Eyes closed single-leg stance test detects subtle sensorimotor decline in early multiple sclerosis.

High-efficacy therapies for multiple sclerosis (MS) have led to an increase in patients presenting with lower Expanded Disability Status Scale (EDSS) scores, necessitating robust, sensitive measures to detect early sensorimotor impairment. In this study, we aimed to identify and validate a balance-based clinical assessment tool capable of detecting subtle sensorimotor deficits in individuals with early-stage MS. This prospective case-control study enrolled 71 patients with MS and 45 matched healthy controls (HCs). Subgroup analysis included patients with early-stage MS (EDSS ≤ 2.0; n = 30) and 28 matched HCs. Participants performed ten postural balance tasks using wearable inertial sensors. We also developed a composite score integrating the most sensitive measures, which was subsequently validated in an independent external cohort. Timed 25-Foot walk (T25FW) failed to distinguish early MS from HCs, whereas eyes-closed single-leg stance (SLS) duration demonstrated superior discriminative ability (AUC = 0.75 ± 0.06; validation: AUC = 0.85 ± 0.07). Only 19% of people with early MS completed the 30-second SLS test versus 71% of HCs. SLS duration showed moderate correlation with the EDSS (r=-0.63). The composite score combining SLS, 9-Hole Peg Test and T25FW improved overall diagnostic performance (AUC = 0.82 ± 0.03, r = 0.74). The eyes-closed SLS test is a simple, no-cost tool that showed moderate to strong clinical validity for detecting early sensorimotor impairment in pwMS. Its diagnostic utility is further optimized when integrated with standard clinical assessments, supporting its potential as a pragmatic outcome measure in the era of high-efficacy therapies.