a very specialized location within the overall algorithm of VBI treatment. Keywords: stroke, vertebral artery, basilar artery, submaximal angioplasty, intracranial stenting

Introduction Intracranial atherosclerotic disease (ICAD) of the major intracranial arteries (carotid, middle cerebral, vertebral, or basilar) is a major cause of stroke and is associated with a high risk of recurrent stroke. The Comparison of Warfarin and Aspirin for Symptomatic Intracranial Arterial Stenosis (WASID) trial demonstrated that symptomatic intracranial basilar or vertebral artery (VA) stenosis is a particularly morbid disease with an extremely poor natural history. The Stenting versus Aggressive Medical Therapy for Intracranial arterial Stenosis (SAMMPRIS) and other randomized controlled trials have demonstrated that the first line of treatment for severe, symptomatic intracranial stenosis is medical treatment with antiplatelet agents; however, in select patients who fail medical therapy and have progressive transient ischemic attacks (TIAs) or stroke, there is a role for endovascular management with angioplasty and/or intracranial stenting. Major controversies in decision making addressed in this chapter include: 1. Whether treatment is indicated or not in vertebrobasilar stenosis. 2. Drug selection and dosing regimens for medical treatment of intracranial vertebrobasilar stenosis. 3. Medical versus interventional treatment for intracranial vertebrobasilar stenosis. 4. Technical nuances for intracranial angioplasty and stenting. 5. Role of cerebrovascular surgery or bypass procedures for vertebrobasilar insufficiency (VBI).

Whether to Treat In all patients with symptomatic stenosis of ≥70% of the vertebral and/ or basilar arteries therapy should be instituted (1, 2 in algorithm). Therapy includes general cardiovascular risk reduction including weight loss, exercise, antihypertensive therapies, smoking cessation, strict diabetic control (if present), and high-dose statin therapy. Patients should also receive treatment with dual-antiplatelet therapy.

Endovascular treatment with intracranial angioplasty and stenting should be considered in patients who fail conservative management. Patients with a documented infarction in the vascular territory served by a severely stenotic vessel while on dual-antiplatelet therapy have a 35% stroke risk at 2 years (3, 4, 6, 7 in algorithm). Patients with vulnerable plaques and/or poor collateral circulation are also considered to be in this high-risk category. Recently, using quantitative magnetic resonance angiography (MRA) evaluation of distal flow in vertebrobasilar disease, Amin-Hanjani et al found patients with greater than 20% reduction in distal flow from normal values had 70 and 78% event-free survival rates at 12 and 24 months compared with patients with preserved distal flow whose event-free rates were 96 and 87%, respectively. Thus, in patients who have been quoted as failed conservative management, the reported periprocedural morbidity and mortality of an intracranial stent, and/or angioplasty may be justified (3, 4, 6, 7 in algorithm).

Conservative Treatment Current evidence supports the use of aspirin and clopidogrel (Plavix). A typical regimen for initiating therapy would be a 650-mg loading dose of aspirin and 300-mg loading dose of clopidogrel, followed by aspirin 325 mg and clopidogrel 75 mg daily (1, 2 in algorithm). Clopidogrel is a prodrug that is absorbed through the intestine and relies on conversion to an active metabolite via enzymes in the cytochrome P450 pathway. Clopidogrel irreversibly binds the platelet P2Y12 receptor, inhibiting ADP-mediated platelet activation and aggregation. The pharmacological response to clopidogrel is variable, with 20 to 40% of patients being classified as nonresponders because of low inhibition of ADP-induced platelet activation. This is believed to be due to polymorphisms in the CYP2C19 and CYP2C9 protein-coding genes. The VerifyNow P2Y12 assay (Accumetrics Inc., San Diego, CA) is one test established to theoretically access the adequacy of platelet inhibition by clopidogrel. The VerifyNow assay is a point-of-care device that measures platelet aggregation as a function of light absorbance. This assay has been shown to be equivalent to other methods for assessing inhibition of platelet aggregation. Glycoprotein IIb/IIIa inhibitors tirofiban (Aggrastat) or eptifibatide (Integrilin) will yield abnormal and unreliable VerifyNow results for 2 days following administration and abciximab (ReoPro) will adversely affect the assay for 2 weeks. Patients with some inherited platelet disorders (e.g., von Willebrand factor deficiency) will not yield reliable test results as well. Prasugrel (Effient) is a newer third-generation thienopyridine-like clopidogrel that does not rely on hepatic prodrug activation. Ticagrelor (Brilinta) is a different class Cyto-pentyl-triazolopyrimidine that in contrast to the thienopyridines reversibly inhibits the P2Y12 component of ADP receptor with similar effects on platelet inhibition. It is important to consider that no data currently support the safety or efficacy of prasugrel for the treatment of intracranial stenosis and its use carries a technical contraindication in patients with history of stroke. Additionally, there are case reports that suggest there may be an increased risk of hemorrhagic complications with the use of prasugrel and aspirin in neurointerventional procedures, but that does not reflect the authors’ current experience.

Anatomical Considerations The VA originates from the first segment of the subclavian arteries, and in about 4% of people they will come off of the aortic arch. The VA has four different segments (►Fig. 8.1). The most common site of stenosis is at the VA ostium (see Chapter 9); however, plaque formation and stenosis can occur at any level of the posterior circulation. VAs

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8  Vertebrobasilar Stenosis and Insufficiency

Algorithm 8.1 Decision-making algorithm for vertebrobasilar stenosis and insufficiency.

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Isc e ic Stro e and Vascular Insufficiency can end in posterior inferior cerebellar artery (PICA) and contribute little or nothing to the contralateral side or basilar artery. This configuration rests the entirety of the basilar artery perfusion on one VA if no PCoAs are present. The basilar and V4 vertebral segments can become extremely tortuous especially in the setting of long-standing hypertension; this only adds to the difficulty of endovascular treatment. The basilar artery is not an uncommon place for fenestrations to occur and these can make endovascular procedures more difficult. Although rare, beware for rare variants such as pro-atlantal or persistent fetal vessels, which can receive all, or most, of their supply from the anterior circulation and care should be taken, as carotid injury can have devastating consequences in this scenario.

Workup Clinical Evaluation Patients with VBI or posterior circulation ischemic symptoms should undergo a complete stroke workup. Cardiogenic etiologies of VBI must be considered and a thorough cardiovascular evaluation should be undertaken. High-grade intracranial stenosis can be dependent on adequate cardiac output. In patients with high-grade intracranial stenosis and concomitant cardiac dysfunction (e.g., dysrhythmia, atrial fibrillation), or hemodynamic instability (e.g., orthostatic hypotension), variations in perfusion pressure can produce symptoms in patients, and patient history should attempt to clarify the etiology of the symptoms.

Imaging

Fig. 8.1 Artist’s illustration depicting the vertebral artery anatomy.

can present different degrees of tortuosity and catheterization from a femoral approach can be challenging: sometimes, a radial or brachial approach is necessary. We suggest obtaining a computed tomography angiography (CTA) in all patients, to have a better understating of the anatomy prior to any interventions. Collaterals play an important role in any stenoocclusive disease. Therefore, a full six-vessel cerebral angiography should be performed. Arterial branches from the external carotid artery (ECA; e.g., occipital artery [OA]) or subclavian artery (e.g., thyrocervical or costocervical branches) can supply the posterior circulation in chronic VA stenosis or occlusion. It is important to know the degree of contribution from anterior circulation through posterior communicating arteries (PCoAs). The VA

In the absence of magnetic resonance imaging (MRI) and documented recurrent diffusion-weighted imaging (DWI)-proven ischemia in patients who will be deemed a medical treatment failure, additional steps should be taken (e.g., loop recorders, tilt-table testing, sleep apnea testing) to clarify presenting complaints. Careful attention also should be paid during follow-up to the interval development of additional silent ischemic “hits,” which can be seen with meticulous comparisons of T2-weighted–fluid-attenuated reversion recovery (FLAIR) sequences on MRI examinations over time. We consider the appearance of new T2/FLAIR lesions referable to the stenotic lesion to represent failure of medical therapy and intervention should now be considered (2 in algorithm). In most instances, noninvasive imaging (i.e., MRA or CTA) is sufficient to establish a diagnosis of ICAD and guide initial treatment medical management; however, formal cerebral digital subtraction angiography (DSA) is also justifiable in the early stages to document the degree and location of stenosis as CTA will frequently overestimate the degree of a stenosis, and both CTA and MRA can be subject to artifact in evaluating the lower cervical vessels. This also allows for the documentation of collateral circulation, as well as proximal access issues, should intervention be entertained. It is important to remember that many of these patients will harbor tandem cervical and/or great vessel lesions, which may be treated more easily and can be obscured by artifact on noninvasive imaging studies. We strongly recommend thoroughly studying patients with ICAD and VBI to elucidate the likely etiology of the presenting event, as the probability of additional future presentations is high.

Treatment Patients should undergo formal DSA and consideration for additional treatment of ICAD lesions if medical management fails as documented by progressive clinical strokes, silent ischemia, or with ongoing hemodynamic failures despite best medical management (►Figs. 8.2–8.4).

Cerebrovascular Management—Operative Nuances Bypass revascularization for VBI is not a common practice and it is limited to tertiary vascular referral centers. Given the results of the EC/IC

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8  Vertebrobasilar Stenosis and Insufficiency patients are loaded with 600 mg of clopidogrel and 650 mg of aspirin. Arterial lines are usually used mainly for peri- and intraprocedural blood pressure control; however, for some patients groin access is “slaved” while induction occurs throughout the remaining portion of the procedure using a larger access sheath 8–9 French [8–9F]. Preprocedural blood pressure is maintained within 10% of the patient’s baseline, which for some patients may be 180 mm/Hg or higher; after opening the vessel, this is brought down to less than 140s mm/Hg for the remainder of the case and patients are hospitalized to decrease the risk of reperfusion hemorrhage. We have found through experience that while transfemoral access is our usual approach, radial or brachial access may simplify access to the proximal cervical vertebral and should be considered in situations of proximal tortuosity or a hostile arch. We have also used with increasing frequency short distal access catheters (DACs), though our typical 6F guide catheter to the V4 segment of the vertebral greatly increases stability of wires and microcatheters during exchanges. This also has an added effect of removing stored energy in the stent/and or balloon systems and may prevent “harpooning” of the stent during navigation. It is important to premeasure working lengths so as to not run out at the time of deployment of devices and minimize the chances of having to re-access a lesion. DACs can also broaden the arsenal of balloons and stents, as we have found that monorail system coronary devices can be used with little difficulty with a high-riding DAC. The use of a DAC has at times simplified cases in an emergency setting when only a single operator is available. Intraprocedural monitoring is not typically used at our institution but is quite reasonable to consider depending on availability and operator comfort.

Complication Avoidance

Fig. 8.2 Midbasilar stenosis. (a) Towne’s projection of a left vertebral artery (VA) injection demonstrating a high-grade stenosis of the midbasilar artery. This patient had persistent symptoms of basilar artery ischemia despite medical treatment. (b) A microcatheter is navigated across the stenosis and into the left posterior cerebral artery. (c) A microcatheter exchange is carried out. This maneuver is typically done with two experienced operators and with the patient under general anesthesia and with full neuromuscular blockade. (d) A Gateway balloon is positioned across the area of stenosis for subnominal angioplasty. (e) A Wingspan stent is delivered across the area of stenosis resulting in a dramatic improvement in distal flow. (f) Final control angiography demonstrating resolution of the midbasilar stenosis.

bypass study and Carotid Occlusion Surgery Study (COSS) for anterior circulation insufficiency, bypass for stenoocclusive ischemic disease has a very limited indication at this time, especially as endovascular techniques and therapies continue to improve. There are case reports and series demonstrating posterior circulation bypass is feasible, but carry 55% reported transient complications and 20% or permanent risk of deficit. Open revascularization procedures include vertebral reimplantation (ostial disease; see Chapter 9), vertebral endarterectomy, occipital to PICA bypass, and superior temporal artery (STA) to superior cerebral artery (SCA) or posterior cerebral artery (PCA) bypass. We feel these strategies should not be ignored but should take a very specialized location within the overall algorithm of VB insufficiency treatment.

Endovascular Management—Operative Nuances Patients are brought to the angiography suite and placed under general anesthesia. For all procedures, full-dose heparin is given with activated clotting time being maintained at 250 to 350. Adequate platelet inactivation should be documented, and if emergent intervention is needed,

Complications from angioplasty and stenting procedures usually occur from • A poor understanding of the anatomy of the target lesion. • Technical mishaps during navigation of the lesion or during angioplasty and/or stenting. • Inadequate platelet aggregation. • Residual flow issues due to stenosis and/or dissection. We have found that time during the procedures clearly relates to complication rate and that the better our preprocedural plan is constructed, including bailouts and alternatives, the lower the complication rate. As stated earlier, a thorough understanding of the anatomy and excellent visualization can minimize the potential for unanticipated intraprocedural events. Accurate stent apposition at the wall of the lesion is important in order not to create pockets of potential thrombus at perforator-rich zones. We also prefer slow inflation times of the balloon (0.5 atm/15–45 seconds) to theoretically prevent barotrauma, plaque deformation, and/ or “snowplowing.” Except in extremely small vessels (i.e., < 1.5 mm), a stent should always be placed following angioplasty (►Figs. 8.2–8.4). The only potential exception to this guideline would be in patients with a suspected symptomatic plaque rupture in a perforator-rich zone (midbasilar) (►Fig. 8.2) who have misery perfusion symptoms and hemodynamic symptoms despite ongoing iatrogenic hypertensive therapy. In these selected and rare patients, we have at times elected to perform a “kiss angioplasty” to establish some flow to the hemisphere at risk, attempting to minimize the risk of dislodging a plaque or thrombus with a goal when the patient is more stable (8–12 weeks) to conduct follow-up and definitive and more aggressive angioplasty once the plaque is stable. For intra- and postoperative thrombotic issues, these usually occur from inadequate platelet inhibition, which can be mitigated with platelet testing preoperatively and, if seen, we have found the use of GP IIIa/IIb inhibitors such as eptifibatide (Integrilin) for 24 hours or longer. Occurrence of in-stent thrombosis during or shortly after the procedure should prompt an immediate search for an anatomical cause, which usually relates to vessel dissection at the level of the stent, residual stenosis or small vessel lumen, poor stent wall apposition, or proximal untreated lesion, which creates static blood at the inflow of the target lesion and poor cerebral flow.

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Isc e ic Stro e and Vascular Insufficiency

Fig. 8.3 Vertebral artery (V4) segment stenosis. (a) Left VA injection demonstrating a high-grade V4 segment stenosis. In this case, the contralateral VA is occluded and the patient had persistent vertebrobasilar insufficiency despite medical treatment. (b) Post initial angioplasty with a Gateway balloon. (c) Poststenting (Wingspan) angiography demonstrating significant improvement of the stenosis.

Fig. 8.4 Vertebral artery (V3–V4) segment stenosis. (a) High-grade stenosis of the right VA at the V3–V4 junction and occluded contralateral VA. (b) Postangioplasty, lateral projection. (c) Unsubtracted lateral angiography, demonstrating microwire placement just prior to microcatheter exchange, in which the Wingspan stent is positioned across the stenotic segment. (d) Poststent placement lateral projection, right VA injection. (e) Towne’s projection postangioplasty and poststent control angiography, demonstrating complete resolution of right VA stenosis.

Stent selection: Wingspan and Neuroform both represent open-cell stents that are self-expandable. Neuroform was initially designed for stent coiling, while Wingspan was utilized for ICAD (►Figs. 8.2–8.4). Enterprise is a closed-cell stent with lower radial opening force but is noted to be more flexible by some authors. Some authors have also noted a lower rate of in-stent stenosis with Enterprise. We typically utilize a Gateway balloon with Wingspan stent (►Figs. 8.2–8.4). Drug-eluting stents are also an excellent option. Most complications occur due to technical failures from wire dissections of a friable plaque with generation of a false lumen and/or embolization of plaque material. Distal wire perforations during exchanges can also occur due to tortuous anatomy storing energy in the triaxial system and meticulous wire management can be improved by an immobile patient. “Watermelon seeding” of the balloon at the time of angioplasty can have a snowplow effect on lipid-laden plaque, which can be avoided by accurate placement of the balloon at the time of inflation. Trying to use a longer balloon in order to prevent this watermelon seeding phenomenon can result in barotrauma at the distal ends of the “dogbone,” resulting in vessel rupture (either gross or microtraumatic dissection) or suboptimal angioplasty prior to stent placement resulting in inadequate vessel lumen that may promote thrombus due to persistently poor flow. All of these complications are usually the result of poor visualization of target lesions or distal anatomy because of poor contrast penetration through a lesion or a general misunderstanding of the lesions' anatomy. Dynamic three-dimensional rotation may also facilitate reduction of error through a better understanding of the anatomy.

Outcome While the best current evidence other than case series regarding outcomes of cerebral angioplasty and stent placement would be SAMMPRIS

reporting a 14.7% periprocedural complication rate favoring medical management, the interim report on the WEAVE trial shows a 4.4% complication rate, which mirrors that of the original trial in selecting on-label patients for use (supports algorithm steps 4 and 6). Recently, Dumont et al reported their results with submaximal angioplasty and while 75% of the vessels were anterior circulation, mean vessel stenosis diameter was improved from 80 to 54% and the study had a 0% ischemic stroke rate at 30 days and 5.5% rate at 1 year, suggesting these interventions can be done with minimal amount of perioperative risk. The U.S. multicenter Wingspan Study for ICAD reported a 6.1% major periprocedural complication rate (supports algorithm steps 4 and 6). Recently, Liu et al carried out a prospective study that evaluated the safety of endovascular therapy for severe symptomatic vertebrobasilar artery stenosis refractory to medical treatment. From 2013 to 2014, a total of 105 patients with stroke or TIA were included and only 97 were treated with stenting angioplasty, 52 patients with BA, and 45 patients with V4 VA stenosis. The rate of 30-day stroke, TIA, and death was 7.1%. All strokes happened in the BA group and were perforator strokes. Successful stent deployment was 100%. Authors concluded that the short-term safety of endovascular stenting for patients with severe symptomatic vertebrobasilar stenosis is acceptable (supports algorithm steps 4 and 7). Ausman et al reported on 85 patients with low-flow intracranial-to-extracranial pedicle bypass anastomosis procedures to the posterior circulation. Patients presented with symptomatic (stroke or TIAs) severe bilateral distal VA or BA disease. Fifteen (17.6%) patients had OA-PICA anastomosis, 20 (23.5%) had OA-anterior inferior cerebellar artery anastomosis, and 50 (58.8%) patients had STA-SCA anastomosis. Resolution of symptoms was reported in 69% of patients. Mortality and morbidity rates were 8.4 and 13.3%, respectively (supports algorithm step 5). Britz et al reported three patients who presented with symptoms suggested of vertebrobasilar ischemia, and the diagnosis was confirmed with

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8  Vertebrobasilar Stenosis and Insufficiency DSA. These three patients subsequently underwent revascularization with radial artery graft. All bypasses were performed from the cervical ICA into the PCA (P2 segment) through a combined middle fossa and translabyrinthine approach. The modified Rankin’s scale at the last clinical visit was 0 on two patients and 2 in one patient (supports algorithm step 5).

certain cases, there is a need for bypass procedures of the posterior circulation; however, these are infrequent.

Durability and Rate of Restenosis

Suggested Reading

Restenosis rates for angioplasty alone are higher than angioplasty and stenting. In the hands of experienced operators, the periprocedural complication rates for angioplasty alone versus angioplasty and stenting are similar, and long-term luminal gains are higher in stented patients. For that reason, we recommend placing a stent for all interventions for ICAD, with the exceptions to this rule having been discussed earlier (i.e., nominal vessel lumen 90 degrees] stenosis, or total occlusion [>3 months old], or lesion with high degree of neovascular proliferation), which have a 50% restenosis rate.

Clinical and Radiographic Follow-up All patients who undergo intracranial angioplasty and stenting should have close clinical follow-up. We recommend overnight observation in the intensive care unit immediately following the procedure. The first outpatient follow-up appointments are at 2 weeks and 3 months. Modification of secondary stroke risk reduction factors are crucial, as is general cardiovascular and hemodynamic optimization. Patients are carefully counseled on the need to report any neurological symptoms urgently and to take their antiplatelet medication as prescribed. While most noninvasive studies cannot accurately show detail of stented lesions, we will study patients immediately postprocedure with CTA head with thin reconstructions and a contrast-enhanced MRA. All of these studies are complimentary and can serve as a baseline in this patient group at high risk for representation for additional events. Most of our patients will undergo another diagnostic angiography at 8 to 12 months along with repeat noninvasive imaging to serve as future baselines as dictated by their respective clinical course. Unless clinically contraindicated, all of these patients are maintained on dual-antiplatelet therapy for life.

