Consequences of Prolonged Febrile Seizures in Childhood

DESCRIPTION (provided by the applicant): Temporal Lobe Epilepsy (TLE) is often associated with Mesial Temporal Sclerosis (MTS). The relationship between Febrile Seizures (FSs) and MTS remains controversial. Retrospective data suggest that prolonged FSs cause MTS, but epidemiological studies have not found this association. Recent data from MRIs performed immediately after FSs provide preliminary evidence that very prolonged FSs (i.e. febrile Status Epilepticus (SE)) sometimes produce acute hippocampal injury that evolves into MTS. Identification of children at high risk to develop MTS is necessary prior to designing interventions aimed at prevention. This study will examine the consequences of febrile SE, and clarify the relationship between febrile SE, MTS, and subsequent epilepsy and cognitive impairment. Short-term consequences will be examined using a cohort of 200 children with febrile SE, who will be recruited at 5 centers. All children will have MRIs within 72 hours of their SE and at one year, as well as viral studies, psychological testing, EEGs and clinical follow-up. Intermediate term outcomes (5-9 years) will be ascertained using a cohort of 40 children recruited between 1995 and 200, all of whom had MRIs within 72 hours of the episode of febrile SE. They will have a follow-up MRI, EEG and psychological testing >5 years later. Long-term (10-20 years) outcomes will be examined using an established epidemiologic cohort of 163 children with febrile SE, prospectively identified between 1984 and 1996. These children will receive an MRI, EEG and psychological testing >10 years later. In those who develop epilepsy, we will characterize seizure types and epilepsy syndromes, and correlate them with the presence or absence of MTS. The following hypotheses will be tested: 1) Hippocampal T2 signal and/or volume abnormalities will be seen on 30-40% of acute MRIs. The occurrence and severity of these abnormalities will correlate with total seizure duration and seizure lateralization, the presence of pre-existing brain abnormalities and febrile SE in the context of human herpes virus 6 or 7 infection; 2) The severity of acute MRI hippocampal abnormalities will predict subsequent MTS; 3) Children developing TLE will have MRI evidence of MTS.; 4) Subjects with MTS will have impaired memory, whether or not they have epilepsy.