Current Clinical Neurology Series Editor: Daniel Tarsy Syed A. Rizvi Jonathan F. Cahill Patricia K. Coyle Editors Clinical Neuroimmunology Multiple Sclerosis and Related Disorders Second Edition Current Clinical Neurology Series Editor Daniel Tarsy Beth Israel Deaconness Medical Center Department of Neurology Boston, MA USA Current Clinical Neurology offers a wide range of practical resources for clinical neurologists. Providing evidence-based titles covering the full range of neurologic disorders commonly presented in the clinical setting, the Current Clinical Neurology series covers such topics as multiple sclerosis, Parkinson’s Disease and nonmotor dysfunction, seizures, Alzheimer’s Disease, vascular dementia, sleep disorders, and many others. Series editor Daniel Tarsy, MD, is professor of neurology, Vice Chairman of the Department of Neurology, and Chief of the Movement Disorders division at Beth Israel Deaconness Hospital, Boston, Massachusetts. More information about this series at http://www.springer.com/series/7630 Syed A. Rizvi • Jonathan F. Cahill Patricia K. Coyle Editors Clinical Neuroimmunology Multiple Sclerosis and Related Disorders Second Edition Editors Syed A. Rizvi, MD, EMHL Jonathan F. Cahill, MD Rhode Island Hospital and Alpert Rhode Island Hospital and Alpert Medical School of Brown University Medical School of Brown University Brown Neurology Brown Neurology Providence, RI Providence, RI USA USA Patricia K. Coyle, MD Department of Neurology MS Comprehensive Care Center Stony Brook University Medical Center Stony Brook, NY USA ISSN 1559-0585 ISSN 2524-4043 (electronic) Current Clinical Neurology ISBN 978-3-030-24435-4 ISBN 978-3-030-24436-1 (eBook) https://doi.org/10.1007/978-3-030-24436-1 © Springer Nature Switzerland AG 2020 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, express 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 Humana imprint is published by the registered company Springer Nature Switzerland AG The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland Preface Immune activation of the central or peripheral nervous system (CNS or PNS) has been shown to play a key role in the pathogenesis of many neurological disorders. Basic concepts in clinical neuroimmunology have changed signifi- cantly during the last 10 years and are constantly evolving. New data has driven treatment concepts for a large number of autoimmune diseases, none more so than multiple sclerosis. As this area of research has become increas- ingly active and productive, the need for a comprehensive up-to-date second edition of this handbook has become apparent. Clinical Neuroimmunology: Multiple Sclerosis and Related Disorders (Second Edition) has been written with the clinician in mind and targets resi- dents, fellows, internists, nurse practitioners, as well as general neurologists. The aim of this book is to make recent developments in neuroimmunology accessible to the clinicians who feel daunted by such advances and requires a clear explanation of the scientific and clinical issues. The chapters have been written by experts in their field and been extensively revised and updated. Two new chapters have been added. Part I provides a logical and straightfor- ward overview of neuroimmunology. Part II consists of eight chapters focused on multiple sclerosis and includes a chapter on clinical decision- making and a chapter on vitamin D in MS. Part III has four chapters and focuses on other CNS inflammatory disorders including neuromyelitis optica, ADEM, vasculitis, autoimmune encephalopathies, and immunological aspects of cancer. Part IV includes two chapters that describe autoimmune disorders of the PNS. Part V, the final part, includes a single chapter that focuses on neurologic manifestation of systemic rheumatologic diseases such as systemic lupus erythematosus (SLE), neuro-sarcoidosis, and Behcet’s. We hope health professionals who are interested in neuroimmunological disor- ders will find this book useful. Finally, we would like to thank our contributing authors for their hard work and guidance. Providence, RI, USA Syed A. Rizvi, MD Providence, RI, USA Jonathan F. Cahill, MD Stony Brook, NY, USA Patricia K. Coyle, MD v Series Editor’s Introduction The role of the immune system in the pathophysiology of central and periph- eral nervous system disorders continues to be a topic of great interest among clinicians and researchers in the field. As stated by Drs. Rizvi, Cahill, and Coyle, the editors of Clinical Immunology, Second Edition, basic concepts in this field have changed significantly due to a constant evolution of knowledge since the publication of the first edition of this book in 2011. This comprehen- sive and up-to-date second edition of this useful handbook is therefore a wel- come addition to the field. Clinical Immunology, Second Edition, continues to be written primarily for clinicians in the field and targets general neurologists, internists, fellows, residents, and nurse practitioners. Although clinically oriented, the chapters all include updated authoritative information on new understandings of the basic mechanisms of