Motor phenotype assessment of patient's with Huntington's disease using a force plate – a new biomarker for clinical studies?

Background: Patients with Huntington's Disease (HD) develop a progressive impairment of stability of stance and walking, frequently resulting in falls and injuries. In the search for objective and quantitative outcome measures for clinical studies in HD, assessment of motor phenotype dysfunction may serve as an useful surrogate marker.

Objective: To investigate whether patients with HD (1) exhibit impairments in the stability of stance compared to controls that can quantitatively be assessed using a force plate and (2) to assess whether these measures correlate to the severity of disease as assessed clinically by the “UHDRS“ (Unified Huntington's Disease Rating Scale) “total motor score“ (TMS) and “functional assessment scale“ (FA).

Subjects and methods: Symptomatic HD patients (n=9) and age-and-sex-matched controls (n=11) were standing on a force plate (Satel, France) with eyes open and closed for 30 seconds. Subjects were instructed to stand still without moving. Stability of center of mass (COM) location was assessed by the variables “surface“ and “distance“ reflecting COM mobility. Data was stored and analyzed using a data acquisition system. All subjects were assessed using the UHDRS-TMS and -FA. Statistics were performed using ANOVA and Spearman correlations (SPSS 13.0).

Results: Both measures surface and distance were significantly increased in HD compared to controls (p<0.001 for all measures and conditions [eyes open and closed]). In HD the measure surface was correlated to the severity of the disease as assessed in the UHDRS-TMS (r=0.9, p<0.001 for “eyes-open“ and r=0.767, p<0.01 for “eyes-closed“) and the UHDRS-FA (r=0.672, p<0.05 for “eyes-open“ and r=0.766, p<0.01 for “eyes-closed“).

Conclusion: Assessment of stance stability using a force plate provides objective and quantitative readouts of motor phenotype dysfunction in HD. The measure surface of COM dislocation was correlated to the severity of both the motor phenotype (TMS) and the general dysfunction (FA) of the patients. A possible use of the force plate as a surrogate marker for treatment trials in HD warrants further exploration, e.g., in a blinded follow-up study.

Acknowledgment: RR was supported by a grant from the High-Q-Foundation and IMF-RE-120225 from the “Innovative Medizinische Forschung“, Faculty of Medicine, University of Münster