Characterization of inferior frontal sulcal hyperintensities in patients with relapsing-remitting multiple sclerosis.

BACKGROUND: Inferior frontal sulcal hyperintensities (IFSH) on fluid-attenuated inversion recovery sequence have been proposed as a sign of glymphatic function, yet their clinical significance in multiple sclerosis remains unclear. OBJECTIVE: To investigate the association between IFSH and brain clearance function, brain structural alterations, cognition, disability, and depression status in patients with relapsing-remitting multiple sclerosis (RRMS). METHODS: We enrolled 150 patients with RRMS and 55 age- and sex-matched healthy controls (HC). IFSH were rated using a standardized scale. Brain clearance function was assessed using the diffusion tensor image analysis along the perivascular space (DTI-ALPS) index and perivascular space scores. Structural metrics were obtained with automated segmentation, followed by comparisons between groups and regression analysis. RESULTS: Compared with HC, patients with RRMS exhibited significantly higher IFSH categorical scores (p < 0.001). In patients with RRMS, higher IFSH categorical scores were associated with greater white matter lesion volume fraction [odds ratio (OR) = 2.646, 95% confidence interval (CI) 1.263 to 5.543, p = 0.010], higher centrum semiovale-perivascular spaces scores [OR = 1.647 (95% CI 1.236 to 2.108), p = 0.024] and a lower brain parenchymal fraction [OR = 0.357 (95% CI 0.146 to 0.873), p = 0.024]. In multivariate models, higher Symbol Digit Modalities Test scores were robustly associated with lower IFSH categorical scores [β = -3.233 (95% CI -5.836 to -0.629), p = 0.015]. CONCLUSION: Patients with RRMS exhibited more severe IFSH than HC. IFSH may serve as a potential imaging sign associated with perivascular clearance-related alterations, white matter lesion load, brain atrophy and cognitive decline in patients with RRMS.