Pediatric Sleep Medicine: Mechanisms and Comprehensive Guide to Clinical Evaluation and Management 3030655733, 9783030655730

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David Gozal Leila Kheirandish-Gozal Editors

Pediatric Sleep Medicine Mechanisms and Comprehensive Guide to Clinical Evaluation and Management

Pediatric Sleep Medicine

David Gozal  •  Leila Kheirandish-Gozal Editors

Pediatric Sleep Medicine Mechanisms and Comprehensive Guide to Clinical Evaluation and Management

Editors David Gozal MU Women’s and Children’s Hospital University of Missouri Columbia, MO USA

Leila Kheirandish-Gozal Child Health Research Institute University of Missouri System Columbia, MO USA

ISBN 978-3-030-65573-0    ISBN 978-3-030-65574-7 (eBook) https://doi.org/10.1007/978-3-030-65574-7 © Springer Nature Switzerland AG 2021 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, expressed or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. This Springer imprint is published by the registered company Springer Nature Switzerland AG The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland

Many people, too many to enumerate, deserve appreciation for their contributions to this work. We will therefore simply thank our children Amin and Imran Gozal for being real troopers and for putting up with us during the many weekends and evenings during which we were busy working on the chapters rather than spending quality time with them. This text is dedicated to several major figures and pioneers of our profession who unfortunately are not with us anymore, but whose legacy will last for many decades to come: Carole L. Marcus, Christian Guilleminault, Mariluz Alonso-Álvarez, and Joaquin Teran-Santos. To us, they were simply dearest of friends, and we terribly miss them!

Preface

It was back in 1980. I was in Jerusalem as a pediatric resident and was on call in the emergency room. It was a cold and dark winter night. At around 2:00 am, a woman arrived with her baby boy wrapped in her arms; there was a look of sheer terror and panic in her eyes. Her baby, who was healthy a few hours earlier, died of SIDS in his sleep. This was the first time in my life that I was exposed to a medical event that exclusively occurred during sleep, and it would guide the remainder of my career. I realized that while I had focused all my efforts to learn what happens when we are awake, I knew simply nothing about what happens when we sleep! Many years later, a formidable ally joined me, and we have since partaken in the challenging task of unraveling sleep secrets in children, one at a time. Over the years, we have been fortunate to train and learn from many fellows along the way, and to interact in lively and sometimes heated discussions with many dear colleagues around the world, all for the simple objective of advancing a nascent field, that of pediatric sleep medicine. As with every discipline that is still at an embryonic yet rapidly developing stage, what today is dogma will likely be wrong tomorrow. So many unknowns, so much more to be done! Over a drink one evening after a long day, Leila and I felt it would be useful to put together a book that summarizes and organizes the current knowledge basis of sleep in children. Still uncertain whether such effort would be worthwhile, we contacted some of our prospective chapter contributors, and their overwhelming positive responses convinced us that even if the overall result was going to be an incomplete and imperfect compendium, it would serve as the basis that informs anyone interested or dealing with children on what, why, and how to approach that huge portion of time that children spend asleep, and what can go well and what can go wrong then. The authors are all experienced clinicians and researchers with considerable experience in the diagnosis, classification, and treatment of sleep and its disorders. We try to expose the science behind sleep and progressively address many of the intrinsic sleep disorders as well as a pragmatic selection of the multitude of pediatric conditions that can affect sleep integrity, quality, or quantity. This is the initial draft of what we hope will progressively evolve to become the go-to source for anyone wanting to learn and be informed about pediatric sleep medicine. With the help of our readers and with every future edition, we hope to refine the book and ultimately bring it to perfection. Till then, it is our ardent desire that this source will serve you well and help the children you care for achieve that ultimate stage of sleep: “sleeping like an angel.” Columbia, MO, USA 

David Gozal Leila Kheirandish-Gozal

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Contents

Part I Basic Introduction to Sleep 1 Normal Sleep in Humans�������������������������������������������������������������������������������������������   3 Saif Mashaqi and David Gozal Part II Physiologic Regulation in Sleep and During Development 2 Control of Breathing During Sleep and Wakefulness in the Fetus, Newborn, and Child�����������������������������������������������������������������������������������������  19 Vincent Joseph, Aida Bairam, and John L. Carroll 3 Normal Respiratory Physiology During Wakefulness and Sleep in Children�������  33 John L. Carroll and Aida Bairam 4 Upper Airway and Motor Control During Sleep�����������������������������������������������������  45 Jean-Paul Praud 5 Endocrinology of Sleep�����������������������������������������������������������������������������������������������  57 Dorit Koren 6 Thermoregulation and Metabolism���������������������������������������������������������������������������  73 Véronique Bach and Jean-Pierre Libert 7 Sleep and Immunity���������������������������������������������������������������������������������������������������  87 Carmen T. Gómez de León and Jorge Morales-Montor 8 Sleep and the Gastrointestinal System ���������������������������������������������������������������������  97 Hari P. R. Bandla 9 Circadian Rhythms in Children ������������������������������������������������������������������������������� 105 Lorenzo Tonetti Part III Sleep Mechanisms: Developmental Aspects 10 Developmental Aspects of Sleep��������������������������������������������������������������������������������� 115 Kamalesh K. Gulia, B. S. Aswathy, and Velayudhan Mohan Kumar 11 Humoral and Other Sleep-Promoting Factors��������������������������������������������������������� 123 Éva Szentirmai and Levente Kapás Part IV Measurement of Sleep 12 Survey Tools and Screening Questionnaires to Pediatric Sleep Medicine������������� 135 Abdullah AlNabhani and Colin M. Shapiro

