Verghese, MC; (2007) Outcome of febrile seizures: A critical review. Doctoral thesis , UCL (University College London).

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Abstract

Background: Knowledge of the outcome of febrile seizures (FS) is important for clinical practice. Reference studies of the outcome were published in the mid 1970s. Since then treatment and investigation has changed, and a review of the literature of the past 15 years can provide an insight into whether outcome has also changed. Aims: To provide a summary of published clinical data of the last 15 years, in relation to: (a) the mortality (b) the later risk of afebrile seizure & epilepsy and (c) the association between FS and hippocampal sclerosis (HS) /mesial temporal sclerosis (MTS). Methodology: The information for the review was extracted from a data base search of the literature in the last 15 years (01/01/1993- 30/06/2007) and from a search of cross-references in these articles. Results: From this literature review, the following findings were derived: (a) Mortality of FS: Simple febrile seizures (SFS) do not carry a risk of death. The risk of death associated with complex febrile seizures (CFS) is 4-13% (from 4 studies), but it is often not possible to differentiate the contribution of the underlying cause from that of the FS. The overall mortality from febrile seizures (both SFS &CFS) is very low (<1%). Febrile status epilepticus (FSE) has only a slightly higher mortality (1.6 %) than FS, and this has not apparently fallen over the past 3 decades (and this surprising finding may reflect selection bias). There is no suggestion in any of the literature that Sudden Unexpected Deaths in Epilepsy (SUDEP) occurs in association with febrile seizures, simple or complex. The longer the FSE proceeds, the worse the outcome. (b) Risk of later afebrile seizures and epilepsy: The mean risk of later afebrile seizures is 5.8 % and 38% of the patients sustaining an afebrile seizure will later develop epilepsy. The risk of a later afebrile seizure in patients with CFS is 44 %. The risk of epilepsy after a FS increases with the duration of follow up, and has been found to lie between 2.5 % and 3.8 % (mean risks from 23 studies). The risk of epilepsy after a CFS is 17 %. In one very large prospective study, with 23 years of follow up, the cumulative risk of epilepsy after a FS was 6.9% compared to 1.8% in controls with no history of a FS. The rate of epilepsy is higher in those with febrile seizures with onset in infancy or after the age of 3 years, then in those with febrile seizure onsets at age 1-3 years. In this study, the risk of subsequent epilepsy is also higher in those with a family history of epilepsy, cerebral palsy and low Apgar score at 5 minutes of birth. These risks do not seem to have fallen in these studies compared with studies 3 decades ago, but this may be due to differences in methodology. (c) The Association of FS to HS/MTS: There is no evidence of any risk of HS/MTS in association with SFS. The risk of HS/MTS associated with CFS is 3 %. There is a 39 % risk of hippocampal or mesial temporal abnormalities on MRI immediately after a CFS. This high figure may be due largely to reversible, possibly oedematous, changes in the hippocampus during a prolonged febrile seizure (PFS). In serial follow up MRI studies, the risk of significant hippocampal or mesial temporal abnormalities developing after longer follow up after a CFS is 9 %. The studies of medically refractory temporal lobe epilepsy (TLE) patients show that 25 % have a history of FS (a summated mean risk from 43 studies). 44% of medically refractory TLE patients with HS/MTS have a history of FS (a summated mean risk from 35 studies). There are a number of associations reported with HS/MTS and with TLE following febrile seizures (in individual studies), including: medical intractability, good outcome following surgical therapy, post-ictal psychosis, severity and laterality of HS, and an association with the duration of the FS. Also, febrile seizures were found in several studies to more commonly result in epilepsy arising in the temporal lobe compared to other seizure locations.

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