Digital Outcomes of Upper Limb Ataxia Capture Meaningful Longitudinal Change and Treatment Response

Digital-motor outcomes promise better responsiveness than clinician-reported outcomes in ataxia trials. However, their patient meaningfulness and sensitivity to change remain to be demonstrated, particularly in the upper limb domain.

Validation of quantitative motor (Q-Motor) assessment for upper limb ataxia against patient-reported outcomes and regarding sensitivity to both longitudinal and treatment-induced change, the latter in n-of-1 treatment settings.

Single-center longitudinal assessment of finger tapping, diadochokinesia, grip-lift, spiral drawing, and target reaching in (1) 36 cross-genotype ataxia patients and 20 controls, validating digital measures for correlations with patient-reported outcome measure (PROM)-ataxia, 2-weeks test-retest reliability, and sensitivity to change within a trial-relevant 1-year follow-up, anchored in Patient Global Impression of Change (PGI-C); and (2) two patients with spinocerebellar ataxia type 27B (SCA27B) on versus off treatment with 4-aminopyridine.

Twenty-four digital measures correlated with the PROM-ataxia upper-limb composite (|ρ| = 0.4-0.7) and had excellent test-retest reliability (ICC = 0.91-0.99). Correlations to individual PROM-ataxia items were specific for functional impairment the respective measure was hypothesized to capture. Speed of finger tapping and diadochokinesia, and smoothness of target reaching (spectral arc length of movement in three dimensions [SPARC_3D]) captured 1-year progression in ataxia patients (|r_prb| = 0.38-0.51), and specifically in patients with worsening PGI-C. Estimated sample sizes to detect longitudinal change were lower for digital than clinical outcomes (SPARC_3D: n = 33, Scale for the Assessment and Rating of Ataxia (SARA): n = 79, nine-hole peg-test: n = 214). Speed of diadochokinesia, stability of grip-lift, and variability of target reaching captured treatment responses to 4-aminopyridine in SCA27B, exceeding minimal detectable and minimal important change.

Digital upper limb measures capture patient-meaningful 1-year longitudinal and treatment-induced change, and are therefore promising outcomes for upcoming ataxia trials. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.