Quantitative motor assessment in X-linked dystonia parkinsonism (1988)

Objective: To perform quantitative motor analysis in X-linked dystonia parkinsonism (XDP) as a potential clinical trial endpoint. Background: XDP is a neurogenetic mixed movement disorder involving both parkinsonism and dystonia. For clinical trial readiness, rater-independent, quantitative assessments of motor function are urgently needed. Complex, overlapping phenotypes result in difficulties in clinical rating scale assessment. Design/Methods: 10 symptomatic XDP patients and 4 healthy controls underwent motion sensor analysis with a standardized examination. Disease severity was assessed with the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) and Burke-Fahn-Marsden scale (BFM). We assessed specific MDS-UPDRS and BFM elements using clinical scores as the dependent variable, segmented the sensor data and derived a set of data features chosen based on prior work. Data feature selection and projection algorithms were used to inspect the data feature space and assess the suitability of the derived data features to build machine learning-based models to estimate clinical scores from sensor data. Results: XDP patients were of varying stages of disease (disease duration 3–28 years) and varied phenotype: parkinsonism-predominant (n=5), dystonia-predominant (n=2) and dystonia parkinsonism (n=3), with BFM scores 0–43.5 and MDS-UPDRS 13–48. Projections showed distinct clusters of data points corresponding to different MDS-UPDRS scores for different tasks (hand pronation/supination, leg agility, foot tapping, finger-to-nose), suggesting that data features derived from the sensor data are suitable to derive reliable estimates of clinical scores. We assessed upper/lower limb and cervical dystonia at rest, during motor tasks and provocative maneuvers, compared to the BFM severity score. Projections of a dystonia-specific features set showed clear cluster separation between controls, XDP with and without dystonia. Conclusions: The analyses of these datasets suggest the feasibility of deriving reliable clinical score estimates from wearable sensor data in detecting both parkinsonian and dystonic features in a complex, mixed movement disorder and suggest the utility of motion sensors in quantifying clinical examination. Disclosure: Federico Parisi has nothing to disclose. Paolo Bonato has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for SwanBio Therapeutics. The institution of Paolo Bonato has received research support from National Institutes of Health. The institution of Paolo Bonato has received research support from National Science Foundation. The institution of Paolo Bonato has received research support from Michael J Fox Foundation. The institution of Paolo Bonato has received research support from Mitsui Chemicals. The institution of Paolo Bonato has received research support from Peabody Foundation. The institution of Paolo Bonato has received research support from Department of Defense. The institution of Paolo Bonato has received research support from BIRD Foundation. Mr. Acuna has nothing to disclose. Dr. Go has nothing to disclose. Dr. Sharma has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Wiley. Dr. Sharma has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Wiley. Dr. Sharma has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Cambridge Expert Witness. The institution of Dr. Sharma has received research support from NIH. Dr. Stephen has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for SwanBio Therapeutics. Dr. Stephen has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Xenon Pharmaceuticals. The institution of Dr. Stephen has received research support from Sanofi.