Rationale:
Despite a growing body of evidence supporting a potential association between impaired glymphatic system and epilepsy, the exact role of glymphatic dysfunction in the prognosis of epilepsy remains elusive. Visual rating of the MRI-visible enlarged perviascular space (EPVS) is a relatively simple method of assessing glymphatic dysfunction. This study aimed to investigate the regional EPVS burden in treatment-naïve patients with temporal lobe epilepsy with hippocampal sclerosis (TLE-HS) and further investigate the prognostic relevance.
Methods:
In this retrospective study, EPVS located in the basal ganglia (BG-EPVS), centrum semiovale (CS-EPVS), and temporal lobe (T-EPVS) were visually rated in 79 treatment-naïve patients with TLE-HS who underwent brain magnetic resonance imaging (MRI) before or within one month after initiation of antiseizure medication (ASM) treatment. The burden of regional EPVS was dichotomized into high and low degrees (cut points of >10 for BG-EPVS / T-EPVS and >20 for CS-EPVS). Seizure freedom (SF) was defined as no seizures including auras for >1 year, and the refractory group consisted of patients with persistent uncontrolled seizures without any SF during the follow-up period. Differences in demographics, seizure-related clinical variables, and regional EPVS burden were compared between the refractory and non-refractory groups. Multiple logistic regression models were constructed to investigate whether the regional EPVS burden may predict the prognosis of TLE-HS.
Results:
Of the 79 patients, 22 were in the refractory group and 57 were in the non-refractory group. The refractory group had a higher proportion of females, patients with aura, and patients with right-sided HS. The seizure frequency in the three months prior to the first visit, total number of ASMs used, and number of patients who underwent temporal lobectomy were significantly higher in the refractory group than in the non-refractory group. However, the three regional EPVS burden did not significantly differ between the refractory and non-refractory group. In a multiple logistic regression analysis adjusting for sociodemographic variables (age at MRI and sex) and T-EPVS, lower age at MRI (odds ratio [OR], 0.953; 95% confidence interval [CI], 0.910–0.999), female sex (OR, 3.827; 95% CI, 1.241–11.796), and high-degree T-EPVS (OR, 4.001, 95% CI, 1.108–14.443) were found to be risk factors for poor medical treatment outcome in TLE-HS. In another multiple logistic regression model adjusting for age at MRI, sex, presence of aura, right-sided HS, and T-EPVS, presence of aura (OR, 6.363; 95% CI, 1.397–28.979), right-sided HS (OR, 4.526; 95% CI, 1.297–15.795), and high-degree T-EPVS (OR, 5.135; 95% CI, 1.237–21.309) were independent predictors of poor prognosis in TLE-HS.
Conclusions:
The high T-EPVS burden observed before or shortly after initiation of medical treatment appears to serve as a potential imaging marker indicating poor prognosis in patients with TLE-HS, especially when adjusted for age. Considering that high EPVS burden may indicate glymphatic dysfunction, further studies with more patients are needed to confirm this finding.
Funding:
Nothing to report.