Invasive network neuromodulation for insular epilepsy: A three-center retrospective study

To characterize invasive neuromodulation for insular drug-resistant epilepsy, we retrospectively evaluated 22 patients treated with responsive neurostimulation (RNS; n = 14) or chronic subthreshold stimulation (CSS; n = 8). Stereoelectroencephalography was performed in 20 cases (91%). Median baseline seizure frequency was 10.5/month. Forty-one percent had prior epilepsy surgery. At year 3, median seizure reduction (MSR) was 83% (p = .01, Wilcoxon signed-rank test), with a responder rate (RR) of 77%; MSR was 92% for CSS and 75% for RNS. There were no significant differences in MSR (p ≥ .4) or RR (p > .9) when comparing RNS versus CSS. Three patients achieved seizure freedom by year 3. Patients undergoing combined insular-thalamic stimulation (n = 5) demonstrated an MSR of 84%, 86%, and 88% at 1, 2, and 3 years; seizure reduction in thalamocortical versus cortical-only stimulation was not different (p ≥ .1). Parasagittal lead trajectories achieved closer insular proximity than transopercular trajectories (p < .0001, Mann-Whitney U-test). Median charge density at last follow-up was 1.3 μC/cm². There were no acute surgical complications and all stimulation-related side effects resolved with programming adjustments. This study expands the limited literature on insular neuromodulation by demonstrating effectiveness of RNS and CSS, suggesting potential benefit from combined thalamocortical targeting, and defining parasagittal trajectories as a surgical approach for optimal lead proximity.