Editor Commentary The diagnosis of VBI can be difficult to make. Initially, patients present with vague symptoms including headaches, nausea, vertigo, dizziness, double vision, and may or may not have cerebellar signs or symptoms. CT scan of the head is almost always normal and MRI of the brain is usually not obtained. It is our job as neurosurgeons and neurologists to make other physicians (primary care, emergency medicine, internal medicine) aware of this disease. Evidence of stroke in posterior circulation territory should prompt a vascular imaging study such as CTA or MRA. DSA should be obtained if results of noninvasive imaging are inconclusive. On DSA, we need to look for patency and dominance of the VAs, basilar artery patency, presence and characteristics of PCAs, evidence of stenosis along the vertebral and basilar arteries, and VA origin stenosis. All patients should receive best medical treatment including dual-antiplatelet therapy. If still symptomatic, endovascular submaximal angioplasty is a great alternative before considering stenting. In

Leonardo Rangel-Castilla, MD Mayo Clinic, Rochester, MN

Akbari SH, Reynolds MR, Kadkhodayan Y, Cross DT III, Moran CJ. Hemorrhagic complications after prasugrel (Effient) therapy for vascular neurointerventional procedures. J Neurointerv Surg 2013;5(4):337–343 Alexander M, Zauner A, Chaloupka J, Baxter B, Callison R, Yu W. O-016 interim report on the weave™ intracranial stent trial: 50 consecutive patients. J NeuroIntervent Surg 2015;7:A9 Amin-Hanjani S, Pandey DK, Rose-Finnell L, et al; Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke Study Group. Effect of hemodynamics on stroke risk in symptomatic atherosclerotic vertebrobasilar occlusive disease. JAMA Neurol 2016;73(2):178–185 Ausman JI, Diaz FG, Vacca DF, Sadasivan B. Superficial temporal and occipital artery bypass pedicles to superior, anterior inferior, and posterior inferior cerebellar arteries for vertebrobasilar insufficiency. J Neurosurg 1990;72(4):554–558 Bouman HJ, Parlak E, van Werkum JW, et al. Which platelet function test is suitable to monitor clopidogrel responsiveness? A pharmacokinetic analysis on the active metabolite of clopidogrel. J Thromb Haemost 2010;8(3):482–488 Brandt JT, Close SL, Iturria SJ, et al. Common polymorphisms of CYP2C19 and CYP2C9 affect the pharmacokinetic and pharmacodynamic response to clopidogrel but not prasugrel. J Thromb Haemost 2007;5(12):2429–2436 Britz GW, Agarwal V, Mihlon F, Ramanthan D, Agrawal A, Nimjee SM, Kaylie D. Radial artery bypass for intractable vertebrobasilar insufficiency: case series and review of the literature. World Neurosurg 2016; 85:106–113 Dumont TM, Sonig A, Mokin M, et al. Submaximal angioplasty for symptomatic intracranial atherosclerosis: a prospective Phase I study. J Neurosurg 2016;125(4):964–971 Feng Z, Duan G, Zhang P, et al. Enterprise stent for the treatment of symptomatic intracranial atherosclerotic stenosis: an initial experience of 44 patients. BMC Neurol 2015;15:187 Fiorella D, Levy EI, Turk AS, et al. US multicenter experience with the wingspan stent system for the treatment of intracranial atheromatous disease: periprocedural results. Stroke 2007;38(3):881–887 Fleg JL, Stone GW, Fayad ZA, et al. Detection of high-risk atherosclerotic plaque: report of the NHLBI Working Group on current status and future directions. JACC Cardiovasc Imaging 2012;5(9):941–955 Gorelick PB, Wong KS, Bae HJ, Pandey DK. Large artery intracranial occlusive disease: a large worldwide burden but a relatively neglected frontier. Stroke 2008;39(8):2396–2399 Hopkins LN, Budny JL. Complications of intracranial bypass for vertebrobasilar insufficiency. J Neurosurg 1989;70(2):207–211 Kurre W, Berkefeld J, Brassel F, et al; INTRASTENT Study Group. In-hospital complication rates after stent treatment of 388 symptomatic intracranial stenoses: results from the INTRASTENT multicentric registry. Stroke 2010; 41(3):494–498 Liebeskind DS, Cotsonis GA, Saver JL, et al; Warfarin-Aspirin Symptomatic Intracranial Disease (WASID) Investigators. Collaterals dramatically alter stroke risk in intracranial atherosclerosis. Ann Neurol 2011;69(6):963–974 Liu L, Zhao X, Mo D, Ma N, Gao F, Miao Z. Stenting for symptomatic intracranial vertebrobasilar artery stenosis: 30-day results in a high-volume stroke center. Clin Neurol Neurosurg 2016;143:132–138 Savi P, Herbert JM, Pflieger AM, et al. Importance of hepatic metabolism in the antiaggregating activity of the thienopyridine clopidogrel. Biochem Pharmacol 1992;44(3):527–532 Siddiq F, Vazquez G, Memon MZ, et al. Comparison of primary angioplasty with stent placement for treating symptomatic intracranial atherosclerotic diseases: a multicenter study. Stroke 2008;39(9):2505–2510 Terada T, Tsuura M, Matsumoto H, et al. Endovascular therapy for stenosis of the petrous or cavernous portion of the internal carotid artery: percutaneous transluminal angioplasty compared with stent placement. J Neurosurg 2003;98(3):491–497 Zhu SG, Zhang RL, Liu WH, et al. Predictive factors for in-stent restenosis after balloon-mounted stent placement for symptomatic intracranial atherosclerosis. Eur J Vasc Endovasc Surg 2010;40(4):499–506

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9 Vertebral Artery Ostium Stenosis Leonardo Rangel-Castilla, Adnan H. Siddiqui, and Peter Nakaji

Abstract The proximal vertebral artery (VA), including VA ostium (VAO) stenosis is the second most common site of stenosis among the blood vessels supplying the brain, and despite the potential consequence of brainstem and cerebellum strokes, this location has not received enough attention. The incidence of extracranial VA atherosclerotic occlusive diseases affects 25 to 40% of patients with cerebrovascular diseases. Symptoms are not specific but usually involve cerebellar, brainstem, and cranial nerve deficits. MRI of the brain and CT angiography of the head and neck should be obtained in patients on whom the diagnosis of posterior circulation ischemia is suspected. The gold standard imaging modality to diagnose VAO stenosis is cerebral angiography. Medical treatment and risk factor management are similar to that of other cerebrovascular disease, including strict diabetes and hypertension control, statins, and antiplatelet therapy. More aggressive management is necessary for patients refractory to medical therapy. Surgical and endovascular interventions include VA transposition and VAO angioplasty and stenting. Outcomes of patients with VAO stenosis treated with open vascular or endovascular techniques are very encouraging. The success rates of both modalities are similar ranging from 93 to 98%. There is a higher incidence or recurrence following endovascular angioplasty and stenting; however, the use of drug-eluting stents and dual-balloon angioplasty has decreased the rate of in-stent stenosis at long-term follow up.

The presence of symptomatic vertebrobasilar stenosis and the risk of recurrent vertebrobasilar ischemia stroke have not been addressed until recently. Prospective hospital-based studies have shown that 16.6% of patients had at least 50% vertebrobasilar stenosis. Taking the first event as an index event, the risk of recurrent stroke is 30.5% in patients with at least 50% stenosis versus 8.9% in individuals without stenosis (1, 2 in algorithm).

Keywords: stroke, vertebrobasilar insufficiency, brainstem, cerebellum, vertebral artery ostium, subclavian artery, angioplasty, stenting, vertebral artery transposition

Pathophysiology/Classification

Introduction Posterior circulation ischemia accounts for 25 to 30% of all ischemic infarctions. Despite medical treatment with anticoagulation or antiplatelet therapy, the annual stroke rate for patients with symptomatic intracranial basilar artery stenosis is 10.7% and for those with symptomatic intracranial vertebral artery (VA) stenosis, it is 7.8%. After the carotid bifurcation, the proximal VA is the most common site of stenosis among the blood vessels supplying the brain. Despite their potential devastating consequences, ischemic events (i.e., transient ischemic attack or stroke) in this location have not received enough attention. Recent studies have shown that such events are associated with a high risk of stroke or early recurrent stroke. The diagnosis and management of posterior circulation ischemia is particularly challenging. Major controversies in decision making addressed in this chapter include: 1. Whether or not treatment is indicated. 2. Timing for intervention. 3. Open vascular versus endovascular treatment.

Whether to Treat Atherosclerotic occlusive disease of the extracranial VA is a common finding on diagnostic imaging. Its incidence in the general population is unknown but is estimated to affect approximately 25 to 40% of patients with cerebrovascular disease. Unlike the carotid circulation, for which the natural history of stenosis is well understood, the natural history of vertebrobasilar insufficiency is less well known. Patients with symptomatic vertebrobasilar artery stenosis are treated with medication alone. However, the effects of novel agents, including antiplatelet agents and statins, on altering the natural history of these lesions have not been elucidated. Endovascular stenting or microsurgical intervention may improve the natural history of VA stenosis with concomitant VA ostium (VAO) stenosis refractory to medical treatment.

Anatomical Considerations Each VA usually arises from the first portion of the subclavian artery or aortic arch. The artery is conventionally divided into four segments: V1, origin to transverse foramen of C6; V2, from the transverse foramen of C6 to the transverse foramen of C2; V3, from C2 to the dura; and V4, from the dura to the confluence of the VAs to form the basilar artery. The normal luminal diameter of the VA is 3 to 5 mm; however, asymmetry is common. Unilateral hypoplasia (80%) then one can ideally manage this with angioplasty and stenting. If the patient is symptomatic with embolic disease and high-grade stenosis from a dominant VA, this is best managed with stenting as well, whereas if the stenosis is not high grade and if the other vertebral is codominant or larger, then this is best managed medically, unless patient has symptoms despite aggressive medical therapy. If the patient is symptomatic from hypoperfusion from isolated vertebral ostial stenosis, then stenting is the best option. We like to address this as a two-stage procedure: first using a balloon expandable, typically drug-eluting coronary system is advanced across the ostia with at least 2 to 3 mm overhang within the subclavian artery. After stent deployment that balloon is exchanged for a specially designed ostial balloon system to allow the subclavian overhang to flare and provide better coverage of the plaque that is in the subclavian as well as permit ostial access in the future. Adnan Siddiqui, MD, PhD and Elad Levy, MD University at Buffalo, Buffalo, NY

Editor Commentary Vertebral artery origin stenosis is found increasingly incidentally on imaging studies such as MRA. The natural history is not as well understood as carotid stenosis. It is likely that for asymptomatic cases, medical management is sufficient. However, for those patients with either symptomatic embolic disease or flow limitation (usually due to inadequate contralateral circulation), revascularization makes sense. Less attention has been focused on accomplishing this, in part because of the lack of a surgical treatment option as well defined as carotid endarterectomy is for carotid stenosis. In fact, vertebral endarterectomy is possible, with the caveat that it is technically more difficult and the restenosis rate is high. Interest has turned to endovascular solutions for VA origin occlusive disease, with some success. However, as noted earlier, vertebral to carotid transposition is a viable option with a lower restenosis rate. While initially it appears technically difficult, in fact it can be mastered like any other vascular procedure. To perform transposition, the carotid sheath is exposed low in the neck behind the sternocleidomastoid sternal head. The posterior wall of the sheath is then opened and the VA is encountered directly behind. The artery is clipped closed at its origin and transected with temporary clipping, then rotated up to the carotid artery. The carotid is temporarily occluded and rotated in clamps 90 degrees to expose its posterior surface. A stab incision and aortic punch are used to create a new ostium in the wall, to which the VA is sewn. Temporary clips are then removed, restoring flow. Using this technique, durable revascularization can be achieved with a decrease in embolic risk. For many patients, it is an option that is superior to stenting, and can be done with aspirin as a single antiplatelet agent. Peter Nakaji, MD and Robert F. Spetzler, MD Barrow Neurological Institute, Phoenix, AZ

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Suggested Reading Compter A, van der Worp HB, Algra A, Kappelle LJ; Second Manifestations of ARTerial disease (SMART) Study Group. Prevalence and prognosis of asymptomatically vertebral artery origin stenosis in patients with clinically manifest arterial disease. Stroke 2011;42:2795–2800 Dumont TM, Kan P, Snyder KV, Hopkins LN, Levy EI, Siddiqui AH. Stenting of the vertebral artery origin with ostium dilation: technical note. J Neurointerv Surg 2013;5(5):e36 Gulli G, Khan S, Markus HS. Vertebrobasilar stenosis predicts high early recurrent stroke risk in posterior circulation stroke and TIA. Stroke 2009;40(8):2732–2737 Langwieser N, Buyer D, Schuster T, Haller B, Laugwitz KL, Ibrahim T. Bare metal vs. drug-eluting stents for extracranial vertebral artery disease: a meta-analysis of nonrandomized comparative studies. J Endovasc Ther 2014;21(5):683–692

Rangel-Castilla L, Ghandi S, Munich SA, et al. Experience with vertebral artery origin stenting and ostium dilatation: results of treatment and clinical outcomes. J Neurointerv Surg 2016;8(5):476–480 Rangel-Castilla L, Kalani MY, Cronk K, Zabramski JM, Russin JJ, Spetzler RF. Vertebral artery transposition for revascularization of the posterior circulation: a critical assessment of temporary and permanent complications and outcomes. J Neurosurg 2015;122(3):671–677 SSYLVIA Study Investigators. Stenting of symptomatic atherosclerotic lesions in the vertebral or intracranial arteries (SSYLVIA): study results. Stroke 2004;35(6):1388–1392 Stayman AN, Nogueira RG, Gupta R. A systematic review of stenting and angioplasty of symptomatic extracranial vertebral artery stenosis. Stroke 2011;42(8):2212–2216

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10 Pediatric Moyamoya Disease Nadia Khan

Abstract Moyamoya disease in children is a progressive angiopathy resulting in spontaneous occlusion of the circle of Willis. Symptoms are usually of ischemic nature and range from headaches and transient ischemic attacks to complete territorial strokes. Both anterior, i.e., internal carotid artery terminus, anterior cerebral artery (ACA), and middle cerebral artery (MCA), and posterior circulation, i.e., posterior cerebral artery (PCA), are involved. Early and correct diagnosis is crucial in long-term clinical management and for favorable outcome. A six-vessel cerebral angiogram is crucial in making correct diagnosis and is able to differentiate moyamoya from vasculitis, one of the main differential diagnoses in small children presenting with acute stroke. Hemodynamic evaluation of cerebral perfusion and reserves (e.g., with H215O-PET; baseline and acetazolamide challenge) is essential in demonstrating territories at risk of stroke. Stroke prevention is the main goal of management, which can be achieved surgically by multiple tailor-made cerebral revascularizations. Expert intraoperative pediatric anesthesia and perioperative maintenance of adequate hydration and mean arterial pressure are critical in avoiding complications. Combined direct and indirect revascularization procedures are performed in one or multiple stages. Direct revascularization procedures include superficial temporal artery (STA)-MCA, STA-ACA, and occipital artery-PCA procedures. Indirect revascularization procedures are performed if the donor or recipient vessels are too small in caliber or too fragile. These include EDAS (encephalo-duro-arterio-synangiosis), EMS (encephalo-myo-synangiosis), and EGPS (encephalo-galea-periost-synangiosis). Endovascular treatment (stenting, angioplasty) is not effective in long-term stroke prevention and should be avoided. Clinical and radiological follow-up continues after surgery, i.e., into puberty and transition period into adulthood. Keywords: moyamoya disease, pediatric stroke, cerebral revascularization, H215O-PET, hemodynamic reserves

Introduction Moyamoya disease (MMD) in children is a progressive angiopathy when compared to adults. Not only is the anterior circulation (i.e., supraclinoidal internal carotid artery [ICA] and its bifurcation, anterior cerebral artery [ACA], middle cerebral artery [MCA]) involved but also posterior cerebral artery (PCA) involvement is observed. Repetitive stroke over a short period of time is a common symptomatology; therefore, early diagnosis and cerebral revascularization of the affected arterial territories is recommended.

Management includes not only early detection and surgical prevention of stroke but also a systematic long-term follow-up. Major controversies in decision making addressed in this chapter include: 1. Whether or not treatment is indicated. 2. Open versus endovascular treatment for pediatric MMD. 3. Role of cerebral revascularization. 4. Ideal timing of the procedure, type of revascularization procedure, and outcomes.

Whether to Treat Majority of children with MMD require cerebral revascularization. The key is to diagnose early and then to treat as soon as possible (1, 2 in algorithm). Since children are constantly growing, the angiopathy is dynamic and progressive. In children younger than 5 years especially, progression from unilateral to bilateral or from one to many cerebral arteries can occur within as little as 8 weeks.

Anatomical Considerations and Pathophysiology Moyamoya angiopathy is characterized by a bilateral stenosis or occlusion of the ICA bifurcation along with the proximal segments of ACA and MCA. In the case of the posterior circulation, the stenotic/occlusive changes may be proximal or distal along the entire PCA segment. Typical moyamoya collaterals (deep: lenticulostriatal, choroidal, thalamoperforators; or transdural: through middle meningeal, ethmoidal arteries) form to compensate for decreased blood flow (►Fig. 10.1). In time, there is a progressive and spontaneous occlusion of the circle of Willis with the external carotid artery supplying the entire cerebral blood flow demand. Histopathological studies of moyamoya-affected ICAs on autopsy show fibrocellular thickening of the intima due to fibroblasts and smooth cell proliferation. It is a complex angiopathy still poorly understood and assumed to be primarily a cause of multiple genetic and angiogenic abnormalities activated through certain trigger phenomenon such as inflammation, stimulation of local immune system, and hemodynamic stress.

Fig. 10.1 Anteroposterior (a) and lateral (b) ICA (internal carotid artery) angiograms showing the tight stenosis at the ICA bifurcation (white arrow) and the deep lenticulostriatal collaterals (red arrows). Anteroposterior vertebral artery injections (c) showing bilateral PCA stenosis (white arrows) and the distal moyamoya collateral formation (red arrows).

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Algorithm 10.1 Decision-making algorithm for pediatric moyamoya disease.

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Ischemic Stroke and Vascular Insufficiency

Workup

4. H215O-PET with Diamox Challenge

Clinical Evaluation

It is valuable in outlining the territorial cerebral blood flow and reserves after acetazolamide challenge. Children are well hydrated a night before and after the positron emission tomography (PET) scan to prevent ischemia. Depending on the availability of hemodynamic scanning, HMPAOSPECT or xenon-CT scanning when locally allowed can be used (2 in algorithm) (►Fig. 10.3). Children, in particular, must receive adequate intravenous hydration before and after any acetazolamide challenge.

Clinical history must be taken extensively to outline the onset of disease and the stroke burden. In the case of a positive family history, magnetic resonance imaging (MRI), magnetic resonance angiography (MRA), or computed tomography angiography (CTA) with perfusion screening must be carried out in the presence of symptoms. Common symptoms vary from simple headaches to migraines and transient ischemic attacks, which may result in sensorimotor or speech disturbances, and changes in visual acuity and fields. Repetitive strokes in any one of the arterial territories are very common in children younger than 5 years in whom cortical infarcts are commonly seen; therefore, a thorough baseline neurological exam as well as a neuropsychological/child development tests is extremely crucial (1, 2 in algorithm).

Imaging 1. MRI-MRA: Outline the stroke burden, i.e., the presence of old and new territorial or watershed strokes and screens for any changes in the intracranial vasculature (2 in algorithm). Furthermore, the presence of deep lenticulostriatal and thalamoperforating moyamoya collaterals can also be detected.

2. CTA with Perfusion Similar to MRA, CTA shows the vasculature of the circle of Willies, site and degree of stenosis, and presence of collaterals. CT perfusion demonstrates whether there is cerebral volume preservation or not, and the risk of infarction (2 in algorithm).

3. A Six-Vessel Cerebral Angiogram Digital subtraction angiography (DSA) must be performed for correct diagnosis and optimal preparation of surgery (2 in algorithm). In the hands of experienced neurosurgeons/interventional neuroradiologists, also selective angiography can be performed in individual cases where the extent of deep and superficial moyamoya collaterals needs to be determined in preparation of surgery (►Figs. 10.1 and 10.2). The unavailability of interventional neuroradiologists trained in performing angiograms in children along with limited medical experience in managing moyamoya in particular always poses to be the main limiting factor in early diagnosis.

Differential Diagnosis Intracranial vasculitis is the major differential diagnosis. Varicella vasculitis is common in children with a unilateral and a single vessel involvement, usually that of the MCA. Clinical history and presence of cells in the cerebrospinal fluid (CSF) usually help in diagnosis. An angiogram must be performed in atypical cases. The involvement of the ICA bifurcation and additional narrowing of MCA assists in clarifying the diagnosis. Also, clinical and angiographic progression under high-dose steroids further confirms moyamoya angiopathy.

Treatment Conservative Management Conservative management begins with hydration, usually twice the necessary daily fluid intake according to weight and age, as well as antiplatelet aggregation therapy using acetylsalicylic acid. Mean arterial pressure (MAP) must be kept at normotensive to hypertensive to the desired blood pressure according to age. This continues for life.

Cerebrovascular Management—Operative Nuances Surgical Technique: Indirect Revascularization (EGPS, EDS, EMS, and EDAS) Larger craniotomies are performed by inverting several flaps of vascularized galea-periosteal flaps (encephalo-galea-periost-synangiosis [EGPS]) or dural inversion flaps (encephalo-duro-synangiosis [EDS]) onto the surface of the brain (4 in algorithm). This technique can be used in any region requiring revascularization: frontal, frontotemporal, frontoparietal, temporo-occipital, and occipital. Either the frontal or parietal branch of the superficial temporal artery (STA) or the occipital artery (OA) can be placed directly on the surface of the brain via a small frontal, temporal, or occipital craniotomy (encephalo-duro-ar-

Fig. 10.2 Lateral ECA (external carotid artery) injections (a,b,c) showing remarkable distal filling after combined indirect and direct STA-MCA bypass (1) for revascularization of the MCA territory as well as frontal EDAS (2) and occipital EDAS (3) for revascularization of the ACA and PCA territories, respectively.

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Fig. 10.3 Preoperative (a) and postoperative H215O-PET scans showing decreased baseline cerebral blood flow (lower rows) as well as decreased response to acetazolamide challenge (upper rows) in the ACA, MCA, and PCA territories bilaterally. After multiple direct and indirect revascularizations (see ►Fig. 10.2), increase in baseline cerebral blood flow and vasomotor response to acetazolamide can be observed.

terio-synangiosis [EDAS]), respectively, to stimulate growth of new vessels (►Fig 10.4). These techniques can be used in combination with the classic STA-to-MCA bypass for revascularization of the motor area or in the frontal (ACA) and/or occipital (PCA) regions when a suitable donor or recipient vessel is unavailable for a direct anastomosis. Increasingly, combined direct and indirect revascularizations are being performed (STA-to-MCA bypass with EGPS, EDS, and encephalo-myo-synangiosis [EMS]). That is, after a direct STA-to-MCA anastomosis is performed, the dura is inverted and placed on the brain surface. Part of the temporalis muscle and the galea-periosteal flap, which is dissected before the craniotomy, are used to close the dural gap (►Fig. 10.5). In children undergoing this procedure, larger craniotomies are performed. The arachnoid membrane is then opened at several locations to allow widespread contact of the hypervascular tissue with the underlying brain to promote the desired neovascularization.

dic branches are common choices. If the craniotomy must be extended because one of these branches is unavailable or its caliber is too small, the craniotomy can be extended anteriorly to locate the operculofrontal branch for a direct anastomosis. The dura must be cut carefully without sacrificing the already present transdural arterial anastomosis. This goal can be achieved by avoiding a single large flap of dura, by limiting dural coagulation, and by using dural clips in case of bleeding. When further revascularization of the frontoparietal region is desired, double anastomoses can be performed. A frontoparietal skin flap must be prepared, and both the parietal and the frontal branches of the STA are dissected. The branches are used individually for the anastomosis in the fronto-opercular and parietal regions, respectively.

Surgical Technique: Direct Revascularization

The frontal branch of the STA is followed and dissected behind the hairline to the midline. If the frontal branch is not long enough and an STAto-MCA bypass is not being performed at the same time, only indirect revascularization with EDAS, EDS, and EGPS can be performed. If an STA-to-MCA bypass is performed during the same setting, a curvilinear skin incision can be performed to dissect both the frontal and parietal branches of the STA followed by the respective craniotomies and anastomoses. Alternatively, two separate linear incisions following the course of the frontal and parietal branches can be used. A problem arises only if the frontal branch fails to reach midline. In such cases, an interposition graft can be performed using the rest of the already prepared parietal branch. The craniotomy is usually placed anterior to the coronal suture and extends from the midline laterally. Distal cortical branches of the ACA (the middle internal frontal artery) can be located in the vicinity of the frontal bridging veins.

Multiple combined direct and indirect territorial revascularizations are the neurosurgical management of choice (3 in algorithm) (►Fig. 10.2). The choice of number and location of revascularization procedures is based primarily on the severity and extent of disease observed in the patient’s clinical presentation, extent of previous ischemia/infarcts, presence of viable brain tissue, preoperative angiography, and decrease or absence of perfusion reserves on acetazolamide challenge studies. Surgery is tailored to the distribution territories of the MCA, ACA, or PCA (unilateral and/or bilateral). The aim is always to perform multiple direct anastomoses in the regions required (STA-to-MCA, STA-to-ACA, OA-to-PCA). When the caliber of the donor or recipient vessels is too small, the vessels are too fragile, or they are unavailable at the desired site, indirect revascularization is performed.

