5.: Dystonic features are common in multiple sclerosis-related tremor and contribute to its severity

Detailed phenomenological studies are needed to characterize multiple sclerosis (MS)-related tremor and investigate factors that may predict its severity. We completed a detailed, blinded study in order to define clinical features that may be unique to MS tremor patients and that may inform the underlying pathophysiology of MS tremor. The objectives of this study were to investigate clinical factors that contribute to tremor severity in patients with MS, and to determine if dystonia is more common in MS tremor patients than disease-matched, non-tremor controls. We recruited 54 MS patients with and without disabling arm tremor matched for age, sex and disability. Both limbs were assessed in bilateral tremor, resulting in 39 limbs per group. Cerebellar function was rated with the Scale for the Assessment and Rating of Ataxia. Assessments of tremor severity (Bain score for tremor severity, writing and drawing) and dystonia (Global Dystonia Scale [GDS] for proximal and distal arms) using video and handwriting recordings were completed. All samples were shuffled and rated by a blinded movement disorder expert. The presence and severity of dystonic posturing, mirror movements and geste antagonistes were scored. We found associations (p < 0.05) between Expanded Disability Status Scale, 9-hole peg test, GDS, cerebellar dysfunction and tremor severity. GDS was worse in MS tremor patients than in controls (p < 0.001). Geste antagonistes, mirror dystonia and dystonic posturing were more frequent (p < 0.001) and more severe in tremor patients than in controls. In multi-variable models, a 1 unit increase in distal GDS predicted a 0.52 unit (p = 0.022) increase in tremor severity and a 1 unit (p = 0.001) increase in drawing scores. One unit increase in proximal GDS predicted a 0.93 unit increase (p < 0.001) in tremor severity, a 0.99 unit (p = 0.050) increase in writing scores and a 1.5 unit (p = 0.002) increase in drawing score. The results of this study demonstrate the importance of recognizing dystonia as part of the complex movement disorder that represents MS tremor. The presence of dystonia points to injury in the cerebello-pallido-thalamo-cortical network and could explain the efficacy of onabotulinumtoxin-A therapy in the treatment of MS tremor.