Pathogenesis, Prevention of Recurrences and Outcome of Febrile Seizures

Febrile seizures (FS) occur in 2–5% of children. Their pathogenesis is unknown. Elevated levels of prostaglandins (PG) have been found in cerebrospinal fluid after such seizures, and a third of all patients have recurrences. No safe ways of reducing the risk of recurrences have been found. The outcome has been shown in prospective studies to be good, by they have been linked to mesial temporal sclerosis (MTS) in patients with severe temporal lobe epilepsy (TLE). The aim was to analyze the records on the role of PGs in the pathogenesis of FS, to find risk factors for recurrences that are amenable to intervention and to evaluate the prevention of recurrences and the connection of FSs with MTS. We performed a systematic review of the effect of PGs and their synthetase inhibitors on seizures and a meta-analysis of the prevention of recurrences. The prophylactic effect of diazepam and acetaminophen on recurrences was evaluated in a placebo-controlled trial with 180 FS patients, and risk factors for recurrences were analysed from these data. To find MTS, MRI volumetry was performed after 12 years of follow-up on 64 cases chosen out of 329 unselected FS patients: twentyfour with a prolonged initial seizure, eight with a later unprovoked seizure and 32 age, sex and handedness-matched controls. PGD2, PGE1 and PGE2 had mainly anticonvulsive effects and PGF2alfa proconvulsive ones. NSAIDs had seizure-modulating effects in adult animals ranging from attenuation to provocation. Each degree of increase in fever doubled the recurrence risk, and each febrile episode increased it by 18%. The meta-analysis showed phenobarbital and valproate to prevent recurrences, but they cannot be recommended for FS as they have severe side-effects. The meta-analysis nullified the alleged effect of diazepam, and neither this nor acetaminophen prevented recurrences in a clinical trial. No MTS was found in any patient group. PGs may be involved in the pathogenesis of FS. No safe prophylaxis for recurrences is available, although the effect of antipyretics needs further evaluation. Measures to reduce feverish infections in order to prevent FS recurrences seem logical. MTS is uncommon even after prolonged FS.