The STA-MCA Bypass A linear incision is placed over the parietal branch of the STA and the artery is dissected (8–10 cm of dissection and free preparation). A craniotomy follows. After a suitable MCA branch is identified, a direct anastomosis between the parietal branch of the STA and the branch of MCA is performed. Preoperative external carotid artery angiography and immediate preoperative Doppler ultrasonography are used to determine the presence of suitable donor vessels (STA, frontal and parietal branches, OA, posterior auricular artery). When the STA is hypoplastic, the OA or the posterior auricular artery can be used. Suprasylvian or infrasylvian cortical branches can be used as recipient vessels. The angular, posterior temporal, posterior parietal, anterior parietal, rolandic, and prerolan-

The STA-ACA Bypass

The OA-to-PCA Bypass This procedure is performed with the patient in the prone position. The OA is located and dissected. An occipital craniotomy is performed, and a suitable cortical branch is located for the direct anastomosis. When a suitable cortical branch is not found, indirect EDAS alone is performed with the OA.

Endovascular Management—Operative Nuances Stenting or angioplasty has no effective long-term role to play in the management of MMD.

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Ischemic Stroke and Vascular Insufficiency

Fig. 10.4 Indirect revascularization–encephalosynangiosis.(a) Artist’s illustration showing both branches (frontal and parietal) of the superficial temporal artery (STA). (b,c) Illustration and intraoperative images showing the STA laying on the brain cortex; the dura has been cut in such a way to preserve branches of middle meningeal (MMA) arteries in direct contact with brain surface. (d) Illustration demonstrating the direct contact of the cortical MCA branch with the STA branch; observe the donor vessel has been sutured down to pia arachnoid to maintain direct contact. (e) Illustration showing the bone flap accommodating the STA branches to avoid kinking and/or occlusion of the donor vessel. (Used with permission from the Barrow Neurological Institute, Phoenix, AZ.)

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Fig. 10.5 Indirect revascularization–encephalomyosynangiosis. (a) Artist’s illustration showing both branches (frontal and parietal) of the superficial temporal artery (STA), the temporalis muscle, and the proposed skin incision for the procedure. (b,c) Illustrations showing different options on how to accommodate both STA branches and muscle to increase contact surface over the surface of the brain. (d) Illustration demonstrating the direct contact of the cortical MCA branch with the STA branch and dura leaflets inverted. (e) Illustration showing the bone flap accommodating the STA branches and temporalis muscle to avoid kinking and/or occlusion of the donor vessel. (Used with permission from the Barrow Neurological Institute, Phoenix, AZ.)

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Ischemic Stroke and Vascular Insufficiency Previous reports of a single case and a small number of cases have shown a high restenosis rate with progression of disease after endovascular treatment. This is due to the pathophysiology of MMD with continued proliferation of smooth muscle cells causing restenosis/occlusion, which is different from atherosclerotic lesions.

Complication Avoidance One- or two-stage surgeries can be performed with no additional anesthesiological or surgical risk to the patient if adequate hydration and MAP is maintained pre-, peri-, and postoperatively. Hypovolemia, hypotension, hypercapnia, and hypocapnia are to be avoided. The presence of an expert anesthesiological team as well as an intensivist is essential. Acetylsalicylic acid is administered before, during, and after surgery. Postoperative analgesia is important for the patient’s comfort, especially in children (preventing crying in children prevents the resultant hypocapnia/hyperventilation). For children, the presence of a dedicated team within a pediatric hospital infrastructure (i.e., with a pediatric inpatient ward, operating room, anesthesia team, and intensive care unit) is crucial.

Clinical and Radiographic Follow-up The first postoperative follow-up includes clinical, neurological, and neuropsychological assessments, MRI stroke protocol study, six-vessel cerebral angiography, and a H215O-PET with acetazolamide challenge 6 months after surgery. Depending on the patient’s age, clinical follow-ups along with MRI and PET are repeated at 1 to 3 years’ intervals. Additional angiography is repeated at puberty or at the time of maximum growth spurt in children. Patients with unilateral MMA, especially in children younger than 5 years, are followed closely for the occurrence of disease on the contralateral side when the disease can progress over a period of months. Boys are usually followed up to 18 years of age. Follow-up in girls is longer and continues till prior to pregnancy and delivery.

Outcome and Durability of Neurosurgical Intervention in Stroke Prevention In our personal experience, the efficacy of multiple combined direct bypass and indirect revascularization procedures performed bilaterally has resulted in clinical improvement/stroke freedom and stabilization or improvement in the hemodynamic reserve capacities as observed on H215O PET studies (►Fig. 10.3). Postoperative angiography also shows an increase in the distal filling in the multiple arterial territories (►Fig. 10.2). Children with MMD have a low cerebral perfusion state, which, when in decompensation, results in repeated ischemia and stroke. Performing cerebral revascularization procedures increases global cerebral perfusion after surgery, reinforcing the usefulness of surgery. This is not only seen in the MCA area but also commonly observed in the ACA and PCA areas. Most papers on choice of surgical techniques for the treatment of MMD describe revascularization of the motor areas (MCA territory), whereas only a few have described additional revascularization in other involved arterial territories. The cerebral perfusion status of the frontal region requires special attention. In children younger than 5 years, MMD associated with repeated frontal ischemia can be devastating in terms of mental and cognitive development. Early revascularization can support normal childhood development and prevent severe mental retardation. The same is true for the posterior circulation. The choice of revascularization technique depends on local understanding of the disease, the dedication of surgeons toward treating more adult patients than children and vice versa, surgeon’s personal surgical expertise and experience, and, of course, the intraoperative anatomical and technical limitations. In literature to date, there is much mention of the classic direct STA-to-MCA bypass procedure used to treat adults with MMD. In children especially younger than 5 years, in whom the technique of direct bypass may be technically challenging, most surgeons perform indirect techniques (supports algorithm step 4). Comparing indirect procedures between adults and children, children fare far better because growth factors activating

neovascularization are expected to be abundant in growing children as induction of neovascularization depends on the condition of both the recipient (condition of brain, CSF) and donor tissue (temporalis muscle; dural, galeal, and periosteal flap; donor arteries). However, neovascularization after indirect anastomosis takes longer to establish than a direct anastomosis. In contrast, direct bypass immediately enhances blood flow. Combined direct and indirect procedures for each territory and only indirect procedures when direct procedure is technically not possible are the current recommended procedures of choice. Long-term studies after cerebral revascularization have shown clinical improvement with decrease in presenting symptoms as well as stroke freedom and overall improvement in quality of life (supports algorithm steps 3 and 4).

Expert Commentary The above preoperative planning and multiple revascularization procedures have been performed since 1999 in more than 105 pediatric patients, with a mean age 3 years, in our center. In the majority of the children, bilateral multiple combined direct bypass and indirect procedures were performed (n = 298 multiple territorial revascularizations). H215O-PET has always been crucial in determining the extent of cerebral perfusion deficits and in individualizing surgery. Over the years, we have modified our strategy from two-stage to one-stage surgeries for both MCA territories. In patients with only unilateral angiopathy and with involvement of more than one territory (MCA, ACA, PCA), all territories have been revascularized successfully. In our experience, well-planned one-stage multiple procedures have not increased the morbidity rate. Adequate hydration before, during, and after surgery remains crucial. In terms of perioperative ischemia, immediate postoperative complications were observed in two earlier operated patients. One patient with postoperative ischemia of the frontoparietal region had recovered completely at 3 months of follow-up. One patient operated in the early 1990s died 1 day after surgery from a massive infarction of the contralateral nonoperated side. At first follow-up 6 months to 1 year after treatment and on an average after 10 years of follow-up, all other patients have been stroke-free. On hemodynamic evaluation, cerebral perfusion had improved as had distal arterial filling on angiography in all patients. Nadia Khan, MD University of Tübingen, Germany

Editor Commentary The benefit of surgery for pediatric moyamoya has been shown with enough validity that it should be considered as standard of care. The surgical options in pediatric MMD are between onlay and direct bypass. While we favor direct bypass when possible, the data for an advantage of direct bypass over indirect bypass are not particularly robust in the pediatric population. In fact, some studies in which multiple burr holes are simply placed have shown excellent efficacy at creating functional anastomoses. Early revascularization may lower the risk of both stroke and hemorrhage. The extra flow can help patients pass through the main risk period in which they fully prune their carotid circulations and form collateral anastomoses. Once they are formed and have good perfusion, many patients can expect clinical stability, though their lifetime risk remains incompletely defined. Peter Nakaji, MD Barrow Neurological Institute, Phoenix, AZ

Suggested Reading Choi JU, Kim DS, Kim EY, Lee KC. Natural history of moyamoya disease: comparison of activity of daily living in surgery and non surgery groups. Clin Neurol Neurosurg 1997;99(Suppl 2):S11–S18 Hayashi T, Shirane R, Tominaga T. Additional surgery for postoperative ischemic symptoms in patients with moyamoya disease: the effectiveness of occipital

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10 artery-posterior cerebral artery bypass with an indirect procedure: technical case report. Neurosurgery 2009;64(1):E195–E196, discussion E196 Khan N, Dodd R, Marks MP, Bell-Stephens T, Vavao J, Steinberg GK. Failure of primary percutaneous angioplasty and stenting in the prevention of ischemia in Moyamoya angiopathy. Cerebrovasc Dis 2011;31(2):147–153 Khan N, Schuknecht B, Boltshauser E, et al. Moyamoya disease and Moyamoya syndrome: experience in Europe; choice of revascularisation procedures. Acta Neurochir (Wien) 2003;145(12):1061–1071, discussion 1071 Kim SK, Seol HJ, Cho B-K, Hwang Y-S, Lee DS, Wang KC. Moyamoya disease among young patients: its aggressive clinical course and the role of active surgical treatment. Neurosurgery 2004;54(4):840–844, discussion 844–846 Kuhn FP, Warnock G, Schweingruber T, Sommerauer M, Buck A, Khan N. Quantitative H2[(15)O]-PET in pediatric moyamoya disease: evaluating perfusion before and after cerebral revascularization. J Stroke Cerebrovasc Dis 2015;24(5):965–971 Kuroda S, Houkin K. Moyamoya disease: current concepts and future perspectives. Lancet Neurol 2008;7(11):1056–1066

Pediatric Moyamoya Disease

Phi JH, Wang KC, Cho BK, et al. Long-term social outcome in children with moyamoya disease who have reached adulthood. J Neurosurg Pediatr 2011;8(3):303–309 Scott RM, Smith ER. Moyamoya disease and moyamoya syndrome. N Engl J Med 2009;360(12):1226–1237 Scott RM, Smith JL, Robertson RL, Madsen JR, Soriano SG, Rockoff MA. Long-term outcome in children with moyamoya syndrome after cranial revascularization by pial synangiosis. J Neurosurg 2004;100(2, Suppl Pediatrics):142–149 Suzuki Y, Negoro M, Shibuya M, Yoshida J, Negoro T, Watanabe K. Surgical treatment for pediatric moyamoya disease: use of the superficial temporal artery for both areas supplied by the anterior and middle cerebral arteries. Neurosurgery 1997;40(2):324–329, discussion 329–330 Suzuki J, Takaku A. Cerebrovascular “moyamoya” disease. Disease showing abnormal net-like vessels in base of brain. Arch Neurol 1969;20(3):288–299 Yeon JY, Shin HJ, Kong DS, et al. The prediction of contralateral progression in children and adolescents with unilateral moyamoya disease. Stroke 2011;42(10):2973–2976

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11 Adult Moyamoya Disease Mario K. Teo, Venkatesh S. Madhugiri, and Gary K. Steinberg

Abstract Moyamoya disease (MMD), a chronic steno-occlusive vasculopathy affecting the vessels at the base of the skull, once thought to only affect the Asian population, has been shown to have increasing incidence worldwide. In this chapter, we review the natural history of MMD, address the controversies associated with this disorder, and present our results based on one of the largest cohorts of treated MMD patients in the western world. Several syndromes and conditions are described as being associated with or causing MMD, and 10 to 15% of MMD cases are familial. We propose screening for MMD in patient subgroups. We also discuss whether treatment is indicated (based on the clinical presentations), and compare the outcome with various management modalities— medical, surgical, or endovascular. A new classification system for MMD is validated, and has clinical implications especially in stratifying preoperative symptomatology. Prior to undertaking surgical treatment for MMD patients, pertinent workup and investigations (including a formal six-vessel cerebral angiogram, MRI [magnetic resonance imaging] brain, and cerebral perfusion imaging with and without Diamox) were carried out for optimal surgical strategies and patient outcomes. Direct or indirect methods of cerebral revascularization are compared. Generally, indirect bypasses were used for younger patients who have higher angioplasticity with better collateralization compared to older adult patients, repeat revascularization cases to avoid compromising prior bypass grafts from initial procedures, or patients who have internal carotid artery/middle cerebral artery (ICA/MCA) stenosis but still with anterograde ICA/MCA angiographic filling and do not require an immediate increase in blood flow.

management of MMD includes antiplatelet therapy, blood pressure regulation, and management of underlying associated medical conditions if present. Patients are also instructed to maintain adequate hydration at all times, as dehydration may precipitate transient ischemic attacks (TIAs) or strokes. Antiplatelet therapy (usually 81 mg acetylsalicylic acid) is recommended to prevent the formation of microthrombi at sites of stasis in stenotic intracranial arteries and to maintain patency of extracranial–intracranial (EC-IC) grafts after surgical revascularization. Although the efficacy of antiplatelet therapy in preventing strokes in MMD has never been proven, it appears safe. Anticoagulation is not recommended due to hemorrhagic risk. The rate of progression of ischemic symptoms or development of a major stroke is as high as 65% over 5 years in medically treated patients. Surgical intervention therefore has become the standard therapy for MMD (2–8 in algorithm). Emerging evidence suggests that surgical revascularization leads to a reduction in stroke and intracranial hemorrhage in symptomatic MMD patients versus medical or conservative management only (2, 4 in algorithm). The recently completed prospective Japanese study randomized 80 patients with hemorrhagic MMD (16–65 years of age) into direct surgical revascularization or medical management arms. At the 5-year follow-up, the rebleed rate was 2.7% per year in the surgical group versus 7.6% per year in the medical group (p = 0.042). The rate of overall morbidity was 3.2% per year in the surgery arm versus 8.2% per year in the medical management arm (p = 0.048) (2, 4 in algorithm).

Keywords: adult MMD, screening, classification, management strategy, types of surgery, direct STA-MCA bypass, indirect bypass, clinical outcome

Several syndromes and conditions have been described as being associated with or causing MMD. These cases were formerly termed the MMD or atypical MMD; however, such distinctions are probably no longer relevant. The various conditions associated with MMD include prior radiation therapy to the head and neck or brain, Down’s syndrome, neurofibromatosis 1, tuberous sclerosis, Majewski’s primordial dwarfism, Fanconi’s anemia, sickle cell disease, autoimmune disorders (including Grave’s disease), Marfan’s syndrome, renal artery stenosis, and even infections such as tuberculous, meningitis, and leptospirosis. Patients who have received any of these diagnoses and have symptoms such as chronic fatigue or headache and refractory or unexpected hypertension should undergo noninvasive radiological testing to screen for MMD (9 in algorithm). The RNF213 gene has been identified as being associated with MMD in the Asian population. In Caucasians, ZXDC (p.P562L), a gene involved in major histocompatibility complex (MHC) class II activation, and OBSCN, a gene involved in myofibrillogenesis, were the most enriched. Between 10 and 15% of all cases of MMD are familial, and the disease prevalence is increased in identical twins. Thus, it is reasonable to screen first-degree family members of patients with MMD with magnetic resonance imaging/ magnetic resonance angiography (MRI/MRA) if headaches or other unexplained symptoms are present. Patients with primarily unilateral MMD also need to be monitored for progression of disease on the opposite side (14 in algorithm).

Introduction Moyamoya disease (MMD) refers to a chronic idiopathic occlusive vasculopathy affecting the vessels at the base of the brain. The first report of the disease was published by Takeuchi and Shimizu in 1957, when they described a case of “hypoplasia of the bilateral internal carotid arteries.” The term “moyamoya” was coined by Suzuki and Takaku in 1969 to describe the appearance of the collateral vessels that form in these patients. Although most initial reports of the disease originated in Japan, it has now been established that MMD occurs all over the world. The incidence, however, may differ with geography. For example, the incidence in the United States reported in 2005 was approximately 0.086 per 100,000, vis-à-vis 0.54 per 100,000 in Japan published in 2003. There is also some evidence that the incidence of the disease has been steadily increasing to 0.94/100,000/year in Japan reported in 2006 and to 0.57/100,000/year in the United States (communicated in 2012). MMD has been classically described as having bimodal age distribution, with the first peak occurring in children in the first decade of life and the second peak occurring between the ages of 30 and 50 years. Major controversies in decision making addressed in this chapter include: 1. Clinical features and syndromes associated with MMD. 2. Whom to screen for MMD? 3. Whether or not treatment is indicated, and how—medical or surgical? 4. Type of surgery.

Whether to Treat The natural history of MMD tends to be progressive, with studies showing that patients with unilateral MMD progressed to bilateral disease in 30 to 40% of adult patients within 2 to 3 years (1, 2 in algorithm). Medical

Whom to Screen

Pathophysiology See Chapter 10: Pediatric Moyamoya.

Classification Suzuki and colleagues categorized the disease into six stages based on the appearance of the intracranial vessels and moyamoya vessels: stage 1: stenosis of the internal carotid arteries; stage 2: initial appearance of moyamoya vessels; stage 3: increasing internal carotid artery stenosis and further definition of collateral vessels; stage 4: occlusion of the circle of Willis,

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11 Adult Moyamoya Disease

Algorithm 11.1 Decision-making algorithm for adult moyamoya disease.

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Ischemic Stroke and Vascular Insufficiency minimization of collateral vessels; stage 5: further reduction of collateral vessels; and stage 6: disappearance of collateral vessels. However, these purely morphological criteria as assessed by cerebral angiography neither reflect the hemodynamic status adequately nor correlate with clinical symptoms or with surgical outcomes. The new MMD preoperative symptomatology grading system proposed by the Berlin group incorporates angiographic findings (digital subtraction angiography, DSA) and features of chronic cerebrovascular insufficiency and hemodynamic reserve (diagnosed on perfusion sequences on MRI or xenon computed tomography [CT]). We have validated this system in the Stanford MMD cohort and routinely employ it as an important tool to stratify preoperative hemispheric symptomatology.

Workup Clinical Evaluation MMD has been classically described as having either a hemorrhagic or an ischemic presentation (1 in algorithm). Typically, adults present with hemorrhagic disease and children with symptoms of ischemia. However, this pattern varies with ethnicity as well as in non-Asian populations. In adults, nearly 50% presented with intracranial hemorrhage in the Japanese series. In the North American cohort, adult MMD largely presented with cerebral ischemia (about 80%). Analysis of the Stanford series of 658 surgically treated adult MMD patients showed that 59% presented with stroke or TIA and 16% with hemorrhage. Hemorrhage in patients with MMD can be intracerebral, intraventricular, or subarachnoid. Forty percent of bleeds are within the basal ganglia, 30% are intraventricular, and 15% are thalamic. Given that several patients with MMD have elevated blood pressure and that these are the typical locations for hypertensive hemorrhage, the diagnosis is often missed. In our initial series of 430 patients with MMD (71% adults), we found that female patients were more likely to experience preoperative TIAs and were more likely to have bilateral MMD. No association was observed between sex and risk of preoperative ischemic or hemorrhagic stroke. Females may also be at higher risk of adverse postoperative events despite successful revascularization; however, there appears to be no sex difference in the ultimate neurological outcome. MMD can also present with nonspecific sensory symptoms. Headache is a common presenting feature in both children and adults. Some patients complain only of chronic fatigue and typically receive a diagnosis of MMD late in the course of the disease (9 in algorithm). Patients can present with cognitive dysfunction and progressive memory loss in the absence of other symptoms. Various movement disorders such as chorea and hemiballismus have also been described as presenting symptoms. MMD can present with very nonspecific symptoms and signs and can also mimic other neurological diseases such as multiple sclerosis. This diversity in clinical presentations often leads to delayed diagnosis in patients. The management of these patients depends on the degree of stenosis on angiography (10, 11 in algorithm) and the MRI findings (12, 13 in algorithm). Patients who are potential candidates for operative cerebral revascularization procedures should undergo a thorough medical, cardiac, and baseline neurological evaluation prior to surgery. In addition, routine preoperative labs and radiological studies should be obtained. Prior to surgery, it is important to measure and record the patient’s mean arterial pressure (MAP). During surgery, the anesthesiologist should be instructed to keep the patient’s MAP at or above the preoperative baseline at all times.

At our institution, we perform quantitative MR perfusion studies without and with Diamox. Patients who have hemodynamic steal demonstrate a decrease in blood flow in affected areas with Diamox administration, whereas those with an impaired cerebrovascular reserve usually have poor or absent augmentation with Diamox administration, indicating that the vessels in the affected vascular territory are already maximally vasodilated to promote flow. Such patients are considered to be at especially high risk for ongoing ischemia without treatment. However, these patients are also at higher risk for perioperative ischemic complications, and therefore, particular care must be taken to avoid hypotension perioperatively and during the recovery period.

Treatment The aim of surgical treatment is to supplement cerebral blood flow in the setting of ongoing poor cerebral perfusion. For patients presenting with a clinical history of TIAs or strokes, MRI changes consistent with ischemia, arterial stenosis or occlusion on angiogram, or decreased hemispheric blood flow on perfusion imaging, an EC-IC bypass should be considered. At Stanford, we have treated a high volume of MMD patients (1,382 bypasses in 861 patients). In this population, especially in those with completely occluded internal carotid and/or middle cerebral arteries (2 in algorithm), direct superficial temporal artery–middle cerebral artery (STA-MCA) bypass is preferred to the indirect procedure as it provides immediate cerebral blood flow augmentation and ameliorates ongoing ischemia (3 in algorithm). However, decisions regarding direct versus indirect bypass procedures should consider patient-specific risk factors as well as the comfort of the individual surgeon and the collective experience at that institution.

Cerebrovascular Management—Operative Nuances Currently, there is no class 1 evidence in the form of randomized controlled trials (RCTs) that establishes whether direct or indirect revascularization is superior in the management of MMD. Some literature on this topic suggests that direct bypass is superior. The main advantages of direct anastomosis are the augmentation of blood flow immediately after surgery, a more consistent and higher extent of collateral vessel formation as demonstrated on angiography, superiority in restoring postbypass cerebrovascular reserve, higher rates of improvement in symptoms, fewer ischemic events, and a higher rate of stroke-free survival. However, as mentioned earlier, a prospective, randomized study of direct revascularization versus conservative therapy in MMD patients presenting with hemorrhage demonstrated a significant decrease in future hemorrhagic or ischemic events, as well as in all morbidity. The principal difference between the two revascularization strategies lies in the method of cerebral reperfusion. Direct methods anastomose scalp arteries to intracranial arteries with the intent of immediately perfusing ischemic cerebral territories, whereas indirect methods aim to stimulate the development of a new vascular network over months or years. Indirect revascularization can be achieved by using adjacent tissues (galea, muscle, scalp arteries, dura) or a distant graft (omentum) to cover the brain surface and promote indirect collateralization. Indirect procedures include encephalomyosynangiosis (EMS), encephalogaleo[periosteo]synangiosis (EGPS), encephaloduroarteriosynangiosis (EDAS), encephaloduroarteriomyosynangiosis (EDAMS), pial synangiosis, multiple burr holes (MBH), and omental transposition (encephalo-omental synangiosis).

