Neuromuscular Disorders in Clinical Practice

Bashar Katirji • Henry J. Kaminski • Robert L. Ruff Editors

Neuromuscular Disorders in Clinical Practice

Second Edition Editors Bashar Katirji Robert L. Ruff Neuromuscular Center & EMG Laboratory Department of Neurology Department of Neurology Louis Stokes Cleveland VA Medical Center and The Neurological Institute Case Western Reserve University School of Medicine University Hospitals Case Medical Center and Mail Stop 127(W) Case Western Reserve University Cleveland , OH , USA School of Medicine Cleveland , OH , USA

Henry J. Kaminski Department of Neurology George Washington University Washington , DC , USA

ISBN 978-1-4614-6566-9 ISBN 978-1-4614-6567-6 (eBook) DOI 10.1007/978-1-4614-6567-6 Springer New York Heidelberg Dordrecht London

Library of Congress Control Number: 2013942017

© Springer Science+Business Media New York 2014 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, speci fi cally the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on micro fi lms 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. Exempted from this legal reservation are brief excerpts in connection with reviews or scholarly analysis or material supplied speci fi cally for the purpose of being entered and executed on a computer system, for exclusive use by the purchaser of the work. Duplication of this publication or parts thereof is permitted only under the provisions of the Copyright Law of the Publisher’s location, in its current version, and permission for use must always be obtained from Springer. Permissions for use may be obtained through RightsLink at the Copyright Clearance Center. Violations are liable to prosecution under the respective Copyright Law. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a speci fi c statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. While the advice and information in this book are believed to be true and accurate at the date of publication, neither the authors nor the editors nor the publisher can accept any legal responsibility for any errors or omissions that may be made. The publisher makes no warranty, express or implied, with respect to the material contained herein.

Printed on acid-free paper

Springer is part of Springer Science+Business Media (www.springer.com) To our families, friends, and colleagues without whose support this work could not have been completed.

To my wife Patricia, our children Linda and Michael, my parents Zakaria and Malak, and my brothers Hassan and Ammar. –BK

To all those dear to me, my father Edmund and mother Janina, my brother Ed, my second mother Louise and her husband Robert, but most of all the source of all that is good in my life, Adam, my boy and Linda, my wife. –HJK

To daughters Emily and Elizabeth; my wife Suzanne and her children Julia, Daniel, and Antoine; Julia’s husband Greg; and Dan’s wife Nicole and grandchildren Matthew, Hannah, and Abigail. –RLR

Preface

Over a decade ago, the editors appreciated a need for a single textbook that would cover comprehensively all aspects of the broad fi eld of neuromuscular disease, which ultimately led to the publication of the fi rst edition of Neuromuscular Disorders in Clinical Practice . The book attempts to be comprehensive and clinically oriented with the goal of discussing all disorders of the peripheral nervous system and the techniques used to assess these disorders. It thus parallels other neurology subspecialty texts, such as those for epilepsy or cerebrovascular disease, or internal medicine subspecialty books, such as those for rheumatology, endocrinology, or cardiology. The second edition mimics the organization of the fi rst. The book is divided into two parts, Part one discusses the approach to neuromuscular disorders followed by Part two dedicated to specifi c neuromuscular disease. Part one begins with an introduction to the clinical assessment of neuromuscular disorders; though it is not meant to duplicate available monographs on neurological examination, the chapter sets the stage for the evaluation of patients with neuromuscular disease. The second chapter provides concise overview of basic anatomy and physiology of nerves and muscles. The next subsection covers investigative techniques used in evaluating neuromuscular diseases. These include laboratory studies (muscle enzymes, autoan- tibodies, and exercise testing) and clinical neurophysiology procedures (clinical EMG, single fi ber EMG, quantitative EMG analysis, quantitative sensory testing, autonomic testing), as well as nerve and muscle pathology. The new edition adds a chapter in skin biopsy performance and evaluation. The chapter on Molecular Diagnosis and Genetic Testing is updated extensively matching the signi fi cant knowledge increase in the last 10 years in this area. The fi nal subsection of Part one is broad with discussions of assessment and treatment of neuromuscular disorders. Individual chapters include quantitative assessment and outcome measures, rehabilitation, immunotherapy, and critical and respiratory care in the management of patients with neuromuscular diseases. Part two provides detailed discussions of speci fi c neuromuscular disorders. Most chapters are organized into etiology and pathogenesis, clinical presentation, differential diagnosis, evaluation and diagnosis, treatment and management, and prognosis. This approach was used in order to highlight the clinical emphasis of the book and correlate the clinical, electrodiag- nostic, pathological, biochemical, and genetic aspects of neuromuscular disorders. Part two is divided into six subparts. Section one deals with disorders of the motor neuron and dorsal root ganglia (neuronopathies). Section two covers all the peripheral neuropathies including inher- ited and acquired polyneuropathies, mononeuropathies, radiculopathies, and plexopathies. Section three discusses neuromuscular junction disorders. Section four reviews muscle chan- nelopathies, with a chapter devoted to disorders of muscle membrane excitability, including the periodic paralyses, non-dystrophic myotonias and related disorders, and a separate chapter on malignant hyperthermia. Section fi ve is devoted to the inherited and acquired myopathies. Section six is devoted to the numerous conditions that do not fi t neatly into one disorder or cross boundaries to other areas of the nervous system. The section discusses disorders of nerve hyperexcitability, including myokymia, neuromyotonia, muscle cramps, and fasciculations, as well as central nervous system disorders with neuromuscular manifestations, including stiff- man syndrome, and tetanus. Miscellaneous syndromes with neuromuscular presentations are

