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Chapter 559

### Epidemiology and Clinical Features

A febrile seizure is defined by ILAE (International League Against Epilepsy) as “a seizure in association with absence of an infection (of the central nervous system) or acute electrolyte imbalance in children older than 1 month of age, without prior non-febrile seizures.”1 Febrile seizures are most commonly seen between 6 months and 5 years, with a peak incidence of approximately 18 months.2 Simple febrile seizures are relatively brief (< 15 minutes), generalized, and do not recur during the same febrile illness. In contrast, complex febrile seizures have focal features, long duration, or recurrence within 24 hours. Prior neurological condition is not part of this classification.1

The prevalence of febrile seizures is 2% to 4% in the United States and Western Europe, and higher in Japan at 9% to 10%, and Guam at 14%. The highest incidence of febrile seizures is at approximately 18 months of age.2 Febrile seizures tend to be more common during winter months, when children are prone to have systemic illnesses.

Risk factors for febrile convulsions include family history, daycare attendance, and underlying developmental abnormality.3 However, most children with febrile convulsions are developmentally normal and do not have any prior brain insults.

Most patients have simple febrile seizures, and the seizures are often seen shortly after onset of fever; many febrile seizures occur before parents are aware that the child has a fever. Certain childhood diseases, such as roseola from human herpes virus-6 infection, appear to be more prone to be associated with febrile seizures.4,5

### Etiology/Genetic Factors

Susceptibility to febrile convulsions appears to be strongly influenced by genetic factors. Approximately 25% to 40% of affected children have a positive family history, and siblings have a 9% to 22% risk for febrile seizures.6 Such observations support the concept that susceptibility to febrile seizures is the result of the interaction of several genes. Linkage studies have identified many loci associated with febrile seizures. These loci include 8q13-q21 (FEB1), 19p (FEB2), 2q23-q24 (FEB3), 5q14-q15 (FEB4), 6q22-q24 (FEB5), and 18p11 (FEB6).7In particular, there are families with strong autosomal-dominant penetrance of febrile seizures, some members with febrile seizures beyond the typical age, even some with epilepsy (mostly generalized); this condition has been described as generalized epilepsy with febrile seizure plus (GEFS Plus)8 or autosomal dominant epilepsy with febrile seizures (ADEFS).9 Some of these have been associated with mutations in alpha 1, alpha 2, and beta 1 subunits of the sodium channel (SCN1A, SCN2A, and SCN1B), or gamma-2 subunit of the GABAA receptor (GABRG2).7

### Diagnosis

History and careful physical and neurological examination will be necessary to identify the source of fever. The main concern in children with febrile seizures is to evaluate for infection of the central nervous system, such as meningitis and encephalitis. This may require neuroimaging studies and lumbar puncture with examination of cerebrospinal fluid, especially in cases of prolonged and focal seizures, or prolonged postictal drowsiness with lethargy. In cases of complex febrile seizures, especially with focal ...

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