Cerebellar pathology in childhood-onset vs. adult-onset essential tremor

Abstract

Although the incidence of ET increases with advancing age, the disease may begin at any age, including childhood. The question arises as to whether childhood-onset ET cases manifest the same sets of pathological changes in the cerebellum as those whose onset is during adult life. We quantified a broad range of postmortem features (Purkinje cell [PC] counts, PC axonal torpedoes, a host of associated axonal changes [PC axonal recurrent collateral count, PC thickened axonal profile count, PC axonal branching count], heterotopic PCs, and basket cell rating) in 60 ET cases (11 childhood-onset and 49 adult-onset) and 30 controls. Compared to controls, childhood-onset ET cases had lower PC counts, higher torpedo counts, higher heterotopic PC counts, higher basket cell plexus rating, and marginally higher PC axonal recurrent collateral counts. The median PC thickened axonal profile count and median PC axonal branching count were two to five times higher in childhood-onset ET than controls, but the differences did not reach statistical significance. Childhood-onset and adult-onset ET had similar PC counts, torpedo counts, heterotopic PC counts, basket cell plexus rating, PC axonal recurrent collateral counts, PC thickened axonal profile count and PC axonal branching count. In conclusion, we found that childhood-onset and adult-onset ET shared similar pathological changes in the cerebellum. The data suggest that pathological changes we have observed in the cerebellum in ET are a part of the pathophysiological cascade of events in both forms of the disease and that both groups seem to reach the same pathological endpoints at a similar age of death.

Climbing fiber-Purkinje cell synaptic pathology across essential tremor subtypes

“…Therefore, we chose the age of onset of 50 to divide the early vs. late onset ET cases. Using data from our previous publications on the PC pathology in subgroups of ET cases and controls [21,24,25], we determined that with each ET group and control group composed of 30 subjects, we would be powered at 90% to detect differences of the magnitude previously detected [21,24,25]. Accordingly, we randomly selected 30 early onset ET cases, 30 late onset ET cases, and 30 controls in the current study.…”

“…Accordingly, we randomly selected 30 early onset ET cases, 30 late onset ET cases, and 30 controls in the current study. Of the selected cases for this study, data from 14 of 30 controls and 15 of 60 ET cases were reported in prior publications [21,24,25]. …”

“…In a third analysis, we compared ET cases with childhood onset (≥18 years) vs. adult onset (>18 years) [25]. …”

Predictors of alcohol responsiveness in dystonia

“…[16][17][18] A significant role of the cerebellum in the pathophysiology of both essential tremor and dystonia has recently been postulated and related to a decreased Purkinje cell density. 19,20 Such pathophysiologic similarities of dystonic and essential tremor could be linked to tremor improvement with alcohol intake in both diseases. Our results thus suggest that alcohol responsiveness may not be a reliable marker to support a diagnosis of essential tremor over a diagnosis of dystonic tremor.…”

How Common is Essential Tremor? Update on the Worldwide Prevalence of Essential Tremor

“…ET is not a disease exclusively of adults; indeed, the disease may begin in childhood [62][63][64]. The majority of these young-onset cases are familial [65,66].…”