vii viii Preface discussed, including paraneoplastic neuromuscular disorders, weakness in the intensive care unit, the fl oppy infant, rhabdomyolysis/myoglobinuria, and the fasciitis syndrome. The book ends with a chapter on neuropathic chronic musculoskeletal pain. The second edition of Neuromuscular Disorders in Clinical Practice is intended to serve as a comprehensive text for both novice and experienced practitioners. General neurologists as well as specialists in neuromuscular medicine and trainees in neuromuscular medicine, clinical neurophysiology, and electromyography should fi nd this book inclusive and compre- hensive, yet practical and clinically relevant. Additionally, specialists in physical medicine and rehabilitation, rheumatology, neurosurgery, and orthopedics will fi nd the book useful in their practice. The contributors are an internationally recognized group of clinicians and scientists special- izing in neuromuscular disorders, which allows for an appreciation of not only the science but the art of patient care. It is our hope that this text will provide the reader with the true fl avor of, the nuances of, and the breadth and depth of the subspecialty fi eld of neuromuscular disorders and thus enhance the care of patients with these conditions.

Cleveland, OH, USA Bashar Katirji Washington, DC, USA Henry J. Kaminski Cleveland, OH, USA Robert L. Ruff Acknowledgments

We gratefully acknowledge our present and former colleagues, fellows, and residents who have taught us and encouraged us throughout our careers. In addition, we are deeply indebted to Dr. Robert B. Daroff, whose guidance, support, and inspiration have been instrumental in our roles as physicians, teachers, and writers. We also thank Maria Smilios for keeping us organized and moving throughout the entire process. We thank Richard Lansing of Springer Publishing for appreciating the value of a new edition of Neuromuscular Disorders in Clinical Practice .

ix

Contents

Part I Approach to Neuromuscular Diseases: Principles and Basics

1 Clinical Assessment in Neuromuscular Disorders ...... 3 Bashar Katirji 2 Nerve and Muscle: Basic Concepts...... 21 Francisco H. Andrade

Part II Approach to Neuromuscular Diseases: Neuromuscular Investigations

3 Serum Muscle Enzymes in Neuromuscular Disease ...... 39 Rahila Ansari and Bashar Katirji 4 Autoantibody Testing in Peripheral Neuropathy ...... 51 Alan Pestronk 5 Autoantibody Testing of Autoimmune Neuromuscular Junction, Hyperexcitability, and Muscle Disorders...... 69 Elham Bayat and Henry J. Kaminski 6 Forearm Exercise Testing ...... 79 Eugene Dulaney and Bashar Katirji 7 Clinical Electromyography (Nerve Conduction Studies and Needle Electromyography) ...... 89 Barbara E. Shapiro, Bashar Katirji, and David C. Preston 8 Single-Fiber EMG ...... 153 James M. Gilchrist and Dinesh G. Nair 9 Quantitative EMG Analysis ...... 165 Sanjeev D. Nandedkar and Paul E. Barkhaus 10 Testing of Autonomic Function...... 201 Kamal R. Chémali and Thomas C. Chelimsky 11 Quantitative Sensory Testing ...... 223 Pariwat Thaisetthawatkul 12 Nerve and Muscle Biopsies ...... 235 J. Douglas Miles and Mark L. Cohen 13 Skin Biopsy ...... 261 Lan Zhou 14 Molecular Diagnosis and Genetic Testing ...... 271 Eric P. Hoffman, Lauren P. Hache, and Rose B. McGee

xi xii Contents

Part III Approach to Neuromuscular Diseases: Assessment and Treatment of Neurological Disorders

15 Outcome Measures and Clinical Assessment Instruments in Neuromuscular Disease...... 287 Jeffrey Rosenfeld and Carlayne E. Jackson 16 Physical Management of Patients with Neuromuscular Diseases ...... 327 John R. Bach and Priya Bolikal 17 Immunotherapy in the Treatment of Autoimmune Neuromuscular Diseases ...... 341 Vibhav K. Bansal and Matthew N. Meriggioli 18 Critical and Respiratory Care in Neuromuscular Disorders...... 363 Osama O. Zaidat, Rana Hejal, and Jose I. Suarez

Part IV Neuromuscular Disorders: Neuronopathies (Motor Neuron and Dorsal Root Ganglion Disorders)

19 Poliomyelitis and Post-poliomyelitis Syndrome ...... 383 Kanokwan Boonyapisit 20 Amyotrophic Lateral Sclerosis ...... 395 Roisin Lonergan, Hiroshi Mistumoto, and Brian Murray 21 Spinal Muscular Atrophies ...... 425 Bakri H. Elsheikh and John T. Kissel 22 Atypical Motor Neuron Disorders ...... 441 J. Americo M. Fernandes Filho and Eroboghene E. Ubogu 23 Dorsal Root Ganglion Disorders...... 467 Ales Hlubocky and Benn E. Smith