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13 Pediatric Patients with Sleep Complaints: Initial Interview and Diagnostic Planning��������������������������������������������������������������������������� 159 Jyoti Krishna 14 Best Practices for Accommodating Children in the Polysomnography Lab: Enhancing Quality and Patient Experience ������������������� 169 Sally Ibrahim, Jennifer Stone, and Carol L. Rosen 15 Technologies in the Pediatric Sleep Lab: Present and Future ������������������������������� 179 Tamar Etzioni-Friedman and Giora Pillar 16 Upper Airway Imaging in Pediatric Obstructive Sleep Apnea������������������������������� 193 Monique A. L. J. Slaats and Stijn L. Verhulst 17 Laboratory Tests in Pediatric Sleep Medicine��������������������������������������������������������� 209 Leila Kheirandish-Gozal and David Gozal 18 The Nocturnal Polysomnogram – Approaches to Recording, Scoring, and Interpretation in Infants and Children ��������������������������������������������� 215 Madeleine Grigg-Damberger and Steven Lopez 19 Multiple Sleep Latency Test��������������������������������������������������������������������������������������� 259 Min Zhang, Marine Thieux, Noémie Vieux, Aurore Guyon, and Patricia Franco 20 Actigraphy������������������������������������������������������������������������������������������������������������������� 271 Hawley E. Montgomery-Downs and Liat Tikotzky 21 Defining Normal in Pediatric Sleep: Some Thoughts and Things to Think About����������������������������������������������������������������������������������������������� 283 David Gozal and Leila Kheirandish-Gozal Part V Pharmacotherapy of Sleep Disorders in Children 22 Stimulants ������������������������������������������������������������������������������������������������������������������� 291 Stéphanie Bioulac and Patricia Franco 23 Somnogenic Agents in Children��������������������������������������������������������������������������������� 299 Rafael Pelayo and Kin M. Yuen 24 Drugs which affect Sleep ������������������������������������������������������������������������������������������� 307 Nicholas-Tiberio Economou, Konstantinos Papoutsis, Luigi Ferini-Strambi, and Georgia Trakada Part VI Acute and Chronic Ventilatory Support in Children 25 Non-invasive Respiratory Support in Children with Sleep Disordered Breathing������������������������������������������������������������������������������������������������� 321 Hui-leng Tan Part VII Disorders of Sleep 26 Pediatric Insomnia: Etiology, Impact, Assessment, and Treatment����������������������� 333 Lisa Medalie, Thuan Dang, and Christina L. Casnar 27 Apnea of Infancy, Apparent Life-­Threatening Events, and Sudden Unexplained Death in Infancy��������������������������������������������������������������������� 341 Dawn E. Elder and Barbara C. Galland

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28 Apnea of Prematurity������������������������������������������������������������������������������������������������� 353 Christian F. Poets 29 Disorders of Respiratory Control and Central Hypoventilation Syndromes��������������������������������������������������������������������������������������� 363 Daniella K. Ginsburg, Thomas G. Keens, and Iris Ambrosio Perez 30 Disorders of Excessive Sleepiness ����������������������������������������������������������������������������� 379 Carey T. Lockhart, Lourdes M. DelRosso, and Oliviero Bruni 31 Restless Legs Syndrome and Periodic Leg Movements of Sleep ��������������������������������������������������������������������������������������������������� 395 Lourdes M. DelRosso and Raffaele Ferri 32 Circadian Sleep Disorders����������������������������������������������������������������������������������������� 403 Jonathan Emens, Elizabeth Rachel Super, and Jillian N. Sanford 33 Parasomnias����������������������������������������������������������������������������������������������������������������� 415 Oliviero Bruni and Silvia Miano Part VIII Obstructive Sleep Apnea 34 Obstructive Sleep Apnea: Definition������������������������������������������������������������������������� 433 Shannon S. Sullivan and Christian Guilleminault 35 Pathophysiology of Obstructive Sleep Apnea Syndrome in Childhood��������������������������������������������������������������������������������������������� 437 Raanan Arens, Sanghun Sin, and David M. Wootton 36 Obstructive Sleep Apnea: Clinical Presentation and Differential Diagnosis������������������������������������������������������������������������������������������������� 459 John E. Pascoe, Sumalee Hantragool, and Narong Simakajornboon 37 Surgical Treatment of Pediatric Obstructive Sleep Apnea������������������������������������� 465 Kathleen M. Sarber and Stacey L. Ishman 38 Obstructive Sleep Apnea: Treatment – Anti-inflammatory Therapy��������������������� 477 Pablo E. Brockmann and Katalina Bertran Salinas 39 Pediatric Obstructive Sleep Apnea: Orthodontic Management����������������������������� 483 Nathalia Carolina Fernandes Fagundes, Fernanda R. Almeida, and Carlos Flores-Mir 40 Myofunctional Approaches to Pediatric Sleep Medicine����������������������������������������� 493 Maria Pia Villa and Melania Evangelisti 41 Illustrative Clinical Cases������������������������������������������������������������������������������������������� 501 Oscar Sans Capdevila, Ehab A. Dayyat, and David Gozal Part IX Sleep in Other Disorders 42 Sleep-Disordered Breathing in Neuromuscular Diseases��������������������������������������� 523 Hemant Sawnani, Neepa Gurbani, and John E. Pascoe 43 Obstructive Sleep Apnea and Asthma����������������������������������������������������������������������� 537 Maya Ramagopal and Steven M. Scharf 44 Cystic Fibrosis������������������������������������������������������������������������������������������������������������� 543 Aarti Shakkottai, Ronald D. Chervin, Samya Z. Nasr, and Louise M. O’Brien

