Febrile status epilepticus and epileptogenesis: The FEBSTAT study

The multicenter FEBSTAT study (Consequences of Prolonged Febrile Seizures in Childhood: https://grantome.com/grant/NIH/R37-NS043209-12; PI S. Shinnar) examined the outcome of febrile status epilepticus (FSE) in over 200 prospectively enrolled infants, with many followed for 10 years after FSE. Initial magnetic resonance images (MRIs), done within days after FSE, showed a unilateral hyperintense hippocampal T2 signal in 10% of subjects. Post-ictal EEGs showed focal slowing maximal in the temporal region in 24% and focal attenuation in 13% of all subjects. There was a significant association between focal slowing and/or attenuation and hippocampal T2 hyperintensity, indicating that a normal EEG would strongly argue against hippocampal injury. Measurements of hippocampal volume and apparent diffusion constants indicated that the T2 changes were acute, and follow-up MRIs at 1, 5, and 10 years post-FSE showed marked hippocampal volume loss by 1 year, sustained through 10 years, evolving into radiological hippocampal sclerosis in 70%. Infants whose acute MRIs did not show T2 hyperintensity did not develop sclerosis. Ten-year cumulative incidence of epilepsy was 30% for the entire FEBSTAT cohort, but was 71% among those with acute hippocampal T2 hyperintensity and 23% among those with a completely normal acute MRI. Medial temporal lobe epilepsy 10 year cumulative incidence was 4% of the entire cohort, with 39% cumulative incidence in those with acute hippocampal T2 hyperintensity, and did not occur in subjects with normal MRIs. PLAIN LANGUAGE SUMMARY: Fever occasionally causes prolonged seizures in infants lasting 30 min or longer. This study demonstrates that in about 10% of these cases, the long seizures can cause injury to the hippocampus, a brain structure in the temporal lobe. The injury is visible on magnetic resonance images (MRIs) of the brain. Years later, infants with this hippocampal injury are at high risk of developing a form of epilepsy called temporal lobe epilepsy, whereas infants with normal MRIs after the long seizures have very little risk of temporal lobe epilepsy; nevertheless, they do have a lower risk of other forms of epilepsy.