Impaired cerebrovascular reactivity is associated with disability and cognitive performance in relapsing–remitting multiple sclerosis

BACKGROUND AND OBJECTIVES: Cerebrovascular reactivity (CVR) reflects the ability of cerebral vessels to adapt to metabolic demands and may be impaired in multiple sclerosis (MS). Its clinical relevance in relapsing-remitting MS (RRMS), particularly in relation to disability and cognition, remains uncertain. We compared CVR, quantified by the Breath-Holding Index (BHI), between patients with RRMS and healthy controls, and examined its associations with neurological disability and cognitive performance. METHODS: In this cross-sectional observational study consecutive RRMS patients and age- and sex-matched healthy controls (2:1 ratio) were enrolled. CVR to hypercapnia was assessed by transcranial Doppler using BHI. Cognitive performance was evaluated with the Brief International Cognitive Assessment for MS battery, and neurological disability with the Expanded Disability Status Scale (EDSS). Multivariable linear regression was used for adjusted analyses. RESULTS: Ninety patients with RRMS and 45 healthy controls were included. BHI was lower in RRMS than in controls (0.88 ± 0.13 vs. 1.13 ± 0.13), with a mean difference of - 0.256 (95% CI - 0.302 to - 0.209). Lower BHI was associated with greater disability (EDSS: ρ=-0.420; 95% CI - 0.581 to - 0.228) and worse processing speed on the Symbol Digit Modalities Test (r = 0.50; 95% CI 0.33 to 0.64). In adjusted models, lower BHI remained independently associated with higher EDSS (B = - 3.51; 95% CI - 5.82 to - 1.20) and lower SDMT performance (B = 3.69; 95% CI 2.11 to 5.26). DISCUSSION: RRMS patients exhibit reduced CVR, independently associated with disability and processing speed. Impaired CVR may represent a clinically relevant marker of disability and cognitive dysfunction in RRMS.