Neuromuscular Disorders in Clinical Practice

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

Neuromuscular Disorders in Clinical Practice

Second Edition

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)

Editors Bashar Katirji 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

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

Robert L. Ruff Department of Neurology Louis Stokes Cleveland VA Medical Center and Case Western Reserve University School of Medicine Mail Stop 127(W)Cleveland , OH , USA

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

vii

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 speci fi 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

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

ix

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 .

xi

Contents

Part I Approach to Neuromuscular Diseases: Principles and Basics

1 Clinical Assessment in Neuromuscular Disorders . . . . . . . . . . . . . . . . . . . . . . . 3Bashar Katirji

2 Nerve and Muscle: Basic Concepts. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21Francisco H. Andrade

Part II Approach to Neuromuscular Diseases: Neuromuscular Investigations

3 Serum Muscle Enzymes in Neuromuscular Disease . . . . . . . . . . . . . . . . . . . . . . 39Rahila Ansari and Bashar Katirji

4 Autoantibody Testing in Peripheral Neuropathy . . . . . . . . . . . . . . . . . . . . . . . . 51Alan Pestronk

5 Autoantibody Testing of Autoimmune Neuromuscular Junction, Hyperexcitability, and Muscle Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69Elham Bayat and Henry J. Kaminski

6 Forearm Exercise Testing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79Eugene Dulaney and Bashar Katirji

7 Clinical Electromyography (Nerve Conduction Studies and Needle Electromyography) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89Barbara E. Shapiro, Bashar Katirji, and David C. Preston

8 Single-Fiber EMG . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153James M. Gilchrist and Dinesh G. Nair

9 Quantitative EMG Analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 165Sanjeev D. Nandedkar and Paul E. Barkhaus

10 Testing of Autonomic Function . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 201Kamal R. Chémali and Thomas C. Chelimsky

11 Quantitative Sensory Testing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 223Pariwat Thaisetthawatkul

12 Nerve and Muscle Biopsies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 235J. Douglas Miles and Mark L. Cohen

13 Skin Biopsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 261Lan Zhou

14 Molecular Diagnosis and Genetic Testing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 271Eric P. Hoffman, Lauren P. Hache, and Rose B. McGee

xii Contents

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

15 Outcome Measures and Clinical Assessment Instruments in Neuromuscular Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 287Jeffrey Rosenfeld and Carlayne E. Jackson

16 Physical Management of Patients with Neuromuscular Diseases . . . . . . . . . . . 327John R. Bach and Priya Bolikal

17 Immunotherapy in the Treatment of Autoimmune Neuromuscular Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 341Vibhav K. Bansal and Matthew N. Meriggioli

18 Critical and Respiratory Care in Neuromuscular Disorders. . . . . . . . . . . . . . . 363Osama 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 . . . . . . . . . . . . . . . . . . . . . . . . . 383Kanokwan Boonyapisit

20 Amyotrophic Lateral Sclerosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 395Roisin Lonergan, Hiroshi Mistumoto, and Brian Murray

21 Spinal Muscular Atrophies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 425Bakri H. Elsheikh and John T. Kissel

22 Atypical Motor Neuron Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 441J. Americo M. Fernandes Filho and Eroboghene E. Ubogu

23 Dorsal Root Ganglion Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 467Ales Hlubocky and Benn E. Smith

Part V Neuromuscular Disorders: Peripheral Neuropathies

24 Approach to Peripheral Nerve Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 495David N. Herrmann and Eric L. Logigian

25 Approach to Small Fiber Neuropathy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 507Giuseppe Lauria, Ingemar S.J. Merkies, Stephen G. Waxman, and Catharina G. Faber

26 Charcot-Marie-Tooth Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 519Florian P. Thomas, Velina Guergueltcheva, Francisco De Assis Aquino Gondim, and Albena Jordanova

27 Inherited Metabolic Neuropathies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 549Perry K. Richardson and Scott T. Demarest

28 Guillain-Barré Syndrome and Related Disorders . . . . . . . . . . . . . . . . . . . . . . . 573Ezequiel Agustin Piccione, Karim Salame, and Bashar Katirji

29 Chronic Inflammatory Demyelinating Polyradiculoneuropathy and Related Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 605Eduardo Nobile-Orazio, Francesca Gallia, and Elda Judica

30 Dysproteinemic Neuropathies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 633Elham Bayat and John J. Kelly

xiiiContents

31 Diabetic Neuropathies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 647Shawn J. Bird and Mark J. Brown

32 Nutritional and Alcoholic Neuropathies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 675Robert W. Shields Jr.

33 Metabolic and Endocrine Neuropathies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 693Beth B. Murinson and Vinay Chaudhry

34 Environmental Toxic Neuropathies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 703Michael T. Pulley and Alan R. Berger

35 Drug-Induced Toxic Neuropathies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 715Kevin R. Hargrave, Gregory J. Ferenz, and Milind J. Kothari

36 Vasculitic Neuropathies and Neuropathies of Connective Tissue Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 733Michael P. Collins and John T. Kissel

37 Nonvasculitic Ischemic Neuropathies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 787Bryan E. Tsao, Mark A. Ferrante, and Asa J. Wilbourn†

