Increased number of Purkinje cell dendritic swellings in essential tremor

Abstract

Background Essential Tremor (ET) is among the most prevalent neurological disorders. Growing clinical and neuro-imaging evidence implicates cerebellar dysfunction in the pathogenesis of ET and emerging postmortem studies have identified structural changes in the cerebellum, particularly in Purkinje cells. In this study we systematically quantified focal Purkinje cell dendritic swellings (DS) in 20 ET vs. 19 control brains. Methods In each brain, a standard parasagittal neocerebellar tissue block was harvested. DS were quantified in one 7-μm thick section stained with Luxol Fast Blue/Hematoxylin and Eosin (LH&E) and one section stained with Bielschowsky method. Results The number of DS were higher in cases than controls by LH&E (1.50 ± 1.79 vs. 0.05 ± 0.23, p = 0.002) and Bielschowsky methods (2.70 ± 3.10 vs. 0.37 ± 0.50, p = 0.002). The number of DS was correlated with the number of torpedoes, and marginally inversely correlated with the number of Purkinje cells. Discussion The current study documents and quantifies an additional structural abnormality in the ET cerebellum, adding to the growing list of such changes in this disease. The mechanisms that underlie this and other structural changes observed in ET are currently unknown, and they deserve additional exploration.

Understanding Essential Tremor: Progress on the Biological Front

“…Postmortem studies in recent years have systematically identified a sizable number of changes in the ET brain, across each of the following cerebellar compartments (Table 2): (1) Purkinje cell dendrites (i.e., an increase in number of Purkinje cell dendritic swellings), 70 (2) Purkinje cell body (i.e., both reductions in Purkinje cell linear density as well as heterotopic placement of Purkinje cell soma), 71–73 (3) Purkinje cell axon (i.e., a broad range of changes in axonal morphology, including torpedoes), 3, 72 and (4) basket cell axonal processes (i.e., hypertrophy of perisomal processes [“hairy baskets”] and elongated LINGO1 labeled pinceau processes). 74, 75 Systematic postmortem study of the other brain regions that form loop connections with the cerebellum (i.e., the thalamus, inferior olivary nucleus, red nucleus, and motor cortex) indicate that significant pathologic changes are not evident in these brain regions, 76, 77 reinforcing the notion that the cerebellum is the focal point of interest in studies of the pathogenesis of ET.…”

Linking Essential Tremor to the Cerebellum: Neuropathological Evidence

“…These changes span across all Purkinje cell compartments (Figs. 1, 2, 3, 4, and 5), including (1) the dendritic compartment, where there is an increase in number of Purkinje cell dendritic swellings, a pruning of the dendritic arbor, and a reduction in spine density [5,6]; (2) the cell body, where aside from reductions in Purkinje cell linear density in some studies, with an increase in the number of empty baskets (i.e., basket cell axonal processes without an accompanying Purkinje cell), there is an increase in the number of heterotopic Purkinje cell soma [7][8][9]; and (3) the axonal compartment, where a broad range of changes in axonal morphology have been observed, including an increase in the number of thickened axonal profiles, torpedoes, arciform axons, axonal recurrent collaterals, axonal branching, and terminal axonal sprouting with increase in the Purkinje cell infraganglionic plexus [8]. Additional changes, possibly the result of secondary remodeling, have also been observed in neighboring neuronal populations.…”

The heterogeneity of drug response as the basis of identification of essential tremor subtypes

“…Вторая группа изменений -на-личие телец Леви в стволе мозга, преимущественно обнаруживающихся в области голубого пятна. Голу-бое пятно, как известно, содержит норадренергиче-ские клетки и имеет эфферентные связи с клетками Пуркинье, поэтому может вовлекаться в генерацию тремора посредством модуляции их ответа по вос-ходящим афферентным волокнам [20,36].…”