Febrile status epilepticus (FSE) has been associated with hippocampal injury and subsequent hipppocampal sclerosis (HS) and temporal lobe epilepsy. The FEBSTAT study was designed to prospectively examine the association between prolonged febrile seizures and development of HS and associated temporal lobe epilepsy, one of the most controversial issues in epilepsy. We report on the baseline phenomenology of the final cohorts as well as detailed aims and methodology.
The “Consequences of Prolonged Febrile Seizures in Childhood” (FEBSTAT) study is a prospective, multicenter study. Enrolled are children, aged 1 month to 6 years, presenting with a febrile seizure lasting 30 minutes or more based upon ambulance, emergency department, and hospital records, and parental interview. At baseline, procedures included an MRI and EEG done within 72 hours of FSE, and a detailed history and neurological examination. Baseline development and behavior are assessed at one month. The baseline assessment is repeated, with age- appropriate developmental testing at one and five years after enrollment as well as at the development of epilepsy and one year after that. Telephone calls every three months document further seizures. Two other groups of children are included: a ‘control’ group consisting of children with a first febrile seizure ascertained at Columbia University and with almost identical baseline and one year follow-up examinations and a pilot cohort of FSE from Duke University.
The FEBSTAT cohort consists of 199 children with a median age at baseline of 16.0 months (Interquartile range (IQR)=12.0–24.0) and a median duration of FSE of 70.0 minutes (IQR=47.0–110.0). Seizures were continuous in 57.3% and behaviorally intermittent (without recovery in between) in 31.2%; most were partial (4;2.0%) or secondary generalized (65.8%), and almost all (98.0%) culminated in a generalized tonic clonic seizure. Of the 199 children, 86.4% had normal development and 20% had prior febrile seizures. In one third of cases, FSE was unrecognized in the emergency department.
The Duke existing cohort consists of 23 children with a median age of FSE onset of 18.0 months (IQR 14.0–28.0) and median duration of FSE of 90.0 minutes (IQR 50.0–170.0).
The Columbia control cohort consists of 159 children with a first febrile seizure who received almost the same work-up as the FEBSTAT cohort at baseline and at one-year. They were followed by telephone every 4 months for a median of 42 months. Among the control cohort, 64.2% had a first simple FS, 26.4% had a first complex FS that was not FSE, and 9.4% had FSE. Among the 15 with FSE, the median age at onset was 14.0 months (IQR 12.0–20.0) and the median duration of FSE was 43.0 minutes (IQR 35.0–75.0).
The FEBSTAT study presents an opportunity to prospectively study the relationship between FSE and acute hippocampal damage, the development of MTS, epilepsy (particularly TLE), and impaired hippocampal function in a large cohort. It is hoped that this study may illuminate a major mystery in clinical epilepsy today, and permit the development of interventions designed to prevent the sequelae of FSE.