Imaging

Direct STA-MCA Bypass

The typical presurgical imaging protocol incorporates a formal six-vessel cerebral angiogram including bilateral external carotid injections, MRI brain, and cerebral perfusion imaging with and without Diamox (PET [positron emission tomography], MR perfusion, SPECT [single-photon emission computed tomography], or TCD [transcranial Doppler]).

Under general anesthesia and mild hypothermia to about 33°C, the patient is positioned supine with the head turned lateral and fixed in a Mayfield clamp (so the operative field is parallel to the floor). The most suitable STA branch (frontal vs. parietal branch) is chosen as the donor based on the preoperative angiogram. In most cases, the parietal branch

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11 Adult Moyamoya Disease is selected as it is behind the hairline and has a straighter course, and there is less risk of damage to the frontalis nerve branches during dissection. Using a handheld Doppler probe, 9 cm of the donor STA branch is transduced above the zygoma and harvested along its course under microscopic magnification. The frontal branch of STA is generally preserved for a potential subsequent revascularization procedure; small distal branches are coagulated and divided to mobilize the STA trunk. Papaverine is intermittently applied to the dissected STA to alleviate spasm, and a doppler probe is used to ensure the patency during STA dissection (►Fig. 11.1). After harvesting the STA vessel off the temporalis fascia, the temporalis muscle is cut and retracted and a craniotomy approximately 6 cm in diameter is performed. Under maximal magnification, 1 to 2 cm of the distal STA is dissected free of the surrounding tissue and skeletonized using fine microscissors. Similarly, a short length of the proximal STA is dissected from its surrounding soft-tissue cuff to create a site for placement of a proximal temporary clip. The ideal site for temporary clipping is distal to the take-off of the unused frontal branch of the STA; this allows continued flow through the STA into the unoccluded branch, reducing stagnant flow and the risk of thrombosis proximal to the temporary clip.

The dura is then opened in a stellate fashion, and the microscope is used to find a suitable recipient cortical MCA branch. The most important considerations are size of the donor and recipient vessels (0.9 mm or greater is optimal), location of the recipient M4 branch of the MCA (away from the craniotomy edges is preferred), and orientation of the vessels (to avoid an acute angulation between the donor and recipient vessels, and facilitate suturing both walls of the recipient artery). The arachnoid over the potential recipient vessel is opened; the MCA M4 branch is prepared for anastomosis by placing a high-visibility background material underneath the vessel. Larger perforators can be spared by including their origin from the MCA segment in the temporary vessel clips. Before temporary clipping, blood flow is measured in the MCA branch and the cut STA using a Transonic’s Charbel ultrasonic flow probe. After the temporary clip is applied to the proximal STA, the STA is cut at a 45-degree angle to create a “fish mouth.” The cut STA segment is then flushed with heparinized saline. MAP is gently raised to over 90 mm Hg. Burst suppression is achieved using propofol. Specially designed Anspach-Lazic temporary mini-clips are placed proximally and distally on the recipient vessel. An arteriotomy is then made over the recipient MCA using microscissors, and the lumen is flushed with heparinized saline. Indigo carmine dye (or a sterile marking pen) is used to stain the walls of the donor and recipient vessel and allow the lumen to be seen more easily and facilitate the microanastomosis. First, 10–0 sutures are placed to anchor the apices of the arteriotomy (toe stitch, followed by heel stitch). Sutures should be passed from outside the donor artery to inside the recipient artery, and then tied on the outer surface of the anastomosis. Once the donor STA has been anchored, interrupted sutures are place on each side of the anastomosis at close intervals, making sure not to catch the back wall of the vessel. Once the anastomosis is complete, the temporary clips on the recipient artery are released, followed by opening of the clip on the proximal STA (►Fig. 11.1). Occasionally, additional sutures are needed to seal the anastomosis. Blood flow in the STA, proximal MCA, and distal MCA to the anastomosis is then measured with the Transonic’s Charbel flowmeter, and intraoperative indocyanine green angiography as well as intraoperative Doppler ultrasonography is performed to confirm patency and quantitative function of the bypass graft. During closure, the dura is loosely replaced, the inferior burr hole is enlarged to accommodate the entering STA graft, the bone is replaced avoiding any kinking or pressure on the vessel, the temporalis muscle is approximated, and the skin is closed with care. The patency of the STA trunk is verified with a Doppler probe at the end of the procedure.

Indirect Extracranial–Intracranial Bypass

Fig 11.1 A 33-year-old man with intermittent right body numbness and speech impairment was diagnosed with left unilateral moyamoya disease. He subsequently underwent left direct STA-MCA bypass. (a) Intraoperative positioning with head fixed in Mayfield pin, and scalp marking of the parietal STA branch for the donor vessel. (b) Microscopic view after STA-MCA direct anastomosis using interrupted 10-0 suture. (c,d) Preoperative cerebral angiogram (AP, lateral views, ICA injection) showing left MCA occlusion (arrowhead) with moyamoya vessels formation (asterisk). (e,f) Six-month postoperative cerebral angiogram (AP, lateral views, ECA injection) showing widely patent direct STA-MCA bypass graft (arrows) using the parietal STA branch, now filling the MCA territories. (g) Preoperative MRI brain perfusion scan showing reduced perfusion in the left hemisphere, MCA region. (h) Six-month postoperative MRI perfusion showed improvement of left hemispheric perfusion. (Reproduced with permission from Elsevier.)

In our adult practice, indirect procedures for MMD tend to be reserved for: 1. Younger patients who have higher angioplasticity with successful collateralization compared to older adult patients. 2. Repeat revascularization for MMD patients who have ongoing symptoms due to inadequate revascularization from initial procedures. 3. Patients with stenosis (but not occlusion) of the internal carotid artery or MCA and persistent anterograde filling of the MCA distribution, as direct bypass graft could promote underlying stenotic vessel occlusion secondary to competing flow between the native and bypass circulation, related to flow stasis at the stenosis site (4 in algorithm). For indirect bypass techniques using adjacent tissue, for example, EDAS, the stages involve a scalp vessel harvest with soft-tissue cuff, craniotomy, stellate dural opening, multiple fenestrations of the pia– arachnoid layer, and scalp vessel placement in intimate contact with the exposed brain (►Fig. 11.2). The dura is then approximated over the vessel, the bone flap is fashioned to allow the artery to enter and exit through the burr holes, and closure is performed while ensuring the patency of the bypass graft (5 in algorithm). In circumstances when no suitable adjacent tissue or scalp vessel is available for indirect bypass, and a large area of brain revascularization is needed, indirect bypass using distant tissue, for example, omental transposition, has

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Ischemic Stroke and Vascular Insufficiency become an attractive option (8 in algorithm). The omentum is harvested laparoscopically while preserving the right gastroepiploic artery and vein pedicle. It is then tunneled laparoscopically to the cranial region, and placed over the hemisphere of interest for indirect collateralization (►Fig. 11.2).

Endovascular Management—Operative Nuances Endovascular treatment involving angioplasty with or without stenting of the stenotic vessels in MMD has been attempted without long-term success. Although there are no prospective trials examining this therapy, a study from our institution reported the failure of angioplasty or stenting in a series of five patients, all within just over a year of treatment. Because of the progressive steno-occlusive nature of the affected vessel, we believe that endoluminal therapy does not provide a durable result.

Complication Avoidance Management after surgical revascularization is a critical part of the treatment of MMD. All patients are monitored in the intensive care unit overnight. We maintain the MAP between 90 and 110 mm Hg for the first 24 hours after surgery. Thereafter, we allow patients to gradually settle at or above their baseline presurgical MAPs. We favor the use of midodrine and fludrocortisone to maintain the MAP within the desired range beyond the first 24 hours. Comorbid conditions such as diabetes are adequately addressed. Patients remain on aspirin (81 mg/day) preoperatively and receive aspirin on postsurgical day 1. We do not routinely image patients perioperatively as inpatients, but obtain postoperative MRIs a week after surgery. For patients who have bilateral MMD, we generally stage the surgeries a week apart. The perioperative ischemic event rate varies between 3.5 and 5% of treated hemispheres. Acute preoperative infarcts and poor cerebrovascular reserve detected on a preoperative Diamox challenge perfusion

MRI have been identified to be independent risk factors for ischemic complications following EC-IC bypass for MMD. The finding of any new neurological deficit after surgery warrants investigation and management. We believe that new ischemic events in the postoperative period are the result of hypoperfusion, rather than hyperperfusion. Therefore, in the event of any new neurological deficit occurring after surgery, we hydrate the patient (target central venous pressure of 8–10 mm Hg) and increase the MAP to above the baseline preoperative level. If the symptoms do not resolve, the patients are evaluated with an MRI, including diffusion and perfusion sequences.

Outcome A recent meta-analysis included 16 papers of RCTs, prospective controlled cohort studies, and retrospective case-controlled studies comparing the treatment efficacy for symptomatic MMD. It concluded that surgical treatment significantly reduced the risk of stroke (odds ratio [OR] of 0.17, 95% confidence interval [CI], 0.12–0.26, p < 0.01), especially for hemorrhagic MMD (OR of 0.23, 95% CI, 0.15–0.38, p < 0.01). Further analysis indicated that compared to direct bypass surgery, indirect bypass surgery had a lower efficacy for secondary stroke risk reduction (OR of 1.79, 95% CI, 1.14–2.82, p = 0.01), while no significant difference was detected for perioperative complications (supports algorithm steps 3, 5, 7, and 8).

Durability and Rate of Recurrence We have previously reported a series of patients with up to 9 years of angiographic follow-up; 99% of bypasses were patent. The cumulative 5-year risk of perioperative or subsequent stroke or death was 5.5%. Of the patients presenting with a TIA, over 90% were TIA-free at 1 year (supports algorithm steps 3, 5, 7, and 8). At Stanford, from 1991 to 2014, 1,244 revascularization procedures (1,107 direct bypass, 137 indirect bypass) have been performed on 765 patients. Of these, 57 patients had repeat revascularization (38 patients had previous indirect procedures [5 originally treated at Stanford], 19 patients had previous direct bypass [12 at Stanford]) of the same hemisphere. The estimated rate of repeat revascularization after previously performed Stanford indirect or direct bypass was 4% (5/137) and 1% (12/1, 107), respectively (p = 0.03). Over 50% of our repeat revascularizations were achieved with direct procedures for patients with previous direct or indirect bypass. However, the choice of procedure depends on the operative findings and the status of donor and recipient vessels (supports algorithm steps 6 and 7).

Clinical and Radiographic Follow-up

Fig. 11.2 An 18-year-old woman with moyamoya disease had a bilateral indirect cranial bypass 3 years previously. She presented with left body numbness, and an angiogram showed right terminal ICA occlusion and inadequate collateralization from previous indirect bypass grafts. She subsequently underwent encephalo-omental synangiosis to revascularize a large area of her right hemisphere. (a) Intraoperative view of exposed skull (note plating system in place due to previous craniotomy), and simultaneous endoscopic harvest of the greater omentum. (b) Omentum is now delivered out of peritoneal cavity and tunneled to the cranial compartment. (c) After dural opening, the omentum is placed over a large surface area of the exposed hemisphere. The skull is then thinned to avoid compression of the underlying brain prior to closure. (d) Preoperative cerebral angiogram (AP view, common carotid injection) showing left terminal ICA occlusion (arrowhead) with moyamoya vessels (asterisk), and reduced perfusion of a large part of the right cerebral hemisphere. (e,f) Postoperative celiac trunk injection showing the pedicle of the omental flap (gastroepiploic artery, arrows) along the thoracic cavity and cervical region to the cranial compartment. (Reproduced with permission from Elsevier.)

Patients are followed up with imaging studies—our protocol includes an MRI with perfusion sequences and catheter angiography at 6 months and at 3, 10, and 20 years after surgery (15 in algorithm). Patients who have unilateral disease need to be followed up with annual noninvasive imaging such as CT angiography (CTA) or MRA. One study demonstrated that even if the arteries on the contralateral side are completely normal at the time of initial diagnosis, 8% of such patients developed progressive disease on the initially normal side. On the contrary, if there is any stenosis (including mild) of the contralateral arteries at initial diagnosis, 71% of such patients develop progressive disease on that side. Seventy-nine percent of patients remained employed or in school at long-term follow-up. Excluding children and adults with learning difficulties, 87% are self-caring and 75% are living independently. Overall, 83% of patients had excellent outcomes (modified Rankin Scale, 0–1) at long-term follow-up. Therefore, about 80% of MMD patients have had excellent longterm physical, social, and functional outcomes post-revascularization, with up to 25 years of follow-up based on our most recent long-term follow-up study. We performed a questionnaire-based survey in which 82% of those who had preoperative headache experienced postrevascularization reduction in their symptoms (supports algorithm steps 3, 5, 7, and 8).

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11 Adult Moyamoya Disease Among those who had hypertension preoperatively, antihypertensives were discontinued in 18% and the dose reduced in 47% postsurgery.

Expert Commentary Adult MMD is a major cause of ischemic and hemorrhagic stroke, causing significant disability often in young patients. Medical therapy has not been shown to improve the natural history in symptomatic patients, while surgical EC-IC revascularization can be performed safely, has longterm durability, and reduces the risk of future ischemic and hemorrhagic events. In general, we prefer direct surgical revascularization to indirect procedures, although indirect grafts play an important role for select cases. Meticulous attention to surgical technique and perioperative management are essential to achieving successful outcomes. Selection of asymptomatic MMD patients for surgical revascularization depends on degree of angiographic arterial stenosis, evidence of prior MR infarcts, and impairment of hemodynamic reserve on cerebral perfusion studies. Nonoperated MMD patients should be followed closely for development of clinical symptoms, as well as for progression of angiographic, MR, and hemodynamic measures. Gary K. Steinberg, MD Stanford University School of Medicine, Stanford, CA

Editor Commentary My preference for adults is for direct or indirect bypass depending on the anatomy and severity of ischemia. Our own study suggests that adult direct bypass recipients have a better outcome than those who received indirect revascularization; however, the selection process for which patient received which procedure makes a post-hoc analysis less than robust. Generally, we select Suzuki grades III and IV patients for surgery when there is sufficient demand to allow the bypass to survive, and before there are so many collaterals that a bypass is no longer needed.

Suggested Reading Acker G, Goerdes S, Schneider UC, Schmiedek P, Czabanka M, Vajkoczy P. Distinct clinical and radiographic characteristics of moyamoya disease amongst European Caucasians. Eur J Neurol 2015;22(6):1012–1017 Czabanka M, Peña-Tapia P, Schubert GA, et al. Proposal for a new grading of Moyamoya disease in adult patients. Cerebrovasc Dis 2011;32(1):41–50 Guzman R, Lee M, Achrol A, et al. Clinical outcome after 450 revascularization procedures for moyamoya disease. Clinical article. J Neurosurg 2009;111(5): 927–935 Han DH, Nam DH, Oh CW. Moyamoya disease in adults: characteristics of clinical presentation and outcome after encephalo-duro-arterio-synangiosis. Clin Neurol Neurosurg 1997;99(Suppl 2):S151–S155 Imaizumi T, Hayashi K, Saito K, Osawa M, Fukuyama Y. Long-term outcomes of pediatric moyamoya disease monitored to adulthood. Pediatr Neurol 1998;18(4):321–325 Kazumata K, Ito M, Tokairin K, et al. The frequency of postoperative stroke in moyamoya disease following combined revascularization: a single-university series and systematic review. J Neurosurg 2014;121(2):432–440 Kelly ME, Bell-Stephens TE, Marks MP, Do HM, Steinberg GK. Progression of unilateral moyamoya disease: a clinical series. Cerebrovasc Dis 2006;22(2–3):109–115 Miyamoto S, Yoshimoto T, Hashimoto N, et al; JAM Trial Investigators. Effects of extracranial-intracranial bypass for patients with hemorrhagic moyamoya disease: results of the Japan Adult Moyamoya Trial. Stroke 2014;45(5): 1415–1421 Qian C, Yu X, Li J, Chen J, Wang L, Chen G. The efficacy of surgical treatment for the secondary prevention of stroke in symptomatic moyamoya disease: a meta-analysis. Medicine (Baltimore) 2015;94(49):e2218 Scott RM, Smith ER. Moyamoya disease and moyamoya syndrome. N Engl J Med 2009;360(12):1226–1237 Shoemaker LD, Clark MJ, Patwardhan A, et al. Disease variant landscape of a large multiethnic population of moyamoya patients by exome sequencing. G3 (Bethesda) 2015;6(1):41–49 Suzuki J, Takaku A. Cerebrovascular “moyamoya” disease. Disease showing abnormal net-like vessels in base of brain. Arch Neurol 1969;20(3):288–299

Robert F. Spetzler, MD Barrow Neurological Institute, Phoenix, AZ

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12 Traumatic and Iatrogenic Carotid Artery Injury Jay U. Howington

Abstract Carotid injuries have multiple causes and are one of the leading causes of ischemic stroke in the younger population. The majority of these are the result of blunt trauma in the setting of a high-speed motor vehicle collision, but the trauma can also be the result of penetrating injuries. With the increase in endovascular neurosurgical procedures, the incidence of iatrogenic injuries has seen a rise in the past decade. The vast majority of carotid injuries can be managed with medical therapy, but there are indications for both endovascular and open surgical treatment. This chapter will review the causes of carotid injury, the different types of injury, and their clinical and radiological assessment, and will present a therapeutic algorithm for these lesions. Keywords: carotid injury, carotid dissection, carotid stenting, blunt carotid trauma

Introduction Carotid artery injury, whether blunt or penetrating, occurs in 1 to 2% of trauma patients, is one of the leading causes of stroke in the younger population, and is most commonly caused by high-energy motor vehicle collisions. Iatrogenic arterial injury is increasingly common and is secondary to a host of procedures including central venous access, endovascular procedures, and endonasal operations. The overwhelming majority of carotid injuries result in dissections, but other notable sequelae include arteriovenous fistulas, pseudoaneurysms, and lacerations/transections. As troublesome as these injuries might be, it must be remembered that the neurological morbidity associated with symptomatic carotid injury has been reported to be as high as 80%, with a mortality of up to 40%. Nonoperative management with antithrombotic therapy is the first-line therapy for carotid injuries and includes both anticoagulation and antiplatelet regimens. Traditional surgical approaches to carotid injuries have had limited success and have been associated with significant morbidity secondary to either ischemic events or cranial nerve injuries. Endovascular techniques offer the following advantages over open surgery: access to injuries at or near the skull base, preservation of flow within the parent artery, the avoidance of cranial nerve injury, and the ability to readily assess the status of the intracranial circulation. Endovascular therapy offers an attractive option for those patients in whom antithrombotic therapy is either contraindicated or poorly tolerated. Major controversies in decision making addressed in this chapter include: 1. The adequate and accurate diagnostic imaging tool. 2. Whether or not treatment is indicated. 3. The role of medical management. 4. Open versus endovascular treatment for carotid artery injury.

Whether to Treat The management of carotid injuries depends largely on the presence of symptoms in conjunction with radiographic abnormalities. The majority of noniatrogenic carotid injuries are blunt injuries and are initially silent in their presentation and are not associated with obvious signs of cervical trauma. Therefore, one must have a relatively high index of suspicion based on the traumatic mechanism in those patients who present with no neurological symptoms (1 in algorithm). Berne et al found a median time to diagnosis of 12.5 hours for survivors of blunt cerebrovascular injury and 19.5 hours for nonsurvivors, which highlights the necessity to adequately diagnose these injuries. Those patients suspected of having a carotid injury should be evaluated with computed tomography (CT) and CT angiography (CTA) initially. This imaging modality is readily

available, and almost every trauma patient undergoes a CT scan as part of their initial trauma protocol (1 in algorithm). The diagnostic accuracy of CTA is directly related to the number of multidetector channels. In centers with eight-channel multidetector CT or less, digital subtraction angiography (DSA) should be considered or the patient transferred to an appropriate trauma center (2 in algorithm). The primary management strategies for carotid injury include observation, antithrombotic regimens, surgical repair, and endovascular therapy. Given the relatively high morbidity and mortality associated with untreated carotid injuries mentioned earlier, observation should be avoided unless there are strong contraindications to other strategies. Aggressive screening to diagnose blunt carotid injury results in early treatment, which leads to improved outcomes and a reduction in stroke rates (1, 2 in algorithm). Asymptomatic patients with radiographic findings should be considered for medical management with antithrombotic agents (3 in algorithm). Asymptomatic patients with a contraindication to anticoagulation or antiplatelet therapy should be considered for endovascular treatment based on the type of injury and its natural history (3, 4 in algorithm). Those patients with symptoms related to a carotid injury should be considered for immediate treatment. Patients in whom the carotid injury is associated with a dense neurological deficit and a large ischemic insult on imaging derive little benefit from either medical treatment or revascularization, and it is generally felt that these patients be managed in a supportive manner with aggressive intracranial pressure management. There is no level I evidence regarding the treatment of blunt carotid injuries, but the preponderance of evidence in the form of retrospective reviews, case series, and meta-analyses points to intervention as an acceptable and safe form of treatment.

Anatomical Considerations/ Pathophysiology The fundamental mechanisms of blunt carotid injury stem from the anatomical juxtaposition of the relatively mobile cervical carotid artery with the fixed intracranial carotid. The cervical carotid is subject to longitudinal and compression forces such as cervical hyperextension or hyperflexion with rotation that stretches the carotid artery over the lateral masses of the upper cervical vertebrae, direct cervical trauma, intraoral trauma, and basilar skull fractures. High-speed motor vehicle collisions are the most common cause of blunt carotid injury, but other causes include chiropractic manipulation, direct blows to the neck, and any mechanism resulting in rapid deceleration or acceleration accompanied with or without rapid head turning. The resultant injuries have been categorized based on a grading scale proposed by Biffl et al (►Table 12.1). The most common injury is a dissection, and symptoms include cervical pain, Horner’s syndrome, and signs of either/both ocular and hemispheric ischemia. As the artery is stretched and compressed over the cervical spine, the intima can tear, leading to spectrum of injuries outlined in ►Table 12.1. The portion of the internal carotid between the cricoid cartilage and the angle of the mandible is the most common site of blunt injury as it is the most vulnerable and mobile portion of the artery. The increasing use of endovascular techniques in the treatment of cerebrovascular diseases has led to a concomitant increase in iatrogenic injuries, and just as with external trauma, dissection is the most common injury. Iatrogenic carotid injuries are associated with an increased morbidity and mortality compared to blunt injuries, and this is likely secondary to the increase in cerebrovascular comorbidity in this particular patient population. Percutaneous deep venous access is associated with a 0.5 to 3.7% risk of arterial puncture, and the incidence is higher when the target vessel is the internal jugular vein compared to the subclavian vein.

