Background: Multiple sclerosis is characterized by a spectrum of motor, sensory, and cognitive impairments often overlooked in low-disabled people with multiple sclerosis (PwMS). The assessment of subtle functional deficits in this population is crucial to track the evolution of impairments and treatments effects. This study aims to explore the prevalence of multidomain impairments and their association with walking disorders in minimally disabled PwMS.

Methods: In this cross-sectional study, 80 PwMS with EDSS scores < 2.5 underwent a comprehensive assessment that included both EDSS Functional Scores (EDSS FS) and clinical scales measuring lower limb strength (Squat Jump test), tactile sensitivity (Monofilament Test), balance (instrumented test), fatigue (Fatigue Severity Scale) and cognitive function (Symbol Digit Modalities Test). Walking performances in PwMS were objectively measured with the Six-Minute Walking Test (6MWT) and subjectively by the MS Walking Scale-12 (MSWS-12).

Results: Abnormalities in EDSS FS were common, with over 50% (95% CI 43-65%) of PwMS exhibiting impaired Pyramidal FS and more than 20% (95% CI 13-32%) showing deficit in sensory FS. Compared with normative values, 30% of PwMS demonstrated reduced lower limb strength (95% CI 21-41%), impaired tactile sensation (95% CI 20-40%), and increased fatigue (95% CI 9-26%). Multivariate analyses indicated that while EDSS FS moderately predicted subjective (MSWS-12) and objective (6MWT) walking impairments, strength (β = 8.62, p < 0.001) and fatigue (β = 0.10, p < 0.001) emerged as stronger predictors.

Conclusions: Low-disabled PwMS exhibit multidomain impairments and incorporating sensitive clinical assessments may facilitate early identification of subtle deficits, thereby enabling targeted interventions to improve mobility. Background: NCT06219291 (09/11/2023).