Abstract
<strong>Background:</strong> Essential tremor (ET) is the most common tremor disorder. In addition to its hallmark feature, kinetic tremor of the upper limbs, patients may have a number of non-motor symptoms and signs (NMS). Several lines of evidence suggest that ET is a neurodegenerative disorder and certain NMS may antedate the onset of tremor. This article comprehensively reviews the evidence for the existence of a ‘‘premotor phase’’ of ET, and discusses plausible biological explanations and implications. <strong>Methods:</strong> A PubMed search in May 2017 identified articles for this review. <strong>Results:</strong> The existence of a premotor phase of ET gains support primarily from longitudinal data. In individuals who develop incident ET, baseline (i.e., premotor) evaluations reveal greater cognitive dysfunction, a faster rate of cognitive decline, and the presence of a protective effect of education against dementia. In addition, baseline evaluations also reveal more self-reported depression, antidepressant medication use, and shorter sleep duration in individuals who eventually develop incident ET. In cross-sectional studies, certain personality traits and NMS (e.g., olfactory dysfunction) also suggest the existence of a premotor phase. <strong>Discussion:</strong> There is preliminary evidence supporting the existence of a premotor phase of ET. The mechanisms are unclear; however, the presence of Lewy bodies in some ET brains in autopsy studies and involvement of multiple neural networks in ET as evident from the neuroimaging studies, are possible contributors. Most evidence is from a longitudinal cohort (Neurological Disorders of Central Spain: NEDICES); additional longitudinal studies are warranted to gain better insights into the premotor phase of ET.
Highlights
Essential tremor (ET) is the most common tremor disorder among adults.[1]
ET has long been regarded as a monosymptomatic benign movement disorder primarily characterized by kinetic tremor of the upper limbs, a range of additional motor and non-motor features has been described
We comprehensively review the evidence for the presence of a premotor phase in ET, and discuss plausible biological explanations and implications
Summary
Essential tremor (ET) is the most common tremor disorder among adults.[1]. ET has long been regarded as a monosymptomatic benign movement disorder primarily characterized by kinetic tremor of the upper limbs, a range of additional motor and non-motor features has been described. Among the non-motor symptoms and signs (NMS) that have been described are cognitive impairment, depression, apathy, anxiety, personality characteristics, olfactory deficits, hearing problems, and sleep disturbances.[2,3] There is evidence to suggest that most of the NMS observed in ET are not just epiphenomena, rather they are parts of the primary disease process.[4] In this backdrop, the question that is thought provoking and the answer to which remains largely elusive is what does appear first in ET: tremor or the NMS? In PD, certain NMS such as rapid eye movement sleep behavior disorder (RBD), depression, and olfactory dysfunction may antedate the onset of motor symptoms by decades.[5,6] patients with HD may have behavioral and/or cognitive problems long before the onset of motor symptoms.[7,8]. We comprehensively review the evidence for the presence of a premotor phase in ET, and discuss plausible biological explanations and implications
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