Cellular density in the cerebellar molecular layer in essential tremor, spinocerebellar ataxia, and controls

Abstract

Background: It would be useful to identify additional postmortem markers of Purkinje cell loss in essential tremor (ET). In hereditary cerebellar ataxia, Purkinje cell loss has been reported to result in a secondary increase in the density of the remaining cell populations in the cerebellar molecular layer. However, this phenomenon has not been studied in ET. We quantified cerebellar molecular layer cellular density in 15 ET cases, 15 controls, and 7 spinocerebellar ataxia (SCA) cases (2:2:1 ratio).

Methods: A standard neocerebellar tissue block was stained with Luxol fast blue Hematoxylin & Eosin. Within 5 selected fields, cell soma (e.g., stellate, basket, and glial cell bodies) were counted. Cellular density was the number of cells/cm(2).

Results: The Purkinje cell count differed across the three groups (p < 0.001), with the highest counts in controls, intermediate counts in ET cases and lowest counts in SCA cases. ET cases and controls had similar molecular layer cellular density (p = 0.79) but SCA cases had higher values than both groups (p < 0.01). A robust inverse correlation between Purkinje cell count and molecular layer cellular density (i.e., brains with more Purkinje cell loss had higher molecular layer cellular density), observed in SCA and controls (r = -0.55, p = 0.008), was not observed in ET cases.

Discussion: Although Purkinje cell counts were reduced in ET cases compared to controls, an increase in molecular layer cellular density was not evident in ET. The increase in molecular layer cellular density, observed in SCA cases, may require a more marked loss of PCs than occurs in ET.

Keywords: Cerebellum; Essential tremor; Molecular layer; Neurodegeneration; Purkinje cell; Spinocerebellar ataxia.