Matthis Synofzik

Objective Voluntary upper limb movements are an ecologically important yet insufficiently explored digital‐motor outcome domain for trials in degenerative ataxia. We extended and validated the trial‐ready quantitative motor assessment battery “Q‐Motor” for upper limb movements with clinician‐reported, patient‐focused, and performance outcomes of ataxia. Methods Exploratory single‐center cross‐sectional assessment in 94 subjects (46 cross‐genotype ataxia patients; 48 matched controls), comprising five tasks measured by force transducer and/or position field: Finger Tapping, diadochokinesia, grip‐lift, and—as novel implementations—Spiral Drawing, and Target Reaching. Digital‐motor measures were selected if they discriminated from controls (AUC >0.7) and correlated—with at least one strong correlation (rho ≥0.6)—to the Scale for the Assessment and Rating of Ataxia (SARA), activities of daily living (FARS‐ADL), and the Nine‐Hole Peg Test (9HPT). Results Six movement features with 69 measures met selection criteria, including speed and variability in all tasks, stability in grip‐lift, and efficiency in Target Reaching. The novel drawing/reaching tasks best captured impairment in dexterity (|rho 9HPT | ≤0.81) and FARS‐ADL upper limb items (|rho ADLul | ≤0.64), particularly by kinematic analysis of smoothness (SPARC). Target hit rate , a composite of speed and endpoint precision , almost perfectly discriminated ataxia and controls (AUC: 0.97). Selected measures in all tasks discriminated between mild, moderate, and severe impairment (SARA upper limb composite: 0–2/>2–4/>4–6) and correlated with severity in the trial‐relevant mild ataxia stage (SARA ≤10, n = 20). Interpretation Q‐Motor assessment captures multiple features of impaired upper limb movements in degenerative ataxia. Validation with key clinical outcome domains provides the basis for evaluation in longitudinal studies and clinical trial settings.

Background With disease‐modifying drugs in reach for cerebellar ataxias, fine‐grained digital health measures are highly warranted to complement clinical and patient‐reported outcome measures in upcoming treatment trials and treatment monitoring. These measures need to demonstrate sensitivity to capture change, in particular in the early stages of the disease. Objective Our aim is to unravel gait measures sensitive to longitudinal change in the—particularly trial‐relevant—early stage of spinocerebellar ataxia type 2 (SCA2). Methods We performed a multicenter longitudinal study with combined cross‐sectional and 1‐year interval longitudinal analysis in early‐stage SCA2 participants (n = 23, including nine pre‐ataxic expansion carriers; median, ATXN2 CAG repeat expansion 38 ± 2; median, Scale for the Assessment and Rating of Ataxia [SARA] score 4.8 ± 4.3). Gait was assessed using three wearable motion sensors during a 2‐minute walk, with analyses focused on gait measures of spatio‐temporal variability that have shown sensitivity to ataxia severity (eg, lateral step deviation). Results We found significant changes for gait measures between baseline and 1‐year follow‐up with large effect sizes (lateral step deviation P = 0.0001, effect size r prb = 0.78), whereas the SARA score showed no change ( P = 0.67). Sample size estimation indicates a required cohort size of n = 43 to detect a 50% reduction in natural progression. Test–retest reliability and minimal detectable change analysis confirm the accuracy of detecting 50% of the identified 1‐year change. Conclusions Gait measures assessed by wearable sensors can capture natural progression in early‐stage SCA2 within just 1 year—in contrast to a clinical ataxia outcome. Lateral step deviation represents a promising outcome measure for upcoming multicenter interventional trials, particularly in the early stages of cerebellar ataxia. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.