Part V Neuromuscular Disorders: Peripheral Neuropathies

24 Approach to Peripheral Nerve Disorders ...... 495 David N. Herrmann and Eric L. Logigian 25 Approach to Small Fiber Neuropathy ...... 507 Giuseppe Lauria, Ingemar S.J. Merkies, Stephen G. Waxman, and Catharina G. Faber 26 Charcot-Marie-Tooth Diseases ...... 519 Florian P. Thomas, Velina Guergueltcheva, Francisco De Assis Aquino Gondim, and Albena Jordanova 27 Inherited Metabolic Neuropathies ...... 549 Perry K. Richardson and Scott T. Demarest 28 Guillain-Barré Syndrome and Related Disorders ...... 573 Ezequiel Agustin Piccione, Karim Salame, and Bashar Katirji 29 Chronic Inflammatory Demyelinating Polyradiculoneuropathy and Related Disorders ...... 605 Eduardo Nobile-Orazio, Francesca Gallia, and Elda Judica 30 Dysproteinemic Neuropathies...... 633 Elham Bayat and John J. Kelly Contents xiii

31 Diabetic Neuropathies ...... 647 Shawn J. Bird and Mark J. Brown 32 Nutritional and Alcoholic Neuropathies ...... 675 Robert W. Shields Jr. 33 Metabolic and Endocrine Neuropathies ...... 693 Beth B. Murinson and Vinay Chaudhry 34 Environmental Toxic Neuropathies ...... 703 Michael T. Pulley and Alan R. Berger 35 Drug-Induced Toxic Neuropathies ...... 715 Kevin R. Hargrave, Gregory J. Ferenz, and Milind J. Kothari 36 Vasculitic Neuropathies and Neuropathies of Connective Tissue Diseases ...... 733 Michael P. Collins and John T. Kissel 37 Nonvasculitic Ischemic Neuropathies...... 787 Bryan E. Tsao, Mark A. Ferrante, and Asa J. Wilbourn† 38 Infectious and Granulomatous Peripheral Neuropathies ...... 803 Susan C. Shin, Sonja Schütz, Anthony P. Geraci, Enrique A. Wulff, and David M. Simpson 39 Peripheral Nerve Injury ...... 825 Amparo Gutierrez and John D. England 40 Compressive and Entrapment Neuropathies of the Upper Extremity ...... 833 David C. Preston 41 Compressive and Entrapment Neuropathies of the Lower Extremity ...... 865 Bashar Katirji 42 Cranial Nerve Palsies...... 915 Vita Grynova Kesner and Christina Fournier 43 Peripheral Nerve Tumors ...... 927 Loyola V. Gressot, Kim Islup, David G. Kline, and Daniel H. Kim 44 Cervical Radiculopathy ...... 943 Kerry H. Levin 45 Lumbosacral and Thoracic Radiculopathies...... 963 Elizabeth M. Raynor, Scott A. Boruchow, Rachel Nardin, and Galit Kleiner-Fisman 46 Brachial Plexopathies ...... 991 Mark A. Ferrante and Bryan E. Tsao 47 Lumbosacral Plexopathies ...... 1025 Seward B. Rutkove and Tracy W. Sax

Part VI Neuromuscular Disorders: Neuromuscular Junction Disorders

48 Myasthenia Gravis ...... 1037 Henry J. Kaminski xiv Contents

49 Lambert-Eaton Myasthenic Syndrome ...... 1051 Jan J.G.M. Verschuuren, Maarten J. Titulaer, and Paul Maddison 50 Botulism ...... 1063 Mark Keezer, Ruba Benini, and Colin Chalk 51 Congenital Myasthenic Syndromes ...... 1073 Andrew G. Engel 52 Toxic Neuromuscular Transmission Disorders ...... 1091 James F. Howard Jr.

Part VII Neuromuscular Disorders: Muscle Ion Channel Disorders

53 Disorders of Skeletal Muscle Membrane Excitability: Myotonia Congenita, Paramyotonia Congenita, Periodic Paralysis, and Related Syndromes ...... 1111 Robert L. Ruff and Barbara E. Shapiro 54 Malignant Hyperthermia ...... 1149 Tulio E. Bertorini

Part VIII Neuromuscular Disorders: Myopathies

55 Approach to Myopathies ...... 1159 Björn Oskarsson 56 Dystrophinopathies ...... 1169 Zarife Sahenk and Louise R. Rodino-Klapac 57 Limb-Girdle Muscular Dystrophies...... 1193 Stanley Jones P. Iyadurai and Darine Kassar 58 Facioscapulohumeral Muscular Dystrophy...... 1213 Rabi Tawil 59 The Myotonic Dystrophies ...... 1221 Pichet Termsarasab, Wadih Baajour, Thananan Thammongkolchai, and Bashar Katirji 60 Oculopharyngeal Muscular Dystrophy ...... 1239 Bernard Brais, Nicolas Chrestian, Nicolas Dupré, Jean-Pierre Bouchard, and Guy Rouleau 61 Emery-Dreifuss Muscular Dystrophy ...... 1247 Luciano Merlini and Nadir Mario Maraldi 62 Congenital Myopathies ...... 1257 John B. Bodensteiner 63 Metabolic Myopathies ...... 1273 Salvatore DiMauro, Hasan Orhan Akman, and Carmen Paradas 64 Mitochondrial Myopathies ...... 1297 Salvatore DiMauro, Ichizo Nishino, and Michio Hirano 65 Inflammatory Myopathies...... 1317 Namita Goyal and David A. Chad Contents xv

