Abstracts

Rationale: Responsive neurostimulation (RNS System) has emerged as an effective treatment modality for drug-resistant focal epilepsy; however, its interaction with anti-seizure medications (ASMs) remains poorly understood. ASMs operate through a diverse set of mechanisms, yet the synergistic or antagonistic effects when combined with neuromodulation have only recently become a focus of investigation. A better understanding of these interactions may inform more effective combination therapies and improve clinical outcomes. In this study, we examine the relationship between ASM mechanisms of action and patient response to RNS System therapy across seizure onset zones.

Methods: The RNS System Post-Approval Study (PAS) 3-year dataset included 324 implanted patients, composed of 178 with mesial temporal onsets (MTL), 110 with neocortical onsets, and the remainder with both MTL and neocortical onsets. Patient outcomes were assessed by seizure diary entries, and outcomes were divided into 90-day intervals for analysis. Medications were categorized by mechanism of action and included in an epoch if administered for more than 45 days within that period. If multiple medication categories were used concurrently during an epoch, the epoch was included in each relevant category.

Results: Analysis of seizure outcomes by medication category revealed distinct patterns between epilepsy onset zones. In the mesial temporal lobe (MTL) patients, no significant differences in seizure reduction were observed across medication categories (p=0.75, Kruskal-Wallis; Figure 1A). However, neocortical patients showed significant differences across the medication classes (p=0.0089, Kruskal-Wallis). Sodium channel blockers were associated with significantly better outcomes than GABA potentiators (p=0.007, Dunn’s post-hoc; Figure 1B), and approached significance relative to SV2A Modulators (p=0.06, Dunn’s post-hoc; Figure 1B).

Conclusions: These results suggest that tailoring medication selection to seizure onset zones may improve the effectiveness of combined RNS System and ASM therapy, while also providing a foundation for future mechanistic studies. Understanding these differential responses could inform more targeted treatment strategies to enhance clinical outcomes.

Funding: Not applicable.