METHODS: This cross-sectional multicenter study (7 centers, 6 countries) analyzed defined laboratory-based walking and uninstructed "supervised free walking" in patients with SPG7 and healthy controls using 3 wearable sensors (Opal APDM). For the extracted digital gait measures, we assessed effect sizes for the discrimination of patients and controls (Cliff δ) and Spearman correlations with measures of functional mobility and overall disease severity (Spastic Paraplegia Rating Scale [SPRS], including mobility subscore SPRSmobility; Scale for the Assessment and Rating of Ataxia [SARA]) and the activities of daily living subscore of the Friedreich Ataxia Rating Scale (FARS-ADL).
RESULTS: Gait was analyzed in 65 patients with SPG7 and 50 healthy controls. Among 30 hypothesis-based gait measures, 18 demonstrated at least moderate effect size (δ > 0.5) in discriminating patients from controls and 17 even in mild disease stages (SPRSmobility ≤ 9, n = 41). Spatiotemporal variability measures such as spatial variability measure SPcmp (ρ = 0.67, p < 0.0001) and stride time CV (ρ = 0.67, p < 0.0001) showed the largest correlations with functional mobility (SPRSmobility)-as with overall disease severity (SPRS, SARA) and activities of daily living (FARS-ADL). The correlations of variability measures with SPRSmobility could be confirmed in mild disease stages (e.g., SPcmp: ρ = 0.50, p < 0.0001) and in "supervised free walking" (e.g., stride time CV: ρ = -0.57, p < 0.0001).
DISCUSSION: We here identified trial-ready digital-motor candidate outcomes for the spastic ataxia SPG7 with proven multicenter applicability, ability to discriminate patients from controls, and correlation with measures of patient-relevant health aspects-even in mild disease stages. If validated longitudinally, these sensor outcomes might inform future natural history and treatment trials in SPG7 and other spastic ataxias.