Diurnal step count patterns in progressive multiple sclerosis

BACKGROUND: Progressive multiple sclerosis (MS) leads to increasing disability, commonly assessed using the Expanded Disability Status Scale (EDSS) and the Timed 25-Foot Walk (T25FW). However, these episodically assessed, in-clinic measures miss diurnal fluctuations in mobility. OBJECTIVE: To evaluate whether diurnal step count patterns reflect MS-related disability and whether these associations persist after accounting for temporal context and Kurtzke Functional Systems Scores (KFS). METHODS: Minute-level step count data were collected from 529 progressive MS patients over 27 months in the placebo-controlled, SPI2 trial of MD1003. Function-on-scalar regression (FOSR) was applied to model average daily step-count curves (30-minute bins) against EDSS, T25FW, and demographics. Analyses included overall averages, temporally aligned scores (±3 months), and KFS components. RESULTS: Higher EDSS and slower T25FW were linked to lower step count patterns, particularly during mid-day hours. EDSS demonstrated stronger associations than T25FW, although both provided complementary predictive value. Temporally aligned (±3 months) scores confirmed robust associations. Among KFS domains, ambulation, pyramidal, and cerebellar functions explained the most variation. CONCLUSIONS: Diurnal step count patterns provide objective markers of disability in progressive MS, reflecting specific neurologic deficits. These findings highlight their potential to complement clinical scales and to inform the timing of mobility-focused interventions.