Glymphatic system dysfunction in temporal lobe epilepsy with hippocampal sclerosis: MRI-based evaluation of circulatory markers and disease progression

Objectives In this study, several MRI-derived glymphatic markers were utilized to evaluate alterations in glymphatic system (GS) function in patients with temporal lobe epilepsy and hippocampal sclerosis (TLE-HS). Methods we assessed 160 participants, including 80 patients with TLE-HS and 80 healthy controls (HCs). Glymphatic circulation was evaluated using MRI-based markers, including choroid plexus volume (CPV), perivascular space (PVS) volume, the fraction of white matter free water (FW-WM), and diffusion tensor imaging along the perivascular space (DTI-ALPS) index. Group differences were evaluated using two-sample tests, and associations were assessed using partial Spearman’s rank correlations (ρ). Results In patients with TLE-HS, the DTI-ALPS index ( t = −2.65, P = 0.001), CPV/TIV ( t = −2.65, P = 0.001), and PVS score [χ 2 ,test χ 2 (3, N = 160) = 15.21, p = 0.0016] were significantly lower than in HCs, whereas the FW-WM ( t = 5.70, P < 0.001) was significantly higher. Additionally, longer disease duration was significantly correlated with a decrease in DTI-ALPS (ρ = −0.375, P = 0.001), an increase in FW-WM (ρ = 0.316, P = 0.001), and an enlargement of CPV (ρ = 0.378, P = 0.001). Furthermore, a reduction in hippocampal volume (HPV) was closely correlative with a decrease in DTI-ALPS (ρ = 0.226, P = 0.048) and an enlargement of CPV (ρ = −0.345, P = 0.002). Conclusion This study offers substantiated evidence of GS function in patients with TLE-HS using multiple MRI-derived indices of GS function. Moreover, longer disease duration was significantly associated with lower DTI-ALPS indices, higher FW-WM levels, and enlarged CPV, while reduced HPV was closely linked to decreased DTI-ALPS and increased CPV. These findings indicate that MRI-derived GS indices may serve as potential imaging biomarkers of disease chronicity in TLE-HS.