Are brief febrile seizures benign? A systematic review and narrative synthesis

Abstract

Febrile seizures affect 2%–5% of U.S. children and are considered benign although associated with an increased risk of epilepsy and, rarely, with sudden unexplained death. We compared rates of mortality, neurodevelopmental disorders, and neuropathology in young children with simple and complex febrile seizures to healthy controls. We systematically reviewed studies of 3‐ to 72‐month‐old children with simple or complex febrile seizures ≤30 min. We searched studies with outcome measures on mortality, neurodevelopment, or neuropathology through July 18, 2022. Bias risk was assessed per study design. Each outcome measure was stratified by study design. PROSPERO registration is CRD42022361645. Twenty‐six studies met criteria reporting mortality (11), neurodevelopment (11), and neuropathology (13), including 2665 children with febrile seizures and 1206 seizure‐free controls. Study designs varied: 15 cohort, 2 cross‐sectional, 3 case–control, 5 series, and 1 case report. Mortality outcomes showed stark contrasts. Six cohort studies following children after febrile seizure (n = 1348) reported no deaths, whereas four child death series and 1 case report identified 24.1% (108/449) deaths associated with simple (n = 104) and complex (n = 3) febrile seizures ≤30 min. Minor hippocampal histopathological anomalies were common in sudden deaths with or without febrile seizure history. Most electroencephalography (EEG) studies were normal. Neuroimaging studies suggested increased right hippocampal volumes. When present, neurodevelopmental problems usually preexisted febrile‐seizure onset. Risk bias was medium or high in 95% (18/19) of cohort and case–control studies vs medium to low across remaining study designs. Research on outcomes after simple or brief complex febrile seizures is limited. Cohort studies suffered from inadequate sample size, bias risk, and limited follow‐up durations to make valid conclusions on mortality, neurodevelopment, and neuropathology. Sudden death registries, focused on a very small percentage of all cases, strongly suggest that simple febrile seizures are associated with increased mortality. Although most children with febrile seizures have favorable outcomes, longer‐term prospective studies are needed.

Febrile seizures in pediatric practice: Risk factors, clinical manifestations, and intensive therapy

“…ФС представляют собой серьёзную проблему в педиатрической практике из-за их высокой распространённости у детей раннего возраста, склонности к рецидивам и частой госпитализации [4]. Хотя ФС считаются доброкачественным неврологическим состоянием они могут быть связаны с повышенным риском трансформации в эпилепсию и, реже, с внезапной смертью, причём развитие данных осложнений возрастает с каждым новым рецидивом ФС [9,14,15]. Недавние исследования выявили положительную корреляцию между ФС, когнитивным дефицитом и нарушениями памяти у детей [16].…”

Clinical features of febrile seizures in children with COVID-19: an observational study from a tertiary care hospital in China

“…Febrile seizures have been categorized as simple febrile seizures and complex febrile seizures. Simple febrile seizures are usually considered to have a good prognosis, whereas complex febrile seizures are associated with recurrent febrile seizures, epilepsy, and neurologic deficits (3,4). There is a genetic predisposition to febrile seizures.…”