Factors that predict recurrence of febrile seizures (FS) were determined in a prospective study of 260 children age 3 months to 6 years followed for a median of 4.3 years after the first FS at Ippokratio Hospital, Aristotle University of Thessaloniki, Greece. The median age of patients at onset of study was 16.5 months (range 3 months to 5.8 years). Final reevaluation was at a median of 6.0 +/- 1.5 years. The sex ratio was 139 boys to 121 girls (1.15 : 1), and recurrence was not higher among boys than girls. Overall recurrence rate was 40.4%. Cumulative recurrence was 24.2% at 6 months, 34.2% at 12 months, 38.1% at 18 months, and 40.4% at 6 years. EEG abnormalities in 12 children at baseline were not significantly associated with FS recurrence. Low age at onset and positive family history of FS, especially maternal, were strong predictors of recurrence. Other risk factors included abnormal perinatal history with low Apgar score and NICU care for >3 days, low temperature (38.9C or below) and short (<12 hrs) duration of fever before initial FS, a history of frequent febrile illness (p<0.0001), focal FS, and recurrence within the same febrile illness. Duration >15 min of first FS was not a factor. Two or more recurrences occurred in 48%; 28 had only 2 and 22 (44%) had 3 or more recurrences. Factors predisposing a child with one recurrence to a second or more are young age at onset and family history of FS (p<0.001). Multiple recurrences were correlated with low temperature elevation (</=38.9C) before initial FS. By multivariate analysis significant risk factors were early age at onset, complex first FS, and family history of FS (p<0.05). 
COMMENT. In confirmation of previous studies, the main predictors of susceptibility to febrile seizure recurrence are young age (<18 mo) at initial FS, family history of FS in first degree relative, lower temperature (</= 38.9C) and shorter fever duration (<12 hrs) before initial seizure. The lower temperature indicates a low threshold to FS. The present authors also found a maternal preponderance in the families of children with FS recurrence. Daycare attendance and frequent viral infection are additional risks.
Cytokines in acute encephalopathy following prolonged febrile seizures. In a study of 13 children with acute encephalopathy following prolonged febrile seizures compared to 23 without encephalopathy, in Yamaguchi University and other centers in Japan, serum IL-6, IL-10, TNFR1 and CSF IL-6 levels were significantly higher in subjects with encephalopathy compared to controls without encephalopathy. The authors speculate that IL-6 is induced in the CNS to protect damaged brain following prolonged febrile seizure.