Essential tremor--neurodegenerative or nondegenerative disease towards a working definition of ET

Abstract

Essential tremor (ET) is a syndrome of tremor in posture and movement, but recent studies have revealed additional cerebellar motor disturbances, cognitive disturbances, personality changes, hearing loss, and olfactory deficits. Even dementia and shortened life expectancy were found in one cohort. Recent postmortem studies have found limited Lewy body pathology in some patients and Purkinje cell loss with torpedoes and Bergmann gliosis in others. These findings have led to the hypothesis that ET is a syndrome produced by at least two neurodegenerative diseases with more widespread clinical consequences than previously appreciated. We review the evidence for and against this hypothesis and conclude that studies purporting to support this hypothesis have failed to control for age-associated comorbidities, depression, medications, and other confounding factors. We propose the alternative hypothesis that abnormal neuronal oscillation is the fundamental abnormality in ET, and the well-documented cerebellar signs and symptoms, the controversial non-motor signs, and even the cerebellar pathology of ET could be caused by this oscillation. A major problem for many studies is the lack of a diagnostic gold standard. Lacking such a standard, we propose a subclassification of ET into three categories: hereditary ET, sporadic ET, and senile ET, which we believe will help researchers resolve many of the controversies in this field.