Progressive Multiple Sclerosis

Progressive Multiple Sclerosis

Alastair Wilkins Editor Progressive Multiple Sclerosis

Editor Alastair Wilkins, M.A., M.B., B.Chir, Ph.D., FRCP Department of Neurology Frenchay Hospital Bristol UK ISBN 978-1-4471-2394- 1 ISBN 978-1-4471-2395-8 (ebook) DOI 10.1007/978-1-4471-2395- 8 Springer London Heidelberg New York Dordrecht Library of Congress Control Number: 2012945748 Springer-Verlag London 2013 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. Exempted from this legal reservation are brief excerpts in connection with reviews or scholarly analysis or material supplied specifically 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 specific 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)

Preface The word progressive holds a number of meanings. In relation to multiple sclerosis, it adopts the familiar meaning of happening or developing gradually and most doctors would recognize the phenotype of this common disease. Another meaning for the word is used when it relates to an idea or a person and is favoring change or innovation, such as a progressive school or a progressive artist. Up until recently, the science and treatment of progressive multiple sclerosis has, however, been anything but innovative and many doctors and indeed patients viewed the stage of the disease as one in which very little could be done. Things have changed and are changing. The drive for therapies to address disease progression is active and our knowledge and understanding of the pathophysiology of the disease grows year on year. There is a real sense of hope that in the coming years better therapies for progressive multiple sclerosis will emerge. Progressive Multiple Sclerosis is intended to give an overview of the current state of knowledge concerning this common disease. Despite many excellent texts on multiple sclerosis, there has been a paucity of books dedicated solely to the progressive phase. Since knowledge is expanding rapidly in the fi eld, it was felt that this book would be a timely addition to the neurological literature. The hope is that this book will be of use to neurologists, both those in training and those who have practiced for many years. The book composes chapters covering the expanse of knowledge on progressive multiple sclerosis from clinical features and epidemiology through to current and potential treatments. Alastair Wilkins v

Acknowledgments The editor would like to acknowledge the hard work and determination of all the authors who contributed to this book. In addition, Maureen Alexander has provided expert editorial services. Thanks to Dr. Kevin Kemp for his help in preparing some of the fi gures for publication. In addition, thanks to Joanna Bolesworth at Springer, all the support staff at Springer and to Manika Power. vii

Contents 1 General Introduction... 1 Alastair Wilkins 2 What Is Disease Progression?... 11 Stanley Hawkins and Alastair Wilkins 3 Epidemiology of Progressive Multiple Sclerosis... 31 Neil Robertson and Claire Hirst 4 The Neuropathology of Progressive Multiple Sclerosis... 51 Lars Bo, Nikos Evangelou, and Emma Tallantyre 5 Mechanisms of Disease Progression... 71 Alastair Wilkins 6 Imaging Disease Progression... 93 Declan Chard and David Miller 7 Biomarkers of Disease Progression... 115 Axel Petzold 8 Symptomatic Treatment for Progressive Multiple Sclerosis... 147 Claire M. Rice and Alastair Wilkins 9 Current Treatments for Progressive Multiple Sclerosis: Disease-Modifying Therapies... 187 Michael Hutchinson 10 Future Therapies for Progressive Multiple Sclerosis... 221 Neil Scolding Index... 245 ix

Contributors Lars Bo Department of Neurology, Haukeland University Hospital, National Competence Center for Multiple Sclerosis, Bergen, Norway Declan Chard, M.B., B.S., Ph.D., MRCP (UK) Department of Neuroinflammation, NMR Research Unit, Institute of Neurology, University College London, London, UK Nikos Evangelou, M.D., D.Phil. Division of Clinical Neurology, Nottingham University Hospital, Queen s Medical Centre, Nottingham, UK Stanley Hawkins Department of Neurology, Royal Victoria Hospital, Belfast, UK Claire Hirst, MB BCh, M.D. Department of Neurology, Morriston Hospital, Swansea, UK Michael Hutchinson, B.Sc., M.B., FRCP, FRCPI Department of Neurology, St Vincent s University Hospital, University College Dublin, Dublin, Ireland David Miller, MD., FRCP., FRACP., FMedSci Department of Neuroin fl ammation, NMR Research Unit, Institute of Neurology, University College London, London, UK Axel Petzold, M.D., Ph.D. Department of Neurology, VUmc Amsterdam, MS Center Amsterdam, Amsterdam, The Netherlands Department of Neuroinflammation, Institute of Neurology, University College London, London, UK Claire M. Rice, M.A., M.R.C.P., Ph.D. Department of Neurology, Institute of Clinical Neurosciences, University of Bristol, Frenchay Hospital, Bristol, UK Neil Robertson, M.B.B.S., M.D. Helen Durham Neuro-inflammatory Centre, Institute of Psychological Medicine and Clinical Neuroscience, University Hospital of Wales, Cardiff, UK xi

xii Contributors Neil Scolding, FRCP, Ph.D. Department of Neurology, Frenchay Hospital, Bristol, UK Emma Tallantyre Division of Clinical Neurology, Nottingham University Hospital, University of Nottingham, Nottingham, UK Alastair Wilkins, M.A., M.B., B.Chir, Ph.D., FRCP Department of Neurology, Frenchay Hospital, Bristol, UK