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.

Wearable Sensors in Huntington Disease: A Pilot Study

“…Study goals included (1) determining the feasibility of capturing motor assessments with sensors at home, (2) comparing sensor data between participants with HD and controls, and (3) comparing sensor data by motor impairment as measured by the UHDRS total motor score. Participants gave informed, written consent for this study and all procedures were approved by the University of Rochester's institutional review board.…”

“…Although valuable, the scale is subjective and categorical [2,3], requires significant training to administer correctly, and only captures impairment in clinic. Quantitative motor tests, notably "Q-Motor" assessments, have helped reduce subjectivity and improve sensitivity of motor assessments in HD [4][5][6][7][8][9][10][11].…”

8OHdG is not a biomarker for Huntington disease state or progression

“…These and other studies have shown differences in neuroimaging, cognitive, and motor measures among control, premanifest, and clinically diagnosed cohorts. 7,8 Although premanifest and clinically diagnosed groups show robust longitudinal changes in neuroimaging measures, the latter shows more easily detectable declines in other measures compared with controls and premanifest HD (preHD). …”

Quantitative Measurements of Motor Function in Alzheimer’s Disease, Frontotemporal Dementia, and Dementia with Lewy Bodies: A Proof-of-Concept Study

“…1), as well as standard deviations for IOI, IPI, ITI, and TD [46]. The grip lift task measures the amount of involuntary movement in the static holding phase and records changes in grip force (N) (GF), GF variability (%) (GFV), orientation index (deg/s) (OI), and position index (cm/s) (PI) [45, 47]. …”

“…In the grip lift task, the force transducer, equipped with an electromagnetic 3D position sensor, placed on a movable grip device, continuously assessed the grip and load force (0.025 N resolution) of the thumb and the position and orientation of the device in the room [45, 47]. Participants grasped and lifted the device with precision grip, using their thumb and index finger, and were instructed to hold it as stable as possible for 20 s over a square on the platform and near to a marker at a height of 10 cm.…”