The decision to initiate treatment in patients with a first unprovoked seizure remains controversial. Studies have reported a recurrence rate ranging from 21-50%, but most have included patients with different etiologies, EEG findings, and seizure types. This study aimed to determine the risk of recurrence in patients with a first unprovoked generalized tonic-clonic (GTC) seizure with evidence of generalized spike-wave discharges (GSWD) on EEG and compare the efficacy of antiseizure medications (ASM) in preventing recurrence. This prospective study included consecutive patients who presented with a single GTC seizure, evidence of GSWD on EEG, and a follow-up period of at least one year. All patients underwent extensive evaluation, including a 3-hour sleep-deprived video-EEG recording and an epilepsy protocol brain MRI. Treatment with ASM was recommended for all patients. The decision regarding the specific ASM to be used was left to the treating physician's discretion. A total of 57 patients with a median age of 19 years were included. A total of 41 patients agreed to be started on an ASM while 16 declined. Seizure recurred in 6/41 (14.6%) patients in the treated group compared to 11/16 (68.8%) in the untreated group (P = 0.00006). Valproate was significantly more efficacious than levetiracetam or lamotrigine (P = 0.04). Of the 15 patients who discontinued ASM treatment after remaining seizure free for an average of 30 months, 6 (40%) experienced a seizure recurrence. Patients with a first unprovoked GTC seizure and evidence of GSWD on EEG have a high risk of recurrence if left untreated. Valproate is the most efficacious ASD for preventing recurrence in this population. A sizeable proportion of patients can be successfully tapered off medication after a period of seizure freedom. This study provides valuable information for guiding treatment decisions in this patient population.
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