Differential glymphatic dysfunction and memory correlation in temporal lobe epilepsy subtypes

This study aims to evaluate the glymphatic system (GS) in different temporal lobe epilepsy (TLE) subtypes using diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) and to explore its correlation with clinical factors and memory performance.

The study encompassed 112 TLE patients with hippocampal sclerosis (TLE-HS), 73 TLE patients with no lesions on magnetic resonance imaging (TLE-NL), and 55 healthy controls. The DTI-ALPS index was calculated based on 3.0T diffusion tensor image sequences, and the memory performance was assessed using the Wechsler Memory Scale-Revised. The DTI-ALPS index was compared among the three groups, and its relationships with clinical characteristics and memory performance were explored.

TLE-HS group showed a significantly lower DTI-ALPS index compared with healthy controls in both hemispheres (ipsilateral: p < 0.001; contralateral: p = 0.002). By contrast, TLE-NL group exhibited a reduced DTI-ALPS index solely in the ipsilateral hemisphere (p < 0.001). Within TLE-NL cohort, those with a history of focal to bilateral tonic-clonic seizures showed reduced DTI-ALPS indices in both hemispheres (ipsilateral: p = 0.037; contralateral: p = 0.004). In the TLE-HS group, DTI-ALPS index positively correlated with memory performance (ps < 0.05). A multiple regression analysis indicated that the average DTI-ALPS index was significantly associated with memory quotient (β = 0.309, p < 0.001; R² = 0.226), independent of the ipsilateral hippocampal volume.

The patterns of reduced DTI-ALPS index differed between TLE-HS and TLE-NL patients. The extent of GS impairment in TLE-HS patients correlated with memory decline, suggesting its potential as a therapeutic target for memory enhancement.

This study employed the DTI-ALPS index, a neuroimaging marker, to assess glymphatic system function in distinct subtypes of temporal lobe epilepsy (TLE). Glymphatic impairment was observed in both TLE with hippocampal sclerosis (TLE-HS) and nonlesional TLE (TLE-NL), exhibiting distinct patterns. Notably, this dysfunction was associated with memory deficits, suggesting that targeting glymphatic clearance may represent a novel therapeutic strategy for memory improvement in epilepsy.