Authors :
Presenting Author: Cynthia Peng, MD – Stanford University School of Medicine
David Lee, BAS – Johns Hopkins University School of Medicine
Yi Li, MD, PhD – Stanford University
Rationale:
Epilepsy surgery is increasingly considered for patients with genetic epilepsy as genetic testing becomes more integrated into presurgical evaluation. While some etiologies, such as mTORopathies, are linked to favorable outcomes, others (e.g., channelopathies, synaptopathies) may respond less well (Seizure 2024; 120:124-134). However, current evidence remains limited, with most studies being small, retrospective, and lacking long-term follow-up—leaving gaps in understanding optimal surgical selection and outcomes in this population.Methods:
We conducted a retrospective chart review of patients seen at the Stanford Comprehensive Epilepsy Center from 2018 to 2024, using the Stanford Research Repository Tool (IRB: 51397). Inclusion criteria were an epilepsy diagnosis (ICD-10 G40.*), documentation of “genetic epilepsy” or “genetic testing,” or relevant lab results. We performed chart review and extracted data on demographics, seizure characteristics, genetic test results, surgical interventions, and surgical outcome by Engel Surgery Outcome Scale (ESOS). The interventions included resection, lesionectomy, corpus callosotomy, laser ablation, vague nerve stimulation (VNS), responsive neurostimulation (RNS), and deep brain stimulation (DBS). Fisher’s exact tests evaluated associations between seizure freedom (ESOS I) and surgical approach or variant status.Results:
Among 514 patients who underwent genetic testing (62% had panel testing; 25% had whole exome/genome sequencing), 113 underwent epilepsy surgery. Of these, 56 (49.5%) had a confirmed genetic epilepsy diagnosis with a pathogenic variant. Among surgical patients, epilepsy type, number of surgeries, and type of intervention did not significantly differ by variant status.
At last follow-up (mean 6±6 years after surgery), ESOS I was achieved in 18% of the genetic epilepsy group and 26% of the non-genetic epilepsy group (p=0.3). Subgroup analyses by surgical approach did not reveal significant differences in outcomes between the two groups.
However, despite similar surgical outcomes between patients with and without confirmed genetic epilepsy, patients who received neurostimulation (VNS, RNS, or DBS) had significantly lower rates of seizure freedom compared to those who underwent other procedure types (p< 0.001). This association remained significant when stratified by variant status (within genetic epilepsy group p< 0.001; non-genetic epilepsy group: p=0.002).