Preserved neurovascular coupling in early multiple sclerosis is associated with reduced white matter lesion burden
Background Multiple sclerosis (MS) is a chronic autoimmune disorder characterized by inflammation, demyelination and axonal degeneration of the central nervous system. Whether these pathological changes impact neurovascular coupling (NVC), which can be compromised in various neurodegenerative disorders, remains unclear in MS. Objectives To investigate the relationship between NVC, clinical characteristics and neuroimaging measures in patients with MS. Design We conducted a cross-sectional study of patients with MS recruited from the Comprehensive Multiple Sclerosis Clinic at Northwestern Medicine, Chicago, USA. Methods Seventy-six patients with MS underwent NVC assessment using transcranial Doppler (TCD) ultrasound in the middle cerebral artery (MCA) and posterior cerebral artery (PCA) territories. Clinical assessment included manual dexterity, cognitive function and gait. Brain magnetic resonance imaging (MRI) quantified white matter hyperintensity (WMH), gray matter (GM) and white matter (WM) volumes. Associations were examined using multivariate linear regression, adjusting for demographic and vascular risk factors, and stratified by disability and cognitive performance. Results Higher NVC in the PCA territory correlated with lower WMH burden (r=−0.32, p=0.02), particularly in patients with lower disability (Expanded Disability Status Scale <2). This association remained significant after adjustment (β=−0.071, 95% CI [−0.135, −0.007], p=0.031). Higher NVC PCA was also associated with lower WMH in patients with better executive (β=−0.104, 95% CI [−0.176, −0.033], p=0.007) and global cognitive scores (β=−0.116, 95% CI [−0.222, −0.009], p=0.035). No association was found with GM volume. Conclusion Preserved PCA neurovascular function is associated with lower WM lesion burden, measured using conventional MRI, in MS patients with lower disability and better cognition, a finding that may inform risk stratification and guide future therapeutic targets.