Quantitative Electrocorticographic Biomarkers of Clinical Outcomes in Mesial Temporal Lobe Epileptic Patients Treated with the RNS® System

Objectives: Find interictal electrocorticographic (ECoG) biomarkers of clinical outcomes in mesiotemporal lobe (MTL) epilepsy patients.

Methods: In the NeuroPace® RNS® System clinical trials with 256 patients, 20 MTL patients with the most reduction in clinical seizures at Year 7 compared to baseline (upper response quartile; -96.5% median change) and 20 with the least reduction in clinical seizures (lower response quartile; -17.4% median change) were evaluated. Clinical and interictal ECoG features from the two response quartiles were compared.

Results: Demographic and clinical features were similar in the upper and lower response quartiles. Interictal spike rate (ISR) was substantially lower (p < 0.0001) in the upper quartile patients, while normalized theta (4-8 Hz) and normalized gamma (>25 Hz) were also different (p < 0.05) between the two response quartiles. ISR was positively correlated (p < 0.05) with clinical seizure rates in 71% of the channels analyzed. ECoG records captured during months with no clinical seizures had the lowest ISR.

Conclusions: ISR is a strong differentiator of clinical response in MTL patients. Normalized theta and gamma also differentiates clinical response.

Significance: In MTL patients, the interictal spike rate along with spectral power computed from chronic ambulatory baseline ECoGs may serve as biomarkers of clinical outcomes and maybe used as treatment endpoints.