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45 Bronchopulmonary Dysplasia����������������������������������������������������������������������������������� 555 Katherine Sullivan and Lawrence Rhein 46 Down Syndrome ��������������������������������������������������������������������������������������������������������� 565 Kate C. Chan and Albert Martin Li 47 Sleep in Obese Children and Adolescents����������������������������������������������������������������� 573 Yael Lebenthal and Riva Tauman 48 Sleep in Sickle Cell Disease ��������������������������������������������������������������������������������������� 581 Alex Gileles-Hillel 49 Epilepsy and Sleep, Common Bedfellows����������������������������������������������������������������� 595 Ivan M. Pavkovic and Sanjeev V. Kothare 50 Autism Spectrum Disorder���������������������������������������������������������������������������������������� 609 Christina S. McCrae, Micah O. Mazurek, Rose Nevill, Mattina Davenport, Erica Fornaris Rouch, and Ashley F. Curtis 51 Sleep and Attention-Deficit/Hyperactivity Disorder����������������������������������������������� 627 Silvia Miano 52 Sleep and Mood Disorder������������������������������������������������������������������������������������������� 639 Maria Cecilia Lopes and Lee Fu-I 53 Prader–Willi Syndrome��������������������������������������������������������������������������������������������� 649 David Gozal 54 Craniofacial Syndromes��������������������������������������������������������������������������������������������� 655 Robin Yang, Jordan W. Swanson, and Christopher M. Cielo 55 Sleep Problems and Developmental Delay��������������������������������������������������������������� 667 Stacey Bissell, Ashley Liew, Caroline Richards, and Andrew Surtees 56 Sleep in Children Following Brain Concussion������������������������������������������������������� 681 Suncica Lah, Stefan Bogdanov, and Bethanie Menzies 57 Diabetes����������������������������������������������������������������������������������������������������������������������� 691 Alexandra D. Monzon, Arwen M. Marker, and Susana R. Patton 58 Cerebral Palsy������������������������������������������������������������������������������������������������������������� 701 Evelyn Constantin 59 Sleep in Children with Myelomeningocele��������������������������������������������������������������� 709 David G. Ingram, Jane B. Taylor, Michael D. Partington, Sehyr Imran, and Renée A. Shellhaas 60 Inborn Errors of Metabolism: Mucopolysaccharidoses and Others��������������������� 719 Zheng Fan, Joseph Muenzer, Laura Dosier, and Bradley V. Vaughn Index������������������������������������������������������������������������������������������������������������������������������������� 727

Contents

Contributors

Fernanda  R.  Almeida, DDS, MSc, PhD Division of Orthodontics, Department of Oral Health Sciences, University of British Columbia, Vancouver, BC, Canada Abdullah  AlNabhani, MD, OMSB (Psychiatry)  Psychiatry Department, Nizwa Hospital, Muscat, Oman Sleep Medicine and Neuropsychiatry, University of Toronto, Toronto, ON, Canada Raanan Arens, MD  Division of Pediatric Respiratory and Sleep Medicine, The Children’s Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY, USA B. S. Aswathy, PhD  Division of Sleep Research, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, Kerala, India Institute for Stem Cell Science & Regenerative Medicine (inStem), Bangalore, India Véronique  Bach, PhD PeriTox, UMR_I 01, Jules Verne University of Picardy, CURS, Amiens, France Aida Bairam, MD, PhD  Pediatric Department, Research Center of IUCPQ; Laval University, Québec, Quebec, Canada Hari  P.  R.  Bandla, MD, MRCP(UK) Department of Pediatrics, Medical College of Wisconsin, Wauwatosa, WI, USA Katalina Bertran Salinas, MD  Pediatric Department, Clinica Alemana de Santiago, School of Medicine Universidad del Desarrollo, Santiago, Chile Stéphanie Bioulac, MD, PhD  CHU Bordeaux, Service Universitaire de Médecine du sommeil, Bordeaux, France Université de Bordeaux, Sommeil, Addiction et Neuropsychiatrie, USR 3413, F-33000, Bordeaux, France CNRS, SANPSY, USR 3413, F-33000, Bordeaux, France Stacey  Bissell, BSc, MRes, PhD School of Psychology, University of Birmingham, Birmingham, West Midlands, UK Stefan Bogdanov, DCP, MSc  School of Psychology, University of Sydney, Sydney, NSW, Australia Pablo  E.  Brockmann, MD, PhD Department of Pediatric Cardiology and Pulmonology, Division of Pediatrics, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile Pediatric Sleep Center, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile Oliviero Bruni, MD  Department of Developmental and Social Psychology, Pediatric Sleep Center, Sapienza University Rome, Rome, Italy

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John  L.  Carroll, MD Pediatrics, Division of Pediatric Pulmonary and Sleep Medicine, Arkansas Children’s Hospital, Little Rock, AR, USA Christina L. Casnar, PhD  Neuropsychology, Children’s National Health System, Washington, DC, USA Kate C. Chan, MBChB (CUHK), MRCP (UK)  Department of Paediatrics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong Ronald  D.  Chervin, MD, MS Department of Neurology, Division of Sleep Medicine, Michigan Medicine, Ann Arbor, MI, USA Christopher  M.  Cielo, DO, MS Pediatrics, Division of Pulmonary & Sleep Medicine, Children’s Hospital of Philadelphia, Philadelphia, PA, USA Evelyn  Constantin, MD CM MSc(Epi) FRCPC Department of Pediatrics, McGill University, Montreal, QC, Canada Pediatric Sleep Clinic and Pediatric Sleep Laboratory, Montreal Children’s Hospital, McGill University Health Centre, Montreal, QC, Canada Research Institute of the McGill University Health Centre, Montreal, QC, Canada Ashley  F.  Curtis, PhD Department of Psychiatry, University of Missouri-Columbia, Columbia, MO, USA Thuan Dang, MD  Pediatric Sleep, Ann and Robert H. Lurie Children’s Hospital, Chicago, IL, USA Mattina  Davenport, MA Educational, School and Counseling Psychology, University of Missouri-Columbia, Columbia, MO, USA Ehab A. Dayyat, MD  Department of Pediatrics, Baylor Scott & White McLane Children’s Medical Center, Texas A&M College of Medicine, Temple, TX, USA Carmen T. Gómez de León, PhD  Departamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad de México, Mexico Lourdes  M.  DelRosso, MD, MEd Pediatrics, Seattle Children’s Hospital, University of Washington, Seattle, WA, USA Laura Dosier, MD  Department of Pediatrics, Duke University Medical Center, Durham, NC, USA Nicholas-Tiberio  Economou, MD, MSci, PhD Division of Pulmonology, Department of Clinical Therapeutics, National and Kapodistrian University of Athens School of Medicine, Alexandra Hospital, Athens, Greece “Enypnion” Sleep/Wake-Epilepsy Center, Bioclinic Hospital, Athens, Greece Dawn  E.  Elder, MBChB, CH, FRACP, PhD  Department of Paediatrics & Child Health, University of Otago, Wellington, New Zealand Jonathan Emens, MD  Department of Psychiatry, Oregon Health & Science University, VA Portland Health Care System, Portland, OR, USA Tamar  Etzioni-Friedman, MD Department of Pediatrics, Carmel Medical Center, Haifa, Israel Melania Evangelisti, MD, PhD  NESMOS Department, Pediatric Unit Sant’Andrea Hospital, Faculty of Medicine and Psychology, “Sapienza” University, Rome, Italy Zheng  Fan, MD Department of Neurology and Pediatrics, University of North Carolina, Chapel Hill, NC, USA