66 Paraspinous Myopathies: The Dropped Head and Bent Spine Syndromes ...... 1331 Numthip Chitravas and Bashar Katirji 67 Endocrine Myopathies...... 1341 Michael R. Douglas, Zaki Hassan-Smith, and Robert L. Ruff 68 Toxic Myopathies ...... 1365 Ralph W. Kuncl and Gary J. Romano 69 Infectious and Granulomatous Myopathies ...... 1389 Kanokwan Boonyapisit

Part IX Neuromuscular Disorders: Miscellaneous Neuromuscular Disorders and Syndromes

70 Myokymia and Neuromyotonia ...... 1411 Anne F. Josiah and Laurie Gutmann 71 Muscle Cramps and Fasciculations ...... 1417 James B. Caress and Bandhu Paudyal 72 Stiff-Man Syndrome ...... 1427 Franco Folli, Annamaria Prioletta, Angelo Quattrini, and Giuseppe Galardi 73 Tetanus ...... 1441 Jayashri Srinivasan and Thomas D. Sabin 74 Neuroleptic Malignant Syndrome ...... 1449 Prachi Mehndiratta, Yonatan Spolter, Blessing Igboeli, Martha Sajatovic, and Peter F. Buckley 75 Paraneoplastic Neuromuscular Disorders...... 1463 Betul Gundogdu, Myrna R. Rosenfeld, and Stacy A. Rudnicki 76 Acute Neuromuscular Weakness in the Intensive Care Unit...... 1477 David Lacomis and Ahmed El-Dokla 77 Floppy Infant ...... 1495 Bassam A. Bassam 78 Rhabdomyolysis and Myoglobinuria ...... 1507 Devanshi Jadhav and Henry J. Kaminski 79 Eosinophilia-Myalgia Syndrome, Eosinophilic Fasciitis, and Related Fasciitis Disorders ...... 1523 Jeffrey A. Allen and John Varga 80 Neuropathic Pain and Other Chronic Musculoskeletal Pain Conditions. . . . . 1537 Steven N. Sykes and Said R. Beydoun

Index ...... 1555

Contributors

Hasan Orhan Akman, PhD Department of Neurology, Columbia University Medical Center, New York, NY , USA Jeffrey A. Allen , MD Division of Neuromuscular Medicine, Department of Neurology , Northwestern University , Chicago , IL , USA Francisco H. Andrade , PhD Department of Physiology , University of Kentucky , Lexington , KY , USA Rahila Ansari , MD, MS Division of Neurology , Case Western Reserve University School of Medicine and Louis Stokes Cleveland Veterans Affairs Medical Center , Cleveland , OH , USA Wadih Baajour , MB, ChB Department of Neurology , The Neurological Institute, University Hospital Case Medical Center, Case Western Reserve University School of Medicine , Cleveland , OH , USA John R. Bach , MD Department of Physical Medicine and Rehabilitation , Rutgers New Jersey Medical School , Newark , NJ , USA Department of Physical Medicine and Rehabilitation , University Hospital B-403 , Newark , NJ , USA Vibhav K. Bansal , MD Department of Neurology , Michigan State University/Sparrow Health Systems , Holt , MI , USA Paul E. Barkhaus , MD Department of Neurology , Medical College of Wisconsin/Froedtert Hospital , Milwaukee , WI , USA Bassam A. Bassam , MD Department of Neurology , University of South Alabama , Mobile , AL , USA Elham Bayat , MD Department of Neurology , George Washington University , Washington , DC , USA Ruba Benini , MD, CM, PhD Department of Neurology & Neurosurgery , McGill University Health Centre, McGill University , Montreal , QC , Canada Alan R. Berger , MD Department of Neurology , University of Florida College of Medicine , Jacksonville , FL , USA Tulio E. Bertorini , MD Department of Neurology , The University of Tennessee Health Science Center , Memphis , TN , USA Department of Neurology, Methodist University Hospital , Memphis , TN , USA Said R. Beydoun , MD, FAAN Department of Neurology, Keck Medical Center , University of Southern California , Los Angeles , CA , USA

