Risk of breakthrough seizures depends on type and etiology of epilepsy

Objective This study was undertaken to analyze whether the rate of breakthrough seizures in patients taking antiseizure medication (ASM) who have been seizure‐free for at least 12 months varies among different types and etiologies of epilepsy. Given the relative ease of achieving seizure freedom with ASM in patients with post‐ischemic stroke epilepsy, we hypothesized that this etiology is associated with a reduced risk of breakthrough seizures. Methods We defined a breakthrough seizure as an unprovoked seizure occurring while the patient was taking ASM after a period of at least 12 months without seizures. Data were analyzed retrospectively from a tertiary epilepsy outpatient clinic. Patients were eligible for inclusion if they either had a breakthrough seizure at any time or a seizure‐free interval of at least 2 years. Our primary endpoint was rate of breakthrough seizures. We conducted univariable and multivariable analyses to identify variables associated with breakthrough seizures. Results Of 521 patients (53% females, median age = 49 years) included, 29% had a breakthrough seizure, which occurred after a median seizure‐free interval of 34 months (quartiles = 22, 62). When controlling for clinically relevant covariates, breakthrough seizures were associated with post‐ischemic stroke epilepsy (odds ratio [OR] = .267, 95% confidence interval [CI] = .075–.946), genetic generalized epilepsy (OR = .559; 95% CI = .319–.978), intellectual disability (OR = 2.768, 95% CI = 1.271–6.031), and the number of ASMs previously and currently tried (OR = 1.203, 95% CI = 1.056–1.371). Of the 151 patients with breakthrough seizures, 34.3% did not reachieve terminal 12‐month seizure freedom at the last visit. Significance This is the first study to show an association between type and etiology of epilepsy and risk of breakthrough seizures. Our data suggest that epilepsies in which seizure freedom can be obtained more easily also exhibit a lower risk of breakthrough seizures. These findings may help to better counsel seizure‐free patients on their further seizure prognosis.