Assessment of involuntary choreatic movements in Huntington's disease—Toward objective and quantitative measures

Abstract

Objective measures of motor impairment may improve the sensitivity and reliability of motor end points in clinical trials. In Huntington's disease, involuntary choreatic movements are one of the hallmarks of motor dysfunction. Chorea is commonly assessed by subitems of the Unified-Huntington's Disease Rating Scale. However, clinical rating scales are limited by inter- and intrarater variability, subjective error, and categorical design. We hypothesized that assessment of position and orientation changes interfering with a static upper extremity holding task may provide objective and quantitative measures of involuntary movements in patients with Huntington's disease. Subjects with symptomatic Huntington's disease (n = 19), premanifest gene carriers (n = 15; Unified-Huntington's Disease Rating Scale total motor score ≤ 3), and matched controls (n = 19) were asked to grasp and lift a device (250 and 500 g) equipped with an electromagnetic sensor. While subjects were instructed to hold the device as stable as possible, changes in position (x, y, z) and orientation (roll, pitch, yaw) were recorded. These were used to calculate a position index and an orientation index, both depicting the amount of choreatic movement interfering with task performance. Both indices were increased in patients with symptomatic Huntington's disease compared with controls and premanifest gene carriers for both weights, whereas only the position index with 500 g was increased in premanifest gene carriers compared with controls. Correlations were observed with the Disease Burden Score based on CAG-repeat length and age and with the Unified-Huntington's Disease Rating Scale. We conclude that quantitative assessment of chorea is feasible in Huntington's disease. The method is safe, noninvasive, and easily applicable and can be used repeatedly in outpatient settings. A use in clinical trials should be further explored in larger cohorts and follow-up studies.