Prediction of evolution to epilepsy or genetic epilepsy with febrile seizures plus (GEFS+) in children presenting with febrile seizures: a retrospective multicenter longitudinal study

Objectives: To identify possible predictors of progression from febrile seizures to epilepsy or genetic epilepsy with febrile seizures plus (GEFS+), and to evaluate the management of febrile seizures in Italian clinical settings. Methods: 231 children with complex febrile seizures, febrile status epilepticus, or recurrent episodes of simple febrile seizures requiring therapy or follow-up, were recruited from four different hospitals. At the baseline evaluation and during follow-up, data were collected regarding each child's febrile seizures (number, duration, triggers, clinical characteristics), psychomotor development, possible neuropsychiatric comorbidities, any family history of neuropsychiatric disorders, as well as findings of electroencephalographic evaluation (EEG), diagnostic tests, and prescribed treatments. The data were analyzed using Mann-Whitney and Fisher tests, and univariate and multivariate logistic models. Results: A family history of epilepsy, a higher absolute number of episodes, an older age at onset of febrile seizures, and the presence of afebrile seizures were found to be factors associated with an increased risk of developing epilepsy or GEFS+. Conversely, a normal EEG at onset and an increase in the number of simple febrile seizures or of complex febrile seizures occurring within the first 24 h were associated with a lower risk. Conclusions: This study provides previously unreported evidence relevant to the prediction of epilepsy or GEFS+ in patients with febrile seizures, which may facilitate the identification of new prognostic factors. It also highlights concerns regarding the current national and international guidelines on febrile seizures.