McAlpine's Multiple Sclerosis (Hardcover)

by Alastair Compston (Author), Ian R. McDonald (Author), John Noseworthy (Author), Hans Lassmann (Author), David H. Miller (Author), Kenneth J. Smith (Author), Hartmut Wekerle (Author), Christian Confavreux (Author)

Editorial Reviews

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
"I can enthusiastically recommend this latest edition of McAlpine's Multiple Sclerosis." -- New England Journal of Medicine, February 1, 2007

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Product Details

• Hardcover: 1008 pages
• Publisher: Churchill Livingstone; 4 edition (December 15, 2005)
• Language: English
• ISBN-10: 044307271X
• ISBN-13: 978-0443072710
• Product Dimensions: 11 x 8.9 x 2 inches
• Shipping Weight: 7 pounds (View shipping rates and policies)
• Average Customer Review: 5.0 out of 5 stars See all reviews (2 customer reviews)
• Amazon.com Sales Rank: #880,634 in Books (See Bestsellers in Books)

Customer Reviews

Most Helpful Customer Reviews

10 of 10 people found the following review helpful:

5.0 out of 5 stars Review of McAlpine's Multiple Sclerosis, Fourth Edition (2005) , February 19, 2008

By	P. Lucht (Utah) - See all my reviews (REAL NAME)

If you are interested in buying this book, examine it first at your local medical library to make sure it is what you are looking for.

This six-pound reference work is updated about every 7 years and serves as a repository for the latest world-wide MS information. It attempts to organize thousands of research study conclusions and to provide the reader with a coherent status report on many different aspects of MS, both clinical and scientific.

Physically, the text is a work of art. Pages are large, thick and opaque with a solid binding and cover. One finds many photos, tables, charts and other color graphic elements. There are 810 pages of text (in a well-chosen font) followed by about 6,600 references (135 pages!).

The writing is excellent, sometimes just a bit formal with a penchant for lengthy sentences. A non-MD reader will need wiki and dictionary.com at the ready. The book is not designed as a primary teaching tool -- the reader is assumed to already know a lot about MS and related scientific subjects (eg, neurobiology). Each of the 19 chapters is written by a declared subset of the eight expert authors.

Here is the structure they chose for this edition, along with a brief outline of the contents of the book: (the full contents appears on the Elsevier site).

Section 1: One chapter (1) reviewing the history of MS up to the start of the modern era, circa 1980. Well-due homage is paid to many workers of the past, from Galen to Charcot to Marburg to Kurtzke to McAlpine.

Section 2: Four chapters covering these topics: (2) the mysterious geographical and racial distribution of MS prevalence throughout the world; (3) results of classical genetics research using linkage and association studies (multiple genes are implicated); (4) details of the (highly variable) course of the disease (the natural history of MS); and (5) a concisely-stated likely theory of how MS arose as mankind spread itself over the earth. The identical twin concordance rate for MS is about 30%, suggesting a definite mix of genetic and environmental factors which conspire to cause MS.

Section 3: Four chapters on clinical aspects of MS: (6) its symptoms of which there are, unfortunately, many; (7) how to diagnose MS, using clinical and paraclinical evidence such as MRI and evoked potentials, with a review of recent McDonald diagnostic criteria; (8) how to differentiate MS from diseases with similar symptoms; (9) a summary giving advice to the neurologist.

Section 4: We leave the clinic and enter the MS research labs. Five chapters cover the following huge subjects: (10) the cell biology of MS: T-cells, B-cells, macrophages, astrocytes, dendritics, microglia, oligodendrocytes and all their precursors, and inter-cell signaling. Topics include demyelination, axon degeneration, and the encouraging remyelination process. (11) MS from the viewpoint of autoimmunity: innate and adaptive components, EAE animal models, penetration of the BBB, antibodies in the CSF, biomarkers. (12) MS pathology: lesions/plaques, inflammation, demyelination, lots of histology here. (13) details of the physical damage done by MS to neurons, methods used to study same, blockage of signal conduction, the scary role of nitric oxide. This is the physiology of the pathology of MS. (14) This short chapter summarizes the way MS is thought to work: T cells are activated possibly by a myelin mimic molecule in the periphery, they cross the BBB and instigate a horrendous CNS battle involving just about all the players and their various weapons. Inflammation, demyelination and axon damage occur, the battle ends, and the result is a lesion which shows up on MRI and results in a clinical deficit if in an "eloquent" location. Progressive disease is thought to be a slow-burning widespread version of the same or a similar battle resulting in gradual loss of brain volume accompanied by increased clinical deficit.

Section 5: The closing five chapters concern the clinical treatment of MS patients. The first chapter (15) reviews issues which characterize the phases of MS, early middle and late. Early diagnosis is desired because early drug application might prevent neural damage. One chapter (16) deals specifically with how to treat the traditional MS acute relapse (steroids). Another (17) discusses the methods, usually drugs, for treating the many symptoms of MS. The authors emphasize disease management and rehab using family, nurses and other specialists and MS centers, in addition to the prescription of drugs. Then a long chapter (18) discusses the disease-modifying drugs discovered relatively recently: the beta interferons, glatiramer acetate, various monoclonal antibodies such as Campath-1H, etc. The final chapter (19) comments on issues involving Big Pharma influence on trials and drug-approving agencies, and foresees the future of MS treatment which will hopefully soon provide neuroprotection and repair.

Certain sections of the book can be rough sailing for the reader, as the authors painstakingly review a long series of research studies on a particular topic, giving a long one-sentence review of the conclusions of each study ( remember those 6600 references). Many study results are actively challenged and critiqued by the authors, who are not averse to stating their own opinions on many issues. Their message concerning trials is loud and clear: studies should be unbiased by drug companies' profit motives, fully randomized, placebo-controlled, fully double-blinded with crossover if possible, not terminated early unless futile or dangerous, and with sufficient statistical power to generate definite conclusions. The era of anecdotal MS trials is over.

Overall, this is an absolutely stunning and excellent book. It must have put a huge time burden on all eight of the authors. One hopes that only a few more editions will ever have to be published.

1 of 2 people found the following review helpful:

5.0 out of 5 stars McAlpine's Multiple Sclerosis, April 5, 2008

By	Andreas Leib (Munich, Germany) - See all my reviews (REAL NAME)

As I am very much interested scientifically in this field, I can very much recommend this book as it represents an enormous collection of information according to this disease and is written in fluent and entertaining style.