Real-life walking speed: A new marker of progression in a primary progressive multiple sclerosis cohort study?

Background: Primary progressive multiple sclerosis (PPMS) involves gradual disability accumulation driven by neurodegeneration. Standard outcomes, including the Expanded Disability Status Scale (EDSS) and timed 25-foot walk (T25FW), lack sensitivity to subtle functional changes. Real-life walking speed (RWS) measured with wearable sensors may offer a more responsive marker of progression. Objectives: In a prospective cohort (2012–2022) at the University Medical Center Hamburg-Eppendorf, adults with PPMS (18–65 years, EDSS ⩽7.0) underwent repeated EDSS, T25FW, Nine-Hole Peg Test (9HPT), and Symbol Digit Modalities Test (SDMT). RWS was recorded using an accelerometer. Disease progression was defined as ⩾20% worsening in T25FW/9HPT, ⩾8-point SDMT decline, EDSS increase (⩾1.0 or ⩾0.5 if >5), or RWS reduction >0.08 m/s. Results: Among 110 participants (mean age: 52 years; baseline EDSS: 3.5) followed for a median of 3 years, RWS showed a symmetric distribution and declined steadily with increasing EDSS, unlike the skewed T25FW distribution. Annual progression was detected in >30% of participants using RWS, compared with <20% for EDSS/SDMT and <10% for T25FW/9HPT. Composite endpoints including RWS identified earlier and more frequent disease progression ( p < 0.01). Conclusion: Continuous RWS monitoring is more sensitive than conventional metrics for detecting functional decline in PPMS and may strengthen progression endpoints.