Contributors

Contributors

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Nathalia  Carolina  Fernandes  Fagundes, MSc, DDS School of Dentistry, University of Alberta, Edmonton, AB, Canada Luigi  Ferini-Strambi, MD, PhD  Sleep Disorders Center, Department of Neurology, Vita-­ Salute San Raffaele University, Milan, Italy Raffaele Ferri, MD  Sleep Research Centre, Department of Neurology I.C., Oasi Research Institute – IRCCS, Troina, EN, Italy Carlos Flores-Mir, BSc, MSc, DSC  School of Dentistry, University of Alberta, Edmonton, AB, Canada Erica Fornaris Rouch, PhD  Curry School of Education, University of Virginia, Charlottesville, VA, USA Patricia Franco, MD, PhD  Pediatric Sleep Unit & National Reference Center for Narcolepsy, Hôpital Femme Mère Enfant, HCL & INSERM U1028, CRNL, Université Lyon 1, Lyon, France INSERM U1028, CRNL, Neurocampus, Université Lyon 1, Bron, France Lee Fu-I, MD, PhD  Institute and Department of Psychiatry, University of São Paulo – School of Medicine, São Paulo, SP, Brazil Barbara  C.  Galland, PhD Department of Women’s & Children’s Health, University of Otago, Dunedin, New Zealand Alex Gileles-Hillel, MD  Faculty of Medicine, Hebrew University of Jerusalem, Israel; The Wohl Center For Translational Medicine; Pediatric Pulmonology and Sleep Unit, Department of Pediatrics, Hadassah University Medical Center, Jerusalem, Israel Daniella  K.  Ginsburg, MD Division of Pediatric Pulmonology and Sleep Medicine, Children’s Hospital Los Angeles, Los Angeles, CA, USA David  Gozal, MD, MBA, PhD (Hon) Department of Child Health, MU Women’s and Children’s Hospital, Columbia, MO, USA Children’s Hospital Research Institute, University of Missouri, Columbia, MO, USA Madeleine  Grigg-Damberger, MD  Department of Neurology, University of New Mexico School of Medicine, Albuquerque, NM, USA Christian Guilleminault, DM, MD, DBiol  Division of Sleep Medicine, Stanford University, Palo Alto, CA, USA Kamalesh K. Gulia, PhD  Division of Sleep Research, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, Kerala, India Neepa  Gurbani, DO Division of Pulmonology & Section of Sleep Medicine, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA Aurore  Guyon, PhD Pediatric Sleep Unit & National Reference Center for Narcolepsy, Hôpital Femme Mère Enfant, HCL & INSERM U1028, CRNL, Université Lyon 1, Lyon, France INSERM U1028, CRNL, Neurocampus, Université Lyon 1, Bron, France Sumalee  Hantragool, MD  Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand Sally Ibrahim, MD  University Hospitals, Rainbow Babies and Children’s Hospital, Division of Pediatric Pulmonology, Allergy/Immunology, and Sleep Medicine, Cleveland, OH, USA

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Sehyr Imran, MD  Division of Pulmonary and Sleep Medicine, Children’s Mercy Hospital, Kansas City, MO, USA David  G.  Ingram, MD Division of Pulmonary and Sleep Medicine, Children’s Mercy Hospital, Kansas City, MO, USA Stacey  L.  Ishman, MD, MPH Department of Otolaryngology – Head & Neck Surgery, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA Vincent Joseph, PhD  Université Laval – Centre de recherche de l’Institut Universitaire de Cardiologie et Pneumologie de Québec, Québec, Quebec, Canada Levente Kapás, MD, PhD  Department of Biomedical Sciences, Washington State University, Spokane, WA, USA Thomas G. Keens, MD  Division of Pediatric Pulmonology and Sleep Medicine, Children’s Hospital Los Angeles, Los Angeles, CA, USA Pediatrics, Physiology and Biophysics, University of Southern California, Los Angeles, CA, USA Leila  Kheirandish-Gozal, MD, MSc Department of Child Health and the Child Health Research Institute, University of Missouri, School of Medicine, Colombia, MO, USA Dorit  Koren, MD, MTR  Pediatric Diabetes Center, Department of Pediatrics, Division of Pediatric Endocrinology and Diabetes, MassGeneral Hospital for Children, Boston, MA, USA Sanjeev V. Kothare, MD, MBBS, FAAN, FAASM  Division of Pediatric Neurology, Pediatric Sleep Program, Department of Pediatrics, Cohen Children’s Medical Center, Lake Success, NY, USA Pediatric Neurology Service Line, Pediatrics & Neurology, Zucker School of Medicine at Hofstra/Northwell, Lake Success, NY, USA Jyoti Krishna, MD, FAAP, FAASM  Sleep Medicine, Department of Pulmonary Medicine, Akron Children’s Hospital, Akron, OH, USA Suncica Lah, PhD, MSc, BA (Hon)  School of Psychology, University of Sydney, Sydney, NSW, Australia Yael  Lebenthal, MD Pediatric Endocrinology and Diabetes Unit, Dana-Dwek Children’s Hospital, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel Albert Martin Li, BSc (Hons), MBBch (Wales)  Department of Paediatrics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong Jean-Pierre  Libert, PhD  PeriTox, UMR_I 01, Jules Verne University of Picardy, CURS, Amiens, France Ashley Liew, MBChB, MRCPsych, MSc  Evelina London Children’s Hospital, London, UK Carey T. Lockhart, MD  Neurology, Division of Pediatric Neurology, Pediatrics Division of Pulmonary and Sleep Medicine, Seattle Children’s Hospital, University of Washington, Seattle, WA, USA Pediatrics Division of Pulmonary and Sleep Medicine, Seattle Children’s Hospital, University of Washington, Seattle, WA, USA Maria Cecilia Lopes, MD, PhD  Institute and Department of Psychiatry, University of São Paulo – School of Medicine, São Paulo, SP, Brazil

