The past decade has witnessed an explosion of interest in multiple sclerosis (MS) sparked by a combination of advances in unraveling the basic science of the disease and the introduction of the first medications that alter the natural history of this still-mysterious disorder. The crowds that overflow the sessions on MS at the American Academy of Neurology's Annual Meeting and the stream of exciting new drugs entering clinical trials at an unprecedented pace attest to this curiosity. The latter development not only provides hope to patients, but also piques the attention of the financial community. In this issue of Continuum, Drs Fred Lublin and Mark Tullman have assembled an experienced, knowledgeable cadre of subspecialists in MS to provide a comprehensive update on the subject.
First, Dr Wee Yong offers a clear and well-illustrated explication of current thoughts about the immunopathogenesis and pathology of the disease. He reviews the lessons we have learned from the animal model of MS, experimental autoimmune encephalomyelitis, which have stimulated our search for effective therapeutic agents. Dr George Rice then explores the tension that exists between the potential causative roles of environment and genetics in MS. He addresses such environmental phenomena as the latitudinal gradient of disease occurrence, the influence of migration, and the existence of MS clusters. On the other hand, he discusses the increased familial risks that clearly imply a role for genetic factors in disease development, while ultimately indicating its apparent genetic complexity.
Turning to the clinical aspects of MS, your editor assumes the additional role of author, teaming with Dr Patricia Coyle to provide an update on clinical features of the disease. The chapter offers a basic review of clinical phenomenonology, highlighted by new observations made in the last few years, as well as a discussion of disorders that are regarded either as variants of MS or closely related illnesses. Since the last issue of Continuum devoted to MS was published in 2000, a new set of criteria for the diagnosis of the disease has been published. The chapter on clinical features provides a comprehensive review and critique of these recommendations by the International Panel. These discussions of the clinical aspects of MS then dovetail with Dr Coyle's comprehensive analysis of the differential diagnosis of the disorder. She provides a lucid, practical framework to help the clinician approach the patient with possible MS and wend his or her way through the maze of diagnostic possibilities that may exist in more unusual situations.
Neuroimaging, especially magnetic resonance imaging (MRI), has contributed mightily both to our understanding of MS and to clinical diagnosis. Dr Jerry Wolinsky gives a very thorough review of MRI, both conventional and more investigative techniques, that not only increases our comprehension of the disease, but also guides the clinician about utilization of these neuroimaging techniques in diagnosis and management of MS. Turning to the subject of treatment, Dr Lublin addresses both the management of acute exacerbations and the use of medication to alter the course of the disease. He discusses thoroughly our existing armamentarium of drugs-five agents have been approved by the US Food and Drug Administration since 1993-and more briefly considers other medications that are sometimes used in more difficult cases. Dr Tullman then turns attention to the symptomatic management of the patient. He provides a very comprehensive blueprint that will enable the clinician to provide optimal treatment for the plethora of symptoms that greatly impact the quality of life for people with MS.
The availability of medications that alter the natural history of MS by reducing relapses, decreasing new lesion formation as demonstrated by MRI, and slowing the progression of disability has provided substantial benefit to people with MS. Clearly, however, our current medications are inadequate and we hope herald only the beginning of the therapeutic era for this often-debilitating disease. Yet the existence of partially effective treatments creates ethical and practical dilemmas in the design of clinical trials to develop new and better therapy. Drs Burton and O'Connor conclude this issue of Continuum with a thoughtful discussion of these research challenges.
Drs Lublin and Tullman have organized this issue on MS in a manner that should guide you sequentially through our basic understanding of the disease, then on to the practical aspects of diagnosis and management, and finally to some of the conundrums we face in attempting to make further progress. We invite you to read, enjoy, and, as always, offer your comments to us.
As an added bonus, a Quintessentials® module on MS complements this issue of Continuum. Under the leadership of Dr Barbara Giesser, ably assisted by Drs Barbara Green and Lawrence Samkoff, Quintessentials® provides readers with the opportunity to put into practice the information acquired through this issue Continuum of and reinforced by the Quintessentials® Phase 2-Education section. Application of one's skills to the Phase 1-Benchmark materials found at the back of this issue and submission of them by fax to the AAN will enroll you in the program. You will then receive a personalized report and other material from the AAN to accompany the Quintessentials® educational material that begins on page 197 of this issue. As you progress through the program you will receive from the AAN Phase 3-Follow-up, which will provide an opportunity to evaluate and document practice improvement, and Phase 4-Feedback, the final phase of the program.
Quintessentials® is a unique learning tool that, like Continuum, has been recently endorsed by the American Board of Psychiatry and Neurology as a valuable instrument for the comprehensive lifelong learning that is required for maintenance of certification. Completion of the module also provides the participant with up to 10 hours of category 1 CME credit.
Aaron E. Miller, MD