Seizure recurrence after prolonged seizure control: Patterns and risk factors

Abstract

OBJECTIVE\nTo identify the patterns and possible predictors of seizure recurrence after durable seizure freedom during maintenance of anti-seizure medication (ASM) treatment.\n\n\nMETHODS\nWe conducted a retrospective longitudinal study that identified all adult individuals with epilepsy (IWE) at the George Washington University outpatient epilepsy clinic between 1/1/2014 and 12/31/2016 who had been seizure free for at least 2\u202fyears. We followed up the patients until 5/30/2020 for seizure recurrence. The data were analyzed using survival analysis, univariate analysis, and multivariate regression with Cox proportional hazard model. Outcomes were dichotomized into seizure relapse and seizure freedom. The total number of relapses and triggers of the initial relapse for individual patient were also analyzed.\n\n\nRESULTS\nThis single-center cohort consisted of 220 IWE (age 21-80) of whom 99 patients had been seizure free for 2-3\u202fyears and 121 patients had been seizure free for more than 3\u202fyears. In this cohort, 48 patients (22%) experienced at least one seizure relapse during the span of the study. Of the relapsing patients, 25 (52%) had a single seizure relapse, and 8 (15%) had frequent seizure relapses (n\u202f≥\u202f5) and developed pharmacoresistance. Half of the initial seizure relapses occurred without a trigger. Among those with at least one year of follow-up after relapsing (n\u202f=\u202f33), 29 (86%) regained seizure freedom for at least 1\u202fyear. Among 26 patients with at least 2\u202fyears of follow-up, only 14 (55%) regained at least 2\u202fyears of seizure freedom. Previous longer duration of seizure freedom and ASM monotherapy predicted less chances of seizure relapse and fewer seizure numbers after relapse. No difference in prognosis was noted among relapsing patients between those with or without triggers.\n\n\nSIGNIFICANCE\nPatients with well-controlled epilepsy may have seizure relapses with or without identifiable triggers. Most patients regained at least 1-year seizure freedom after the initial relapse, whereas about half patients reachieved 2-year seizure remission. About 15% of the relapsing patients may subsequently develop pharmacoresistance. Prognostic factors of seizure recurrences include duration of initial seizure remission and the number of ASMs used during remission. The presence of identifiable triggers for the initial seizure relapse does not predict future outcome.