Contributors

Contributors

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Steven  Lopez, RPSGT  Sleep Disorders Center, University of New Mexico, Albuquerque, NM, USA Arwen M. Marker, MA  Clinical Child Psychology Program, University of Kansas, Lawrence, KS, USA Saif Mashaqi, MD  Department of Pulmonary, Critical Care & Sleep Medicine, University of Arizona College of Medicine, Tucson, AZ, USA Micah O. Mazurek, PhD  Curry School of Education and Human Development, University of Virginia, Charlottesville, VA, USA Christina  S.  McCrae, PhD Department of Psychiatry, University of Missouri-Columbia, Columbia, MO, USA Lisa  Medalie, PsyD, DBSM Behavioral Sleep Medicine, Departments of Pediatrics and Medicine, Pritzker School of Medicine, University of Chicago, Chicago, IL, USA Bethanie Menzies, BSci (Hon)  School of Psychology, University of Sydney, Sydney, NSW, Australia Silvia Miano, MD, PhD  Sleep and Epilepsy Center, Neurocenter of Southern Switzerland, Civic Hospital of Lugano (EOC), Lugano, Tessin, Switzerland Velayudhan  Mohan  Kumar, PhD Division of Sleep Research, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, Kerala, India Hawley E. Montgomery-Downs, PhD  Department of Psychology, West Virginia University, Morgantown, WV, USA Alexandra  D.  Monzon, MA Clinical Child Psychology Program, University of Kansas, Lawrence, KS, USA Jorge  Morales-Montor, PhD Departamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad de México, Mexico Joseph  Muenzer, MD, PhD Department of Pediatrics and Genetics, University of North Carolina, Chapel Hill, NC, USA Samya  Z.  Nasr, MD, CPI Department of Pediatrics, Division of Pediatric Pulmonology, Michigan Medicine, Ann Arbor, MI, USA Rose  Nevill, PhD Curry School of Education and Human Development, University of Virginia, Charlottesville, VA, USA Louise  M.  O’Brien, PhD, MS Department of Neurology, Division of Sleep Medicine, Department of Obstetrics & Gynecology, Department of Oral & Maxillofacial Surgery, Michigan Medicine, University of Michigan, Ann Arbor, MI, USA Konstantinos  Papoutsis, BSc(Hons) “Enypnion” Sleep/Wake-Epilepsy Center, Bioclinic Hospital, Athens, Greece Michael D. Partington, MD, MS  Division of Neurosurgery, University of Kansas School of Medicine, Children’s Mercy Hospital, Kansas City, MO, USA John  E.  Pascoe, MD Division of Pulmonology & Section of Sleep Medicine, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA Susana  R.  Patton, PhD, ABPP, CDE Center for Healthcare Delivery Science, Nemours Children’s Health System, Jacksonville, FL, USA

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Ivan M. Pavkovic, MD  Division of Pediatric Neurology, Department of Pediatrics, Cohen Children’s Medical Center, Lake Success, NY, USA Zucker School of Medicine at Hofstra/Northwell, Lake Success, NY, USA Rafael Pelayo, MD  Psychiatry and Behavioral Medicine, Sleep Medicine Division, Stanford University School of Medicine, Stanford, CA, USA Iris Ambrosio Perez, MD  Department of Pediatrics, Children’s Hospital Los Angeles, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA Maria Pia Villa, MD  NESMOS Department, Pediatric Unit Sant’Andrea Hospital, Faculty of Medicine and Psychology, “Sapienza” University, Rome, Italy Giora Pillar, MD, PhD  Department of Pediatrics and Sleep Clinic, Carmel Medical Center and Technion Faculty of Medicine, Haifa, Israel Christian  F.  Poets, MD Department of Neonatology, Tuebingen University Hospital, Tuebingen, Baden-Württemberg, Germany Jean-Paul Praud, MD, PhD  Pediatrics/Pediatric Pulmonology, CHUS Fleurimont-Université de Sherbrooke, Sherbrooke, Quebec, Canada Maya  Ramagopal, MD  Department of Pediatrics, Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ, USA Lawrence Rhein, MD, MPH  Department of Pediatrics, University of Massachusetts Medical School, Worcester, MA, USA Caroline Richards, BSc, PhD, ClinPsyD  School of Psychology, University of Birmingham, Birmingham, West Midlands, UK Carol L. Rosen, MD  Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, OH, USA Jillian N. Sanford, MD, ABP, DABSM  Department of Pediatrics, Oregon Health & Science University, Portland, OR, USA Oscar Sans Capdevila, MD  Pediatric Sleep Unit, Pediatric Neurology, Hospital Sant Joan de Déu, Esplugues Llobregat, Barcelona, Spain Kathleen  M.  Sarber, MD  Department of Surgery, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA Hemant Sawnani, MD  Division of Pulmonology & Section of Sleep Medicine, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA Steven  M.  Scharf, MD, PhD  Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA Aarti Shakkottai, MD  Department of Neurology, Division of Sleep Medicine and Department of Pediatrics, Division of Pediatric Pulmonology, Michigan Medicine, Ann Arbor, MI, USA Colin M. Shapiro, MBChB, PhD, MRCPsych, FRCP(C)  Department of Psychiatry, The Youthdale Child and Adolescent Sleep Center, University of Toronto, Toronto, ON, Canada Renée  A.  Shellhaas, MD, MS  Department of Pediatrics, Division of Pediatric Neurology, Michigan Medicine, C.S. Mott Children’s Hospital, Ann Arbor, MI, USA Narong  Simakajornboon, MD Division of Pulmonology & Section of Sleep Medicine, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

