Essential tremor: evolving clinicopathological concepts in an era of intensive post-mortem enquiry.

Essential tremor (ET) is one of the most common neurological disorders. In recent years, as a result of systematic post-mortem examinations, our knowledge of the pathophysiology of this disease has grown substantially. Clearly identifiable structural changes (ie, Purkinje cell loss, Lewy bodies) have been observed in the brains of individuals with ET. These changes are not uniform and seem to follow several patterns, localising to the cerebellum itself or to a collection of brainstem neurons that synapse directly with Purkinje cells. Furthermore, these changes are similar to those seen in degenerative diseases. A wealth of clinical, epidemiological, and now post-mortem data indicate that this disease, or perhaps this family of diseases, is likely to be neurodegenerative. The molecular mechanisms that underlie these structural changes in ET are unknown. However, with more controlled, tissue-based studies being done, it is hoped that these mechanisms will be elucidated, thereby laying the foundation for the development of more targeted, effective pharmacotherapeutic interventions.