The emerging neuropathology of essential tremor

Abstract

Essential tremor (ET) is one of the most prevalent neurological disorders. At the same time, it is among the most poorly-understood of these disorders. The underlying anatomical pathology of ET has been elusive until recently. Postmortem studies have begun to display some of the underlying brain changes in patients with this disease. These types of investigations are likely to lead the way to additional insights into the pathophysiology of ET and guide the development of therapies for this common movement disorder.

FIG. 1

Two LBVET cases. Two panels on left are Hematoxylin and Eosin (H&E) or Luxol Fast Blue and H&E (LH&E) stained sections of the LC in a first ET case (top, 400×) and a second ET case (bottom, 200×) showing multiple Lewy bodies (arrows). The top right panel (200×) shows an alpha-synuclein-stained section of numerous Lewy bodies in the LC of one of these ET cases. The bottom right panel is an alpha-synuclein-stained section of the substantia nigra pars compacta (100×) showing normal pigmentation and cellularity, and complete absence of Lewy bodies or Lewy neurites in one of these ET cases. (Permissions for Figure 1 as follows: Figure 1, top left and top right: Archives of Neurology, 2005, volume 62, page 1006, Copyright © 2005, American Medical Association. All rights reserved. Figure 1, bottom left and bottom right: Louis et al. Neuropathologic findings in essential tremor. Neurology, 2006;66:1756–1759.)

FIG. 2

Cerebellar tissue from several ET cases showing two torpedoes in close proximity (top, LH and E 200× magnification), (bottom left, LH and E 400× magnification), and one torpedo (bottom right, Bielschowsky-stained, 400× magnification). (Permissions for Figure 2 as follows: Figure 2, top: Archives of Neurology, 2006, volume 63, page 1191, Copyright © 2006, American Medical Association. All rights reserved. Figure 2, bottom left: Louis et al. Neuropathologic findings in essential tremor. Neurology, 2006;66:1756–1759.)

FIG. 3

Top panel shows a cerebellar cortical section of a control at 40× magnification immunostained with rabbit anti-calbindin D28k antibody. In age-matched ET case (bottom panel), Purkinje cells occur sparsely and Purkinje cell linear density was greatly reduced.

FIG. 4

(A and B): LH and E stained cerebellar cortical sections (200× magnification). Purkinje cell heterotopias and dendrite swellings in cerebellum from an ET case. The cell bodies of occasional Purkinje cells are displaced upward into the molecular layer (red arrows). (C and D): LH and E stained cerebellar cortical sections (400× magnification). Eosinophilic swellings in the molecular layer adjacent to Purkinje cell bodies (blue arrows). Their connection to a Purkinje cell dendrite (blue arrowheads in D) identifies this as a dendrite swelling. (Figure provided by Phyllis Faust MD, PhD).