Longitudinal association of subjective sleep quality and health-related quality of life improvements with Vagus nerve stimulation in drug-resistant epilepsy: a 24-month retrospective cohort study.

OBJECTIVE: To evaluate the longitudinal trajectories of subjective sleep quality and health-related quality of life (HRQOL) over a 24-month period in adult patients with drug-resistant epilepsy (DRE) following vagus nerve stimulation (VNS) implantation, and to explore the adjusted longitudinal association of these improvements alongside concurrent seizure-frequency reduction. METHODS: This retrospective cohort study consecutively enrolled 29 adult patients (≥18 years) with DRE who underwent VNS implantation. Data regarding seizure frequency, Pittsburgh Sleep Quality Index (PSQI), and Quality of Life in Epilepsy-31 (QOLIE-31) scores were extracted from medical records at baseline, 6, 12, and 24 months post-implantation. Repeated-measures analysis of variance (RM-ANOVA) and generalized estimating equations (GEE) were utilized to assess temporal trends and adjust for concurrent seizure frequency (as a continuous, time-varying covariate) and baseline psychiatric comorbidities. RESULTS: Over the 24-month follow-up, the cohort demonstrated a significant and progressive reduction in mean monthly seizure frequency. Concurrently, profound and sustained improvements were observed in both overall PSQI scores and total QOLIE-31 scores (all p < 0.001). Crucially, the re-analyzed GEE model revealed that the temporal improvements in sleep and HRQOL demonstrated a significant adjusted longitudinal association with VNS therapy. The time factor remained a highly significant predictor for improvements in both PSQI and QOLIE-31 (p < 0.01 for all time points) even when continuously adjusting for concurrent seizure frequency and baseline psychiatric comorbidities. CONCLUSION: VNS therapy provides significant, progressive, and sustained improvements in subjective sleep quality and overall HRQOL in adult patients with DRE. Furthermore, these neurobehavioral benefits demonstrate a robust adjusted longitudinal association that is not exclusively tethered to the degree of seizure-frequency reduction. However, causality and complete physiological independence cannot be established due to the observational, uncontrolled design.