Advances in Our Understanding of Dystonia—Pathophysiology and Treatment Options
and lesions along different points in interconnected pathways can yield similar motor dysfunction. Although the basal ganglia is clearly a crucial brain region, abnormalities exist in many other regions throughout the motor circuit. The existence of dystonia endophenotypes in genetic forms of dystonia, i.e. abnormalities related to the gene mutation regardless of clinical manifestation of dystonia, suggest that it may be a ‘second hit’ disorder in which genetically predisposed brains can be thrown into an unbalanced dystonic state by environmental or genetic factors. Major challenges for future investigations include searching for common molecular pathways among the various genetic dystonias, production of an animal model that manifests a clearly dystonic phenotype, exploration of the question of the extent to which the identified mechanisms in the genetic primary dystonias are involved in the more common primary focal dystonias or secondary dystonia, further exploration of which neurophysiologic or metabolic abnormalities are true endophenotypes and which are related to clinical penetrance of dystonia, and further investigation of the basic question of how the cell biologic effects of the identified mutant proteins translate into the motor systems-level effects that result in clinical dystonia. Ultimately, a more complete understanding of the pathophysiology of dystonia should lead to better, more rational, targeted therapies. n
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Naomi Lubarr, MD, is an Attending Neurologist in the Divisions of Pediatric Neurology and Movement Disorders in the Department of Neurology at Beth Israel Medical Center in New York. Her clinical and research interests focus on pediatric movement disorders, particularly dystonia. Dr Lubarr attended the University of Pennsylvania School of Medicine and completed her residency in pediatric neurology at Columbia University Medical Center. She then completed a movement disorders fellowship also at Columbia University under Dr Stanley Fahn.
Susan Bressman, MD, is Alan and Joan Mirken Chair of the Department of Neurology at Beth Israel Medical Center and Professor of Neurology at Albert Einstein College of Medicine in New York. Dr Bressman’s primary research interests have been to identify genes for dystonia and parkinsonism, to characterize genotype–phenotype relations, and to identify imaging and other endophenotypes. Dr Bressman is a member of numerous professional organizations. She is a Director of the
American Academy of Neurology and serves on the scientific advisory boards of the Michael J Fox Foundation for Parkinson’s Research, Bachmann–Strauss Foundation for Dystonia, and Parkinson’s Research, Dystonia Medical Research Foundation and Benign Essential Blepharospasm Foundation. Dr Bressman has more than 125 published articles in peer-reviewed journals and is a co-editor of two books.
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