Prognosis of acute symptomatic seizures and impact of prolonged treatment with anti‐seizure medication

Abstract Objectives Acute symptomatic epileptic seizures (ASySs) occur in temporal proximity to acute brain insults. Given their low risk of subsequent unprovoked seizures, current guidelines recommend either no treatment with anti‐seizure medication (ASM) or early discontinuation, yet ASM treatment is often continued beyond hospital discharge. We aimed at investigating the cumulative 3‐year risk and predictors of unprovoked seizures after ASySs and assessing the effect of ASM treatment duration. Methods The prospective, multicenter register on the prognosis of acute symptomatic seizures (PROSE register) recruited adults with clinically apparent, acute symptomatic, first‐ever epileptic seizure, excluding status epilepticus. Primary endpoint was occurrence of a first unprovoked seizure. The impact of ASM treatment duration was assessed through a Cox regression correcting for treatment selection bias. The chance of occurrence of a seizure in the next year (COSY) was calculated to evaluate driving eligibility. Results The 3‐year cumulative incidence of unprovoked seizures was 14% [95% confidence interval (CI): 7%–21%] among 122 participants with structural etiologies. Male sex (hazard ratio [HR] 9.3; 95% CI 19–45.1), early epileptiform electroencephalography (EEG) activity (HR 7.4; 95% CI 1.8–31.1), and latency ≥48 h between onset of underlying condition and ASyS (HR 4.8; 95% CI 1.3–18.1) were independently associated with unprovoked seizures. ASM treatment duration had no apparent effect (HR 1; 95% CI 1–1; p = .84). The initial COSY was 10% and fell below 2% within 2 years. Significance Even in structural etiologies, ASySs bear a relatively low risk of later unprovoked seizures. There is still no evidence favoring prolonged ASM treatments. These findings may help preventing ASM overtreatment and guide counseling on driving eligibility.