Tremor in multiple sclerosis is associated with cerebello-thalamic pathology

Frederique Boonstra,Scott Kolbe,Anneke Van Der Walt,Brad Moffat,Patricia Desmond,Grace Florescu,Andrew Evans,Chris Steward,Helmut Butzkueven,Peter Mitchell

doi:10.1007/s00702-017-1798-4

Abstract

Tremor in people with multiple sclerosis (MS) is a frequent and debilitating symptom with a relatively poorly understood pathophysiology. To determine the relationship between clinical tremor severity and structural magnetic resonance imaging parameters. Eleven patients with clinically definite MS and right-sided upper limb tremor were studied. Tremor severity was assessed using the Bain score (overall severity, writing, and Archimedes spiral drawing). Cerebellar dysfunction was assessed using the Scale for the Assessment and Rating of Ataxia. Dystonia was assessed using the Global Dystonia Scale adapted for upper limb. For all subjects, volume was calculated for the thalamus from T1-weighted volumetric scans using Freesurfer. Superior cerebellar peduncle (SCP) cross-sectional areas were measured manually. The presence of lesions was visually determined and the lesion volumes were calculated by the lesion growth algorithm as implemented in the Lesion Segmentation Toolbox. Right thalamic volume negatively correlated with Bain tremor severity score (ρ = − 0.65, p = 0.03). Left thalamic volume negatively correlated with general Bain tremor severity score (ρ = − 0.65, p = 0.03) and the Bain writing score (ρ = − 0.65, p = 0.03). Right SCP area negatively correlated with Bain writing score (ρ = − 0.69, p = 0.02). Finally, Bain Archimedes score was significantly higher in patients with lesions in the contralateral thalamus. Whole brain lesion load showed no relationship with tremor severity. These results implicate degeneration of key structures within the cerebello-thalamic pathway as pathological substrates for tremor in MS patients.

Highlights

Tremor in multiple sclerosis (MS) is a common and disabling symptom
There were no significant correlations between whole brain lesion load and any of the tremor severity scores; patients with lesion(s) within the contralateral thalamus had an increased Bain Archimedes
This study investigated the involvement of the cerebellothalamic tract in the pathogenesis of unilateral MS upper limb tremor

Summary

Introduction

Epidemiological data suggest that tremor affects 26–58% of people with MS and can significantly impact their quality of life (Alusi et al 2001; Pittock et al 2004). MS tremor has postural components and intention components (Koch et al 2007), and these features can limit patients’ daily functions such that those affected are more likely to be unemployed or retired as a result of their disability (Pittock et al 2004). Studies on the pathophysiology in ET suggest an important role for the cerebellum and the cerebello-thalamocortical pathways (Bucher et al 1997; Colebatch et al 1990; Deuschl et al 2001; Louis et al 2002; Feys et al 2005a, b)

Methods

Results

Conclusion