xvii xviii Contributors

Shawn J. Bird Department of Neurology , Perelman School of Medicine, University of Pennsylvania , Philadelphia , PA , USA John B. Bodensteiner , MD Child and Adolescent Neurology, Department of Neurology , Mayo Clinic , Rochester , MN , USA Priya Bolikal , MD Department of Physical Medicine and Rehabilitation , New Jersey Medical School , Newark , NJ , USA Kanokwan Boonyapisit , MD Division of Neurology, Department of Internal Medicine, Faculty of Medicine , Siriraj Hospital , Bangkok , Thailand Scott A. Boruchow , MD Department of Neurology , Beth Israel Deaconess Medical Center , Boston , MA , USA Jean-Pierre Bouchard , MD, FRCPC, FANN Department of Neurological Sciences , Universite Laval , Montreal , QC , Canada Bernard Brais , MD, MPhil, PhD, FRCP Department of Neurology & Neurosurgery and Department of Human Genetics , Montreal Neurological Institute, McGill University , Montreal , QC , Canada Mark J. Brown , MD Department of Neurology , Perelman School of Medicine, University of Pennsylvania , Philadelphia , PA , USA Peter F. Buckley , MD Dean, Medical College of Georgia, Georgia Regents University , Augusta , GA , USA James B. Caress , MD Department of Neurology , Wake Forest School of Medicine, Medical Center Boulevard , Winston-Salem , NC , USA David A. Chad , MD Department of Neurology , Massachusetts General Hospital, Harvard Medical School , Boston , MA , USA Colin Chalk , MD,CM, FRCPC Department of Neurology & Neurosurgery , McGill University Health Centre, McGill University , Montreal , QC , Canada Vinay Chaudhry , MD, MBA, CPE, FAAN, FRCP (UK) Department of Neurology , Johns Hopkins University School of Medicine , Baltimore , MD , USA EMG Laboratory, Neurology Outpatient Center, Johns Hopkins Hospital, Baltimore , MD , USA Numthip Chitravas , MD Department of Neurology, The Neurological Institute , University Hospitals Case Medical Center and Case Western Reserve University School of Medicine , Cleveland , OH , USA Thomas C. Chelimsky , MD Department of Neurology , Medical College of Wisconsin/ Froedtert Hospital , Milwaukee , WI , USA Kamal R. Chémali , MD Department of Clinical Neurology, Eastern Virginia Medical School, Neuromuscular and Autonomic Center, Music and Medicine Center, Sentara Health Care Norfolk , VA , USA Nicolas Chrestian , MD Department of Neurological Sciences , CHAUQ (Enfant-Jésus) , Montreal , QC , Canada Mark L. Cohen , MD Department of Pathology , University Hospitals Case Medical Center, Institute of Pathology, Case Western Reserve University School of Medicine , Cleveland , OH , USA Contributors xix

Michael P. Collins , MD Department of Neurology , Medical College of Wisconsin , Milwaukee , WI , USA Scott T. Demarest , MD Department of Neurology , Children’s National Medical Center , Washington , DC , USA Salvatore DiMauro , MD Department of Neurology , Columbia University Medical Center, 4-424B College of Physicians & Surgeons , New York , NY , USA Michael R. Douglas , MBChB, BSc, PhD, MRCP (UK) Russells Hall Hospital, Dudley Group of Hospitals NHS Foundation Trust , Dudley, West Midlands , UK Eugene Dulaney Department of Neurology , University of Vermont , Burlington, VT , USA Nicolas Dupré , MD, MSc Department of Neurological Sciences , CHAUQ (Enfant-Jésus) , Montreal , QC , Canada Ahmed El-Dokla , MD Department of Neurology , University of Pittsburgh School of Medicine , Pittsburgh , PA , USA Andrew G. Engel , MD Department of Neurology , Mayo Clinic College of Medicine, Mayo Clinic , Rochester , MN , USA John D. England , MD Department of Neurology , Louisiana State University Health Sciences Center-New Orleans , New Orleans , LA , USA Bakri H. Elsheikh , MBBS, FRCP (Edin) Neuromuscular Division, EMG Laboratory , Wexner Medical Center and The Ohio State University , Columbus , OH , USA Catharina G. Faber , MD, PhD Department of Neurology , Maastricht University Medical Center , Maastricht , The Netherlands Gregory J. Ferenz , DO Department of Neurology , Penn State Hershey Medical Center , Hershey , PA , USA J. Americo M. Fernandes Filho , MD Department of Neurological Sciences , University of Nebraska Medical Center, Neurology Section, VA Nebraska Western Iowa Health Care System , Omaha , NE , USA Neurology Section , VA Nebraska-Western Iowa Health Care System , Omaha , NE , USA Mark A. Ferrante , MD Department of Neurology , University of Tennessee Health Science Center , Memphis , TN , USA Franco Folli , MD, PhD Diabetes Division, Department of Medicine , University of Texas Health Science Center at San Antonio , San Antonio , TX , USA Christina Fournier , MD Department of Neurology , Emory University , Atlanta , GA , USA Giuseppe Galardi , MD Department of Rehabilitation and Neurophysiology , Fondazione Istituto San Raffaele Ð Giglio , Cefalù Ð Palermo , Italy Francesca Gallia , MD Department of Medical Biotechnology and Translational Medicine (BIOMETRA) , Milan University, 2nd Neurology, IRCCS Humanitas Clinical Institute , Milan , Rozzano , Italy Anthony P. Geraci , MD Department of Neurology , Mount Sinai School of Medicine , Spring fi eld , IL , USA James M. Gilchrist , MD Department of Neurology, Southern Illinois University School of Medicine , Spring fi eld , IL , USA xx Contributors

