'Essential tremor' or 'the essential tremors': is this one disease or a family of diseases?

Abstract

There is accumulating evidence that the entity referred to as 'essential tremor' (ET) is not a single disease. It may be a family of diseases better referred to as 'the ETs'. This review will summarize the following evidence: (1) the presence of etiological heterogeneity; (2) the heterogeneity of findings in postmortem studies, thus suggesting several diseases; (3) the recent discussion that age of onset may be an important marker of disease heterogeneity; (4) the clinical expansion of the concept of ET in recent years to include a broader range of tremor phenomenology, other motor features (gait ataxia), other involuntary movements (dystonia), and nonmotor features (cognitive problems, psychiatric problems), some of which could be primary; (5) the heterogeneity of pharmacological response profiles and clinical progression, and (6) the association of ET with Parkinson's disease, Alzheimer's disease, and possibly progressive supranuclear palsy, with the possibility that some ET patients are more predisposed to develop one of these. © 2013 S. Karger AG, Basel.

Figure 1

The disease process in ET as an etiological-biological-clinical continuum.

Figure 2

A variety of structural microscopic changes have been described in the ET cerebellum on postmortem examination, and these seem to be centered on the Purkinje cell and surrounding neuronal populations (i.e., Basket cells). Cerebellar cortical sections in ET cases: A. Relatively normal Purkinje cell layer (gray arrow on right) near an area with segmental loss of Purkinje cells (black arrow on left). Bielschowsky stain. B. A heterotopic Purkinje cell (gray arrow) is adjacent to two normal Purkinje cells (black arrow). Calbindin-stained section. C. A swelling (arrow) of the Purkinje cell dendrite. Bielschowsky stain. D. A torpedo, thickened axon, and recurrent axonal collateral (arrow). Calbindin stain. E. Two torpedoes adjacent to their respective Purkinje cell soma. Luxol fast blue Hematoxylin and eosin stain. F. Sprouting of Purkinje cell axonal end processes in the upper granular layer. Calbindin stain. G. Hypertrophic Basket cell processes and an empty basket (arrow). Bielschowsky stain.

Figure 3

Three different ET cases showing a heterogeneity of pathological findings in the ETs. A. Representing cerebellar pathology, a Purkinje cell axon is shown with three torpedoes. Calbindin stain. B. Multiple Lewy bodies in the locus ceruleus. Hematoxylin and eosin stain. C. Ubiquitin positive Purkinje cell intranuclear inclusion.