Essential Tremor: A Common Disorder of Purkinje Neurons?

Essential tremor (ET) is one of the most common neurological diseases, with an estimated 7 million affected individuals in the United States. Postmortem studies in the past few years have resulted in new knowledge as well as a new formulation of disease pathophysiology. This new formulation centers on the notion that ET might be a disease of the cerebellum and, more specifically, the Purkinje cell (PC) population. Indeed, several investigators have proposed that ET may be a "Purkinjopathy." Supporting this formulation are data from controlled postmortem studies demonstrating (1) a range of morphological changes in the PC axon, (2) abnormalities in the position and orientation of PC bodies, (3) reduction in the number of PCs in some studies, (4) morphological changes in and pruning of the PC dendritic arbor with loss of dendritic spines, and (5) alterations in both the PC-basket cell interface and the PC-climbing fiber interface in ET cases. This new formulation has engendered some controversy and raised additional questions. Whether the constellation of changes observed in ET differs from that seen in other degenerative disorders of the cerebellum remains to be determined, although initial studies suggest the likely presence of a distinct profile of changes in ET.