Francisco De Assis Aquino Gondim , MD, PhD, FAAN Division of Neurology, Departamento de Medicina Clínica , Universidade Federal do Ceará, Faculty of Medicine Christus , Fortaleza , Ceará , Brazil Namita Goyal , MD Department of Neurology , Massachusetts General Hospital, Harvard Medical School , Boston , MA , USA Loyola V. Gressot , MD Department of Neurosurgery , Baylor College of Medicine , Houston , TX , USA Velina Guergueltcheva , MD, PhD Department of Neurology , University Hospital Alexandrovska, Medical University-So fi a , So fi a , Bulgaria Betul Gundogdu , MD Department of Neurology , University of Arkansas for Medical Sciences , Little Rock, AR , USA Amparo Gutierrez , MD Department of Neurology , Louisiana State University Health Sciences Center-New Orleans , New Orleans , LA , USA Laurie Gutmann , MD Department of Neurology , West Virginia University School of Medicine , Morgantown , WV , USA Lauren P. Hache , MS Center for Genetic Medicine Research, Children’s National Medical Center , Washington , DC , USA Zaki Hassan-Smith , MBBS, BMedSci, MRCP (UK) Centre for Endocrinology, Diabetes and Metabolism , University of Birmingham, Institute for Biomedical Research, School of Clinical and Experimental Medicine , Birmingham, West Midlands , UK Kevin R. Hargrave , DO Department of Neurology, Lafayette , LA , USA Rana Hejal , MD Division of Pulmonary/Critical Care and Sleep Medicine , Department of Medicine, University Hospital Case Medical Center, Case Western Reserve University School of Medicine , Cleveland , OH , USA David N. Herrmann , MBBCh Department of Neurology , University of Rochester Medical Center and Strong Memorial Hospital , Rochester , NY , USA Michio Hirano , MD Department of Neurology , Columbia University Medical Center , New York , NY , USA Ales Hlubocky , MD EMG Laboratory, 3B, Mayo School of Graduate Medical Education , Mayo Clinic , Scottsdale , AZ , USA Eric P. Hoffman , PhD Department of Integrative Systems Biology , George Washington University School of Medicine , Washington , DC, USA Center for Genetic Medicine Research, Children’s National Medical Center , Washington , DC , USA James F. Howard, Jr., MD Laboratory for Myasthenia Gravis Research, Department of Neurology, School of Medicine , The University of North Carolina at Chapel Hill , Chapel Hill , NC , USA Blessing Igboeli , MD Department of Psychiatry , University Hospitals Case Medical Center, Case Western Reserve University School of Medicine , Cleveland , OH , USA Kim Islup , MD Department of Neurosurgery, St. Vincent’s Hospital, The Catholic Univesity of Korea , Suwon, Kyounggi-do , South Korea Stanley Jones P. Iyadurai , Msc, PhD, MD Department of Neurology & Psychiatry , Saint Louis University , St. Louis , MO , USA Contributors xxi

Carlayne E. Jackson , MD, FAAN Departments of Neurology and Otolaryngology , University of Texas Health Science Center , San Antonio , TX , USA Devanshi Jadhav , MD Department of Neurology , George Washington University , Washington , DC , USA

Albena Jordanova , PhD Department of Molecular Genetics, Molecular Neurogenomics Group , VIB, and University of Antwerp , Antwerp , Belgium Department of Chemistry and Biochemistry , Molecular Medicine Center, Medical University-So fi a , So fi a , Bulgaria Anne F. Josiah , MD Department of Neurology , West Virginia University School of Medicine , Morgantown , WV , USA Elda Judica , MD Department of Medical Biotechnology and Translational Medicine (BIOMETRA) , Milan University, 2nd Neurology, IRCCS Humanitas Clinical Institute , Milan , Rozzano , Italy Henry J. Kaminski , MD Department of Neurology , George Washington University , Washington , DC , USA Diane Kassar , MD Department of Neurology , St. Louis University , St. Louis , MO , USA Bashar Katirji , MD, FACP Neuromuscular Center & EMG Laboratory , Department of Neurology, The Neurological Institute, University Hospitals Case Medical Center and Case Western Reserve University School of Medicine , Cleveland , OH , USA Mark Keezer , MD, CM Department of Neurology & Neurosurgery , McGill University Health Centre, McGill University , Montreal , QC , Canada John J. Kelly , MD Department of Neurology , Cooper Medical Center , Camden , NJ , USA Vita Grynova Kesner , MD, PhD Department of Neurolgoy , Emory University , Atlanta , GA , USA Daniel H. Kim , MD, FACS Department of Neurosurgery , University of Texas , Houston , TX , USA John T. Kissel , MD Department of Neurology and Pediatrics , Wexner Medical Center and The Ohio State University , Columbus , OH , USA Galit Kleiner-Fisman , MDCM Division of Neurology, Department of Medicine , University of Toronto, Baycrest Geriatric Center , Toronto , ON , Canada David G. Kline , MD Department of Neurosurgery, LSU Health Science Center , New Orleans , LA , USA Milind J. Kothari , DO Department of Neurology , Penn State Hershey Medical Center , Hershey , PA , USA Ralph W. Kuncl , PhD, MD Of fi ce of the President , University of Redlands , Redlands , CA , USA David Lacomis , MD Departments of Neurology and Pathology (Neuropathology) , University of Pittsburgh School of Medicine , Pittsburgh , PA , USA Giuseppe Lauria , MD Neuromuscular Diseases Unit , IRCCS Foundation, Carlo Besta Neurological Institute , Milan , Italy Kerry H. Levin , MD Department of Neurology , Neuromuscular Center, Cleveland Clinic, Cleveland Clinic Lerner College of Medicine , Cleveland , OH , USA xxii Contributors