Contributors

Contributors

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Department of Pediatrics, University of Cincinnati College of Medicine,, Cincinnati, OH, USA Sanghun  Sin, MS Division of Pediatric Respiratory and Sleep Medicine, The Children’s Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY, USA Monique A. L. J. Slaats, MD, PhD  Department of Pediatrics, Antwerp University Hospital, Edegem, Antwerp, Belgium Jennifer  Stone, BSN, RN  University Hospitals, Rainbow Babies and Children’s Hospital, Division of Pediatric Pulmonology, Allergy/Immunology, and Sleep Medicine, Cleveland, OH, USA Katherine Sullivan, MD, MS  Department of Pediatrics, University of Massachusetts Medical School, Worcester, MA, USA Shannon S. Sullivan, MD  EvalStat Research Institute (EVALRI), Palo Alto, CA, USA Elizabeth Rachel Super, MD  Department of Pediatrics, Oregon Health & Science University, Portland, OR, USA Andrew  Surtees, BSc, PhD, ClinPsyD  School of Psychology, University of Birmingham and Birmingham Children’s Hospital, Birmingham, West Midlands, UK Jordan  W.  Swanson, MD, MSc  Surgery, Division of Plastic and Reconstructive Surgery, Children’s Hospital of Philadelphia, Philadelphia, PA, USA Éva Szentirmai, MD, PhD  Department of Biomedical Sciences, Washington State University, Spokane, WA, USA Hui-leng  Tan, MBBChir, MD Department of Paediatric Respiratory Medicine, Royal Brompton Hospital, London, UK Riva Tauman, MD  The Sleep Disorders Center, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel Jane  B.  Taylor, MD Division of Pulmonary Medicine, UPMC Children’s Hospital of Pittsburgh, Pittsburgh, PA, USA Marine Thieux  Pediatric Sleep Unit & National Reference Center for Narcolepsy, Hôpital Femme Mère Enfant, HCL & INSERM U1028, CRNL, Université Lyon 1, Lyon, France INSERM U1028, CRNL, Neurocampus, Université Lyon 1, Bron, France Liat Tikotzky, PhD  Department of Psychology, Ben-Gurion University, Beer-Sheva, Israel Lorenzo Tonetti, MS, PsyD, PhD  Department of Psychology “Renzo Canestrari”, University of Bologna, Bologna, Italy Georgia Trakada, MD, PhD  Division of Pulmonology, Department of Clinical Therapeutics, National and Kapodistrian University of Athens School of Medicine, Alexandra Hospital, Athens, Greece Bradley  V.  Vaughn, MD  Department of Neurology, University of North Carolina, Chapel Hill, NC, USA Stijn L. Verhulst, MD, PhD  Department of Pediatrics, Antwerp University Hospital, Edegem, Antwerp, Belgium Noémie  Vieux  Pediatric Sleep Unit & National Reference Center for Narcolepsy, Hôpital Femme Mère Enfant, HCL & INSERM U1028, CRNL, Université Lyon 1, Lyon, France

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David M. Wootton, PhD  Department of Mechanical Engineering, The Cooper Union for the Advancement of Science and Art, New York, NY, USA Robin  Yang, MD, DDS Craniofacial Surgery, Department of Plastic and Reconstructive Surgery, Johns Hopkins Medicine, Baltimore, MD, USA Kin  M.  Yuen, MD, MS Department of Medicine, Pulmonary, Critical Care, Allergy and Sleep Medicine Division, University of California, San Francisco, San Francisco, CA, USA Psychiatry and Behavioral Medicine, Sleep Medicine Division, Stanford University School of Medicine, Stanford, CA, USA Min Zhang, MD  INSERM U1028, CRNL, Neurocampus, Université Lyon 1, Bron, France

Contributors

Part I Basic Introduction to Sleep

1

Normal Sleep in Humans Saif Mashaqi and David Gozal

Introduction

Sleep Neurobiology: The Basics

Sleep is defined as a physiological, reversible, and recurrent behavioral state of perceptual disengagement from the surrounding environment and relative unresponsiveness to external stimuli. In Greek mythology, sleep was designated as Hypnos and the Latin equivalent of sleep is “Somnus.” Hypnos is the God of Sleep. His brother is Thanatos, which is the God of Death. Both are the children of Nyx, “The Night,” and Erebus, “The Darkness” [1]. Hypnos used to live in a big cave where the day and night met. Many poppy flowers, “which are the source of the narcotic opium,” used to grow at the entrance of this cave. His bed was made of ebony wood. He is said to be a very gentle God and to help many humans who had sleep issues. As retribution for such favors, Hypnos owned half of their lives [2]. During sleep, several physiological changes affect different organs and systems in our body—such as cardiovascular, endocrine, respiratory, musculoskeletal, and gastrointestinal. The brain wave activities change with peculiar patterns and waves, which assume distinct different sleep stages when compared to the waking state. In this chapter, we review sleep architecture (including sleep stages) and the neurobiology of sleep, and describe the changes in sleep architecture and circadian rhythm that occur with age, from infancy to the elderly.

