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

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.

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).

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.

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].

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.