Advances in Our Understanding of Dystonia—Pathophysiology and Treatment Options

Abstract

Although the pathophysiology of dystonia remains incompletely understood, advances in two major areas of research over the past two decades have led to important insights into the mechanisms of dystonia. First, with the identification of dystonia genes, investigations using cellular and animal models of dystonia have become possible. Second, advances in functional neuroimaging have led to the possibility of identification of distinct functional, anatomic, and neurochemical abnormalities in dystonia patients. Dystonia is currently conceptualized as a neurofunctional disorder characterized by alterations at various levels and multiple points along the sensorimotor circuit. There are multiple causes of these disruptions, and lesions along different points in interconnected pathways can yield similar motor dysfunction. The existence of dystonia endophenotypes in genetic forms of dystonia suggests 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. Ultimately, a more complete understanding of the pathophysiology of dystonia should lead to better, more rational, targeted therapies.