The neurobiology of sleep has been the subject of intense study for more than a hundred years. In 1917, the Austrian psychiatrist and neurologist Constantin von Economo was the first physician to study the epidemic of Encephalitis Lethargica, “sleeping sickness,” which affected more than five million people (between 1915 and 1926), with one-third of the patients succumbing in the acute stage of illness. Studying the autopsies of many of these patients, von Economo noticed that patients who had lesions within the posterior hypothalamus and rostral midbrain also manifested severe excessive daytime sleepiness while those who had evidence of damage to the anterior hypothalamus suffered from insomnia. Based on such findings, he formulated the hypothesis that the posterior hypothalamus contains wakefulness-­promoting neurons and the anterior hypothalamus contains sleep-promoting neurons [3]. The easiest way to understand sleep neurobiology is to examine the neuroanatomy and the neurotransmitters that are operationally involved in wakefulness, then in non-rapid eye movement (NREM) sleep, and finally in rapid eye movement (REM) sleep.

S. Mashaqi (*) Department of Pulmonary, Critical Care & Sleep Medicine, University of Arizona College of Medicine, Tucson, AZ, USA e-mail: [email protected] D. Gozal Department of Child Health, MU Women’s and Children’s Hospital, Columbia, MO, USA Children’s Hospital Research Institute, University of Missouri, Columbia, MO, USA

Wakefulness Wakefulness is maintained predominantly by a structure in the brainstem called the reticular formation (RF). A group of fibers traverse rostro-caudally through the midbrain, pons, and medulla, and form the diffuse ascending arousal system (DAAS). It seems that more rostral fibers are critical in wakefulness (e.g., rostral pons and midbrain) compared to the more caudal fibers (e.g., medulla). DAAS fibers consist of two types: monoamine neurotransmitter-releasing fibers and cholinergic fibers [4]. Monoamine fibers release monoamine neurotransmitters (such as norepinephrine, histamine, serotonin, and dopamine). Norepinephrine-releasing fibers originate from the

© Springer Nature Switzerland AG 2021 D. Gozal, L. Kheirandish-Gozal (eds.), Pediatric Sleep Medicine, https://doi.org/10.1007/978-3-030-65574-7_1

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S. Mashaqi and D. Gozal

Fig. 1.1  Monoaminergic and cholinergic nerve fibers involved in the wake process and NREM sleep

locus coeruleus (LC) and fire at the highest intensity and frequency during wakefulness. Histamine-releasing fibers originate from tuberomammillary nucleus and play a critical role GABA in the onset of wakefulness—this explains why anti-­ galanin histaminic agents, particularly the first generation of these – compounds (e.g., diphenhydramine), induce sleepiness. Serotonin-releasing fibers originate from dorsal raphe nucleus. Serotonin plays a role in both wake and sleep and its Amines VLPO ACh role is very complicated due to the presence of many serotonin receptors (up to 15 receptor subtypes). Dopamine-­ – releasing fibers originate from the ventral tegmental area and periaqueductal gray nuclei. Dopamine is the most common NE, 5-HT, ACh target clinically, and most of wake-promoting agents used in clinical practice work on dopaminergic pathways [5]. Cholinergic fibers release acetylcholine and gamma aminobutyric acid (GABA). They originate from the basal forebrain. Cholinergic neurons directly excite the pyramidal cells in the cortex, while GABAergic neurons inhibit the Sleep Wake inhibitory neurons in the cortex, and subsequently cause excitation. Other cholinergic fibers originate from latero-­ Fig. 1.2  The flip-flop switch mechanism that explains the bidirectional dorsal and pedunculopontine tegmental nuclei (LDT and transition between wake and NREM sleep PPT) and ascend to the thalamo-cortical area [5] (Fig. 1.1). “called synchronized EEG,” and this transition from asynchronous to synchronous firing accounts for the slowing in the EEG rhythm from wake to NREM sleep (Fig. 1.2). NREM Sleep In order to maintain sleep and guarantee a rapid sleep During wakefulness, there is a continuous excitation to the onset, we need a system that will continuously suppress the thalamo-cortical neurons that leads to regular tonic firing monoamine fibers. The source of such inputs resides in the called “desynchronized EEG.” In this process, continuous ventrolateral preoptic nucleus (VLPO) and median preoptic depolarization of the thalamo-cortical neurons takes place. area (MnPO), located in the preoptic area of the hypothalaAs we transition from wake to NREM sleep, the EEG rhythm mus. These are inhibitory nuclei and release GABA and slows down and hyperpolarization of thalamo-cortical neu- galanin. VLPO and MnPO project inhibitory neurons to the rons takes place leading to high-frequency burst-pause firing monoaminergic neurons (NA, 5HT, DA, Ach) and to orexin-

1  Normal Sleep in Humans

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+ GABA? Homeostatic sleep drive

Glutamate orexin

WAKE

NREM

–

ORX Stabilizes Behavioral state

Circadian waking drive

GABA galanin –

EEG2

ORX +

Amines ACh

VLPO – NE, 5-HT, ACh

Sleep

Wake

Fig. 1.3  Orexin as a regulator of the flip-flop switch mechanism

ergic neurons [6, 7] (Fig. 1.3). This creates a flip-flop circuit that switches on (initiates sleep) and switches off (initiates wake) [8]. To further fine-tune and stabilize this flip-flop circuit, a peptide called orexin (also termed hypocretin) is produced by hypothalamic neurons. It was described first as an appetite regulator and later as a sleep–wake cycle regulator. Orexin producing neurons are excitatory neurons that stimulate monoamine neurons and subsequently enhance wakefulness (Process C). At the same time, orexinergic neurons also exhibit an autocrine excitation pattern. With increasingly extended wakefulness, sleep pressure builds on to a point that VLPO and MnPO inhibitory neurons inhibit orexinergic neurons, and such processes enhance sleep propensity and onset (Process S: Fig. 1.4).

