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The New England Journal of Medicine October 7, 1999 Vol. 341, No. 15 BOOK REVIEW Parkinson's Disease: The Treatment Options Edited by Peter A. LeWitt and Wolfgang H. Oertel. 260 pp. London, Martin Dunitz, 1999. £65. ISBN 1-85317-379-7 The introduction more than 30 years ago of the dopamine precursor levodopa as a treatment for symptoms of Parkinson's disease was a dramatic breakthrough in neurologic therapeutics. Levodopa, now administered in combination with a peripheral decarboxylase inhibitor to minimize nausea, remains the cornerstone of symptomatic therapy for Parkinson's disease. It consistently ameliorates clinical signs of the disease, enhances motor function, and decreases mortality. Yet devastating disability develops over time. After a few years of improved function, the signs of Parkinson's disease again advance, and treatment-associated complications emerge. Fluctuations in clinical response (motor fluctuations) develop, mirroring fluctuations in serum levodopa concentration: patients exhibit choreiform twisting and turning movements during peaks of dopamine stimulation (peak-dose dyskinesias). In addition, signs such as imbalance and dementia that often accompany advanced disease are not amenable to levodopa therapy. Recognition of these inadequacies in therapy set the stage for an intensive search for treatments that would improve long-term care. The past few years have seen an explosion of new medical and surgical therapies for Parkinson's disease. These advances are succinctly described in Parkinson's Disease: The Treatment Options, which provides a convenient means for interested readers to bring themselves quickly up to date. The subtitle of the book is something of a misnomer, since the book's scope extends considerably beyond "the treatment options." Chapters covering diagnosis, pathology, functional imaging, epidemiology, and characterization of the motor dysfunction provide a broad description and a foundation for understanding the nature of the disease. Golbe's analysis of the epidemiology of Parkinson's disease is particularly thoughtful and instructive. The heart of the book, and its greatest strength, is the two chapters by LeWitt, who discusses new medications to treat Parkinson's disease. LeWitt provides an interesting historical perspective and reviews the details of pivotal clinical trials. Three new dopamine agonists (pramipexole, ropinirole, and cabergoline) have been approved in the past few years. Each is effective as monotherapy early in the course of Parkinson's disease and as an adjunct to levodopa in more advanced stages. Currently there is great interest in determining whether the use of a dopamine agonist early in the course of the disease, with the addition of levodopa later when necessary, can yield a better long-term outcome than levodopa alone. Clinical trials are under way to test this hypothesis and to assess the effect of these medications on the underlying rate of loss of dopaminergic neurons. Catechol O-methyltransferase inhibitors are a new class of medications that slow the peripheral metabolism of levodopa and thereby make more of the drug available for transport across the blood-brain barrier over a longer period. Other chapters review approaches to neuroprotection and the treatment of neuropsychiatric and autonomic symptoms. The elucidation of a model of the motor circuit in Parkinson's disease has helped to propel innovations in surgical treatments. Thalamotomy and thalamic stimulation are effective for ameliorating medically refractory tremor. Pallidotomy and pallidal stimulation alleviate dyskinesias. Stimulation of the subthalamic nucleus holds great promise for smoothing motor fluctuations, lessening dyskinesias, and improving signs of Parkinson's disease. The transplantation of dopaminergic cells has been proved to benefit at least some patients, and advances from the laboratory should allow this approach to grow beyond its infancy. My main criticism of the book is that although information about the efficacy of new treatments is well presented and critically reviewed, there is very little synthesis of this information to help physicians formulate a coherent plan for treatment over the course of their patients' disease. Although such algorithms can be pedantic and arbitrary, most readers would benefit from learning how the distinguished experts who write about these treatments approach patient care. When we look back years from now, we may find that the seminal discovery leading to a cure for Parkinson's disease was the identification of a mutation in the gene that encodes (alpha)-synuclein in a large family with autosomal dominant Parkinson's disease. Although mutations in this gene are a very rare cause of Parkinson's disease, it was recently shown that (alpha)-synuclein is a major component of Lewy bodies, which are a histologic hallmark of the disease. Abnormal aggregation and inadequate clearance of (alpha)-synuclein may play an integral part in the pathogenesis of the disease. Researchers will seek to define the pathways leading to abnormal accumulation of (alpha)-synuclein and to develop treatments to block that process. Unfortunately, recognition of (alpha)-synuclein as a major component of Lewy bodies came too recently to be included among the topics covered in this book. reviewed by Robert A. Hauser, M.D. University of South Florida Tampa, FL 33606 Copyright 1999 by the Massachusetts Medical Society All rights reserved <http://www.nejm.org/content/1999/0341/0015/1159a.asp> janet paterson 52 now / 41 dx / 37 onset 613 256 8340 po box 171 almonte ontario canada K0A 1A0 a new voice: <http://www.geocities.com/SoHo/Village/6263/> <[log in to unmask]>