Alterations in glymphatic system and brain morphology in patients with temporal lobe epilepsy

Although the diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) method has been widely applied to gauge glymphatic function in temporal lobe epilepsy (TLE), glymphatic microstructure remains underexplored. Furthermore, the choroid plexus and ventricles are key elements of the brain clearance network. This study aimed to comprehensively evaluate changes in ALPS indices alongside hippocampal, choroid plexus, and lateral ventricular volumes in unilateral TLE. We recruited 14 healthy controls (HCs) and 30 TLE patients, including 16 left TLE (LTLE) and 14 right TLE (RTLE) patients. We evaluated differences in ALPS indices and morphological metrics, including hippocampal volume/total intracranial volume (HV/TIV), choroid plexus volume/TIV (CPV/TIV), lateral ventricular volume/TIV (LVV/TIV), and their asymmetry indices (AIs), between TLE patients and HCs. Furthermore, we assessed correlations among ALPS indices, morphological metrics, and clinical characteristics in TLE patients. Compared to HCs’ bilateral means, TLE patients exhibited significantly decreased ipsilateral HV/TIV (p = 0.003); both ipsilateral and contralateral CPV/TIV (p = 0.039 and p = 0.042 respectively) and LVV/TIV (p = 0.030 and p = 0.032 respectively) were significantly increased; both the ipsilateral DTI-ALPS and diffusion kurtosis imaging analysis along the perivascular space (DKI-ALPS) indices were significantly decreased (p = 0.011 and 0.008 respectively). In LTLE patients, only AI of the DKI-ALPS index showed a significant increase (p < 0.001). Within the RTLE group, AI of HV/TIV correlated with both onset age and disease duration (p = 0.009 and p = 0.008 respectively). In the TLE cohort, correlations were observed between onset age and both ipsilateral HV/TIV and AI of CPV/TIV (both p < 0.05). Furthermore, AI of HV/TIV was positively associated with disease duration (p = 0.011), and AI of LVV/TIV was positively linked to seizure frequency (p = 0.032). Our study demonstrated alterations beyond hippocampal atrophy in TLE, involving the brain waste clearance network. LTLE and RTLE might exhibit distinct alteration patterns. These findings could provide new insights into TLE pathogenesis.