Digital gait outcomes for ARSACS: discriminative, convergent and ecological validity in a multi-center study (PROSPAX)

BackgroundWith treatment trials on the horizon, this study aimed to identify candidate digital-motor gait outcomes for Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS), capturable by wearable sensors with multi-center validity, and ideally also ecological validity during free walking outside laboratory settings. MethodsCross-sectional multi-center study (4 centers), with gait assessments in 36 subjects (18 ARSACS patients; 18 controls) using three body-worn sensors (Opal, APDM) in laboratory settings and free walking in public space. Sensor gait measures were analyzed for discriminative validity from controls, and for convergent (i.e. clinical and patient-relevance) validity by correlations with SPRSmobility (primary outcome) and SARA, SPRS and FARS-ADL (exploratory outcomes). ResultsOf 30 hypothesis-based digital gait measures, 14 measures discriminated ARSACS patients from controls with large effect sizes (|Cliffs {delta}| > 0.8) in laboratory settings, with strongest discrimination by measures of spatiotemporal variability Lateral Step Deviation ({delta}=0.98), SPcmp ({delta}=0.94) and Swing CV ({delta}=0.93). Large correlations with the SPRSmobility were observed for Swing CV (Spearmans {rho} = 0.84), Speed ({rho}=-0.63) and Harmonic Ratio V ({rho}=-0.62). During supervised free walking in public space, 11/30 gait measures discriminated ARSACS from controls with large effect sizes. Large correlations with SPRSmobility were here observed for Swing CV ({rho}=0.78) and Speed ({rho}=-0.69), without reductions in effect sizes compared to lab settings. ConclusionWe identified a promising set of digital-motor candidate gait outcomes for ARSACS, applicable in multi-center settings, correlating with patient-relevant health aspects, and with high validity also outside lab settings, thus simulating real-life walking with higher ecological validity.