Language and voice analysis as multidimensional biomarkers of silent progression in relapsing–remitting multiple sclerosis.

Background and aims: Progression independent of relapse activity (PIRA) is a major contributor to disability accumulation in MS but is difficult to detect in patients with low EDSS scores. Language and speech impairments are common yet underrecognized in MS and may reflect early cognitive and motor network dysfunction not captured by conventional disability measures. This study investigated whether multidimensional language and voice assessments could serve as sensitive functional biomarkers of subclinical progression in relapsing–remitting MS (RRMS). Methods: Twenty- eight patients with RRMS and mild disability and eight age- and sex-matched healthy controls underwent comprehensive cognitive, linguistic, and speech evaluations. Cognitive assessment included MoCA and domain-specific neuropsychological tests. Language was examined using verbal fluency and comprehension tasks. Speech and voice were evaluated with a standardized dysarthria profile, the Voice Handicap Index, and automated acoustic analysis using VoxPlot software. Acoustic parameters included Cepstral Peak Prominence Smoothed (CPPS), Acoustic Voice Quality Index (AVQI), and Acoustic Breathiness Index (ABI). Results: Compared with controls, patients with RRMS showed reduced phonemic and semantic verbal fluency with preserved language comprehension. Mild but significant dysarthria was observed, mainly affecting respiration, diadochokinesis, and reflexes. Acoustic analysis revealed reduced CPPS and increased AVQI and ABI, indicating impaired voice quality. While several measures correlated with EDSS and disease duration, multivariate analyses showed that acoustic and dysarthric parameters were largely independent of global disability, age, and disease duration. Conclusion: Language and voice assessments detect subtle multidimensional dysfunction in RRMS not captured by conventional disability scales, supporting their potential role as bio-markers of silent progression and PIRA particularly in patients with low physical disability