Glymphatic Dysfunction in Mesial Temporal Lobe Epilepsy: Insights From DTI-ALPS Index and FDG-PET

While recent studies have linked glymphatic function to PET-based molecular and metabolic markers, its relationship with cerebral glucose metabolism in mesial temporal lobe epilepsy (MTLE) remains unclear. We investigated glymphatic function using diffusion tensor image analysis along the perivascular space (DTI-ALPS), characterized FDG-PET metabolic alterations, and assessed their interrelationship in MTLE.

Thirty patients with drug-resistant unilateral MTLE undergoing stereo-electroencephalography (SEEG) implantation and sixteen matched healthy controls were retrospectively analyzed. All patients underwent preoperative MRI, diffusion-weighted imaging, and ¹⁸F-FDG PET. Glymphatic function was quantified using bilateral and global DTI-ALPS indices. Glucose metabolism in medial temporal lobe regions was assessed using standardized uptake value ratios (SUVR) and asymmetry index. Group comparisons were performed using nonparametric tests, and associations between ALPS and PET measures were evaluated using Spearman correlation.

Patients with left MTLE exhibited significantly reduced bilateral and global DTI-ALPS indices compared with both healthy controls and right MTLE patients, whereas right MTLE patients did not differ from controls. FDG-PET demonstrated marked ipsilateral medial temporal hypometabolism in all MTLE patients, with comparable metabolic asymmetry between left and right MTLE. Strong interhemispheric correlations were observed for bilateral ALPS indices and SUVR values. However, no significant correlations were found between ALPS indices and PET-derived metabolic measures.

MTLE is associated with both glymphatic-related microstructural alterations and focal metabolic dysfunction, which appear to be dissociable. These findings suggest that glymphatic impairment and glucose hypometabolism reflect complementary but distinct pathophysiological mechanisms in MTLE.