Abstract Background Subclinical disease activity and progression independent of relapse activity (PIRA) contribute to long-term disability in relapsing–remitting multiple sclerosis (RRMS) but are insufficiently captured by conventional clinical measures. Sensitive functional biomarkers capable of detecting early, silent progression are needed. To determine whether quantitative balance and oculomotor assessments detect subclinical disease activity and predict PIRA in patients with RRMS and minimal clinical disability. Methods In this prospective cohort study, 50 patients with RRMS and 50 matched healthy controls underwent computerized dynamic posturography (CDP) and video-nystagmography (VNG) at baseline. RRMS patients were followed every six months for 24 months. Balance performance, sensory organization ratios, and oculomotor parameters were analyzed cross-sectionally and longitudinally. Subclinical disease activity was defined by objective functional and/or MRI activity in the absence of clinical relapse or EDSS worsening. Results At baseline, RRMS patients demonstrated significantly reduced postural stability across all CDP conditions compared with controls (all p < 0.001), with the greatest impairment under vestibular-dependent conditions. Sensory organization analysis revealed predominant vestibular dysfunction, followed by visual dependence, with relative preservation of somatosensory input. VNG showed significant oculomotor abnormalities, including reduced saccadic velocity, prolonged latency, and impaired smooth pursuit (all p < 0.01). Over 24 months, progressive deterioration in CDP and VNG parameters was observed, with significant changes detectable by 12 months and preceding PIRA by 6–12 months in most patients. The vestibular ratio predicted PIRA with an AUC of 0.89, while combined CDP and VNG assessment achieved superior discrimination (AUC 0.92). EDSS remained stable in 89% of patients with abnormal functional measures. Conclusion Quantitative balance and oculomotor impairments are common and progressive in early RRMS despite clinical stability. CDP and VNG detect subclinical disease activity, precede relapse-independent progression, and outperform conventional clinical measures, supporting their potential role as complementary functional biomarkers for monitoring silent disease progression in RRMS.
Elshazly et al. (Mon,) studied this question.