White Matter Hyperintensities Are Associated With Severity of Essential Tremor in the Elderly.

Jos S Becktepe,Ulf Jensen-Kondering,Kirsten E Zeuner,Johannes Busse,Oliver Granert,Günther Deuschl,Daniela Berg,Inken Toedt,Stephan Wolff

doi:10.3389/fneur.2021.694286

Abstract

Background: Essential tremor (ET) occurs with steeply increasing prevalence in the elderly, and apart from disease duration, age is independently associated with an increase of tremor amplitude and a decrease of frequency. White matter hyperintensities (WMHs) are a common finding in the elderly, and their role in the pathophysiology of ET is unknown. The aims of this study were to examine whether ET patients differ in their total or region-specific WMH volumes from healthy controls and to determine the impact of WMH on tremor characteristics.Methods: A total of 47 elderly ET patients with a mean age of 72 years and 39 age-matched healthy controls underwent a thorough clinical assessment and 3T MRI. Total WMH volumes were derived from T2-weighted fluid-attenuated inversion recovery (FLAIR) MR images. Additionally, region of interest-based WMH volumes for the Johns Hopkins University (JHU) white matter tracts and labels were calculated, and WMHs were assessed semiquantitatively using the Fazekas scale.Results: Essential tremor patients and healthy controls did not differ in their total or tract-specific WMH volumes or Fazekas scores. However, WMH volume was significantly positively correlated with tremor severity on the TETRAS scale, and there was a significant negative correlation with the mean accelerometric tremor frequency. In a multiple linear regression model including disease duration, age, and age-adjusted total WMH volume, only the WMH volume significantly predicted tremor severity, while age and disease duration were not significant.Conclusion: We found evidence for a direct association between WMH volume and tremor severity. If confirmed by larger studies, our findings could explain the well-known relation between age and tremor severity.

Highlights

Essential tremor (ET) is the most common movement disorder, with steeply increasing prevalence in the elderly [1]
Epidemiologic studies have shown that apart from disease duration, age is independently associated with an increase in tremor severity as measured with clinical tremor scores and a decrease in accelerometric tremor frequency [8,9,10,11]
Since no group differences were found between patients with and those without additional soft signs regarding total or ROI-specific White matter hyperintensities (WMHs) volumes, all ET patients were pooled for further analyses to increase statistical power

Summary

Introduction

Essential tremor (ET) is the most common movement disorder, with steeply increasing prevalence in the elderly [1]. The etiology for the syndrome (axis II) remains unclear in the majority of patients, pathological oscillations within the cerebello-thalamo-cortical circuit are proposed as a common pathophysiologic correlate [3]. The source for these oscillations has not been determined yet, but several imaging and pathological studies point toward a central role of the cerebellum for the pathogenesis [4,5,6,7]. Essential tremor (ET) occurs with steeply increasing prevalence in the elderly, and apart from disease duration, age is independently associated with an increase of tremor amplitude and a decrease of frequency. The aims of this study were to examine whether ET patients differ in their total or region-specific WMH volumes from healthy controls and to determine the impact of WMH on tremor characteristics

Objectives

Results

Conclusion