Purkinje Cell Loss in Essential Tremor: Collective Data From 215 Brains Over a 21-Year Period.

objectiveEssential tremor is a highly prevalent movement disorder. Pathological changes observed in essential tremor cerebella center around Purkinje cells and neighboring neuronal populations. Postmortem studies have variably, but not always, shown reduced Purkinje cell counts in essential tremor compared to controls. Here we present collective data on 215 essential tremor brains obtained over a 21-year period.

methodsPurkinje cell loss was assessed through linear densities and empty basket percentages in a standard cerebellar tissue block from 215 essential tremor brains and brains from two comparison groups, 72 spinocerebellar ataxia and 165 controls (452 brains). An age-matched sub-sample comprised 195 essential tremor and 79 control brains.

resultsEssential tremor cerebella had 15.0% lower Purkinje cell linear density and 37.8% higher empty basket percentage than age-matched controls (both p < 0.0001). In the full dataset, Purkinje cell decline with age was identified in controls, with a 4.2% decrease in linear density and a 12.5% increase in empty basket percentage per decade (p < 0.0001), but not in essential tremor. Comparisons of Purkinje cell linear density and empty basket percentage with spinocerebellar ataxias placed essential tremor on the milder end of a cerebellar neurodegenerative spectrum. Purkinje cell decline in essential tremor was not driven by Alzheimer's disease neuropathological changes, Lewy pathology, or clinical confounders.

interpretationA diminished Purkinje cell population in essential tremor was demonstrated using two methods in this extensive dataset. Continued histopathological studies of Purkinje cell-associated morphological changes, in the context of both neurodegeneration and normal aging, will help elucidate the degenerative cascade in essential tremor.