Movement Disorders

There has been a remarkable explosion of knowledge about the etiopathogenesis and therapy of movement disorders since the identification of dopamine as a critical central nervous system neurotransmitter in the 1950s. Advances in our understanding of this and other neurotransmitters have led to rational pharmacotherapy of several movement disorders, most notably Parkinson's disease. Elucidation of basal ganglia circuitry has had similar therapeutic impact, and, more recently, rapidly accruing discoveries in molecular biology have given promise to the possibility of neuroprotection, the true holy grail of movement disorders research. The articles in this issue of Seminars in Neurology reflect both the achievements and the hope brought about by this rising tide of knowledge.

This issue appropriately begins with three articles that center on the current treatment, future therapeutic possibilities, and diagnostic dilemmas associated with the movement disorder that is arguably the most important in terms of societal impact, Parkinson's disease. In the first article, Hermanowicz clearly details current state-of-the-art pharmacotherapy of Parkinson's disease. Next, Biglan and Ravina discuss the biologic basis and clinical potential for neuroprotective therapies in Parkinson's disease. Finally, Tuite and Krawczewski provide useful guidelines to help the clinician distinguish Parkinson's disease from other conditions, especially the akinetic rigid syndromes known collectively as the parkinsonisms. Following these articles on Parkinson's disease and parkinsonian syndromes, Pfeiffer describes the pathophysiology, clinical features, and treatment of still another potential mimicker of Parkinson's disease, Wilson's disease. This is a condition that is relatively rare compared with Parkinson's disease but one that every neurologist must be able to recognize because it is eminently treatable.

The notion that the future treatment of many movement disorders will depend on the partnership of clinical neurology and molecular biology is amply demonstrated by the next three articles focusing on heritable movement disorders. The first article by Paulson describes the expanding universe of trinucleotide repeat disorders and focuses on one, Machado-Joseph disease, as a paradigm for this class of disorders. Next, Walker provides a practical approach to the diagnosis and treatment of perhaps the most common trinucleotide expansion disorder, Huntington's disease. Finally, in this group of articles, Gonzalez-Alegre discusses the spectrum of conditions resulting in dystonia, several of which are heritable, such as DOPA-responsive dystonia and DYT1 dystonia. These three articles not only describe the clinical features, inheritance patterns, and therapeutic approaches to these conditions, but also provide the reader with a glimpse into the future and an appreciation of potential interventions, such as RNA interference therapy, that are poised to bridge the translational gap between bench and bedside.

Soares-Weiser and Fernandez next discuss one of the most important groups of iatrogenic movement disorders, the tardive syndromes. These conditions now appear somewhat less frequently than in years past, but unfortunately are still with us and are still a major source of disability for those who are afflicted. The authors provide useful recommendations for treatment of these syndromes based on a critical review of numerous reports in the literature purporting to demonstrate efficacy.

The last two articles in this issue focus on two widely employed novel movement disorders therapies that were introduced within the past two decades. Uc and Follett provide a comprehensive overview of the rationale, indications, and benefits of deep brain stimulation therapy for Parkinson's disease. A critical component of their article is a discussion of the proper mode of identification of patients who might benefit from this therapy. Papapetropoulos and Singer follow with a thorough discussion of the utility and proper application of botulinum toxin therapy for a variety of movement disorders, most notably the dystonias, whose management has been revolutionized by the introduction of this therapeutic approach.

As amply illustrated in the articles of this issue of Seminars in Neurology, the modern approach to the diagnosis and therapy of movement disorders impressively represents the universe of techniques available to today's neurologist. Dazzling advances have been made in our ability to modify central and peripheral neurotransmission, redirect brain circuitry, and possibly neutralize molecular genetics gone awry. Patients have considerable reason to take heart. Many of these therapies, considered futuristic not that long ago, are components of everyday neurology practice today, and others, still more impressive, may be coming to a clinic near them very soon.