Essential tremors: a family of neurodegenerative disorders?

Abstract

Essential tremor (ET) is the most common pathologic tremor in humans. The traditional view of ET, as a monosymptomatic condition, is being replaced by an appreciation of the spectrum of clinical features, with both motor and nonmotor elements. These features are not distributed homogeneously across patients. In addition, postmortem studies are now demonstrating distinct structural changes in ET. There is growing evidence that ET may be a family of diseases rather than a single entity. Furthermore, this aging-associated, progressive disorder is associated with neuronal loss and postmortem changes that occur in traditional neurodegenerative disorders.

Figure 1

Kinetic tremor is apparent in an ET patient’s drawing of an Archimedes spiral.

Figure 2

The heterogeneity in ET may be organized by (1) disease etiology, (2) tissue-level changes that occur after the disease process is initiated and as it develops, and (3) clinical features that are the end product of these underlying pathological processes. Here is one such possible schema.

Figure 3

When quantified using different methods, Purkinje cell loss in ET is significant compared to age-matched controls. Bielschowsky-stained section (50× magnification) of the cerebellar cortex in a 79 year old ET case showing normal Purkinje cellularity (right) vs. a region with segmental loss of Purkinje cells (left).