38 Infectious and Granulomatous Peripheral Neuropathies . . . . . . . . . . . . . . . . . 803Susan C. Shin, Sonja Schütz, Anthony P. Geraci, Enrique A. Wulff, and David M. Simpson

39 Peripheral Nerve Injury . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 825Amparo Gutierrez and John D. England

40 Compressive and Entrapment Neuropathies of the Upper Extremity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 833David C. Preston

41 Compressive and Entrapment Neuropathies of the Lower Extremity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 865Bashar Katirji

42 Cranial Nerve Palsies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 915Vita Grynova Kesner and Christina Fournier

43 Peripheral Nerve Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 927Loyola V. Gressot, Kim Islup, David G. Kline, and Daniel H. Kim

44 Cervical Radiculopathy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 943Kerry H. Levin

45 Lumbosacral and Thoracic Radiculopathies. . . . . . . . . . . . . . . . . . . . . . . . . . . . 963Elizabeth M. Raynor, Scott A. Boruchow, Rachel Nardin, and Galit Kleiner-Fisman

46 Brachial Plexopathies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 991Mark A. Ferrante and Bryan E. Tsao

47 Lumbosacral Plexopathies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1025Seward B. Rutkove and Tracy W. Sax

Part VI Neuromuscular Disorders: Neuromuscular Junction Disorders

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

xiv Contents

49 Lambert-Eaton Myasthenic Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1051Jan J.G.M. Verschuuren, Maarten J. Titulaer, and Paul Maddison

50 Botulism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1063Mark Keezer, Ruba Benini, and Colin Chalk

51 Congenital Myasthenic Syndromes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1073Andrew G. Engel

52 Toxic Neuromuscular Transmission Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . 1091James 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 . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1111Robert L. Ruff and Barbara E. Shapiro

54 Malignant Hyperthermia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1149Tulio E. Bertorini

Part VIII Neuromuscular Disorders: Myopathies

55 Approach to Myopathies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1159Björn Oskarsson

56 Dystrophinopathies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1169Zarife Sahenk and Louise R. Rodino-Klapac

57 Limb-Girdle Muscular Dystrophies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1193Stanley Jones P. Iyadurai and Darine Kassar

58 Facioscapulohumeral Muscular Dystrophy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1213Rabi Tawil

59 The Myotonic Dystrophies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1221Pichet Termsarasab, Wadih Baajour, Thananan Thammongkolchai, and Bashar Katirji

60 Oculopharyngeal Muscular Dystrophy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1239Bernard Brais, Nicolas Chrestian, Nicolas Dupré, Jean-Pierre Bouchard, and Guy Rouleau

61 Emery-Dreifuss Muscular Dystrophy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1247Luciano Merlini and Nadir Mario Maraldi

62 Congenital Myopathies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1257John B. Bodensteiner

63 Metabolic Myopathies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1273Salvatore DiMauro, Hasan Orhan Akman, and Carmen Paradas

64 Mitochondrial Myopathies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1297Salvatore DiMauro, Ichizo Nishino, and Michio Hirano

65 Inflammatory Myopathies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1317Namita Goyal and David A. Chad

xvContents

66 Paraspinous Myopathies: The Dropped Head and Bent Spine Syndromes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1331Numthip Chitravas and Bashar Katirji

67 Endocrine Myopathies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1341Michael R. Douglas, Zaki Hassan-Smith, and Robert L. Ruff

68 Toxic Myopathies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1365Ralph W. Kuncl and Gary J. Romano

69 Infectious and Granulomatous Myopathies . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1389Kanokwan Boonyapisit

Part IX Neuromuscular Disorders: Miscellaneous Neuromuscular Disorders and Syndromes

70 Myokymia and Neuromyotonia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1411Anne F. Josiah and Laurie Gutmann

71 Muscle Cramps and Fasciculations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1417James B. Caress and Bandhu Paudyal

72 Stiff-Man Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1427Franco Folli, Annamaria Prioletta, Angelo Quattrini, and Giuseppe Galardi

73 Tetanus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1441Jayashri Srinivasan and Thomas D. Sabin

74 Neuroleptic Malignant Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1449Prachi Mehndiratta, Yonatan Spolter, Blessing Igboeli, Martha Sajatovic, and Peter F. Buckley

75 Paraneoplastic Neuromuscular Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1463Betul Gundogdu, Myrna R. Rosenfeld, and Stacy A. Rudnicki

76 Acute Neuromuscular Weakness in the Intensive Care Unit . . . . . . . . . . . . . . . 1477David Lacomis and Ahmed El-Dokla

77 Floppy Infant . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1495Bassam A. Bassam

78 Rhabdomyolysis and Myoglobinuria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1507Devanshi Jadhav and Henry J. Kaminski

79 Eosinophilia-Myalgia Syndrome, Eosinophilic Fasciitis, and Related Fasciitis Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1523Jeffrey A. Allen and John Varga

80 Neuropathic Pain and Other Chronic Musculoskeletal Pain Conditions . . . . . 1537Steven N. Sykes and Said R. Beydoun

Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1555

xvii

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

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

xixContributors

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 – Giglio , Cefalù – 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

xxiContributors

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

xxiiiContributors

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 – 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

xxvContributors

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