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12 Traumatic and Iatrogenic Carotid Artery Injury

Algorithm 12.1 Decision-making algorithm for traumatic and iatrogenic internal carotid artery injury.

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Ischemic Stroke and Vascular Insufficiency

Table 12.1 Blunt carotid injury grading scale

Injury grade

Description

I

Luminal irregularity or dissection with 37 years), male sex, coma, seizure, deep CVST, intraparenchymal hemorrhage, and other significant hematologic and hematopoietic comorbidities (e.g., systemic malignancy, infection, inflammation). Anticoagulation therapy: In the early 1990s, a randomized, placebo-controlled, prospective study examined the safety and efficacy of dose-adjusted IV heparin compared with no treatment in patients with CVST/CVO. The study was halted prematurely following the recruitment of 20 patients given that a statistically significant beneficial effect of heparin was seen after 3 days of therapy (and at every subsequent time point up to 3 months) (supports algorithm steps 6, 8, 9). In the late 1990s, another randomized, placebo-controlled, multicenter trial examined whether treatment with weight-adjusted subcutaneous LMWH for 3 weeks, followed by oral anticoagulation for 3 months, was superior to placebo in patients with CVST/CVO. After 12 weeks, 4/30 (13%) of patients in the treatment group and 6/29 (21%) in the placebo group had a poor outcome. While not statistically significant, there was a trend toward favorable outcome in the treatment group. A Cochrane review of anticoagulation therapy in patients with CVST/ CVO—which included the above-mentioned trials—found an absolute reduction in the risk of death and dependency of 13% (95% confidence interval, 30 to -3%) as compared to no treatment. Importantly, there were

Cerebral Venous Thrombosis and Occlusion

no new symptomatic ICHs. Based on these data, the authors concluded that anticoagulation for CVST/CVO appeared to be safe and was associated with a potentially important reduction in morbidity and mortality (supports algorithm steps 6, 8, and 9). Another large retrospective review of 62 randomized controlled trials and observational studies found that the overall rate of death with therapeutic heparin was significantly less than that without anticoagulation in patients with CVST/CVO (9.1 vs. 14%, respectively; p = 0.0007) (supports algorithm steps 6, 8, and 9). Despite these data, however, many investigators oppose the routine anticoagulation of these patients given the side effects of acute heparin therapy (e.g., new hemorrhage, heparin-induced thrombocytopenia). There are currently no controlled trials or observational studies investigating the use of antiplatelet medications in CVST/CVO. Medical treatment of elevated ICPs: Elevated ICP leading to a cerebral herniation syndrome is the most common acute cause of death in patients with CVST/CVO. Despite this, there remains a paucity of evidence supporting the escalation of medical therapy (e.g., head of bed elevation, PCO2 modulation, diuretics, acetazolamide, hyperosmolar therapy) and bedside surgical procedures (serial lumbar punctures, spinal subarachnoid drain, ventriculostomy) in patients with CVST/CVO and elevated ICPs. There are currently no randomized clinical trials ongoing to investigate these treatment options. DHC: In 2011, Ferro et al performed a multicenter, retrospective review of 69 patients with acute CVST/CVO and herniation due to a large parenchymal ischemic or hemorrhagic lesion who underwent DHC (with or without ICH evacuation). At a follow-up period of 1 year, only 12 patients (17%) had an unfavorable functional outcome (mRS of 5, or death). A total of 26 patients (38%) had mRS of 0 to 1, 39 patients (57%) had mRS of 0 to 2, 4 patients (6%) were alive with mRS of 4 to 5, and 11 patients (16%) died. Three patients who had experienced clinical symptoms of brain herniation (e.g., bilateral fixed, nonreactive pupils) prior to DHC recovered completely. Results from this trial, along with data from more recent studies, suggest that DHC (with or without ICH evacuation) in patients with CVST/CVO and impending herniation due to a large parenchymal ischemic or hemorrhagic lesion was lifesaving and often resulted in acceptable functional outcomes (supports algorithm step 7). There is currently a prospective registry of patients undergoing DHC for CVST/CVO with malignant intracranial hypertension (DECOMPRESS-2 study). We anticipate that the results of this study will help to further delineate the clinical outcomes of DHC in this setting. Endovascular intervention: In 2003, Canhão et al performed a literature review (169 patients from 72 studies) to assess the safety and efficacy of intravascular thrombolytic therapy in CVST/CVO. Most patients (~78%) exhibited very poor baseline neurological exams, including coma and/or encephalopathy. Treatment included microcatheter-guided local thrombolytic therapy with or without systemic thrombolytics. Remarkably, 86% of patients were functionally independent at discharge (mortality rate of ~5%; functional dependence of ~7%) (supports algorithm step 11). More recently, in 2014, Borhani et al performed a literature review of 64 patients who underwent mechanical thrombectomy for CVST/CVO. Devices employed and techniques used varied considerably between operators. At last follow-up, 40 (63%) patients had no disability or minor disability, 7 (11%) patients had major disability, and 9 (16%) patients died (supports step 11 in algorithm). Another group retrospectively analyzed patients with CVST/CVO undergoing mechanical thrombectomy with or without IV thrombolysis (185 patients from 42 studies). Good functional outcomes (mRS 0–2) were seen in 84% of cases; the mortality rate was 12% and the rate of new ICH was 10%. Notably, nearly half (~47%) of these patients were in a comatose neurological state prior to intervention (supports algorithm step 11). In a prospective study by Stam et al in 2008, 20 patients with CVST/CVO were selected for endovascular intervention if they had altered mental status, a large mass lesion, or straight sinus thrombosis. Most patients had poor neurological exams prior to the intervention (12 patients were comatose). Techniques included urokinase thrombolysis with aspiration via a rheolytic catheter (n = 15), chemical

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Ischemic Stroke and Vascular Insufficiency thrombolysis alone (n = 4), and no intervention (n = 1) due to challenging venous access. Nine patients made an excellent recovery, three had a minor disability, two had a moderate-to-severe disability, and six patients died (supports algorithm step 11). The Thrombolysis or Anticoagulation for Cerebral Venous Thrombosis (TO-ACT) trial is an ongoing prospective, multicenter, randomized study examining the safety and efficacy of endovascular thrombolysis (with or without mechanical thrombectomy) with traditional medical treatment (systemic heparinization) in patients with CVST/CVO. The results of this trial should help to elucidate the role of endovascular interventions in the management of CVST/CVO.

unsuccessful after multiple passes, chemical thrombolysis with tPA may be considered. However, given that the patient is already being systemically anticoagulated at the time of the procedure, we would consider chemical thrombolysis largely as a salvage procedure given the likely increased risks of ICH.

Rates of Recurrence

The main problem with venous sinus thrombosis is typically delayed diagnosis. While locales with higher incidence such as the Rocky Mountain West is used to such presentations, lower altitude communities routinely misdiagnose the symptoms as drug intoxication or psychosis until a CT turns positive with a hemorrhage. The symmetry of presentation symptoms because of bilaterality of involvement, elevation of ICP, and the young age at presentation all contribute to delayed diagnosis. Once the diagnosis is made with plain CT, CTV, MRI, or MRV, further diagnosis does not require conventional angiography. The patient should be emergently heparinized with a full loading dose even in the setting of a brain hemorrhage since it is directly a result of venous hypertension. If the patient declines despite systemic heparinization or presents in extremis, then emergent endovascular therapy should be considered. For intervention, essentially any technique that disrupts and removes clot is effective and many modalities have been reported with demonstrated effectiveness. Personally, after having tried local infiltration of tPA, aspiration alone, or with largest stent retrievers as well as peripheral tools such as Angiojet, I have settled on Fogarty balloon thrombectomy. I use a 3 or 4F Fogarty balloon catheter depending on diameter on CT of occluded sinus through a long 6F sheath placed in the jugular bulb and use simultaneous aspiration through the long sheath. Of all strategies, I have found this to be most effective and expeditious. Even when a patient presents with a focal ICH, we try to recanalize emergently and limit going to operating room for imminent herniation.

With appropriate medical therapy, patients with CVST/CVO experience recanalization in about 85% of cases. Recanalization is more common in the SSS and straight sinus (more than transverse and sigmoid sinuses) and generally does not improve radiographically after 4 months of anticoagulation therapy. While the risk of recurrent CVST/CVO varies across studies and the follow-up times are short, multiple authorities have estimated the rate of restenosis and/or occlusion to be 0 to 10%.

Clinical and Radiographic Follow-up Patients with treated and nontreated CVST/CVO should have regular clinical and radiographic follow-up. Repeat dedicated venous imaging (most commonly MRV) is recommended in all patients with persistent, worsening, or recurrent clinical signs and symptoms despite adequate therapy. Repeat venous imaging at 3 to 6 months after initiation of anticoagulation treatment should be performed in all patients to evaluate recanalization. However, it is important to note that CVST/CVO recanalization may not necessarily correlate with the resolution of the patient’s clinical symptoms.

Expert Commentary The protean signs and symptoms of CVST/CVO necessitate that physicians maintain a high degree of clinical suspicion in the diagnosis and treatment of this uncommon disease. This is particularly true when clinical risk factors are present in a patient that suggests a hypercoagulable state. In general, most patients with CVST/CVO never come to neurosurgical attention given the current standard of medical management (e.g., systemic anticoagulation). However, in select patients (e.g., those who experience clinical deterioration despite anticoagulation therapy, those with tenacious clot burden, and those who exhibit signs and symptoms of medically refractory malignant intracranial hypertension), surgical and/or endovascular neurosurgical intervention may be warranted. Surgical therapies mostly consist of large calvarial decompressive procedures for the immediate relief of elevated ICP (+/− hematoma evacuation; +/− resection of nonviable brain tissue). Endovascular strategies focus mainly on chemical or mechanical clot disruption. Our preferred approach in these circumstances is mechanical thrombectomy with a stent retrieval device. Our endovascular practice consists of placement of an 8F transvenous femoral sheath with insertion of a 6F guide catheter into the jugular vein. This platform provides maximal support to navigate the tortuosity of the intracerebral venous system. In a triaxial fashion, the microcatheter/microwire is advanced retrogradely through the venous system to the level of the thrombus. The thrombus is traversed with the microwire/microcatheter and the stent retrieval device is deployed proximal to the thrombus. Then, using an aspiration/thrombectomy technique, the thrombus is mechanically disrupted and removed. We have found that a larger diameter stent retriever (e.g., 6 × 30 mm) in the venous dural sinuses and large cerebral cortical veins may be superior to a smaller device as it affords greater radial outward force on the compliant venous wall. Rarely, if mechanical thrombectomy is

Robert H. Rosenwasser, MD Thomas Jefferson University, Philadelphia, PA

Editor Commentary

Adnan H. Siddiqui, MD, PhD University at Buffalo, Buffalo, NY

Suggested Reading Borhani Haghighi A, Mahmoodi M, Edgell RC, et al. Mechanical thrombectomy for cerebral venous sinus thrombosis: a comprehensive literature review. Clin Appl Thromb Hemost 2014;20(5):507–515 Canhão P, Falcão F, Ferro JM. Thrombolytics for cerebral sinus thrombosis: a systematic review. Cerebrovasc Dis 2003;15(3):159–166 Coutinho J, de Bruijn SFTM, Deveber G, Stam J. Anticoagulation for cerebral venous sinus thrombosis. Cochrane Database Syst Rev 2011(8):CD002005 Coutinho JM, Ferro JM, Canhão P, Barinagarrementeria F, Bousser MG, Stam J; ISCVT Investigators. Unfractionated or low-molecular weight heparin for the treatment of cerebral venous thrombosis. Stroke 2010;41(11):2575–2580 Ferro JM, Canhão P, Stam J, Bousser MG, Barinagarrementeria F; ISCVT Investigators. Prognosis of cerebral vein and dural sinus thrombosis: results of the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT). Stroke 2004;35(3):664–670 Ferro JM, Crassard I, Coutinho JM, et al; Second International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT 2) Investigators. Decompressive surgery in cerebrovenous thrombosis: a multicenter registry and a systematic review of individual patient data. Stroke 2011;42(10):2825–2831 Saposnik G, Barinagarrementeria F, Brown RD Jr, et al; American Heart Association Stroke Council and the Council on Epidemiology and Prevention. Diagnosis and management of cerebral venous thrombosis: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2011;42(4):1158–1192 Stam J, Majoie CB, van Delden OM, van Lienden KP, Reekers JA. Endovascular thrombectomy and thrombolysis for severe cerebral sinus thrombosis: a prospective study. Stroke 2008;39(5):1487–1490

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Section II Aneurysms—Anterior Circulation

18 Cervical Carotid Artery Aneurysms

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19 Cavernous Carotid Artery Aneurysms

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20 Cave Carotid Artery Aneurysms

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21 Superior Hypophyseal Artery Aneurysms 135 22 Ophthalmic Artery Aneurysms

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23 Posterior Communicating Artery Aneurysms

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24 Anterior Choroidal Artery Aneurysms

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25 Internal Carotid Artery Bifurcation Aneurysms

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26 Middle Cerebral Artery Aneurysms

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27 Distal Middle Cerebral Artery Aneurysms

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28 Anterior Cerebral Artery Aneurysms

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29 Anterior Communicating Artery Aneurysms

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30 Pericallosal Artery Aneurysms

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31 Giant Aneurysms of the Anterior Circulation

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32 Fusiform Aneurysms of the Anterior Circulation

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33 Dissecting Intracranial Aneurysms of the Anterior Circulation 220 34 Traumatic Intracranial Aneurysms of the Anterior Circulation

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35 Previously Coiled Recurrent Aneurysms of the Anterior Circulation 232 36 Previously Clipped Recurrent Aneurysms113 the Anterior Circulation 240 Rangel-Castilla et al. Decision Making in Neurovascular Disease (ISBNof 978-1-68420-057-3), copyright © 2018 Thieme Medical Publishers. All rights reserved. Usage subject to terms and conditions of license.

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18 Cervical Carotid Artery Aneurysms Vernard S. Fennell, Peter Nakaji, and Robert F. Spetzler

Abstract Cervical carotid artery (CCA) aneurysms account for 0.4 to 4% of all peripheral artery aneurysms. Their pathogenic origin can be atherosclerosis, arterial dissection, mycotic, and secondary to previous neck surgery or collagen diseases. Patients with CCA aneurysms can be asymptomatic or present with mass effect symptoms, cranial nerve dysfunction, or cerebral ischemia. Computed tomography (CT) and magnetic resonance imaging (MRI) of the brain as well as CT or MR angiography of the head and neck should be obtained. Digital subtraction angiography should also be obtained. Asymptomatic patients can be managed conservatively. Patients with cerebral ischemia symptoms can be treated with antiplatelet therapy. Symptomatic patients, patients who fail medical therapy, or asymptomatic aneurysms with evidence of growth should be treated. There are several cerebrovascular (direct clipping, resection with graft or direct repair, vessel ligation) or endovascular (coil, stenting, flow diversion, vessel sacrifice) techniques available. The type of intervention depends on type of symptoms, patient’s clinical condition, angioarchitecture of the aneurysm, location of aneurysm, and presence of hostile neck. Data on the outcome of treatment are sparse and heterogeneous. All patients should be followed up closely with vascular imaging. Keywords: carotid artery, carotid artery aneurysm, cervical carotid artery, cervical carotid artery aneurysms, extracranial carotid artery aneurysms, pseudoaneurysms

a

d

Introduction Extracranial carotid artery aneurysms—mainly aneurysms of the cervical segment of the internal carotid artery (ICA)—are rare, accounting for only 0.4 to 4% of all peripheral artery aneurysms. Invasive treatment of extracranial carotid aneurysms comprises 0.6 to 3.8% of all extracranial carotid interventions. Furthermore, the morphology and causes of these aneurysms are diverse. Therefore, few reliable epidemiological data are available regarding immediate surgical outcomes or long-term follow-up. A retrospective review of aneurysm repair at one institution noted 67 cervical carotid aneurysms in 65 patients, representing a variety of causes, including atherosclerotic and traumatic factors and previous carotid procedures resulting in pseudoaneurysm. This observation was similar to the results of a review by Welleweerd and colleagues of pooled data on 1,239 patients from published reports of series with 10 or more patients available in the medical literature up to 2014. The presenting symptoms of cervical carotid aneurysms vary but are due to mass effect in 33 to 58% and cerebral ischemia in 36 to 43% of cases (1, 3, 4 in algorithm ). Some patients may have no symptoms at all (2, 5, 8 in algorithm). A large number of other signs and symptoms have been noted in individual patients; these include cranial nerve dysfunction, pain (including headache), dysphagia, dizziness, tinnitus, hoarseness, pharyngeal mass, tracheal obstruction, and rupture (►Figs. 18.1 and 18.2).

b

c

e

Fig 18.1 Representative case of a 39-year-old woman with a cervical carotid artery aneurysm who presented with headache as her chief complaint. Saccular right internal carotid artery aneurysm (a, axial magnetic resonance angiogram). Large saccular cervical carotid aneurysm can be seen just distal to the bifurcation (b, sagittal computed tomography angiogram). Cervical carotid artery aneurysm (c, three-dimensional reconstruction). Resection of the internal carotid artery (ICA) aneurysm with clip showing (d, axial computed tomography angiogram). Aneurysm after being clipped (e, sagittal three-dimensional reconstruction). (Used with permission from Barrow Neurological Institute, Phoenix, AZ.)

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Aneurysms—Anterior Circulation

Algorithm 18.1 Decision-making algorithm for cervical carotid artery aneurysm.

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18 Cervical Carotid Artery Aneurysms

Fig. 18.2 Pulsatile neck mass in a 9-year-old boy with no good endovascular option (a, preoperative sagittal computed tomography angiogram; and b, preoperative digital subtraction angiogram of the left common carotid artery, cervical injection, lateral view). Treatment included aneurysmorrhaphy, direct reanastomosis, and clip-wrapping (c and d, postoperative digital subtraction angiogram of the left common carotid artery, cervical injection, lateral view [c] and anteroposterior view [d]). (Used with permission from Barrow Neurological Institute, Phoenix, AZ.)

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Whether it is necessary to treat cervical carotid aneurysms is indeed an intriguing question. Because of their rarity, not enough data are available to accurately know the natural history and where the starting points for treatment should be. A review of the available data shows that there may be a difference, at least in 30-day outcomes, between surgically (open vascular and endovascular) treated cervical carotid aneurysms and conservatively managed cervical carotid aneurysms. However, as a result of the heterogeneous nature of the existing data and the diversity of open surgical, endovascular, and conservative treatments that have been reported, it is challenging to arrive at a single clinically reliable treatment method.

vein often helps to complete the venous dissection. Medial dissections along the jugular vein to identify the common, external, and internal portions of the carotid artery are critical steps in safe exposure. Identification and control of the superior thyroid artery are necessary to properly ensure vascular control. It is important to identify nerve structures that are likely to be distorted, depending on the location of the aneurysm. The hypoglossal nerve often travels medially to the jugular vein and courses laterally to medially over the cervical ICA. Careful dissection of the hypoglossal nerve at this juncture is crucial, given the likely distortion of the local anatomy. If the nerve is not adequately visualized and is retracted without identification, it may result in palsy. It is also essential to understand the relationship between the spinal accessory nerve and the sternocleidomastoid. The vagus nerve lies deep to the common carotid artery in the carotid sheath and could be injured when the vessels are clamped. With medial retraction in a high exposure of the cervical ICA, the marginal mandibular branch of the facial nerve is at risk. Injury to the pericarotid sympathetic chain has been described as resulting in transient Horner’s syndrome. Also, with high exposure of the ICA, identification of the posterior belly of the digastric muscle is useful, as its sacrifice can improve exposure without clinically significant morbidity.

Anatomical Considerations

Pathophysiology/Classification

Anatomical considerations are similar to those for occlusive carotid disease. It is imperative to know the location of the common carotid artery bifurcation in relation to the cervical level, particularly with regard to the mandible. Determining its location is important because 65% of common carotid bifurcations occur between C3 and C4. Retrospective surgical and endovascular data show that complications are most commonly reflected in ischemic sequelae and cranial nerve dysfunction. Exposure of the carotid artery requires identification of critical neurovascular structures. First, the jugular vein is encountered, and its medial and lateral borders are identified. Locating the common facial

The pathophysiological classifications of cervical carotid aneurysms in the literature are varied. These aneurysms can be classified morphologically as fusiform, saccular, or pseudoaneurysms (►Fig. 18.3). They can be further classified by their pathogenic origin as atherosclerotic, traumatic, mycotic, or other/miscellaneous. However, it is notable that many reports identify neither the morphological shape nor the pathophysiological source of cervical carotid aneurysms. In up to 16 to 20% of cases, the pathogenic origin is classified as other/miscellaneous (e.g., iatrogenic, Behçet’s disease, Ehlers–Danlos syndrome, or cryptogenic), or this information is missing.

Major controversies in decision making addressed in this chapter include: 1. Whether or not treatment is indicated. 2. Open versus endovascular treatment for cervical ICA aneurysms. 3. Management of cervical ICA aneurysms causing mass effect. 4. Management of cervical ICA pseudoaneurysms associated with arterial dissection.

Whether to Treat

Fig. 18.3 Pulsatile neck mass in a 60-year-old woman who presented with transient ischemia 4 years after a carotid endarterectomy. A large cervical carotid artery pseudoaneurysm was identified (a, magnetic resonance angiogram of the neck, three-dimensional reconstruction). The planned reconstruction involved a bypass using the internal maxillary segment of the external carotid artery (b, magnetic resonance angiogram of the neck, three-dimensional reconstruction; bottom dotted line, up arrow) and the cervical internal carotid artery (top dotted line, down arrow), which resulted in resolution of the deficit (c, postoperative magnetic resonance angiogram of the neck, sagittal view). (Used with permission from Barrow Neurological Institute, Phoenix, AZ.)

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18 Cervical Carotid Artery Aneurysms

Workup

Conservative Management

Clinical Evaluation

The conservative measures discussed in the medical literature have included anticoagulant therapy, no therapy, antiplatelet therapy, medical management (not specified), and conservative therapy (not specified). Asymptomatic aneurysms may be treated with antiplatelet therapy and followed with serial CT angiography of the neck (2, 5 in algorithm). When CTA documents enlargement of an aneurysm (8 in algorithm), treatment should proceed as for ischemia (6, 9, 10 in algorithm). There are, however, a few patients who have had documented conservative management, and no superior conservative treatment paradigm has emerged.

Patients who present with possible cervical carotid aneurysms may be symptomatic or asymptomatic (1, 2 in algorithm). Clinical evaluation is necessary for symptomatic patients (1, 3, 4 in algorithm), whereas asymptomatic patients may be followed more conservatively (5 in algorithm). Clinical evaluation of symptomatic patients includes a workup for a suspected transient ischemic attack (TIA) (6 in algorithm). An exhaustive review of the workup for TIA is outside the scope of this chapter. However, the workup should include several key elements, such as determining potential contributing mechanisms, identifying contributing risk factors, and using safe and relevant evaluation techniques. A complete clinical examination, especially with evaluation of motor and cranial nerve function, is a key initial step. Routine laboratory evaluation (complete blood cell count, coagulation studies, electrolytes, glucose, and basic inflammatory markers), electrocardiogram, and chest radiographs are also useful.

