Thalamic Volume Asymmetry as a Potential Predictor of Vagus Nerve Stimulation Outcomes in Refractory Epilepsy

Vagus nerve stimulation is an established treatment for refractory epilepsy, but predictors of treatment response remain unclear. Given that left-sided vagus nerve stimulation preferentially modulates the left thalamus and that epileptic networks induce thalamic structural damage, we investigated whether preoperative thalamic volume asymmetry predicts vagus nerve stimulation outcomes. This retrospective study included 17 patients with refractory epilepsy who underwent vagus nerve stimulation implantation. Patients were classified as responders (≥50% seizure reduction at 24 months, n = 9) or non-responders (n = 8). Thalamic volumes were manually segmented on preoperative T2-weighted magnetic resonance imaging by 2 blinded raters, and we used the rater-averaged values to calculate the left/right volume ratio and asymmetry index. The mean thalamic volume ratio (left/right) was significantly higher in responders than non-responders (1.00 [95% confidence interval 0.97-1.03] vs 0.96 [95% confidence interval 0.92-0.99], p = 0.027), and the asymmetry index also differed between groups (0.00 [95% confidence interval -0.015 to 0.017] vs -0.023 [95% confidence interval -0.040 to -0.006], p = 0.027). Inter-rater reliability was acceptable for absolute volumes but was lower for ratio-based asymmetry indices, suggesting that these derived metrics may be more suitable for group-level comparisons than for single-patient prediction. Epileptogenic laterality determined by electroencephalography did not predict thalamic asymmetry. Relative left thalamic volume reduction was associated with poor vagus nerve stimulation treatment response. Assessment of preoperative thalamic asymmetry on routine structural magnetic resonance imaging may represent a candidate biomarker for predicting vagus nerve stimulation efficacy, pending validation in larger cohorts.