Department of Neurology, University Hospital ‘‘12 de Octubre’’, Madrid; Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid; Department of Medicine, Complutense University, Madrid, ES
Division of Movement Disorders, Department of Neurology Yale School of Medicine, Yale University, New Haven, CT; Department of Chronic Disease Epidemiology, Yale School of Public Health, Yale University, New Haven, CT; Center for Neuroepidemiology and Clinical Neurological Research, Yale School of Medicine, Yale University, New Haven, CT, US
Background: 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.
Methods: A PubMed search in May 2017 identified articles for this review.
Results: 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.
Discussion: 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.