Pathophysiology of Hyperkinetic Movement Disorders

Abstract

Hyperkinetic movement disorders are phenotypically linked by the presence of excess unwanted movements. In addition, they share common, neural pathways involved in voluntary motor control including primary and secondary motor and sensory cortices, the basal ganglia, thalamus, and cerebellum. The pathophysiology of these disorders appears to include similar alterations in physiological properties of neurons in these areas. Phenotypic differences in the hyperkinetic disorders, however, speak to the differing influence and degree of each of these changes and the various motor and, in some cases, non-motor pathways involved in mediating each disorder. In support of the commonality of neural pathways that underlie the development of different hyperkinetic disorders, surgical therapies may target common regions of the brain for the treatment of each of these disorders, and pharmacological therapies are aimed at receptors that regulate these same neural pathways. Much of our understanding of the physiological differences underlying hyperkinetic movement disorders has stemmed from comparisons to hypokinetic movement disorders as well as comparisons across the different hyperkinetic disorders. This chapter will detail (1) the anatomy of the basal ganglia and thalamocortical circuits and their role in the genesis of hyperkinetic disorders and (2) describe current knowledge of the neurophysiological changes that occur in each of these disorders. We will then present a general unified model of hyperkinetic movement disorders using hemiballism, dyskinesia, and dystonia as examples, outlining some of the differences that may occur in each. Tourette syndrome will be discussed separately since it would appear to have greater involvement of non-motor circuits. Finally, we will discuss myoclonus, a condition in which the anatomical areas involved are more diverse. While we often lose site of the role of non-motor and non-basal ganglia pathways in the development of these movement disorders, myoclonus serves as a reminder that many of these disorders have varying degrees of involvement of non-motor pathways and extra-basal ganglia pathology. As such, the presentation of each disorder and its response to the various treatment modalities may differ.