Eric L. Logigian , MD Department of Neurology , University of Rochester Medical Center and Strong Memorial Hospital , Rochester , NY , USA Roisin Lonergan, MB, BCh, BAOMRCPI Department of Neurology , Mater Misericordiae Hospital , Dublin , Ireland Paul Maddison , MD, FRCP Department of Neurology , Queen’s Medical Centre , Nottingham , UK Nadir Mario Maraldi , MD Laboratory of Muscoloskeletal Cell Biology , Istituto Ortopedico Rizzoli , Bologna , Italy Ingemar S. J. Merkies , MD, PhD Department of Neurology , Spaarne Hospital , Hoofddorp , The Netherlands Department of Neurology , Maastricht University Medical Center, Maastricht , The Netherlands Rose B. McGee Center for Genetic Medicine Research, Children’s National Medical Center, Washington , DC , USA Department of Human Genetics , University of Pittsburgh School of Public Health , Pittsburgh , PA , USA Prachi Mehndiratta , MD Department of Neurology , The Neurological Institute, University Hospitals Case Medical Center, Case Western Reserve University School of Medicine , Cleveland , OH , USA Matthew N. Meriggioli , MD Novartis Institute for Biomedical Research , Cambridge , MA , USA Luciano Merlini , MD Laboratory of Musculoskeletal Cell Biology , Istituto Ortopedico Rizzoli , Bologna , Italy J. Douglas Miles , MD, PhD Department of Medicine, University of Hawaii John A. Burns School of Medicine , Honolulu , HI , USA Neurohospitalist and Neuroscience Education , The Queen’s Medical Center, Honolulu , HI , USA Hiroshi Mistumoto , MD, DSc Department of Neurology , Columbia University Medical Center , New York , NY , USA Beth B. Murinson , MS (Biomath), MD, PhD Department of Neurology , Johns Hopkins University School of Medicine , Baltimore , MD , USA Brian Murray, MB, BCh, BAO, MSc Department of Neurology, Hermitage Medical Clinic , Dublin , Ireland Dublin Neurological Institute, Mater Misericordiae University Hospital , Dublin , Ireland Dinesh G. Nair , MD, PhD Department of Neurology , Rhode Island Hospital , Providence , RI , USA Sanjeev D. Nandedkar , PhD Natus Medical Inc. , Hopewell Junction , NY , USA Rachel Nardin , MD Division of Neurology , Cambridge Health Alliance , Cambridge , MA , USA Ichizo Nishino , MD, PhD Department of Neuromuscular Research , National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP) , Tokyo , Japan Contributors xxiii

Eduardo Nobile-Orazio , MD, PhD, FAAN Department of Medical Biotechnology and Translational Medicine (BIOMETRA) , Milan University, 2nd Neurology, IRCCS Humanitas Clinical Institute , Milan , Rozzano , Italy Björn Oskarsson , MD Department of Neurology, UC Davis ALS Clinic , UC Davis Medical Center , Sacramento , CA , USA Carman Paradas , MD, PhD Department of Neurology , Columbia University Medical Center , New York , NY , USA Bandhu Paudyal , MD Department of Neurology , Wake Forest Health Sciences , Medical Center Boulevard, Winston-Salem , NC , USA Alan Pestronk , MD Departments of Neurology, and Pathology and Immunology , Washington University in Saint Louis School of Medicine , Saint Louis , MO , USA Ezequiel Agustin Piccione , MD Department of Neurology , The Neurological Institute, University Hospitals Case Medical Center and Case Western Reserve University School of Medicine , Cleveland , OH , USA David C. Preston , MD Department of Neurology, Neurological Institute, University Hospitals Case Medical Center and Case Western Reserve University School of Medicine, Cleveland , OH , USA Annamaria Prioletta , MD Diabetes Center Acismom , ACISMOM Associazione Dei Cavalieri Italiani, Sovrano Militare Ordine di Malta , Rome , Italy Michael T. Pulley , MD, PhD Department of Neurology , University of Florida , Jacksonville , FL , USA Angelo Quattrini , MD Division of Neuroscience Ð INSPE , San Raffaele Scienti fi c Institute , Milan , Italy Elizabeth M. Raynor , MD Department of Neurology , Beth Israel Deaconess Medical Center and Harvard Medical School , Boston , MA , USA Perry K. Richardson , MD Department of Neurology , The George Washington University , Washington , DC , USA Louise R. Rodino-Klapac , PhD Department Pediatrics and Center for Gene Therapy , The Research Institute at Nationwide Children’s Hospital and The Ohio State University , Columbus , OH , USA Gary J. Romano , MD Neuroscience Biomarkers , Janssen Research and Development , Titusville , NJ , USA Jeffrey Rosenfeld , PhD, MD, FAAN Division of Neurology , UCSF Fresno, Central California Neuroscience Institute, University Neurology Associates , Fresno , CA , USA Myrna R. Rosenfeld , MD, PhD Department of Neurology , Institute of Biomedical Investigations (IDIBAPS), Clinic Hospital , Barcelona , Spain Guy Rouleau , MD, PhD Department of Research Center, Department of Medicine, Faculty of Medicine , Université de Montréal, CHU Sainte-Justine , Montreal , QC , Canada Stacy A. Rudnicki , MD Department of Neurology , University of Arkansas for Medical Sciences , Little Rock, AR , USA Robert L. Ruff , MD, PhD Department of Neurology , Louis Stokes Cleveland VA Medical Center, Case Western Reserve University School of Medicine , Cleveland , OH , USA xxiv Contributors