Imaging Depending on the presenting symptoms of the patient, multiple imaging methods should be explored. If a TIA is the main clinical presentation, a likely diagnostic sequence could include noncontrast computed tomography (CT) of the head, followed by magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) of the head and neck, and possibly a carotid Doppler ultrasound study (6 in algorithm). If a pulsatile or large mass is part of the clinical presentation, then MRI and MRA of the neck may be the initial studies, possibly followed by CT angiography (CTA) of the neck, particularly if the osseous–vascular relationships are unclear (7 in algorithm). Depending on the results of these initial studies, digital subtraction angiography should be obtained, especially if the vascular relationships are unclear or if anatomical or other clinical factors indicate the need for endovascular treatment.

Differential Diagnosis After imaging, the differential diagnosis may include vascular anomalies, hemangioma, and hemangiolymphangioma of the neck. Inflammatory pathology, such as cervical lymphadenopathy and sarcoidosis, should also be considered. Neoplastic pathology, such as carotid body tumor, paraganglioma, schwannoma, lymphoma, and metastatic neck carcinoma, should be part of the differential diagnosis as well.

Treatment Choice of Treatment Conservative management may be an option, depending on the clinical presentation (2, 5, 8 in algorithm). However, as noted below, conservatively treated patients, such as those on antiplatelet therapy, appear to have less favorable outcomes than surgically treated patients with regard to mortality and stroke. Diverse options for surgical treatment have been reported, but the rare nature of cervical carotid aneurysms has led to the lack of any one single operative strategy. In the Welleweerd et al review of pooled data from 1,239 patients, conservative treatment was chosen in 11% of the cases and invasive treatment in 89%. Of the cases with invasive treatment, direct surgery was selected in 94%, endovascular intervention in 5%, and a hybrid approach in 1%. More than 10 different surgical approaches were reported. Various types of endovascular procedures and tools were also used. The type of intervention depends on the angioarchitecture of the aneurysm (fusiform or saccular), whether it occupies a high position in the ICA, and whether hostile neck due to previous neck surgery or irradiation is present (9, 10 in algorithm).

Cerebrovascular Management—Operative Nuances Reported surgical approaches to treatment of cervical carotid aneurysms have included resection with interposition graft, resection with direct anastomosis, partial resection with vessel reconstruction, aneurysmorrhaphy, extracranial-to-intracranial transposition bypass, extracranial-to-intracranial bypass with graft, vessel ligation, and various combined approaches. A large number of patients have undergone surgery not otherwise specified. Resection with interposition graft and resection with direct anastomosis are the two most commonly reported surgical interventions. Fitzpatrick et al and Sundt et al described the use of a saphenous vein graft for extracranial-to-intracranial bypass (from the extracranial ICA or the common carotid artery). They reported good results, albeit for a limited number of patients. The use of a cerebrovascular surgical team is ideal for tackling cervical carotid aneurysms. It is critical to implement copious intraoperative anticoagulation, neuroanesthesia with targeted burst suppression, and neurophysiological monitoring. Depending on the surgical approach, it may also be necessary to use various types of intraoperative vascular imaging surveillance (e.g., Doppler ultrasound, indocyanine green angiography, or digital subtraction angiography). Some combined approaches may necessitate collaboration with otolaryngology colleagues.

Endovascular Management—Operative Nuances Reported endovascular treatment methods have involved stent placement, balloon exclusion, stent-assisted coil embolization, balloon-assisted embolysate placement, intraluminal flow diversion, and unspecified endovascular procedures (9, 10 in algorithm). As endovascular technology continues to advance, more options are certain to become available. In a 2011 review of reports from 1995 through 2010, involving a total of 224 patients with endovascular stenting of extracranial carotid aneurysms, Li and colleagues found wide-ranging variability in stent type, diameter, and length, and in the number of stents that were used. A total of 22 different brands of stent grafts were reported, with the most commonly used brand being the Wallstent (Boston Scientific Corp.). There were also a considerable number of cases for which the stent type was either unknown or data were not available. Recently, the use of flow-diverting stents has become more popular with excellent results (►Fig. 18.4).

Complication Avoidance Outcome Data on the outcome of treatment are sparse and heterogeneous, and the reported morbidity and mortality rates have been less than optimal. A 1990 review reported a stroke risk of 25% and a mortality of 20% for carotid ligation. The 2015 review by Welleweerd and colleagues noted that the 30-day mortality was 4.67% for patients with conservatively managed aneurysms, compared with 1.91% for those with surgically treated aneurysms; the stroke rate was 6.67% for patients with

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Fig. 18.4 A 66-year-old woman presented with recurrent transient ischemia attacks and strokes occurring over the last 2 years. A large cervical internal carotid artery (ICA) pseudoaneurysm and dissection were identified. (a) Digital subtraction angiography (DSA) demonstrated a large pseudoaneurysm secondary to arterial dissection at the upper cervical ICA. Endovascular repair with a flow-diverting stent was then performed. (b) DSA demonstrating the guide catheter at the common ICA and distal access. (c) Balloon angioplasty performed at the segment of dissection/stenosis. (d) Flow-diverting stent being deployed. (e) Immediate poststenting DSA demonstrating reconstruction of the ICA stenosis and dissection and intrapseudoaneurysm flow stasis. (Images provided courtesy of Leonardo Rangel-Castilla, Mayo Clinic, Rochester, MN and Adnan H. Siddiqui, University at Buffalo, Buffalo, NY.)

conservative management, compared with 5.16% for those who underwent surgery (supports algorithm steps 2 and 5). The reported rate of cranial nerve injury after surgery was 12%. In the above-mentioned 2011 review of the literature on endovascular treatment of extracranial carotid aneurysms, the procedure was reported to be successful in 93% of cases. In-hospital mortality was 4.1%, the stroke rate was 1.8%, and the rate of cranial nerve injury was 0.5%. The stent graft patency rate was 93.2%, and the most common postoperative complication was type I or type III endoleak, which was reported in 8.1% of cases (supports algorithm steps 2 and 5). Potential conclusions from these outcome data must be tempered with the understanding that the best—and only—data were pooled from multiple studies with widely diverse treatment types and patient heterogeneity, and possible adjustments for confounding clinical variables were not available. It is important to reiterate that no available prospective evidence exists to clearly validate any one treatment over another.

Durability and Rate of Recurrence Given the nature of the data, the surgical reports do not yield reliable estimates of durability and recurrence. The pooled retrospective data from endovascularly treated cervical carotid aneurysms showed a mean follow-up of 15.4 ± 15.3 months. Again, only limited conclusions can be drawn from such a wide range in a relatively small collective sample.

Clinical and Radiographic Follow-up The lack of data on the natural history of such a rare pathologic condition makes it difficult to determine the timing of clinical or radiographic follow-up. CTA of the head and neck could be considered for surveillance imaging supports (supports algorithm steps 5–7). Because the natural history of this condition is elusive, it would be prudent to use a shorter time frame initially, with progressively longer intervals between imaging.

Editor Commentary Extracranial cervical aneurysms are frequently noted during follow-up of patients with cervical carotid dissections. In most cases, they are asymptomatic, and radiographic surveillance with aspirin monotherapy is adequate prophylaxis against future embolic events. Rarely, patients with these aneurysms present with an embolic event, and in these cases one may employ either antiplatelet therapy if the patient is treatment naïve or consider repair. Most rare are presentations with space-occupying lesions causing symptoms from direct compression of oropharyngeal structures or compressive cranial neuropathies. Treatment depends on precise anatomy. The vast majority of pseudoaneurysms that occur postdissection in patients who are symptomatic and on antiplatelet therapy can be treated with a peripheral closed-cell stent construct. It is important to note that if the aneurysm is close to or

abuts the petrous carotid, most peripheral stents cannot easily navigate the proximal petrous bend and an intracranial stent is required for the distal segment, following which the proximal segment can be bridged using a peripheral stent if needed. If the cervical parent artery is severely tortuous, then only intracranial stents may be able to navigate, and in that regard flow diverters are ideal for recreating normal vessel anatomy. The main concern in this regard is stent foreshortening especially with neck movement; therefore, one should size adequately and use multiple overlapping stents if a long segment is involved. Additionally, if the aneurysm is large or giant, then consideration should be given to placement of coils to further support the flow diverter remaining in the parent vessel rather than prolapsing into the aneurysm. If the cervical artery anatomy is too tortuous to navigate via endovascular tools for stent reconstruction, then one should consider open microsurgical repair. The most important element here is the distance from the skull base to the normal vessel, as getting distal cervical access beyond the second cervical vertebra requires adjunctive surgical maneuvers with added morbidity, and surgical control becomes harder to maintain with increased depth. If, however, the distal normal vessel is easily accessible, then either an end-to-end reanastomosis (vessel-shortening procedure using natural tortuosity) or an interposition graft may be an excellent option. In cases where revascularization is needed and tortuosity prevents endovascular access and distal cervical involvement precludes a direct cervical repair, one may use a radial or saphenous vein graft to perform a high-flow extracranial-tointracranial bypass with proximal cervical vessel ligation/occlusion. While it is ideal to allow continued patency of the cervical carotid artery, one has to balance the risk of thromboembolic events during or following an endovascular or microsurgical reconstruction. Therefore, while simple endovascular repair with a single peripheral stent construct for symptomatic aneurysm is reasonable, if the anatomy is complicated for either endovascular or microsurgical repair, then one should perform a balloon test occlusion to see if the vessel can be sacrificed. That may be the intervention with the lowest risk, especially in older patients. Finally, my approach is endovascular first in these cases as I believe these dissected vessels have intrinsic fragility that may complicate open repair more so than endovascular reinforcement with stenting well proximal and distal to the affected segment. Adnan H. Siddiqui, MD, PhD University at Buffalo, Buffalo, NY

Suggested Reading Attigah N, Külkens S, Zausig N, et al. Surgical therapy of extracranial carotid artery aneurysms: long-term results over a 24-year period. Eur J Vasc Endovasc Surg 2009;37(2):127–133 Ausman JI, Pearce JE, de los Reyes RA, Schanz G. Treatment of a high extracranial carotid artery aneurysm with CCA-MCA bypass and carotid ligation. Case report. J Neurosurg 1983;58(3):421–424

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18 Cervical Carotid Artery Aneurysms Countee RW, Vijayanathan T, Barrese C. Cervical carotid aneurysm presenting as recurrent cerebral ischemia with head turning. Stroke 1979;10(2):144–147 El-Sabrout R, Cooley DA. Extracranial carotid artery aneurysms: Texas Heart Institute experience. J Vasc Surg 2000;31(4):702–712 Fitzpatrick BC, Spetzler RF, Ballard JL, Zimmerman RS. Cervical-to-petrous internal carotid artery bypass procedure. Technical note. J Neurosurg 1993;79(1):138–141 Hertzer NR. Extracranial carotid aneurysms: a new look at an old problem. J Vasc Surg 2000;31(4):823–825 Li Z, Chang G, Yao C, et al. Endovascular stenting of extracranial carotid artery aneurysm: a systematic review. Eur J Vasc Endovasc Surg 2011;42(4):419–426 Sundt TM Jr, Pearson BW, Piepgras DG, Houser OW, Mokri B. Surgical management of aneurysms of the distal extracranial internal carotid artery. J Neurosurg 1986;64(2):169–182

Welleweerd JC, den Ruijter HM, Nelissen BG, et al. Management of extracranial carotid artery aneurysm. Eur J Vasc Endovasc Surg 2015;50(2):141–147 Wemple JB, Smith GW. Extracranial carotid aneurysm. Report of four cases. J Neurosurg 1966;24(3):667–671 Wolfe SQ, Mueller-Kronast N, Aziz-Sultan MA, Zauner A, Bhatia S. Extracranial carotid artery pseudoaneurysm presenting with embolic stroke in a pediatric patient. Case report. J Neurosurg Pediatr 2008;1(3):240–243 Zhou W, Lin PH, Bush RL, et al. Carotid artery aneurysm: evolution of management over two decades. J Vasc Surg 2006;43(3):493–496, discussion 497

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19 Cavernous Carotid Artery Aneurysms Karam Moon, Giovanni R. Malaty, Bradley A. Gross, and Felipe C. Albuquerque

Abstract Cavernous carotid aneurysms (CCAs) account for 2 to 9% of all intracranial aneurysms. Their position in the extradural space and within dural walls limits their growth and risk of rupture. The majority of CCAs are asymptomatic. If CCAs are large, patients can present with cranial nerve palsies, and if CCAs are ruptured, patients can present with carotid-cavernous fistula, severe epistaxis, or occasionally with subarachnoid hemorrhage. CCAs are generally considered to be lower-risk aneurysms compared to other intracranial aneurysms. Digital subtraction angiography is the gold standard for aneurysm visualization and characterization. Small asymptomatic CCAs should remain under observation. Large or giant CCAs with irregular features, extending into subarachnoid space, bony erosion, or documented growth should be considered for treatment. Symptomatic and ruptured CCAs must be treated. Endovascular procedures have become the preferred method of treatment, including coiling, stent-assisted coiling, flow diversion, or parent vessel occlusion. Flow diversion has become the first-line therapy for most CCAs. Nowadays, open cerebrovascular techniques are rarely used. Complete obliteration rates with flow diversion are 66 to 100%, with a recent meta-analysis demonstrating an occlusion rate of 76%. Keywords: balloon test occlusion, cavernous carotid artery, cavernous carotid artery aneurysm, cavernous sinus, flow diversion, Pipeline Embolization Device

Introduction Cavernous carotid aneurysms (CCAs) are located within the cavernous segment of the internal carotid artery (ICA). According to Bouthillier’s classification, the cavernous segment begins at the petrolingual ligament and extends to the proximal dural ring. CCAs account for 2 to 9% of all intracranial aneurysms, with a high proportion of wide-necked aneurysms. Their position in the extradural space of the cavernous sinus, with the dural walls isolating the cavernous segment from the brain, limits growth and lowers the risk of rupture. However, their proximity to multiple cranial nerves can lead to mass effect symptoms. When a rupture does occur, CCAs can present with carotid-cavernous fistulas, severe epistaxis, or, in rare cases, subarachnoid hemorrhage (SAH). The location of the cavernous ICA within the cavernous sinus relative to several cranial nerves and postganglionic sympathetic fibers makes CCAs difficult to manipulate via microsurgical techniques. Therefore, endovascular procedures have become the preferred method of treatment, most notably with flow diversion devices such as the Pipeline Embolization Device (PED; eV3). Given the current widespread acceptance of flow diversion as a first-line therapy for most CCAs, this chapter will focus on the details of this approach. Major controversies in decision making addressed in this chapter include: 1. Whether or not treatment is indicated. 2. Open versus endovascular treatment for ruptured and unruptured cavernous ICA aneurysms. 3. The role of flow diversion stents and other endovascular techniques. 4. Whether an advanced surgical technique is indicated (ICA sacrifice and bypass) and, if so, when.

Whether to Treat CCAs are generally considered to be lower-risk aneurysms compared with other intracranial aneurysms, with an estimated cumulative annual risk of rupture of 0 to 1.6% and a reported cumulative annual risk of SAH of 0.2 to 0.4%. According to the International Study of Unruptured Intracranial Aneurysms (ISUIA), the 5-year cumulative rupture rate for CCAs with no previous history of SAH is 0% for aneurysms less than 7 mm, 0%

for aneurysms 7 to 12 mm, 3% for aneurysms 13 to 24 mm, and 6.4% for aneurysms larger than 25 mm. Therefore, the decision making for CCAs relies heavily on the presence of symptoms, size, and rupture status of the aneurysm (1–5 in algorithm). In general, unruptured asymptomatic CCAs should be handled on a case-by-case basis, with the morphology and size of the aneurysm taken into consideration along with serial imaging results. Small asymptomatic CCAs should remain under observation (2 in algorithm). Large or giant aneurysms with irregular features or extension into the subarachnoid space, bony erosion, or lesions exhibiting significant growth over interval imaging should be considered for treatment (3 in algorithm). Patients with ruptured CCAs who present with either SAH or carotid-cavernous fistulas should be treated to preserve the function of the proximate cranial nerves and prevent future repeated rupture (4 in algorithm). Most cases will require formal angiography for definitive diagnosis, with treatment often carried out in the same setting. Patients with unruptured symptomatic CCAs may present with cranial nerve palsies affecting vision (e.g., diplopia and blurred vision), headaches, facial pain and numbness, and embolic complications. These symptoms can be secondary to both mass effect and acute thrombotic changes. Patients with unruptured CCAs who present with intolerable symptoms should be considered for treatment (5 in algorithm).

Anatomical Considerations CCAs form on the cavernous segment of the ICA, which is located within the extradural space of the cavernous sinus, bounded anteriorly by the superior ophthalmic fissure and posteriorly by the petrous apex. The cavernous segment sits adjacent to several cranial nerves, most notably cranial nerves II, III, V, and VI. Thus, CCAs may present with cranial neuropathy as a result of mass effect or arterial pulsations. The orientation of the segment within the ICA is superior to the petrous segment and inferior to the supraclinoid segment. After passing through the carotid bifurcation and petrous segment, blood flows through the foramen lacerum, exits the skull, and passes the petrolingual ligament before entering the cavernous segment known as the C4 segment in Bouthillier’s classification. This segment is one of the few to feature nonmajor separate branches, supplying the posterior pituitary and portions of the clivus, cranial nerves III, IV, V, and VI, pituitary gland, tentorium cerebelli, and adjacent dura. The meningohypophyseal trunk consists of the lateral tentorial artery, marginal tentorial artery, inferior hypophyseal artery, and lateral clival artery. This branch of the cavernous segment is easily seen on angiographic imaging. The inferolateral trunk, which arises from the lateral aspect of the cavernous segment, supplies adjacent dura and cranial nerves and has extensive anastomoses with the extracranial circulation.

Workup Clinical Evaluation Although most CCAs are discovered incidentally during diagnostic imaging for other indications, some may produce intolerable symptoms. Patients with symptomatic CCAs commonly present with cranial nerve palsies, including symptoms such as diplopia, decreased visual sharpness, and facial pain or loss of sensation. Very rarely are these aneurysms discovered because of rupture or SAH.

Imaging Initial noninvasive imaging workup typically consists of computed tomography angiography (CTA) or magnetic resonance imaging (MRI)

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19 Cavernous Carotid Artery Aneurysms

Algorithm 19.1 Decision-making algorithm for cavernous carotid artery aneurysms.

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Aneurysms—Anterior Circulation and magnetic resonance angiography (MRA). Digital subtraction angiography, combined with three-dimensional rotational angiography, is the gold standard for aneurysm visualization. Computed tomography (CT) without contrast allows for identification of SAH.

Differential Diagnosis The differential diagnosis for CCAs depends largely on the imaging method. On studies without contrast, large space-occupying lesions in the region of the cavernous segment of the ICA or the cavernous sinus can include primary or metastatic neoplasms. Opacification on CTA in the region of the cavernous segment can also represent a carotid-cavernous fistula.

Treatment Choice of Treatment and the Influence of Intracerebral Hematoma Small unruptured CCAs are generally managed conservatively (2 in algorithm). For patients with large or giant asymptomatic CCAs requiring treatment and for patients with symptomatic unruptured CCAs who have no contraindications to dual antiplatelet therapy, flow diversion should be considered as the first-line treatment (3, 6 in algorithm). If dual antiplatelet therapy is contraindicated, a balloon test should be performed (7 in algorithm). Surgical ligation or coiling should be considered if the test indicates tolerance for carotid artery occlusion (8 in algorithm); bypass surgery should be considered for patients unable to tolerate the test occlusion (9 in algorithm). Given that CCAs rarely present with intracranial or intracerebral hemorrhage/hematoma, this is seldom a consideration in the choice of treatment.

Drake et al observed 1.3% morbidity and 1.3% mortality in a series of 77 patients with CCAs treated by ligation that included preoperative balloon test occlusion, with most complications due to thromboembolism. Ligation has historically been shown to successfully thrombose CCAs, and introduction of balloon test occlusion has made the procedure safer and more reliable. However, the persistence of postoperative ischemic complications and deaths makes ligation a last-resort procedure.

Clipping The open surgical approach of clipping, introduced by Dandy in the 1930s, was first applied to CCAs via pilojection by Gallagher and Baiz in 1964. The method has since been refined by surgeons such as Dolenc, and microscope technology has improved to reduce risks. In a 1988 series of 32 patients who underwent clipping, Diaz et al found complete resolution of CCAs in 20 patients (62.5%), with no neurological deficit. However, clipping remains a high-risk procedure because the presence of surrounding structures of the skull base not only raises the surgical risk but also steepens the learning curve for surgeons. An extensive understanding of the anatomy of the cavernous sinus is required to navigate the spaces of exposure through the nearby cranial nerves. The Parkinson triangle offers exposure of the cavernous sinus and is made up superiorly by the oculomotor and trochlear nerves, and inferiorly by the abducens nerve. Proximal control must be obtained by exposing the ICA at the neck or the intrapetrous carotid artery through Glasscock’s triangle, made up of the mandibular nerve, greater superficial petrosal nerve, and foramen spinosum. Because of the complexity of this approach, high surgical risk, and efficacy of endovascular modalities, microsurgical clipping for CCAs has fallen out of favor.

Endovascular Management—Operative Nuances

Conservative Management

Coiling and Stent-Assisted Coiling

Most asymptomatic unruptured CCAs are found incidentally during noninvasive imaging for other disorders. Decisions on management must take into account the natural history and etiology of the aneurysm, patient age and smoking history, and risk to the patient. Because of their low risk of rupture, asymptomatic aneurysms smaller than 13 mm are managed conservatively with periodic follow-up imaging, most commonly angiography and MRI, to monitor growth (2 in algorithm). Asymptomatic CCAs 13 mm or larger may be kept under observation or flow diversion may be considered (3 in algorithm).

After the U.S. Food and Drug Administration approval of the Guglielmi detachable coil in 1995, coiling gained popularity as an endovascular treatment for cerebral aneurysms, primarily because it allows the parent artery to remain in circulation. Class 1 (complete) occlusion, as assessed with the Raymond system for classification of aneurysm occlusion, by coiling has been reported in up to 80% of CCAs. In cases of wide-neck aneurysms with unfavorable geometries inaccessible to direct surgical intervention, coiling with adjunctive stents or balloons is a viable alternative. These include aneurysms of neck width greater than 4 mm or a dome-to-neck ratio less than 2. However, patients with large symptomatic aneurysms may not always be ideal candidates for primary coil embolization, because of the risk of worsening cranial neuropathies by continued or increased mass effect from the aneurysm dome. Although this mechanism of effect has not been confirmed in laboratory models, this risk should be minimized by considering flow diversion before primary coil embolization.

