Asymmetry in the diffusion tensor image analysis along the perivascular space index predicts seizure outcome in MRI-negative focal epilepsy

Abstract

Purpose We evaluated diffusion tensor image analysis along the perivascular space (DTI-ALPS) index asymmetry as an imaging correlate of glymphatic activity and its prognostic value in MRI-negative focal epilepsy. Methods We retrospectively studied 134 patients with MRI-negative focal epilepsy who underwent DTI (3T MRI) with >2-year follow-up. DTI-ALPS asymmetry index (AI) was calculated as |left-right|/mean. Multivariable logistic regression identified predictors of seizure freedom (SF; >1 year seizure-free) at last follow-up. Significant AI-correlated variables underwent mediation analysis. Cox proportional hazards models evaluated the association between DTI-ALPS AI and time to (1) first post-MRI SF and (2) final SF. Results Of the 134 patients (median age, 31 years; 72 female), 76 (57%) achieved SF at last follow-up. Compared to those without SF, patients with SF had significantly shorter epilepsy duration (median, 8 years vs. 15 years; p = 0.029), lower seizure frequency (median, 1 vs. 5; p < 0.001), and lower DTI-ALPS AI (median, 0.064 vs. 0.119; p < 0.001). In multivariable logistic regression, DTI-ALPS AI (odds ratio [OR] per 0.1 increase, 0.271; 95% confidence interval [CI], 0.135-0.493; p < 0.001) and seizure frequency (OR, 0.967; 95% CI, 0.940-0.992; p = 0.013) predicted SF at last follow-up. The effect of DTI-ALPS AI on long-term seizure outcomes was not significantly mediated by disease duration (average direct effect, -0.670; 95% CI, -0.841 to -0.486; p < 0.001; average causal mediated effect, -0.098; 95% CI, -0.259 to 0.056; p = 0.266). Patients with low DTI-ALPS AI (< 0.074) achieved SF earlier after MRI (p(Log-rank) = 0.012, p(Cox regression) = 0.006) and were more likely to be seizure-free at last follow-up (both p(Log-rank) and p(Cox regression) < 0.001). Conclusion Asymmetry in the DTI-ALPS index may reflect interhemispheric differences in glymphatic function that are driven by localized, lateralized seizure activity, and may thereby serve as a prognostic marker in MRI-negative focal epilepsy.