Purkinje Cell Loss and Changes in Basket Cell Morphology in Essential Tremor and Other Cerebellar Degenerative Diseases: A Postmortem Study of 332 Brains

Essential tremor (ET) is among the most prevalent neurological diseases. Postmortem studies have demonstrated Purkinje cell (PC) loss in ET. In addition, PCs and their micro-circuitry in the cerebellar cortex-including basket cells and climbing fibers-display several characteristic pathological features in these studies. While several studies in ET have focused on the interactions between PCs and climbing fibers, less has been written about basket cells and their interactions with PCs (i.e., formation of empty baskets and hypertrophy of basket cell axonal processes around the PC soma). These changes are not unique to ET, yet scarcely anything has been written about basket cells and their interactions with PCs more broadly across disorders of cerebellar degeneration. We examined the relationship between three metrics (PC linear density, percentage of empty baskets, basket plexus rating [a measure of basket cell axonal process hypertrophy]) in 332 brains: 178 ET, 56 with a range of spinocerebellar ataxias, 13 Friedreich's ataxia, and 85 controls. We hypothesized that there would be overlapping but not uniform findings across these disorders. In all groups, PC linear density significantly negatively correlated with percentage of empty baskets, although to differing degrees. Basket plexus ratings were significantly associated with PC linear density and percentage of empty baskets only in some diseases. In summary, PC linear density, percentage of empty baskets and basket plexus rating were associated metrics across a range of cerebellar degenerative conditions and even in control brains. However, their relationships with one another were variable.