Cerebrovascular Management—Operative Nuances Hunterian Ligation (Surgical Parent Artery Sacrifice) Proximal artery ligation was an early treatment for carotid artery aneurysm popularized by Hunter in the eighteenth century and developed further by Abernethy to treat cerebral vasculature. Ligation involves either directly sealing the carotid artery in the neck or occluding it at both the neck and the distal end near the brain base. From 1868 to 1966, ligation treatment for ICA aneurysm was accompanied by high rates of morbidity and mortality, with over 20% mortality, most commonly due to cerebral infarction. Inadequate cross-circulation upon carotid occlusion led to various ischemic complications. The introduction of the Serbinenko balloon catheter in 1970 allowed the use of balloon test occlusions to determine whether patients could handle ligation (7 in algorithm). In some cases, circulation through the anterior and posterior communicating arteries will offset carotid occlusion (8 in algorithm). When the circulation is not strong enough, a bypass may be needed (9 in algorithm) (►Fig. 19.1). After the introduction of preoperative balloon tests, mortality associated with ligation declined. In 1994,

Endovascular Parent Artery Occlusion Since the introduction of the Serbinenko balloon catheter, detachable transcatheter balloons have been used to test patient tolerance for carotid artery occlusion and to occlude the vessel long term. Modern parent artery occlusion involves partly coiling the aneurysm and fully coiling the thickness of the carotid artery. As with surgical ligation, balloon test occlusion is advised in conjunction with electroencephalography to determine whether the patient can maintain stable cerebral blood flow or neurological exam in awake patients (7 in algorithm). If test results indicate poor circulation, extracranial-to-intracranial bypass before carotid sacrifice is advisable (9 in algorithm). Endovascular carotid sacrifice typically results in complete occlusion and resolves cranial nerve symptoms in nearly 100% of aneurysms. However, although rare, remote aneurysms may form after carotid occlusion because of differential flow, thus requiring continued radiographic follow-up.

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19 Cavernous Carotid Artery Aneurysms

Fig. 19.1 A 54-year-old woman presented with a several-months-long concern of diplopia (a, axial computed tomography angiography [CTA] demonstrating a 3.2-cm left cavernous internal carotid artery [ICA] aneurysm). The patient underwent proximal clip occlusion and distal bypass (b, anteroposterior, and c, lateral ICA angiography, revealing postoperative stasis within the aneurysm; d, oblique external carotid artery angiography revealing a patent bypass; e, postoperative CTA demonstrating thrombosis of the aneurysm without evidence of flow; f, drawing demonstrating the treatment strategy used for petrous ICA aneurysms, in which proximal occlusion with distal revascularization may be a treatment strategy). This same strategy could be applied for cavernous and supraclinoid ICA aneurysms. (Used with permission from Barrow Neurological Institute, Phoenix, AZ.)

Parent artery occlusion therefore offers a high rate of aneurysm obliteration, but should be considered without bypass only for patients who pass balloon occlusion tests.

Flow Diversion Flow diversion for intracranial aneurysms represents perhaps the most significant transformation in traditional paradigms for CCA treatment. With implementation of the PED, endovascular flow diversion has grown as a novel treatment, especially for large or complex intracranial aneurysms. Initial series demonstrated 6-month occlusion rates of 69 to 94%, and 1-year occlusion rates of 87 to 95%. The Pipeline Embolization Device for the Intracranial Treatment of Aneurysms (PITA) trial demonstrated 82.9% complete obliteration in 30 patients after 6 months, with a complication rate of 6.3% (supports algorithm steps 3, 6). The appeal of flow diversion for CCAs is multifold. Its ability to achieve endoluminal reconstruction of the parent vessel is well suited for CCAs, because aneurysms in this location tend to feature sidewall morphology and to lack critical perforators along the diseased segment. In addition, flow-diverting stents induce delayed thrombosis of the aneurysm dome, with resultant reduction in mass effect that often leads to improvement in concomitant cranial neuropathies. A 2014 cohort compariso n study demonstrated the superiority of flow diversion over conventional techniques (coiling or carotid vessel sacrifice) in rates of clinical improvement, aneurysmal obliteration by angiographic follow-up, retreatment, and complications (supports algorithm steps 3, 6). Finally, to help precipitate aneurysm thrombosis, adjunctive coil embolization may be carried out for larger aneurysms when a

flow diverter is placed (►Fig. 19.2). Of note, flow diversion can only be carried out in patients in whom dual-antiplatelet therapy is not contraindicated (6 in algorithm). Treatment with both aspirin and clopidogrel (or a second-generation agent such as prasugrel) is recommended for the first 6 months after the procedure, when most patients can be transitioned to single-agent therapy if follow-up angiography shows no in-stent stenosis. We generally recommend that patients be preloaded on antiplatelets 3 to 7 days before the procedure, or be given a loading dose of abciximab immediately after stent placement, followed by an oral antiplatelet load.

Technical Pearls of Pipeline Embolization Device Deployment 1. Deployment of the PED requires a 0.027-in microcatheter, such as a Marksman Micro Catheter (eV3), Headway 27 (MicroVention), and Excelsior XT-27 (Stryker Neurovascular). Distal purchase of approximately 2 cm past the lesion is required with the microcatheter, given the stiff delivery system of the PED. 2. For adjunctive coil embolization, we generally recommend “jailing” the coiling microcatheter in the aneurysm dome by placement before stent deployment. When using a Marksman for delivery of the PED, a larger guide catheter, such as a 0.088-in Neuron MAX (Penumbra) is required to accommodate an additional coiling microcatheter. 3. Use of a single device sized to span the entire length of the lesion neck is recommended. However, giant CCAs often require telescoping, or overlapping, constructs. In these cases, devices of smaller diameter should be deployed distally before deployment of larger diameter stents, so that

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Fig. 19.2 A 79-year-old woman presented with a 3-week history of acute-onset headache, associated with nausea and horizontal diplopia. (a, Imaging demonstrating a 20-mm cavernous segment internal carotid artery aneurysm.) She underwent treatment with two Pipeline Embolization Devices, along with adjunctive coil embolization. At 6-month follow-up, she had near-complete occlusion of the lesion and resolution of symptoms (b). She was neurologically intact at 19-month follow-up. (Reproduced with permission from Moon K, Albuquerque FC, Ducruet AF, Crowley RW, McDougall CG. Resolution of cranial neuropathies following treatment of intracranial aneurysms with the Pipeline Embolization Device. J Neurosurg 2014;121(5):1085–1092.)

stent apposition is optimal within each device. A more proximal stent should never be deployed or telescoped into a smaller diameter stent. 4. After deployment is initiated at the distal end of the device, the remainder of the stent can often be deployed by pushing the delivery wire, especially when trying to achieve apposition against the back wall of a curve. After the device is unsheathed, the delivery wire should be recaptured but removed with the microcatheter maintaining access through the stent, in case an additional device is necessary.

Complication Avoidance The success of flow diversion of CCAs is based on lower rates of morbidity and mortality than with conventional surgical or endovascular intervention. Total rates of complications were 2 to 36%, with most involving transient or self-limited events such as groin or access complications. Still, major complication rates of 6% or more have been reported, including major stroke, aneurysm rupture, vessel perforation, or delayed distal hemorrhages. However, intraprocedural rupture of CCAs secondary to microwire or coil perforation is rare, given that direct catheterization of the dome is not needed when placing a flow diverter. Nonetheless, numerous steps can be taken to minimize the risk of complications. Proper sizing of all devices and flow-diverting stents is critical, as parent vessel anatomy can often lead to difficult deployments and unpredictable variations in final stent length. Foreshortening the device can often lead to prolapse into the aneurysm; thus, precise catheter positioning is essential before deployment. Adequate catheter construct support ensures “one-to-one” catheter movements when deploying the stent, and a triaxial system employing a large-bore guide catheter (e.g., Neuron MAX) is often beneficial. Finally, microcatheter access should be maintained after deployment until satisfactory working-angle angiographic views are obtained, in case further devices are required.

Durability and Rate of Recurrence Clinical and radiographic outcomes for patients undergoing flow diversion for CCAs are promising and have led to its widespread acceptance as

a first-line therapy for large or giant symptomatic CCAs. Overall, complete obliteration rates evaluated with formal angiography are 66 to 100%, with a recent meta-analysis demonstrating occlusion rates of 76%. Retreatment is required in cases of recanalization, failure of aneurysmal obliteration, or lack of symptomatic improvement (supports algorithm steps 3, 6). The decision to retreat an incompletely obliterated aneurysm is often based on the clinical status of the patient—patients with mild residual lesions may reasonably be observed if symptomatically improved, because complete thrombosis may take several years. Retreatment options include placement of additional flow-diverting devices or parent vessel occlusion with or without bypass in salvage cases (►Fig. 19.3).

Clinical and Radiographic Follow-up Patients with smaller or asymptomatic lesions can often be observed instead of undergoing treatment. Spacing of clinical and radiographic follow-up differs from patient to patient but, in general, patients may be followed with either CTA or MRA. For patients undergoing endovascular treatment with placement of a flow diverter, angiographic follow-up is recommended within 6 months after stent placement. This ensures that thrombosis of the aneurysm has occurred and that the stent remains widely patent. If there is no in-stent stenosis at this time, patients may stop treatment with the second antiplatelet agent (e.g., clopidogrel) and continue on aspirin daily. Patients should also be counseled that symptoms may worsen in the interim period after stent placement because of aneurysm thrombosis, which may be palliated with a short course of oral corticosteroids. This worsening is typically transient, with patients returning to baseline within a few weeks.

Expert Commentary The evolution and history of treatment modalities for CCAs is rich and fascinating. Aneurysms within the cavernous segment of the ICA are often benign in terms of rupture and SAH, but patients present with mass effect symptoms, specifically cranial neuropathies affecting vision and debilitating headache. Although only a small subset of patients with these lesions require treatment, various forms of open and endovascular meth-

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19 Cavernous Carotid Artery Aneurysms

Fig. 19.3 A 47-year-old woman presented with a 3-day history of acute-onset headache and double vision, with left-sided cranial nerve III and VI palsies on examination (a and b, imaging demonstrating a giant 30-mm cavernous segment internal carotid artery aneurysm). She underwent treatment with two Pipeline Embolization Devices and achieved near-complete resolution of her visual complaints. However, she still suffered from constant daily headaches. At 16 months, a magnetic resonance angiography study demonstrated some residual filling (c, arrow), and at 18 months she underwent follow-up angiography (d, angiography demonstrating separation of the overlapping constructs, with prolapse into the aneurysm dome). At this time, she underwent placement of two additional Pipeline Embolization Devices. At 28 months after her initial treatment, follow-up angiography demonstrated continued filling of the lesion. Her clinical status remained stable, with only mild residual diplopia but burdensome chronic daily headaches. She then underwent microsurgical clip occlusion of the left internal carotid artery with an STA-MCA (superficial temporal artery–middle cerebral artery) bypass (e and f). (Reproduced with permission from Moon K, Albuquerque FC, Ducruet AF, Crowley RW, McDougall CG. Resolution of cranial neuropathies following treatment of intracranial aneurysms with the Pipeline Embolization Device. J Neurosurg 2014;121(5):1085–1092.)

ods have been explored historically. Although some surgical techniques remain important in salvage cases, most CCAs can now be treated safely and effectively with flow diversion. Even in experienced hands, placement of a device in this location can often be difficult, and it relies on the operator’s understanding of numerous technical nuances. Nevertheless, flow diversion has become a durable first-line therapy for large symptomatic lesions and undoubtedly will continue to improve in its safety and efficacy profile as flow-diverting stent technology improves over time.

including cervical ICA-MCA (middle cerebral artery) and petrous ICA-MCA or supraclinoid ICA. I favor bypass over carotid sacrifice even if a balloon test occlusion is negative due to a significant incidence of false-negatives.

Felipe C. Albuquerque, MD Barrow Neurological Institute, Phoenix, AZ

Brinjikji W, Murad MH, Lanzino G, Cloft HJ, Kallmes DF. Endovascular treatment of intracranial aneurysms with flow diverters: a meta-analysis. Stroke 2013; 44(2):442–447 Drake CG, Peerless SJ, Ferguson GG. Hunterian proximal arterial occlusion for giant aneurysms of the carotid circulation. J Neurosurg 1994;81(5):656–665 Kim LJ, Tariq F, Levitt M, et al. Multimodality treatment of complex unruptured cavernous and paraclinoid aneurysms. Neurosurgery 2014;74(1):51–61, discussion 61, quiz 61 Moon K, Albuquerque FC, Ducruet AF, Crowley RW, McDougall CG. Resolution of cranial neuropathies following treatment of intracranial aneurysms with the Pipeline Embolization Device. J Neurosurg 2014;121(5):1085–1092 Puffer RC, Piano M, Lanzino G, et al. Treatment of cavernous sinus aneurysms with flow diversion: results in 44 patients. AJNR Am J Neuroradiol 2014;35(5):948–951

Editor Commentary For most of these aneurysms, no treatment is required as the natural history is remarkably benign. For patients with CCAs who become symptomatic from mass effect or symptomatic thrombosis, endovascular flow diversion is the first option. In a few patients, surgical treatment with ICA occlusion and revascularization becomes necessary because despite multiple flow-diverting stents, the aneurysm continues to grow and become progressively more symptomatic. A range of revascularization options are available,

Robert F. Spetzler, MD Barrow Neurological Institute, Phoenix, AZ

Suggested Reading

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Aneurysms—Anterior Circulation Raymond J, Guilbert F, Weill A, et al. Long-term angiographic recurrences after selective endovascular treatment of aneurysms with detachable coils. Stroke 2003;34(6):1398–1403 Serbinenko FA. Balloon catheterization and occlusion of major cerebral vessels. J Neurosurg 1974;41(2):125–145 Starke RM, Chalouhi N, Ali MS, et al. Endovascular treatment of carotid cavernous aneurysms: complications, outcomes and comparison of interventional strategies. J Clin Neurosci 2014;21(1):40–46

Tanweer O, Raz E, Brunswick A, et al. Cavernous carotid aneurysms in the era of flow diversion: a need to revisit treatment paradigms. AJNR Am J Neuroradiol 2014;35(12):2334–2340 Zanaty M, Chalouhi N, Starke RM, et al. Flow diversion versus conventional treatment for carotid cavernous aneurysms. Stroke 2014;45(9):2656–2661

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20 Cave Carotid Artery Aneurysms Laurent Pierot and Jean-Paul Lejeune

Abstract The carotid cave is an intradural pouch that extends below the level of the distal dural ring between the wall of the internal carotid artery (ICA) and the dural collar surrounding the ICA. Cave carotid artery aneurysms project medially from the ICA in this location and may be entirely extradural or may have an intradural component. According to their small size and location, most unruptured cave carotid aneurysms will be silent and fortuitously discovered. Their most frequent clinical expression is subarachnoid hemorrhage (SAH) in case of rupture. For ruptured aneurysms, the treatment is clearly indicated in most cases, except in high-grade SAH and very old patients. For unruptured aneurysms, the threshold for treatment indication is probably 4 to 5 mm, balanced with patient age and remaining life expectancy. For both ruptured and unruptured cave carotid artery aneurysms, the endovascular treatment is the first-line treatment. Several endovascular options are available for the treatment of cave carotid aneurysms including standard coiling, balloon-assisted coiling, stent-assisted coiling, flow diversion, or parent artery occlusion. The surgical treatment of ventral ICA aneurysms (including carotid cave aneurysms) is difficult. Keywords: intracranial aneurysms, cave carotid, endovascular treatment, clipping, coiling, stenting, flow diversion

Introduction Kobayashi et al initially described carotid cave aneurysms in 1989. The carotid cave is an intradural pouch that extends below the level of the distal dural ring between the wall of the internal carotid artery (ICA) and the dural collar surrounding the ICA. It has been reported to be present in 80% of cadaveric specimens. The clinical significance of this region lies in the fact that aneurysms that project medially from the ICA in this location may be entirely extradural or may have an intradural component. These aneurysms are buried in the dural pouch and are often difficult to find, dissect, and clip during microsurgery; therefore, the majority of these aneurysms nowadays are treated endovascularly. Major controversies in decision making addressed in this chapter include: 1. How to recognize cave carotid aneurysms? 2. When is treatment for cave carotid aneurysms indicated? 3. Open vascular versus endovascular treatment.

Whether to Treat Carotid cave artery aneurysms have their fundus totally or partially in the carotid cave and can be responsible for subarachnoid hemorrhage (SAH). For ruptured aneurysms, the treatment is clearly indicated in most cases. Only in high SAH grades and in very old patients, the treatment has to be discussed in detail with family as outcome is usually very poor (1 in algorithm). In case of unruptured aneurysms, a treatment still has to be proposed and several factors are part of the decision making including patient’s age, risk factors (singularly smoking and elevated blood pressure), aneurysm size, multiple aneurysms, and familial aneurysms (2 in algorithm). The fact is that the carotid cave is a small space that limits the growth of aneurysms. In a recent anatomical report, Joo et al indicate that the depth and the length of the cave averages 2.4 and 9.9 mm, respectively. According to Tanaka et al, the mean size of cave carotid artery aneurysms is 4 mm. Therefore, the 7 mm threshold depicted by the International Study of Unruptured Intracranial Aneurysms (ISUIA) probably does not apply really to this subgroup of aneurysms and aneurysms less than 7 mm have to be treated (3, 4, 7, 8, 9 in algorithm). In their large review of the management of unruptured paraclinoid aneurysms, Iihara

et al indicate that until 2000 they were treating all cave carotid aneurysms larger than 3 mm in patients younger than 70 years. From 2001, they changed their strategy and decided to treat in principle all aneurysms larger than 5 mm. However, from 2001, still 30% of aneurysms treated were smaller than 5 mm. The threshold for treatment indication is probably 4 to 5 mm, balanced with patient age and remaining life expectancy (3, 4, 7, 8, 9 in algorithm).

Anatomical Considerations The carotid cave, identified in 68 to 90% of the cadaveric specimens, is a small recess of the dura mater that extends below the level of the distal dural ring on the posteromedial side of the wall of the ICA. On the medial side, this recess is bounded by bone, i.e., the sphenoid body and/ or the sella turcica. The carotid cave contains in most cases subarachnoid space, sometimes the arachnoid membrane or the extra-arachnoid spaces. Identification of the distal dural ring and the carotid cave with imaging is not easy. In their detailed anatomical and radiographic evaluation performed in cadaveric specimens, Oikawa et al demonstrated that the plane of the distal dural ring inclines in the posteromedial direction. For them, the marker of the most distal point of the distal dural ring situated to the anterolateral side of the ICA is the superior border of the anterior clinoid process. The marker for the most proximal point of the distal dural ring located posteromedially is the tuberculum sellae. Recently, Watanabe et al reported the usefulness of fusion images with 3D magnetic resonance (MR) cisternography and MR angiography (MRA) to identify these anatomical structures. According to the previous anatomical description, cave carotid artery aneurysms originate from the most proximal part of the intradural ICA. As they develop in an intradural space, they have a potential of causing SAH. Cave carotid artery aneurysms are in the carotid cave mainly proximal to the origin of the ophthalmic artery. They arise just cranial to the genu of the ICA and the turbulent and high flow caused by the changing course of the ICA will contribute to their growth. However, they are usually small as their growth is limited medially by the sphenoid and laterally by ICA. They grow ventromedially and may extend in the cavernous sinus. In their radiometric analysis of paraclinoid carotid artery aneurysms, Tanaka et al showed that aneurysms located at the supraclinoidal level had a mean size of 7.3 mm, those located at the clinoidal level 5.2 mm, and those located at the infraclinoidal level (most of them cave carotid aneurysms) 4 mm. In some cases, cave carotid aneurysms develop in relation with the superior hypophyseal artery.

Classification Several classifications of ICA aneurysms located close from the distal dural ring have been proposed. In 1993, al-Rodhan et al suggested the following classification: • Group I: Aneurysms with necks that arose intradurally from the ophthalmic segment of the ICA. This group includes the ventral paraclinoid carotid aneurysms (also called Nutik aneurysms) that originate on the ventral surface of the ICA at or just distal to the ophthalmic artery. These aneurysms originate opposite to the ophthalmic artery origin. • Group II: True ophthalmic artery aneurysms with necks that arise at the junction of the ophthalmic artery and the ICA. • Group III: Cave carotid aneurysms. • Group IV: Transitional aneurysms include cavernous aneurysms in which the neck arises from the cavernous segment of the ICA but the dome projects superiorly into the intradural extracavernous subarachnoid space. • Group V: Intracavernous aneurysms.

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Algorithm 20.1 Decision-making algorithm for cave carotid artery aneurysms.

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20 In 1996, Kyoshima et al classified these aneurysms in three groups: • Paraclinoid intradural aneurysms arise from the ICA distal to the origin of the ophthalmic artery. They include carotid-ophthalmic and posterior communicating aneurysms. • Carotid cave aneurysms are located in the carotid cave and proximal to the origin of the ophthalmic artery. • Infraclinoid extradural aneurysms.

Workup Clinical Evaluation According to their small size and location, most unruptured cave carotid aneurysms will be silent and fortuitously discovered. Their most frequent clinical expression is SAH in case of rupture. As aneurysm fundus can be located in the cavernous sinus, their rupture can potentially induce a carotid-cavernous fistula. It has not been reported in the literature except during the endovascular treatment of a cave carotid aneurysm, probably created iatrogenically. According to their location, these aneurysms can sometimes induce optic nerve compression, and in patients with unruptured aneurysms, the performance of an ophthalmic evaluation (including evaluation of visual acuity and visual field) is mandatory.

Imaging Direct visualization of the carotid cave is difficult whatever the imaging modality used, including computed tomography (CT) and MR. In a recent paper, Watanabe et al showed that fusion images with 3D-MR cisternography and MRA were helpful to identify the distal dural ring and to locate the aneurysms in this region. Angiographic identification of cave carotid artery aneurysms is based on criteria proposed by Zhang et al. In the anteroposterior view, carotid cave aneurysms project medially in a semicircular berry shape. In the lateral view, no space is visible between the axilla (area inside the genu of the ICA) and the anterior or anteroinferior view of the aneurysm. On the contrary to cave carotid aneurysms, ventral paraclinoid carotid aneurysms (Nutik aneurysms) are usually superimposed to ICA in anteroposterior view and a space is usually visible between their anterior wall and the axilla.

Treatment Choice of Treatment As outlined in several series dealing with paraclinoid aneurysms, the surgical treatment of ventral ICA aneurysms (including carotid cave aneurysms) is difficult. In their series dealing with unruptured paraclinoid aneurysms, Iihara et al reported that most cave carotid aneurysms (36/37, 97.3%) were treated endovascularly and concluded that endovascular treatment was the acceptable first line of therapy (supports steps 3, 6, and 8 in algorithm). Notably, the only aneurysm treated by surgery was not clipped but coated. Then, for both ruptured and unruptured cave carotid artery aneurysms, the endovascular treatment is the first-line treatment. As several endovascular options are available (see below), most cave carotid aneurysms will be treatable by this approach (3, 5, 7, 9 in algorithm). Surgical approach has to be proposed only in case the endovascular treatment failed (4, 8 in algorithm).

Conservative Management As discussed previously, carotid cave aneurysms are developed in a relatively small intradural space that probably limit their development in size. Accordingly, as their possibility to grow is relatively limited by anatomical constraints, they have probably a relatively high chance to rupture before reaching an important volume. For this reason, for unruptured aneurysms in this location, the 7 mm threshold depicted by ISUIA is probably

Cave Carotid Artery Aneurysms

not applicable, and depending of the patient’s age, aneurysms with a size greater than 5 mm have probably to be treated (even greater than 4 mm for young patients) (supports algorithm steps 3, 4, 7, 8, 9). For aneurysms smaller than 5 mm (or 4 mm), a conservative treatment is certainly an option and a regular follow-up with MRA or CT angiography is important to depict any aneurysm modification.