Seward B. Rutkove , MD Department of Neurology , Beth Israel Deaconess Medical Center and Harvard Medical School , Boston , MA , USA Thomas D. Sabin , MD Department of Neurology , Tufts Medical Center and Tufts University School of Medicine , Boston , MA , USA Zarife Sahenk , MD, PhD Department of Pediatrics and Center for Gene Therapy , The Research Institute at Nationwide Children’s Hospital and The Ohio State , Columbus , OH , USA Martha Sajatovic , MD Department of Psychiatry, Neurological Institute , Neurological and Behavioral Outcomes Center, University Hospitals Case Medical Center, Case Western Reserve University School of Medicine , Cleveland , OH , USA Karim Salame , MD Department of Neurology , The Neurological Institute, University Hospital Case Medical Center and Case Western Reserve University School of Medicine , Cleveland , OH , USA Tracy W. Sax , MD Department of Neurology , Peace Health Southwest Medical Center , Vancouver , WA , USA Sonja Schütz , MD, MSc Department of Neurology , Mount Sinai Medical Center , New York , NY , USA Barbara E. Shapiro , MD, PhD Department of Neurology , Neurological Institute, University Hospitals Case Medical Center and Case Western Reserve University School of Medicine , Cleveland , OH , USA Robert W. Shields, Jr., MD Department of Neurology , Center for Syncope and Autonomic Disorders, Neuromuscular Section , Neurological Institute, Cleveland Clinic , Cleveland , OH , USA Susan C. Shin , MD Department of Neurology , Mount Sinai Medical Center , New York , NY , USA David M. Simpson , MD, FAAN Department of Neurology , Mount Sinai Medical Center , New York , NY , USA Benn E. Smith , MD EMG Laboratory, 3B, Mayo Medical School , Mayo Clinic , Scottsdale , AZ , USA Yonatan Spolter , MD Department of Neurology , Neurological Institute, University Hospital Case Medical Center, Case Western Reserve University School of Medicine , Cleveland , OH , USA Jayashri Srinivasan , MBBS, PhD, FRCP (UK) Department of Neurology , Lahey Clinic , Burlington , MA , USA Department of Neurology , Tufts University School of Medicine , Boston , MA , USA Jose I. Suarez , MD Department of Neurology , Baylor College of Medicine , Houston , TX , USA Steven N. Sykes , MD Department of Neurology , Cedars-Sinai Medical Center , Beverly Hills , CA , USA Rabi Tawil , MD Department of Neurology , University of Rochester School of Medicine and Dentistry , Rochester , NY , USA Pichet Termsarasab , MD Department of Neurology , The Neurological Institute, University Hospital Case Medical Center, Case Western Reserve University School of Medicine , Cleveland , OH , USA Contributors xxv

Pariwat Thaisetthawatkul , MD Department of Neurological Sciences , University of Nebraska Medical Center , Omaha , NE , USA Thananan Thammongkolchai , MD Department of Neurology , The Neurological Institute, University Hospitals Case Medical Center, Case Western Reserve University School of Medicine , Cleveland , OH , USA Maarten J. Titulaer , MD, PhD Departments of Neurology , Hospital Clinic/Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) and Leiden University Medical Center , Barcelona , Spain Florian P. Thomas , MD, MA, PhD, FAAN, FANA Department of Neurology and Psychiatry , Institute for Molecular Virology, Saint Louis University School of Medicine , St. Louis , MO , USA Bryan E. Tsao , MD Department of Neurology , School of Medicine Loma, Linda University , Loma Linda , CA , USA Eroboghene E. Ubogu , MD Department of Neurology, Neuromuscular Immunopathology Research Laboratory , Baylor College of Medicine , Houston , TX , USA John Varga , MD Department of Rheumatology , Northwestern University , Chicago , IL , USA Jan J. G. M. Verschuuren , MD, PhD Department of Neurology , Leiden University Medical Center , Leiden , The Netherlands Stephen G. Waxman , MD, PhD Department of Neurology , Yale University School of Medicine, and Center for Neuroscience and Regeneration Research, Veterans Affairs Medical Center , CT , USA Asa J. Wilbourn † , MD Department of Neurology, Cleveland Clinic, Case Western Reserve University School of Medicine , Cleveland , OH , USA Enrique A. Wulff , MD Department of Neurology , St. Benedict’s Hospital Mission Doctors Association , Los Angeles , CA , USA Osama O. Zaidat , MD, MSc Department of Neurology , Medical College of Wisconsin and Froedtert Hospital , Milwaukee , WI , USA Lan Zhou , MD, PhD Department of Neurology , Mount Sinai School of Medicine , New York , NY , USA