Abstract #12: Computerized Essential Tremor Spirography: Development of a Rater-Independent Outcome Measure for Clinical Trials

Abstract

Action tremor represents the cardinal symptom of essential tremor (ET) impairing patients' activities of daily living such as handwriting. Although visually rated Archimedes spirals are used to document tremor intensities, computerized methods of spiral analysis have been presented to quantify ET tremor. Here, we describe a method to objectively quantify tremor using digitizing tablet–based spirography and compare the measures with standardized visual rating after treatment intervention. Nine ET patients underwent a standardized ethanol challenge. Spirals were drawn at six time-points (baseline, 15, 30, 45, 60, and 75 min post-ethanol) using a digitizing tablet. Two methods for data-selection were applied (T: fixed number of time-points of the time-series, S: fixed space by capturing 3.75 spiral turns). After numerical differentiation of the time series, velocity spectra were calculated. Velocity at the spectral peak frequency was used as measure of tremor amplitude. As reference method, visual ratings (VR) were obtained from seven raters using a standard rating scale. Per method, values were normalized to baseline. Larger amplitude changes between time-points were considered as higher sensitivity in demonstrating changes after treatment intervention. Repeated measures ANOVA was used to calculate differences between methods, with Bonferroni correction for post hoc comparisons. For each method, repeated measures ANOVA showed a significant time effect, demonstrating a reduction in tremor amplitudes after ethanol intake (VR: p = 0.001; T: p = 0.008; S: p = 0.003). After normalizing to baseline, the method effect across time-points was significant ( p = 0.001), as well as factor time ( p = 0.002). Method S exhibited larger changes from baseline across time-points ( p = 0.041), whereas method T showed no significant differences compared with VR. Ethanol significantly reduced tremor amplitudes across all methods. Computerized method T equally documented change across time-points as VR; method S, however, showed a significantly higher sensitivity to change, compared with the reference method. In conclusion, the proposed methods of spiral analysis are either equally sensitive (method T) or more sensitive (method S) to treatment-induced changes of tremor intensity and therefore might be useful as outcome measures in clinical trials in ET.