Objective assessment of gait and posture in premanifest and manifest Huntington disease - A multi-center study

Abstract

Background: Deficits in posture and gait are known to contribute to the complex motor phenotype of Huntington disease (HD). Objective and quantitative measures of posture and gait provided by posturography and GAITRite^® assessments may supplement categorical rating scales such as the UHDRS-TMS and increase power and sensitivity of clinical trials.

Objectives: To investigate whether posturography and GAITRite^® measures reveal (1) changes in manifest or premanifest HD mutation-carriers, (2) a correlation to the UHDRS-TMS and functional measures in manifest HD, and (3) a correlation to the disease-burden-score (based on CAG-repeat-length and age).

Methods: Posturography and GAITRite^® were applied in premanifest (n = 26) and manifest HD gene-mutation-carriers (n = 40) in different paradigms compared to age-matched controls (n = 30) in a cross-sectional multi-site study conducted in three centers. Subjects were assessed clinically with the UHDRS Total-Motor-Score, Total-Functional-Capacity and Functional-Assessment-Scale.

Results: Several posturography measures were able to discriminate between controls, premanifest, and manifest mutation-carriers in both conditions assessed. Only one GAITRite^® measure separated controls and premanifest participants, while discrimination between controls and manifest same as between premanifest and manifest participants was possible in several measures. Correlation with all clinical measures was seen in only one measure per device while correlations to the disease-burden-score seen in posturography only.

Conclusion: Overall the results suggests that posturography detects alterations in premanifest and manifest mutation-carriers more reliably than GAITRite^® measures. Correlations with clinical assessment scores are limited; correlation with disease-burden-score is seen in posturography only. Data acquisition and analysis was easier with posturography than GAITRite^® assessments in out-patient settings.

Keywords: Clinical trial; Endpoint; Gait; Huntington disease; Posture.