REM Sleep REM sleep originates in the pons [9]. It was first described by the French neuroscientist and medical researcher Michel Jouvet (1925–2017) at the University of Lyon in France, and called it “sommeil paradoxale” (i.e., paradoxical sleep). In 1961, he categorized sleep into two stages, “telencephalic” (slow wave) sleep and “rhombencephalic” sleep (REM sleep), for the first time and mapped the area producing REM sleep in the brain [10]. Parallel work at the University of Chicago by Drs. Aserinsky and Kleitman led to nearly simultaneous discovery of rapid eye movements as a discrete state during sleep [11–13], and Dr. William Dement, then a graduate student, further elucidated the association of these events with dreams [14]. As mentioned earlier, in the LDT and PPT nuclei, cholinergic fibers originate and project to the thalamo-cortical area (excitatory neurons). From the same nuclei, another group of

Depolarization (excitation)

Regular, repetitive tonic firing (Desynchronized EEG)

Hyperpolarization (inhibition)

High frequency burst-pause firing (Synchronized EEG)

Fig. 1.4  The EEG rhythm in wake and NREM sleep (synchronized and desynchronized EEG)

cholinergic fibers descends downward to the ventral medial medulla (VMM) and pontine reticular formation (PRF) and subsequently induces muscle atonia [15] and rapid eye movements [16]. These neurons are called “REM-ON” neurons [4] (Fig. 1.5).

Sleep Architecture in Adults Sleep is categorized into four stages: stage N1, stage N2, stage N3 (delta wave or slow wave sleep), and stage REM (rapid eye movement). This applies to all age groups except infants. They have a relatively different sleep architecture due to immaturity of many of the neural networks described above and therefore their sleep architecture will be discussed at the end of this chapter. The polysomnographic features of each sleep stage are based on The American Academy of Sleep Medicine (AASM) Manual for the Scoring of Sleep and Associated Events (Version 2.6). Stage N1 is the first sleep stage. We spend about 5–10% of total sleep time in this stage [17]. This stage is characterized by slow eye ­movements

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TH LDT&PPD Locus coeruleus

Subcoeruleus nucleus (believe to cause REM atonia)

Excitatory cholinergic (REM-OFF)

Medial medulla

Inhibitory cholinergic (REM-OFF) TH

Thalamus

Motor neuron

Fig. 1.5  The role of REM-ON nerve fibers in REM sleep and muscle atonia

Fig. 1.6  The EEG and EMG characteristics of stage N1. (From Wikipedia, NascarEd, Creative Commons Attribution-ShareAlike 4.0 International [CC BY-SA 4.0]. Available at: https://www.wikiwand.com/en/Non-rapid_eye_movement_sleep)

(sometimes called rolling eye movements) on the electrooculogram (EOG), which are sinusoidal, regular, and conjugated movements lasting >500  msec. On electroencephalogram (EEG), the rhythm starts to slow down compared to alpha waves, “which are present during wakefulness with closed eyes.” The frequency of the EEG rhythm is usually 4–7 Hz, with low amplitude forming the low-amplitude mixed-frequency pattern (LAMF). Sometimes, vertex sharp wave (V waves) can be seen during N1; however, this is not specific for N1 and can be seen in other sleep stages. The duration of this wave (i.e., the width) is 0.5 seconds and K-complexes are more frequently seen in the frontal EEG derivations [18]. The history of K-complex is quite interesting. It was first described in a private laboratory built in a luxurious mansion in Tuxedo Park, New York. This laboratory was owned by Alfred Lee Loomis who graduated from Harvard Law School and worked as a corporate attorney and then became a bond trader for a while. He con-

1  Normal Sleep in Humans

solidated some of his money to build his private laboratory. He used silver leads to cover the scalp for EEG recordings [19]. In his ninth EEG paper in the early 1930s, Loomis described K-complex for the first time and remarked on the ability to evoke these complexes by external auditory stimuli. The exact physiological function of K-complexes is not totally clear to date. However, several papers after the initial Loomis publication agreed on at least one function for K-complexes. Indeed, Walter et al. [20], in 1953, described the K-complex as “a sign that sleep is deep and hard to disturb and seems to act as to muffle the arousal stimulus.” Still, the question whether K-complex is “a sign of sleep arousals” [21–23] or “a sleep disruption protector” [24–26] has yet to be answered. The other feature of stage N2 is sleep spindles, which are distinct sinusoidal waves at a frequency range of 11–16 Hz. They are more distinctly recognizable in the central EEG derivations. Like K-complexes, the exact physiological function of sleep spindles is poorly understood. However, there is an evidence that sleep spindles play a role in the reinstatement of newly formed memories preparing for their integration into long-term memory during the sleep spindle refractory period. Memory reinstatement indicates the re-emergence of a newly learned-related neural activity. The sleep spindle refractory period blocks any further memories that subsequently reprocess and facilitate the integration of the new memory into the long-term storage [27] (Fig. 1.7). Following stage N2 comes stage N3, also termed slow wave sleep (SWS). This stage represents the deep stage

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of sleep and is characterized by the presence of delta waves. The frequency of delta waves is 0.5–4.0 Hz and the peak– peak amplitude is >75 μV. Delta waves are best observed in the frontal EEG derivations (Fig.  1.8). SWS constitutes 15–20% of total sleep time. Although K-complexes and sleep spindles are typical features of stage N2, they can be seen in stage N3. Stage N3—according to the AASM scoring system, which was introduced in 2007—replaced the previous Rechtschaffen and Kales scoring system that was introduced in 1968 and used stage 3 and stage 4 [28]. The last sleep stage is stage R (REM), which accounts for about 20% of total sleep time. This is usually referred to as the dream stage and is characterized by generalized muscle atonia (except the extraocular muscles and the diaphragm) manifesting as a low to virtually absent chin electromyography (EMG) amplitude. Stage R is characterized by rapid eye movements in the EOG derivations, which is defined as sharp deflections lasting