Surgical Management Exposing the carotid artery in the neck is recommended to control a premature rupture of the aneurysm if it happens. Through an ipsilateral pterional or modified orbitozygomatic craniotomy, the sylvian fissure and carotid cistern are opened to expose the ICA. The anterior clinoid process is drilled extra- and intracranially, and the optic canal is unroofed with large opening of the falciform dura fold to allow a safe mobilization of the optic nerve. The ophthalmic artery is dissected free from the optic nerve. The next step is the opening of the distal dural ring, which may be difficult because of its tight adherence to the carotid artery wall, and because of venous bleeding from the cavernous sinus. Kobayashi et al emphasized the need to expose the axilla of the ICA, which is formed by the angle between the C2 and C3 segments of the ICA. The aneurysm is then exposed and can de dissected free, but the neck remains hidden under the carotid artery. The space usable to apply the clip is narrow and careful intermittent retraction of the optic nerve is often necessary. Clipping requires a fenestrated clip with curved blades because of the curvature of the ICA in this area. It is difficult to make sure that the proximal end of the neck is secured by the clip, and intraoperative indocyanine green video-angiography is very useful to control the exclusion of the aneurysm and the patency of ICA.

Endovascular Management—Operative Nuances Several endovascular options are available for the treatment of cave carotid aneurysms including standard coiling, balloon-assisted coiling, stent-assisted coiling, flow diversion, or parent artery occlusion (3, 5, 7, 9 in algorithm) (►Figs. 20.1 and 20.2). Considering the selection between the different endovascular options, several factors have to be taken into account: aneurysm status (ruptured/unruptured), aneurysm size, neck size (or the dome-toneck ratio), and neck position in relation with the parent vessel. Several anatomical factors are often encountered with cave carotid aneurysms that may have some influence on the endovascular strategy. Aneurysms are often small, and often have a wide neck or an unfavorable dometo-neck ratio. Moreover, the neck is usually located ventromedially just after the first proximal loop of the carotid siphon. This particular location combined with the frequent small size of these aneurysms explains why placement and stabilization of a microcatheter into the aneurysm will sometimes be difficult. For this reason, it is certainly helpful to use a microcatheter with a sharp and relatively short curve at its distal end. Moreover to stabilize the microcatheter into the aneurysm and to deploy safely the coils into the aneurysm, it will be frequently useful to use the balloon remodeling technique. In this specific subgroup of aneurysms that are often small, the use of a balloon will also permit stoppage of a bleeding in case of intraoperative rupture. Using a stent to jail the microcatheter in the aneurysm will also be useful to stabilize the microcatheter and the coils in the aneurysm at the price of the use of a dualantiplatelet treatment (3, 7 in algorithm), but the stent is not helpful in case of intraoperative rupture. Use of flow diverters in cave carotid aneurysms is limited as the majority of them are small. For the same reason, ICA occlusion has very limited indications. However, recently the use of flow diverters in small aneurysms has increased with excellent results (9 in algorithm). For ruptured aneurysms, the first endovascular option is definitely coiling (3 in algorithm). The combined use of a balloon will in a high number of cases be helpful for aneurysm microcatheterization, coil deployment, and in case of aneurysm rupture. This aneurysm location

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Fig. 20.1 A 50-year-old woman with an unruptured right carotid cave artery aneurysm discovered fortuitously (a and b, DSA frontal and lateral view demonstrating a 5-mm aneurysm). Treatment was performed with a combination of placement of coils into the aneurysm and deployment of a stent in the carotid siphon (c and d, DSA unsubtracted frontal and lateral view showing the coils in the aneurysm. The stent is barely visible.) Six-month control DSA shows a complete occlusion of the aneurysm (e and f, DSA frontal and lateral view).

is typically one where the remodeling technique has to be widely used (5 in algorithm). Stent-assisted coiling is probably not a good option for ruptured aneurysms as dual-antiplatelet treatment is mandatory during and after the procedure to avoid in-stent thrombosis and distal embolic complications. It has to be used only when treatment is not feasible with standard coiling or balloon-assisted coiling. As mentioned before, flow diversion and occlusion of the parent vessel have limited indications in this group of aneurysm due to their frequent small size. Moreover, flow diversion is also not a good option for ruptured aneurysms for at least two reasons: (1) antiplatelet treatment is also mandatory as for stenting, and (2) aneurysmal thrombosis is progressively obtained in several days or weeks and that limits the efficacy of this treatment against rebleeding at the acute phase of bleeding. As for other aneurysmal location, the treatment with occlusion of the parent vessel is not a good option at the acute phase of bleeding, because it will dramatically modify the brain arterial circulation during a period where vasospasm can occur. For unruptured aneurysms, coiling is also the first endovascular approach associated with remodeling technique or stenting if the neck is wide or if the dome-to-neck ratio is unfavorable (3, 7 in algorithm). In these situations, the best approach (remodeling or stenting) is difficult to determine. From the literature, balloon-assisted coiling has a similar safety compared to standard coiling and that is probably not the case for stenting. On the other hand, the quality and stability of aneurysm occlusion is probably improved by stenting. As the neck of cave carotid aneurysm is directly facing the high arterial flow present in the carotid artery, the use of stenting has probably a larger place in this location compared to more distally located aneurysms (7 in algorithm). Moreover, in case of unfavorable dome-to-neck ratio, it will be sometimes impossible to treat the aneurysm just with the remodeling balloon and stenting will

be mandatory. In case of unruptured large and giant aneurysms, coiling even with associated remodeling or stenting is certainly not the appropriate technique as the recanalization rate with this kind of treatment is high. In these rare cases of large and giant cave carotid artery aneurysms, the use of flow diversion is a good option, probably with partial coiling to prevent delayed rupture (9 in algorithm) (►Fig 20.2). However, if flow disruption has a very high efficacy in terms of aneurysm occlusion, its safety is less compared to other techniques (standard coiling, balloon-assisted coiling, stent-assisted coiling) (see below). For this reason, ICA occlusion will sometimes be selected for the treatment of these large and giant aneurysms as its efficacy is also high with a great safety. If this approach is used, an occlusion test has to be performed before ICA occlusion to evaluate the anastomoses of the circle of Willis. If they are not sufficient and if ICA occlusion is still a good option, an arterial bypass has to be done (7, 9 in algorithm).

Complication Avoidance Outcome In their initial series, Kobayashi et al reported the treatment of seven cave carotid artery aneurysms by surgery. In the first two cases, due to the lack of knowledge about the carotid cave, the aneurysms could not be exposed. Two patients exhibited decreased vision after the operation. In the large series reported by Iihara et al, 36/37 cave carotid artery aneurysms were treated by endovascular approach. There were permanent andtransient thromboembolic complications in two (5.6%) and three patients (8.3%), respectively. There was no visual field deficit after the treatment. A high rate of postoperative complete aneurysm

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Fig. 20.2 (a) Lateral angiography views, intracranial internal carotid artery injection, demonstrating a carotid cave aneurysm in a 34-year-old woman who presented to the emergency department with severe headaches. (b) Angiography immediate after flow-diverter embolization, lateral view, demonstrating intra-aneurysmal flow stasis. (c) Lateral angiography views at 6 months postprocedure demonstrating complete obliteration of the aneurysm. (Images provided courtesy of Leonardo Rangel-Castilla MD, Mayo Clinic, Rochester, MN)

occlusion was achieved (77.8%) with a limited number of aneurysm remnants (8.3%) (supports algorithm steps 3, 5, 7, and 9). D’Urso et al reported a large series of 118 patients with 128 paraclinoid aneurysms treated with coiling and adjunctive therapy (balloon-assistance or stenting in 54% of cases) when necessary. Only four patients had cave carotid artery aneurysms. In the whole group, the rate of complications was low and included aneurysms perforation in 3% and distal emboli in 3% leading to transient morbidity in 0.8%, permanent morbidity in 0.8%, and no mortality. Early (within 1 month) thromboembolic complications occurred in 4% resulting in transient mortality in all cases. Postoperatively aneurysm occlusion was complete in 38% of cases, neck remnant in 54% of cases, and aneurysm remnant in 8% of cases with some improvement during the follow-up. There are no specific data in the literature regarding the treatment of cave carotid aneurysms or paraclinoid aneurysms with flow diverters. In general, the treatment safety with flow diverters is less compared to coiling. In the large meta-analysis published by Brinjikji et al and dealing with all aneurysmal locations, the rate of procedure-related morbidity and mortality were 5 and 4%, respectively. On the contrary, treatment with flow diverters has a high efficacy. Complete aneurysmal occlusion was observed in 76% of cases at 6 months and was increasing along the time.

Durability and Rate of Recurrence/Clinical and Radiographic Follow-up There is very little information regarding this important point in the literature. In D’Urso et al series dealing with paraclinoid aneurysms treated by endovascular approach, after an average time of 31.9 months, complete aneurysm occlusion was observed in 62% of aneurysms, neck remnant in 30% of cases, and aneurysm remnant in 8%. Retreatment was performed in 9% of aneurysms. Clinical follow-up of patients with ruptured and unruptured aneurysms is similar to what is performed for other locations. A precise ophthalmic evaluation has to be performed as soon as the patient has some visual complaint. Radiographic follow-up after endovascular treatment is not different compared to other aneurysm locations. It is mainly based on MRA, the appropriate MRA sequence being 3D-TOF (time of flight) in case of coiling and CE-MRA in case of stenting or flow diversion. Digital subtraction angiography is also helpful singularly in this location that is not always easy to evaluate with MRA. Early imaging has to be performed 3 to 6 months after the treatment followed by another control 12 to 18 months after the treatment. Then the follow-up is dependent on the anatomical results as depicted by the initial follow-up imaging. The total follow-up duration is unknown, but has probably to be extended to a very long period at least 10 years.

Expert Commentary Carotid cave aneurysms are located adjacent to the distal dural ring just as the ICA enters the subarachnoid space. They are oriented medially and should not be taken for superior hypophyseal artery aneurysms, which also point in the same direction but are located slightly more distally. Also carotid cave aneurysms arise at a nonbranching site of the ICA. Because

of their location in a very restricted space, they are small. Being so closely attached to the dura may also explain why the majority do not bleed. These aneurysms are usually found incidentally, and when there is an SAH, most of the time the bleeding is due to rupture from another aneurysm. Ruptured carotid cave aneurysms are, of course, treated and those found incidentally may probably be left for observation, unless they are already 7 mm in diameter or, for smaller ones, unless they increase in size. Generally, for other aneurysms, size is a determining factor for the ease of surgical treatment. However, in the case of carotid cave aneurysms, because of their location at the base of the skull, attached to the dura and hidden behind the carotid, surgery is very challenging despite their small size. Therefore, endovascular treatment is always the first consideration. Surgery is reserved only for those aneurysms not amenable to endovascular techniques. Surgeons must have a deep and thorough knowledge of all the curves along the carotid and their intimate relationship with the dural folds in this area. This is essential to safely remove the anterior clinoid process and to open the dural ring surrounding the carotid, both of which are mandatory. For ruptured aneurysms, it is recommended to expose the ICA at the neck, in order to obtain proximal control. For unruptured aneurysms, proximal control is obtained after exposure of the clinoidal portion of the ICA. However, the neck should have at least already been prepped in case of rupture during exposure. Clipping may be difficult not only because the aneurysmal neck is not in view, but also because it is located in the anterior curve of the carotid. Working partially blindly, with the tips of the clip not always in view, the surgeon must be particularly vigilant to avoid pushing through any resistance, which may provoke profuse bleeding from the aneurysm, the carotid, or the cavernous sinus. Intraoperative angiography is very useful. Michel W. Bojanowski, MD, FRCSC University of Montreal, Montreal, Quebec

Editor Commentary Carotid cave aneurysms arise from the most proximal portion of the intradural segment of ICA, projecting posterior, inferior, and medially from the wall of the vessel. These aneurysms are usually small in size, as their growth is limited by the sphenoid bone medially and by the parent vessel laterally. The risk of SAH from extradural location of some of these aneurysms is nonexistent. However, these aneurysms are typically at least partially intradural and rupture can potentially cause SAH. Microsurgical clipping for carotid cave aneurysm have been used for treatment of these aneurysms. The approach requires anterior clinoidectomy to expose the region of carotid cave, with subsequent incision into the dural ring around the ICA to visualize the structures within the carotid cave and gain proximal control. Venous bleeding from the cavernous sinus, while easy to control, can add complexity to the procedure when encountered. Additionally, optic nerve can be obtrusive in the dissection of the parent vessel and aneurysm requiring incision of the falciform ligament prior to manipulation. This can lead to a risk of visual problems postoperatively. The aneurysm is often pointing in the opposite direction, making it difficult to adequately visualize the neck. Overall, the surgical approach to treating carotid cave aneurysm is complex and can lead to significant morbidity and lengthy recovery time.

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Aneurysms—Anterior Circulation Endovascular approaches to treat carotid cave aneurysms include primary coiling, stent-assisted coiling, or balloon-assisted coiling. A satisfactory rate of obliteration, with a very small risk of complication has been noted with endovascular treatment of carotid cave aneurysm with coils. With the advances in endovascular technology, flow diversion has emerged as a treatment of choice. A single flow diversion device can be sufficient to achieve complete obliteration in the majority of cases. Occasionally, retreatment with a second flow diversion device may be needed for persistent aneurysm or endoleak on follow-up. At our institution, we prefer treatment of carotid cave aneurysms and most wide-necked paraclinoid aneurysms by flow diverters. The risks of hemorrhagic and thromboembolic complications is low and good obliteration rate can be achieved. Elad I. Levy, MD, MBA University at Buffalo, Buffalo, NY

Suggested Reading Hitotsumatsu T, Natori Y, Matsushima T, Fukui M, Tateishi J. Micro-anatomical study of the carotid cave. Acta Neurochir (Wien) 1997;139(9):869–874 Iihara K, Murao K, Sakai N, et al. Unruptured paraclinoid aneurysms: a management strategy. J Neurosurg 2003;99(2):241–247

Joo W, Funaki T, Yoshioka F, Rhoton AL Jr. Microsurgical anatomy of the carotid cave. Neurosurgery 2012;70(2, Suppl Operative):300–311, discussion 311–312 Kato Y, Sano H, Hayakawa M, et al. Surgical treatment of internal carotid siphon aneurysms. Neurol Res 1996;18(5):409–415 Kobayashi S, Koike G, Orz Y, Okudera H. Juxta-dural ring aneurysms of the internal carotid artery. J Clin Neurosci 1995;2(4):345–349 Kobayashi S, Kyoshima K, Gibo H, Hegde SA, Takemae T, Sugita K. Carotid cave aneurysms of the internal carotid artery. J Neurosurg 1989;70(2):216–221 Kyoshima K, Koike G, Hokama M, et al. A classification of juxta-dural ring aneurysms with reference to surgical anatomy. J Clin Neurosci 1996;3(1):61–64 Nutik SL. Anatomical location of carotid cave aneurysms. J Clin Neurosci 1997;4(1):87–90 Oikawa S, Kyoshima K, Kobayashi S. Surgical anatomy of the juxta-dural ring area. J Neurosurg 1998;89(2):250–254 Tanaka Y, Hongo K, Tada T, et al. Radiometric analysis of paraclinoid carotid artery aneurysms. J Neurosurg 2002;96(4):649–653 Watanabe Y, Nakazawa T, Yamada N, et al. Identification of the distal dural ring with use of fusion images with 3D-MR cisternography and MR angiography: application to paraclinoid aneurysms. AJNR Am J Neuroradiol 2009;30(4):845–850 Zhang QJ, Kobayashi S, Toriyama T, Kyoshima K, Hongo K, Kuroyanagi T. Angiographic differentiation of carotid cave aneurysms from ventral paraclinoid carotid aneurysms of Nutik type. Neurosurg Rev 1993;16(4):283–289

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21 Superior Hypophyseal Artery Aneurysms Oliver Bozinov, Jan-Karl Burkhardt, Anton Valavanis, and Luca Regli

Abstract Superior hypophyseal artery aneurysms are usually described as part of paraclinoid aneurysms; therefore, their incidence and prevalence are not clear. Their anatomical location in proximity to the proximal dural ring, in the posteromedial part of the internal carotid artery (ICA), and close to the optic nerve make their surgical approach difficult. Symptomatic patients present with subarachnoid hemorrhage; they rarely present with optic nerve or pituitary stalk compression. Digital subtraction angiography is the gold standard for aneurysm visualization and characterization. Asymptomatic and small aneurysms are treated conservatively. Large or ruptured aneurysms should be treated. Nowadays, microsurgical clipping is rarely performed due to the anatomical complexity and the need for optic nerve or stalk manipulation. The majority of these aneurysms are treated endovascularly with coiling, stent-assisted coiling, or flow diversion techniques with good to excellent results. Appropriate clinical and radiological follow-up is mandatory in all intracranial aneurysms.

size, patient age is important to be considered in the decision-making process. Aneurysms greater than 7 mm and young patients should be treated, rather than patients with short remaining life expectancy (2 in algorithm).

Anatomical Considerations

Keywords: internal carotid artery, superior hypophyseal artery, dural ring, superior hypophyseal artery aneurysms, subarachnoid hemorrhage, endovascular coiling, microsurgical clipping

The close location of the SHA to the proximal dural ring in the posteromedial part of the ICA makes a direct surgical approach sometimes difficult for proximal control. The optic nerve is always very close to these aneurysms and sometimes hides the complete aneurysm from an ipsilateral approach. Therefore, a contralateral approach, which gives the surgeon a direct view between the optic nerves, should be considered as well. The circumferential anastomosis made by both SHA is another important anatomical consideration. In case the SHA is at risk to be occluded during aneurysm treatment, each patient’s SHA anatomy needs to be understood or at least estimated before treatment to secure a retrograde flow in case of SHA occlusion. Insufficient anastomosis may lead to visual deficits or pituitary insufficiency (2 in algorithm).

Introduction

Classification

The superior hypophyseal artery (SHA) is a complex summary of about one to five vessels, which arise from the paraclinoid segment of the internal carotid artery (ICA) between the distal dural ring of the ICA and the posterior communicating artery. Located in the medial wall of the ICA, this artery supplies the pituitary stalk and both optic nerves and the chiasm. Both the right- and left-sided SHA form a circumferential anastomosis to adequately supply these important pathways. SHA aneurysms are rarely described in the literature and are mostly summarized together with other paraclinoid aneurysms. This makes it difficult to give clear evidence-based treatment recommendations for this rare disease. A female predominance is reported. Further, there is a tendency of multiple aneurysms when SHA or paraclinoidal aneurysms are reported. Major controversies in decision making addressed in this chapter include: 1. Whether or not treatment is indicated. 2. Open versus endovascular treatment for ruptured and unruptured SHA aneurysms. 3. Management of complex SHA aneurysms using advanced surgical or endovascular techniques.

There are many classifications of paraclinoid aneurysms, which all include SHA aneurysms at least in one group. Horiuchi et al classified SHA aneurysms based on the relationship between aneurysm and the SHA. The SHA can originate from the proximal neck, the medial neck, the distal neck, and the aneurysm body or has no relation to the aneurysm. Mostly SHA can be found in the proximal neck of the aneurysm.

Whether to Treat Ruptured SHA aneurysms are clearly recommended for immediate treatment as with other intracranial ruptured aneurysms to prevent the risk of rebleeding. Also, unruptured but symptomatic SHA aneurysms including patients with visual deficits or pituitary insufficiency should be considered for treatment to improve the symptoms or prevent further decline. In asymptomatic patients with unruptured SHA aneurysms (incidental SHA aneurysms), the decision for treatment is based on aneurysm size, patient age, previous aneurysmal subarachnoid hemorrhage (SAH) from another aneurysm, and cardiovascular risk factors. As with other intracranial aneurysms, the PHASES or the UIATS scores may help for the decision-making process to weigh up aneurysm rupture risk with treatment risk. There is no specific treatment regimen proposed for SHA aneurysms compared to all other aneurysms. No increased risk of hemorrhage is reported specifically. Ruptured and symptomatic SHA aneurysms need immediate treatment (1 in algorithm). Unruptured SHA aneurysms should be treated if the rupture risk is higher than the treatment risk. Besides aneurysm

Workup Clinical Evaluation Clinical evaluation is important in both ruptured and unruptured SHA patients. In ruptured aneurysms, the clinical status as summarized in the World Federation of Neurological Surgeons (WFNS) score gives the treating surgeon an idea about the prognosis and influences the decision to treat or not to treat. In unruptured aneurysms, an ophthalmologic and endocrinologic workup is mandatory to rule out any visual deficits such as vision loss or visual field deficits as well as deficits in one of the hormonal axes.

Imaging Angiography such as computed tomography angiography (CTA), magnetic resonance angiography (MRA), and/or digital subtraction angiography (DSA) are important to understand the exact origin, projection, size, and relationship to neighboring structures. Since SHA aneurysms are located close to the skull base, the quality of CTA might be diminished by artifacts but demonstrates the close relationship to the bone better than most MRIs. The DSA clearly has an advantage in this location, since treatment of aneurysm might be possible in the same session. Magnetic resonance imaging (MRI)/ MRA might be important to rule out differential diagnoses.

Differential Diagnosis If the aneurysm in this location is clearly detected by angiography, differentials are rare. Located closely to the pituitary stalk/gland and especially in patients with pituitary dysfunction, a pituitary adenoma/cyst needs to be excluded in case of doubt (e.g., with MRI of the sellar region). Other tumors including tuberculum sellae meningiomas or optic nerve tumors are rarely but sometimes misdiagnosed with SHA aneurysms.

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Aneurysms—Anterior Circulation

Algorithm 21.1 Decision-making algorithm for superior hypophyseal artery aneurysms.

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21 Superior Hypophyseal Artery Aneuryms

Treatment Choice of Treatment and the Influence of Intracerebral Hematoma The choice of treatment in SHA aneurysms depends on many factors. Similar to aneurysms in other locations, surgical hematoma evacuation and clipping is indicated in a space occupying intracerebral hemorrhage (ICH) in ruptured SHA aneurysms, but this is very rare for SHA aneurysms. In all other scenarios (ruptured SHA aneurysm without ICH and unruptured SHA aneurysms with indication for treatment), endovascular DSA and coiling should be considered first, if feasible. The complication rates of surgically treated SHA aneurysms (>15%) are reported higher than embolized ones in larger series (2%). However in experienced surgical hands, those complication rates should be much lower but still higher than 2%, due to the close proximity of these aneurysms with the optic nerve and the clinoid process. In case of an SHA aneurysm with a wide neck or incorporation of the SHA, which makes the endovascular approach difficult and surgical reconstruction possible, stent-assisted coiling or flow diversion should be considered as well as surgical reconstruction (3 in algorithm). If aneurysm occlusion is not possible with standard techniques and occlusion is highly recommended, then more advanced endovascular or surgical techniques should be considered. For instance, an extracranial– intracranial (IC-EC) high-flow bypass or flow-diverter devices could be considered in large and/or fusiform aneurysms incorporating the whole wall of the ICA segment (4 in algorithm).

Conservative Management Conservative management definitely applies to small aneurysms (