Date of Award

January 2026

Document Type

Open Access Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Imran Quraishi

Abstract

Drug-resistant focal epilepsy accounts for a significant portion of patients with epilepsy. These patients many times experience persistent seizures despite several ASM (anti-seizure medication) trials. RNS (Responsive neurostimulation) has demonstrated efficacy in reducing seizure frequency in patients that are resistant to drug trials, and provide continuous intracranial electroencephalographic monitoring. This longitudinal data may offer an opportunity to identify potential early biomarkers of ASM trial effectiveness, which could lead to quicker optimization of pharmacological therapy. This study in particular evaluated whether early changes in RNS-detection of seizure activity can predict a clinical response to ASMs in patients with drug-resistant focal epilepsy. We retrospectively analyzed a cohort of patients affiliated with Yale that were implanted with the RNS device. Medication trials initiated after implantation were identified from clinical records, and early response was assessed using RNS detection metrics and pre-defined windows. Through this, clinical response was defined as a greater than or equal to 50% reduction in seizure frequency in relation to each patient’s baseline. A total of 74 patients contributing multiple ASM trials were included for analysis. It was found that early reductions in RNS detected seizure activity (defined based on predefined detection metrics) correlated with an increased likelihood for a clinical response. Models that analyzed early percent changes in seizure detection showed a moderate ability to distinguish responders to ASM trials from non-responders. Nonetheless response varied between patients and medication trials. With these findings, it is suggested that data derived via RNS may provide potentially useful early indicators for ASM trial effectiveness. This data potentially may be incorporated into clinical practice, where earlier identification of ineffective trials would lead and support elevated patient care. Further validation of current analysis and prospective studies with larger cohorts are needed to validate these findings.

Comments

This is an Open Access Thesis.

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