Evaluating Clinical Presentation and Long-Term Outcomes in Individuals with Genetic and Non-Genetic Epilepsy Treated with Epilepsy Surgery: A Single-Center Study

Abstract

AbstractBackgroundMany genetic epilepsy disorders are characterized by focal epilepsy or exhibit focal or lateralized features, which make individuals with such conditions potential surgical candidates. However, surgical outcomes in epilepsy caused by germline genetic variants and value of genetic testing in presurgical assessment remains unclear.MethodsThis retrospective cross-sectional study included people with germline genetic epilepsy and non-genetic epilepsy identified among 2879 people with epilepsy who underwent resective surgery or laser ablation at Cleveland Clinic in years 1997-2022. We separated individuals with germline genetic epilepsies into mTORopathies (clinically or genetically diagnosed tuberous sclerosis and genetically diagnosed GATOR-related epilepsies) and other genetic etiologies. We compared clinical variables between the groups using Kruskal-Wallis and Fisher tests as appropriate. We analyzed cumulative seizure recurrence risk over 5 years with Kaplan-Meier curves and used Cox proportional hazards model for univariate and multivariate analysis. We repeated the analysis after matching both genetic sub-groups to non-genetic group 1:1 by propensity scores estimated by a generalized linear model.ResultsWe included 49 individuals with genetic epilepsies (32 individuals with mTORopathies and 17 individuals with other genetic etiologies) and 585 individuals with non-genetic epilepsy. Individuals with genetic epilepsies in both groups were younger at seizure onset (p<0.001) and at surgery (p<0.001), had a higher preoperative seizure frequency (p<0.001), higher rate of developmental delay (p<0.001), lower rate of focal interictal (p=0.005) and ictal (p<0.001) findings on EEG, and more extratemporal and extensive resections (p<0.001). At the last follow-up, individuals with other genetic etiologies had a lower rate of seizure freedom than individuals with mTORopathies and non-genetic etiologies; still, 70.6% achieved seizure reduction. Individuals with other genetic etiologies had a higher cumulative risk of seizure recurrence at 5 years both in univariate (HR 3.07, 95% CI 1.4-6.74) and multivariate (HR 3.81, 95% CI 1.69-8.62, p=0.001) analyses, which was reproducible in a matched cohort analysis.ConclusionsPeople with germline genetic epilepsy across multiple etiologies could be surgical candidates. However, seizure recurrence may be faster in genetic epilepsies other than mTORopathies. Further studies are required to clarify surgical candidacy in different genetic epilepsy disorders and establish value of presurgical genetic testing.