? ? Dystonia is a neuorologic syndrome characterized by involuntary muscle contractions and/or abnormal postures. The majority of patients with dystonia have primary dystonia with no known pathologic changes identified in the brain. Primary Dystonia is thus, viewed as a neurochemical disorder with a great potential for successful treatment if the pathophysiologic basis were better understood. Young-onset dystonia has a poor prognosis typically beginning in a limb and spreading to involve most limbs and trtmk (generalized dystonia). The gene for this young-onset, limb-onset dystonia has been named DYT1, is due to the deletion of one of a pair of GAG triplets in the gene for torsin A located on the long arm of chromosome 9. Little is known about the function of torsin A. Torsi A is a member of the AA+ family of proteins, a group that includes heat shock proteins and chaperones. The purpose of this proposed workshop is to bring together leading researchers with expertise in areas specifically relevant to elucidating the pathophysiology of primary dystonia. Critical aspects to be discussed at this workshop include: possible functions of torsin A in stress, protein folding and degradation and cellular polarity; cellular and molecular aspects of neuronal plasticity during development and motor learning; and neuronal systems involved in motor learning. Researchers in these disparate areas, as well as clinicians/scientists treating dystonia patients, will be able to cross fertilize each other in order to identify the most promising research directions and opportunities as well as the major gaps remaining in our understanding. Discussion will focus on understanding the neuronal events that take place during motor learning which could be disrupted by mutant torsin A during childhood, that is the susceptible period for onset of young onset torsion dystonia, and by repetitive movement and sensory insults that can trigger adult onset dystonia. Data from animal and cellular models as wells as data from human subjects undergoing electrophysiologic, and neuroimaging studies and neurosurgical procedures will be discussed. Emphasis will be given to means of reprogramming the nervous system to reverse the physiologic impact of changes in circuitry associated with dystonia. The conference is scheduled to take place in Atlanta, GA on January 10-11, 2004. ? ?
