Reduced Purkinje Cell Number in Essential Tremor

Abstract

Background: Clinical and functional imaging evidence suggests that cerebellar dysfunction occurs in essential tremor (ET). In recent postmortem studies, we documented increased numbers of torpedoes (Purkinje cell axonal swellings) in ET patients without Lewy bodies. Purkinje cell loss, however, has never been rigorously assessed. Objective: To quantitatively assess the number of Purkinje cells in brains of ET patients and similarly aged controls. Methods: Postmortem cerebellar tissue was available in 14 ET cases (6 with Lewy bodies and 8 without Lewy bodies) and 11 controls. Calbindin immunohistochemistry was performed on paraffin sections of the cerebellum. Images were digitally recorded and blinded measurements of the number of Purkinje cells per millimeter of cell layer (linear density) were made. Results: Purkinje cell linear density was inversely correlated with age (r=−0.53, P=.006) and number of torpedoes (r=−0.42, P=.04). Purkinje cell linear density differed by diagnosis (mean [SD], controls, 3.46 [1.27] cells/ mm; ET cases with Lewy bodies, 3.33 [1.06] cells/mm; and ET cases without Lewy bodies, 2.14 [0.82] cells/ mm; P = .04), with the most significant difference between ET cases without Lewy bodies and controls, where the reduction was 38.2% (P=.04). In an adjusted linear regression analysis that compared ET cases without Lewy bodies with controls, decreased linear density (outcome variable) was associated with ET (␤=.56, P=.03). Conclusions: We demonstrated a reduction in Purkinje cell number in the brains of patients with ET who do not have Lewy bodies. These data further support the view that the cerebellum is anatomically, as well as functionally, abnormal in these ET cases.

Essential Head Tremor Is Associated with Cerebellar Vermis Atrophy: A Volumetric and Voxel-Based Morphometry MR Imaging Study

“…Although our methodologic approach speaks to the robustness of our findings, neuropathologic confirmation of our preliminary data is warranted. A recent neuropathologic study found mild and inhomogeneous cerebellar pathologic changes in patients with sporadic ET, 26 but the underlying neurodegenerative processes in head and arm ET have not yet been reported.…”

The cognitive side of essential tremor: what are the therapeutic implications?

“…Much of the literature supports that ET is a disorder of cerebellar dysregulation, including the presence of intention tremor [Leegwater- Kim et al 2006;Louis et al 2009b], gait ataxia [Singer et al 1994;Stolze et al 2001], oculomotor abnormalities [Helmchen et al 2003] and problems with dysrhythmia and motor learning [Trillenberg et al 2006;Avanzino et al 2009;Bares et al 2010;Farkas et al 2006;Shill et al 2009;Kronenbuerger et al 2007]. In addition, postmortem studies in ET have indicated the presence of a variety of structural and degenerative changes in the cerebellum, including increased number of Purkinje cell axonal swellings ('torpedoes') [Louis et al 2007b;Axelrad et al 2008], increased number of displaced or heterotopic Purkinje cells [Kuo et al 2011], reduction in number of Purkinje cells in some studies [Axelrad et al 2008] [Bucher et al 1997], positron emission tomography [Jenkins et al 1993;Wills et al 1994;Colebatch et al 1990], 1 H magnetic resonance spectroscopic imaging [Louis et al 2002;Pagan et al 2003], diffusion tensor imaging [Shin et al 2008;Klein et al 2011;Nicoletti et al 2010], voxelbased morphometry [Benito-Leon et al 2009;Quattrone et al 2008] and studies using other automated volumetric methods [Cerasa et al 2009] which demonstrate the presence of functional, metabolic and structural abnormalities in the cerebellum of ET patients.…”

Protective role of coenzyme Q 10 against high cholesterol dietinduced histological and biochemical changes in cerebellar cortex of adult albino rats

“…2. Linear density of Purkinje cells was determined by counting Purkinje cells nuclei per millimeter line length throughout the section [19]. 3.…”