This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Temporal epilepsy (TLE) is often associated with mesial temporal sclerosis (MTS). The relationship between febrile seizures (FC) and MTS remains controversial. Retrospective data suggest that prolonged FCs cause MTS but epidemiological studies have not found this association. Recent data from MRIs performed immediately after FCs provide some preliminary evidence that very prolonged FCs (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 causes and consequences of febrile SE and clarify the relationship between 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 five centers. Forty children with febrile SE will be recruited at Children's Memorial Hospital. 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. Children and two of their biological relatives can also be enrolled in the optional genetic testing portion of the study which focuses on the genetics of seizures. Intermediate and long term outcomes (5-9 years and 10-20 years respectively) will be ascertained using cohorts of previously recruited children at other research sites. The following hypotheses will be tested: 1) Hippocampal T2 signal and/or volume abnormalities will be seen on 30-40% of acute MRIs and their severity will correlate with seizure duration and focality. Furthermore, severe MRI changes will occur primarily in those with either preexisting abnormalities or 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 5) Genetic testing of children with prolonged febrile seizures and their family members will demonstrate genetic predisposition to seizures and to the later development of epilepsy.
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