Responsive neurostimulation leads targeting intracranial sites with ictal high‐frequency oscillation onset patterns are associated with better 2‐year seizure control outcomes

Abstract Objective Responsive neurostimulation (RNS) offers an effective and safe treatment for people living with refractory focal‐onset epilepsy. Many RNS candidates need intracranial electroencephalography (IEEG) monitoring to locate seizure‐onset zones (SOZs), which is a difficult procedure with variable yields. High‐frequency oscillations (HFOs) are a common ictal‐onset feature, and our study seeks to explore ictal HFOs as a marker for targeting RNS. Methods We screened patients who underwent IEEG then RNS implantation at our center from 2015 to 2022. While blinded to outcomes, we analyzed IEEG using standard clinical software to detect ictal HFO‐onset patterns at the previously identified onsets. Then we examined RNS lead placement in relation to the SOZs and seizure control outcomes after 2 years post‐implantation. Results A total of 62 patients received RNS during the study period. Excluding those patients with insufficient follow‐up and combined surgeries (RNS + resection/ablation), 33 patients remained. At 2 years, 26 (~78.8%) had ≥50% seizure reduction, and 7 (~21.2%) were free of debilitating seizures (super‐responders). We excluded an additional 8 patients due to having skipped IEEG and early explantation, leaving 25 study subjects. Ictal HFOs were present in all SOZs for 17 patients, and 14 patients (including all 7 super‐responders) had RNS leads implanted in all of these SOZs. When ictal HFOs were absent or not covered by RNS leads, the patients did not achieve seizure freedom. There was a statistically significant association between targeting SOZs with ictal HFO onsets and outcomes (Fisher's exact test p ‐value 0.0078). Significance Our results suggest that ictal HFOs provide additional localization value. Ictal HFOs represent very local epileptiform activity that may reflect closer proximity to epileptogenic tissue than conventional features such as spiking and slower rhythms. Because stimulation acts by focal tissue activation, increased targeting precision may be more important in RNS than surgeries such as resection or ablation.