Neuropathology of Dystonia

Background: Dystonia is characterized by sustained or intermittent muscle contractions resulting in abnormal, often repetitive, movements, postures, or both. Neuropathologic research has been essential in understanding the etiology and disease progression of other movement disorders, including Parkinson’s disease and cerebellar ataxias. In the field of dystonia, however, research is stymied by the paucity of post-mortem tissue available and the phenotypic heterogeneity found in those with dystonia.

Methods: A PubMed search was conducted using the term ‘‘neuropathology of dystonia’’. The resulting list of references was limited to English-language human neuropathology articles. A total of 20 publications were retrieved and reviewed.

Results: Historically, based on study of acquired forms of dystonia, lesions of the putamen and globus pallidus have been identified as causing dystonia. After the identification of genetic causes of dystonia and the study of limited tissue available from those cases, as well as findings from cases of isolated focal and segmental dystonia, there is evidence that brainstem cholinergic neurons and specific cell populations within the cerebellum also play a role in the pathophysiology of dystonia.

Discussion: Based on limited available brain tissue, there is evidence that the pathophysiology of dystonia may involve a combination of dysfunction within neurons of the brainstem, cerebellum, putamen, and globus pallidus. In order to gain a better understanding of the pathophysiology of dystonia, a prospective, quantitative study in well-phenotyped subjects with different types of genetic and isolated dystonia is required.