Differential glymphatic dysfunction and memory correlation in temporal lobe epilepsy subtypes

Abstract

Objective: 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.

Methods: 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.

Results: 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.

Significance: 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.

Plain language summary: 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.

Keywords: glymphatic system; hippocampal sclerosis; memory; no lesions on magnetic resonance imaging; temporal lobe epilepsy.