Book Review

Multiple Sclerosis as a Neuronal Disease

N Engl J Med 2005; 353:1305September 22, 2005

Article

Multiple Sclerosis as a Neuronal Disease
Edited by Stephen G. Waxman. 484 pp., illustrated. San Diego, Calif., Elsevier Academic Press, 2005. $170. ISBN: 0-12-738761-7

On the basis of the title of this book, the reader may wonder if the intent is to develop a theory of multiple sclerosis as a primary axonal disease, as some investigators have suggested. Actually, the editor writes in the preface that “the title . . . is not meant to imply that MS is a primary neuronal disease.” Instead, most of the chapters focus on a detailed examination of the biology of the axon, measures that can be used to identify axonal damage, mechanisms that may lead to axonal damage, and some approaches to protection or repair.

As with any book with multiple contributors, the strengths of the chapters are variable, and there is some redundancy. Without doubt, the strength of the book as a whole is the examination of the biology of the axon. The book begins with an almost poetic description of the axon, and the first chapter is followed by several others that examine specific aspects of axonal structure and function. These aspects include a comparison of central and peripheral axons, the relationship between the myelin sheath and the axon, and the importance of other supporting glial cells. There are excellent discussions of the conduction properties of axons as well as the structure, physiology, and pathophysiology of channels.

The book is organized around eight general topics. After the chapters on the biology of the axon, the emphasis falls on a clinical examination of axonal damage. Unfortunately, at this point the degree of redundancy increases. For example, there are two excellent chapters on the pathology of multiple sclerosis with an emphasis on axonal damage, and although the emphasis is slightly different in each chapter, both discuss the evidence for axonal damage in the white matter as well as changes in the gray matter. The next chapters are focused on biologic measures, especially the use of magnetic resonance imaging, to assess axonal damage. Although each of these chapters is well done, some redundancy remains — for example, each deals in some depth with brain atrophy.

One topic that is unfortunately missing from the book is an in-depth examination of the use of diffusion-weighted magnetic resonance imaging to assess axonal damage. Also lacking is a discussion of the data emerging from the use of animal models that suggest that diffusion-weighted imaging may be a useful tool for distinguishing axonal damage from myelin damage. If these reports prove to be correct, the use of diffusion-weighted imaging in assessing axonal damage in humans will have considerable value in the study of patients with multiple sclerosis.

A later part of the book begins with an examination of mechanisms of axonal damage; the chapters are well written and provide the reader with an excellent overview of the pathways to axonal damage. The chapters also begin the discussion of possible therapeutic approaches to protection and repair of the axon. Since the discussion of clinical applications generally occurs at the end of the chapters dealing with mechanisms of damage, the approaches discussed have a fairly narrow focus. One chapter does deal entirely with approaches that might be used in the clinic. The book ends with a very nice chapter discussing the potential of the brain to reorganize and the use of imaging to examine this issue.

Despite some weak spots and a few omissions, this book offers an excellent overview of the biology of the axon, the clinical assessment of axonal damage, and the mechanisms contributing to axonal damage. The first chapters, on the biology of the axon, overcome any subsequent weaknesses. The book should provide valuable reading for the student of neurology as well as for those less familiar with the subtleties of the axon. It will also be of value to those knowledgeable about multiple sclerosis who are beginning to move into clinical studies of neuroprotection and repair. The editor says in the preface that he hopes that one of the outcomes of the book will be to encourage scientists who are interested in the axon to extend their interest to the study of axonal damage and repair in multiple sclerosis. I am also hopeful that this will happen, since neuroprotection is without doubt the emphasis that is now needed in treating the disease.

Henry McFarland, M.D.
National Institutes of Health, Bethesda, MD 20892