Preoperative correlations between glymphatic function and glucose metabolism in drug-resistant temporal lobe epilepsy: divergent patterns and postoperative outcomes

Brain glymphatic dysfunction may impair cerebral metabolism and contribute to surgical prognosis in Temporal Lobe Epilepsy (TLE). To evaluate presurgical glymphatic dysfunction in TLE using the diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) index and determine its correlation with cerebral glucose metabolism in patients with different surgical outcomes. This retrospective study included drug-resistant TLE patients (n = 123) and controls (n = 48) who underwent preoperative 3.0-T MRI with DTI and ¹⁸F-FDG PET/CT. Based on postoperative seizure outcomes (Engel class Ia vs. Ib–IV), patients were classified into seizure-free (SF) (n = 83) and non–seizure-free (NSF) (n = 40) groups. Comparisons of the ipsilateral, contralateral, and mean ALPS indexes (ips-ALPS, con-ALPS, and mean-ALPS), and standardized uptake value ratio (SUVR) maps were performed among three groups. General linear regression analysis between the ALPS indexes and SUVR maps was conducted in SF and NSF group respectively. Metabolic network parameters were evaluated in the TLE cohort, and the correlations between ALPS indexes and metabolic network parameters were calculated. Compared to healthy controls (HC), both the patient groups showed lower ips-ALPS and mean-ALPS (both p < 0.05). The ips-ALPS and mean-ALPS demonstrated a progressive decline across groups in the order: HC > SF > NSF. No significant differences in SUVR or metabolic network parameters were observed between SF and NSF groups. However, surgical outcome–dependent correlation patterns were identified: in the SF group, ips-ALPS was correlated with regional SUVR of multiple brain areas (GRF corrected, voxel p < 0.005 and cluster p value < 0.05), and the ips-ALPS related hypometabolic regions were localized to the ipsilateral frontal and cingulate areas; whereas in NSF group, ips-ALPS was correlated with metabolic network parameters including \:λ\: (r =-0.37, p = 0.017), Lp (r =-0.36, p = 0.023), and Eglo (r = 0.38, p = 0.016). In drug-resistant TLE, preserved glymphatic-metabolic coupling is associated with seizure freedom and a shift toward network-level covariance indicates a poorer prognosis. Glymphatic dysfunction is more severe in non-seizure-free TLE patients, indicating its preoperative prognostic value. TLE patients with different postoperative outcomes show divergent preoperative patterns: seizure-free patients show regional glymphatic-metabolic coherence, while non-seizure-free patients display disrupted global network efficiency, which is correlated with the extent of glymphatic dysfunction.