Poster Abstract #4: Development of Long-Duration Accelerometry for Use in Clinical Trials of Essential Tremor

Abstract

Background Essential tremor (ET) is a common movement disorder affecting 0.4% of the general population and 14% of people 65 years and older. Current therapies provide modest tremor suppression and are often accompanied by intolerable side effects. Key to the success of future studies is the development of objective biomarkers to assess tremor in a sensitive and unbiased manner. Numerous subjective and objective tremor measures are available, including laboratory-based accelerometry, electromyography, spirography, and surveys assessing quality of life or impact on activities of daily living. The utility of objective measures are limited by time and expense, and subjective measures lack sensitivity and rely heavily on standardization of ratings or patient responses. Furthermore, all these methods are temporally biased, in that they reflect only brief time intervals. We hypothesized that portable uniaxial monitoring devices could be used to reliably measure tremor over long durations in patients with ET. Methods The study population consisted of adults with ET who underwent an ethanol challenge to assess tremor response, prior to enrollment in a clinical trial at NIH. Wrist-based accelerometers were used (Cambridge Neurotechnology, Cambridge, UK) to record the intensity and duration of tremor and nontremor movements. We developed an algorithm to calculate a Tremor Severity Score (TSS) characterizing tremor patterns over extended time periods. To assess individual subject changes, we normalized the TSS at each timepoint by each subject's own baseline TSS. The primary outcome measures were TSS at baseline, 0–30, 30–60, and 60–90 minutes after ethanol challenge. Results Thirteen patients were included in the analysis. Mean percent reduction in tremors from baseline TSS was 165%, 408%, and 423% at 0–30, 30–60, and 60–90 minutes after ethanol challenge, respectively. A post hoc linear regression of the TSS total score and baseline TSS revealed high correlation ( R 2 = 0.77). Conclusions Our results show that the TSS, based on long-duration accelerometry data, provides a sensitive and reliable method for objectively measuring ET outcomes. This method could serve as a model for the development of low-cost, high-throughput clinical trials. Further work is needed to validate this method with tremor measures in current use.