the disorders being discussed. Section 1 begins with two useful chapters which provide an excellent introduction and overview of clin- ical neuroimmunology and the principles of immunotherapy. Section 2 cov- ers multiple sclerosis and includes new chapters on clinical decision-making in the management of multiple sclerosis and the role of vitamin D in this disease. Section 3 covers other central nervous system inflammatory disor- ders, such as neuromyelitis optica, acute disseminated encephalomyelitis, and CNS vasculitis, and a new chapter on paraneoplastic disorders. Section 4 covers immunologic disorders of muscle and peripheral nerve, and Section 5 provides a new chapter concerning the neurologic manifestations of systemic rheumatologic disorders. The readers of this volume will discover that the quantity of new knowledge accumulated in the past 10 years is worthy of this new and highly comprehensive summary of the field. Daniel Tarsy, MD Professor in Neurology, Harvard Medical School Beth Israel Deaconess Medical Center Boston, MA, USA vii Contents Part 1 Introduction 1 Introduction to Neuroimmunology . . . . . . . . . . . . . . . . . . . . . . . . 3 Patricia K. Coyle 2 Principles of Immunotherapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 Jennifer Joscelyn, Javier Ochoa-Repáraz, and Lloyd Kasper Part II M ultiple Sclerosis 3 Immunopathogenesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45 Patricia K. Coyle 4 Epidemiology and Genetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71 Tina Roostaei and Philip L. De Jager 5 Clinical Features, Symptom Management, and Diagnosis . . . . . 89 Jacqueline F. Rosenthal, James M. Stankiewicz, and Guy J. Buckle 6 Magnetic Resonance Imaging and Analysis in Multiple Sclerosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 109 Dejan Jakimovski, Deepa P. Ramasamy, and Robert Zivadinov 7 Disease-Modifying Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137 Syed A. Rizvi 8 Clinical Decision-Making in the Management of Multiple Sclerosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 159 Syed A. Rizvi, Joshua A. Stone, Saima T. Chaudhry, Nichola Haddad, Brian Wong, and Jennifer O. Grimes 9 Multiple Sclerosis in Children . . . . . . . . . . . . . . . . . . . . . . . . . . . . 179 Charles D. Tyshkov, Leigh Elkins Charvet, and Lauren B. Krupp 10 Vitamin D and Multiple Sclerosis . . . . . . . . . . . . . . . . . . . . . . . . . 197 Michael J. Bradshaw, Michael F. Holick, and James M. Stankiewicz ix x Contents Part III Other CNS inflammatory Disorders 11 Acute Disseminated Encephalomyelitis . . . . . . . . . . . . . . . . . . . . 215 Patricia K. Coyle 12 Neuromyelitis Optica Spectrum Disorders . . . . . . . . . . . . . . . . . . 227 Jonathan F. Cahill 13 Paraneoplastic and Other Autoimmune Disorders . . . . . . . . . . . 235 Alexander Mohler, Mayra Montalvo, and Julie Roth 14 Adult and Childhood Vasculitis of the Nervous System . . . . . . . 257 David S. Younger Part IV P eripheral Nervous System Disorders 15 Immunologic Disorders of Neuromuscular Junction and Muscle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 285 James M. Gilchrist and John E. Donahue 16 Autoimmune Neuropathies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 299 Jacques Reynolds and George Sachs Part V S ystemic Disorders 17 Neurologic Manifestations of Systemic Rheumatologic Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 321 Michael J. Bradshaw, Shamik Bhattacharyya, Nagagopal Venna, and Jonathan F. Cahill Index � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � 343 Contributors Shamik Bhattacharyya, MD, MS Department of Neurology, Brigham and Women’s Hospital, Boston, MA, USA Michael J� Bradshaw, MD Department of Neurology, Chicago Medical School, Rosalind Franklin University of Medicine and Science, Billings Clinic, Billings, MT, USA Guy J� Buckle, MD, MPH Shepherd Center, Multiple Sclerosis Institute, Atlanta, GA, USA Jonathan F� Cahill, MD Rhode Island Hospital and Alpert Medical School of Brown University, Brown Neurology, Providence, RI, USA Leigh Elkins Charvet, PhD Department of Neurology, Multiple Sclerosis Comprehensive Care Center, NYU Langone Health, New York, NY, USA Saima T� Chaudhry, MD MS Fellow, Brown Neurology, Providence, RI, USA Patricia K� Coyle, MD Department of Neurology, MS Comprehensive Care Center, Stony Brook University Medical Center, Stony Brook, NY, USA Philip L� De Jager, MD, PhD Department of Neurology, New York – Presbyterian Hospital, New York, NY, USA John  E�  Donahue, MD Department of Neuropathology, Rhode Island Hospital, Providence, RI, USA James  M�  Gilchrist, MD Department of Neurology, Southern Illinois University School of Medicine, Springfield, IL, USA Jennifer O� Grimes, MA, MD Candidate Alpert Warren Medical School of Brown University, Providence, RI, USA Nichola Haddad, BA Alpert Warren Medical School of Brown University, Providence, RI, USA Michael F� Holick, PhD, MD Department of Medicine, Boston University Medical Center, Boston, MA, USA Dejan  Jakimovski, MD Department of Neurology, Buffalo General Hospital, University of Buffalo, Buffalo, NY, USA xi