Risk factors for acute encephalitis and early seizure recurrence in complex febrile seizures

Eur J Pediatr. 2022 Aug;181(8):3103-3110. doi: 10.1007/s00431-022-04529-1. Epub 2022 Jun 17.


The purpose of this study is to elucidate risk factors for central nervous system infection and early seizure recurrence in children with febrile seizures (FSs) and thus facilitate outpatient management of complex FS. This single-center, retrospective cohort study investigated 688 children (6-60 months old) with FSs in Japan during 2011-2021. We investigated the incidence and clinical manifestations of children with acute encephalitis or bacterial meningitis. Logistic regression modeling was used to examine risk factors for seizure recurrence within 24 h. Among children with recurrent FSs, the distribution of intervals between first and second FS was assessed. Among 145 children with complex FSs, 2 patients (1.4%) had acute viral encephalitis and none had bacterial meningitis. Acute encephalitis was found in 2 of 8 patients (25%) with FSs prolonged ≥30 min and 2 of 3 patients (67%) requiring ≥2 intravenous anticonvulsants to stop seizures. Seizure recurrence within 24 h was observed in 16% of participants and was independently associated with preceding use of diazepam and family history of FS. In 82% of patients with FS recurrence within 24 h, early recurrences occurred within 8 h of the first seizure. Conclusion: Patients with prolonged or refractory FSs are still indicated for hospital admission due to the risk of acute encephalitis. FS patients with a family history of FS may be managed safely by 8-h observation or single-dose rectal diazepam as prophylaxis against early recurrent seizure. What is Known: • Hospitalization has been recommended for children with complex febrile seizures due to the increased risk of central nervous infections. • Recent studies showed low incidences of bacterial meningitis (<1%) in children with complex febrile seizures in the presence of routine immunization. What is New: • Acute encephalitis was identified in 1.4% of children with complex febrile seizures, characterized by prolonged seizures ≥30 min and refractory seizures. • Early recurrent seizures may be safely managed by prophylactic diazepam or 8-h expectant observation.

Keywords: Anticonvulsants; Disease management; Primary prevention; Status epilepticus; Time-to-treatment.

MeSH terms

  • Child
  • Child, Preschool
  • Diazepam
  • Encephalitis* / chemically induced
  • Encephalitis* / complications
  • Humans
  • Infant
  • Recurrence
  • Retrospective Studies
  • Risk Factors
  • Seizures, Febrile* / drug therapy
  • Seizures, Febrile* / epidemiology
  • Seizures, Febrile* / etiology


  • Diazepam