Association between epilepsy duration and glymphatic dysfunction assessed by DTI-ALPS: A systematic review and meta-analysis

Abstract

Objective: To systematically evaluate whether epilepsy duration is associated with glymphatic dysfunction as measured by diffusion tensor image analysis along the perivascular space (DTI-ALPS). Methods: A systematic review and correlation-based meta-analysis were conducted in accordance with PRISMA guidelines. PubMed, Embase, Scopus, Web of Science, and Google Scholar were searched from inception through January 20, 2026, for observational studies reporting correlations between epilepsy duration and DTI-ALPS values. Correlation coefficients were pooled using random-effects models after Fisher's z transformation. Subgroup analyses and meta-regression were performed to explore heterogeneity. Results: Ten observational studies comprising 449 patients with epilepsy were included. Pooled analysis demonstrated a significant negative association between epilepsy duration and the DTI-ALPS index (r = -0.37, 95% confidence interval [CI]: -0.53 to -0.19), indicating lower glymphatic function with longer disease duration. A significant association persisted in temporal lobe epilepsy (r = -0.30, 95% CI: -0.54 to -0.02) and was stronger in late-onset epilepsy (r = -0.68, 95% CI: -0.79 to -0.54). Meta-regression identified age as a significant moderator of effect size, whereas mean disease duration did not significantly explain variability. Sensitivity analyses confirmed the robustness of findings, and no publication bias was detected. Conclusion: Longer epilepsy duration is associated with greater glymphatic dysfunction as measured by DTIALPS. Age significantly modulates this relationship, suggesting that seizure chronicity and aging-related vulnerability may synergistically influence perivascular clearance pathways. These findings support DTI-ALPS as a promising non-invasive marker of cumulative glymphatic burden in epilepsy and provide a quantitative framework for future longitudinal studies.