Comparison of Temporal Lobe Epilepsy Outcomes With Open-Loop Thalamic Versus Closed-Loop Hippocampal Neurostimulation Strategies

Introduction: Bilateral temporal lobe epilepsy (TLE) is unamenable to surgical resection. Closed-loop responsive neurostimulation (RNS) of bilateral temporal lobes and open-loop deep brain stimulation (DBS) of the anterior thalamic nucleus (ANT) are both approved treatments for such patients. Seminal studies demonstrated seizure freedom rates of 18.4% with RNS and 16% with DBS. Our institutional series has a higher-than-expected rate of seizure freedom amongst ANT DBS patients, so we compared the two treatment strategies to identify factors associated with seizure freedom.

Methods: Retrospective chart review of patients treated with bi-hippocampal RNS and ANT DBS from 2014-2023 was performed. Postoperative seizure frequency was determined by patients’ epileptologists. LeadDBS was used to generate volume of tissue activated (VTA) models using patient-specific stimulation settings. Clinical seizure outcomes were compared between open (DBS) & closed-loop (RNS) cohorts, with 6 months minimum follow-up.

Results: Of 10 patients treated with bilateral ANT DBS, 6 had bitemporal seizures. 4/6 (67%) achieved seizure freedom (median follow-up: 25.9 months; median seizure-free duration: 22.5 months). Of 23 patients treated with closed-loop bi-hippocampal RNS, 21 had bitemporal seizures. 5/21 (24%) patients achieved seizure freedom (median follow-up: 56.9 months; median seizure-free duration: 12 months). VTA analysis of DBS patients revealed a Sweetspot intersecting with anterior ANT, corroborating published literature. VTA analysis of RNS patients showed a Sweetspot within hippocampal body and head.

Conclusion : In our cohort, open-loop ANT DBS resulted in higher seizure freedom rate than closed-loop bi-hippocampal RNS in patients with bitemporal epilepsy. Higher-than-published rate of seizure freedom (67%) in the DBS cohort is associated with stimulation of the anterior ANT. Improved seizure outcomes with hippocampal RNS are associated with stimulation of hippocampal head and body. Analysis of presurgical factors & structural connectivity that may explain this outcome are underway. Further generalization of our results will require a larger sample size.