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McAlpine's Multiple Sclerosis 4th Edition. Alastair Compston, Ian R. McDonald, John Noseworthy, Hans Lassmann, David H. Miller, Kenneth J. Smith, Hartmut Wekerle, Christian Confavreux

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McAlpine's Multiple Sclerosis 4th Edition Alastair Compston, Ian R. McDonald, John Noseworthy, Hans Lassmann, David H. Miller, Kenneth J. Smith, Hartmut Wekerle, Christian Confavreux ebook pdf
Publisher:
Language: English
Page: 1008
ISBN: 044307271X, 9780443072710

From The New England Journal of Medicine

Multiple sclerosis was first described about 160 years ago by Jean Martin Charcot. Since then, it has become one of the most common conditions faced by clinical neurologists and one of the most intriguing puzzles for neuroscientists. Multiple sclerosis is a relatively frequent disease in Western countries, mainly affecting young people and causing, in many of them, severe and irreversible disability during the 10 to 15 years after onset. Despite its frequency, the causes and pathogenesis of multiple sclerosis remain uncertain, our understanding of its natural evolution is still in its infancy, and our ability to alter its course is limited.

Nevertheless, as a result of three factors, we have recently been witnessing major advances in our understanding of the dynamics of the disease. First, flourishing activity in the basic sciences, such as genetics, immunology, and immunopathology, has helped to elucidate the mechanisms responsible for neurologic damage and repair related to multiple sclerosis. Second, the development and intensive clinical application of sophisticated magnetic resonance imaging technology have helped to show in vivo how the complex and heterogeneous pathological features of the disease progress to cause acute and permanent disability. Third, the availability of treatment that is able to modify, albeit only slightly, the evolution of multiple sclerosis is providing information about the mechanisms of the disease and is also attracting attention from individual neuroscientists and research support from both public and private institutions.

The history of multiple sclerosis is also the history of the many authoritative reviews of the topic. The first chapter of this history was written by W.A. Hammond in 1871, and the latest is the third edition of the classic McAlpine's Multiple Sclerosis by Alastair Compston and colleagues, published in 1998. The principal merit of this book is the clear and coherent approach of the six authors, who are the world's leading figures in the field, to describing and interpreting the many complex and variable aspects of multiple sclerosis. The book does not attempt to be a comprehensive work on multiple sclerosis, as has been the declared intent since the first edition was published in 1985, but rather, it emphasizes what is considered by the authors to be relevant to the understanding of the mechanisms and dynamics of the disease and what still needs to be further clarified.

In this light, section 4, which provides a comprehensive, thoughtful, and up-to-date overview of the current state of knowledge of the pathogenesis of multiple sclerosis, can be considered the heart of the book. All the evidence, both in support of and against a given hypothesis, is clearly and comprehensively discussed, and the areas of uncertainty that are ripe for future research are indicated.

Inflammation is one of the earliest events in the evolution of multiple sclerosis, and it starts with the migration of activated T lymphocytes into the central nervous system. Inflammation is maintained by the interaction of the activated lymphocytes with antigen-presenting cells in the central nervous system through the release of proinflammatory cytokines. These cytokines increase the permeability of the blood-brain barrier and recruit secondary effector cells and humoral factors, which can lead to varying degrees of damage to the myelin sheath and death of oligodendrocytes. In the meantime, however, several other mechanisms down-regulate the process. These mechanisms include apoptosis of lymphocytes, release of antiinflammatory cytokines, and systemic endocrine responses. Progressive and irreversible loss of myelin is the result of the variable and complex interplay between the number of dead oligodendrocytes and oligodendrocyte progenitor cells and the ability of the remaining oligodendrocytes to promote remyelination. The pathologic progression of the disease is completed by astroglia reaction and axonal loss, which can occur through wallerian degeneration or loss of nerve cells.

Each of those events is expressed clinically. Acute symptoms are due to the blocking of nerve conduction, which, in turn, results from the opening of the blood-brain barrier, inflammation, and demyelination. Recovery from acute symptoms is the result of down-regulation of the inflammatory process, the ability to remyelinate, and the restoration of conduction through the insertion of new sodium channels into the demyelinated axolemma. Persistent and severe demyelination and, more important, axon depletion are the most likely causes of irreversible and severe disability.

From this brief description of the pathogenesis of multiple sclerosis, it will be clear that many aspects of the disease are still poorly understood. These range from the definition of the cause of multiple sclerosis to the role of individual pathogenetic mechanisms in determining persistent demyelination and axonal loss in the various phenotypes of the disease and, in these same phenotypes, during the various clinical phases. One illustration of the degree to which multiple sclerosis remains a mystery is our lack of understanding of the contributions of remyelination and astroglia reaction to the evolution of the disease. Although it may seem that remyelination is beneficial and gliosis harmful, there is evidence that remyelinated lesions can become targets for new waves of demyelination, and the gliotic ensheathment of the demyelinated axons may favor the restoration of nerve conduction.

The multidisciplinary and coherent nature of McAlpine's Multiple Sclerosis is shown in its other sections. An example is the second section of the book, entitled "Genetic Epidemiology," in which the usual approach of listing the evidence for a genetic or an environmental origin of the disease has been replaced by a thoughtful and up-to-date description of the complex interplay between environmental triggers and genetic susceptibility. Another example is the first section, entitled "The Story of Multiple Sclerosis," which is not merely a list of names and dates, but also an elegant and informative chapter about the history of our comprehension of the disease, providing readers with the necessary background for understanding the present state of knowledge of the disease.

We are facing rapid changes in our understanding of multiple sclerosis. Nevertheless, the principles and much of the detailed information in this book are likely to have lasting value. McAlpine's Multiple Sclerosis will appeal to a broad spectrum of neuroscientists and health care professionals, regardless of the stage of their involvement in the field. For those experienced in the study of multiple sclerosis or in the management of the disease, it constitutes a valuable summary of the state of the art. For residents and students interested in multiple sclerosis, it is a valuable cornerstone from which they can start to build their future professional lives. The moderate optimism that permeates the book is well summarized in the last sentence of the preface by Compston: "We chart systematic and steady progress in understanding this difficult disease... but the final solution to the problem must wait for another edition."

Reviewed by Massimo Filippi, M.D.
Copyright © 1999 Massachusetts Medical Society. All rights reserved. The New England Journal of Medicine is a registered trademark of the MMS.
--This text refers to an out of print or unavailable edition of this title.

Review

REVIEWS OF THE LAST EDITION:

"The principal merit of this book is the clear and coherent approach of the six authors, who are the world's leading figures in the field, to describing and interpreting the many complex and variable aspects of multiple sclerosis."-NEJM
" Since its inception, McAlpine's Multiple Sclerosis has achieved the rare distinction of becoming one of the classical neurological texts of the last century. The possession of this book was a priority for anyone practising neurology and a necessary acquisition for any self-respecting medical library."-Brain
"The authors must be warmly congratulated on producing an outstanding reference text that Nigel Compston and his original coauthors would be immensely proud of, their intention at the outset being that of simulating interest 'in the ever widening field of demyelinating disease'. This book clearly fulfils that legacy and definitively presents the current state of knowledge."- J Neurol Neurosurg Psychiatry

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