The ILAE defines a febrile seizure as “a seizure in association with a febrile illness in the absence of a CNS infection or acute electrolyte imbalance in children older than 1 month of age without prior afebrile seizures.” Febrile seizures are the most common cause of convulsions in children: Between 2% and 4% of all children in the United States and Europe and 9% to 10% of children in Japan have at least one febrile seizure before age 5 years. Hauser (1994) estimated that in 1990, there were 100,000 cases of newly diagnosed febrile seizures in the United States. Genetic predisposition is an important factor. Overall, siblings and offspring of affected probands have a two- to threefold increased risk of seizures with fever. Based on studies of large families with simple febrile seizures, various genetic loci have been mapped. The literature on the genetics of febrile seizures is substantial and it continues to grow. Linkage analysis has implicated many different chromosomes including 1q, 2q, 2p, 5q, 6q, 8q, 12q, 19p, and 19q. An important linkage has been with genes residing on 2q, which is the location of sodium channel genes, including SCN1A. Recently, another gene, SEZ-6, located on chromosome 17q, has been implicated. Some families have a susceptibility to febrile seizures that persists to an unusually late age, and some of these family members later develop epilepsy. These traits are inherited in an autosomal dominant fashion, and the condition has been termed genetic epilepsy febrile seizures plus (GEFS+). Mutations in the voltage-gated sodium channel genes SCN1A, SCN1B, and SCN2A are involved as well as the GABRG2 gene.
About two-thirds of febrile seizures occur in the first 24 hours of illness. Indeed, in some children, the seizure is the first indication of illness. Febrile seizures are subdivided into simple and complex types. Simple febrile seizures are most common, representing 80% to 90% of all febrile seizures. Simple febrile seizures are isolated, brief generalized convulsions. Parents commonly report diffuse stiffening followed by rhythmic jerking of all limbs lasting less than 1 to 2 minutes. Complex febrile seizures are those that are focal or followed by a postictal deficit (Todd paresis), last more than 10 to 15 minutes, or occur more than once within 24 hours. Factors predisposing to febrile status epilepticus include a younger age (mean age 15 months vs. 19 months for benign febrile seizures), a lower temperature (102.3°F vs. 103.6°F), female gender, first-degree family history of febrile seizures, and structural temporal lobe abnormalities.
About one-third of children with febrile seizures have more than one attack. Independent risk factors for recurrence are first febrile seizure before the age of 18 months, a family history of febrile seizures, a low peak temperature, and a short duration of fever before the seizure. Febrile seizures represent acute symptomatic seizures, also referred to as reactive seizures, and even when recurrent, do not warrant the designation of epilepsy. However, they do have an epileptic pathophysiology.
Children who have an isolated febrile seizure have a risk of developing epilepsy that is similar to that of the general population. This risk increases if simple febrile seizures recur (2% to 3%), if the febrile seizures are complex, there is a family history of afebrile seizures, or neurologic abnormalities were detected before the first febrile convulsion (10% to 13%). When all three features of complex febrile seizures are present (prolonged, focal, repeated), the risk of subsequent epilepsy may be as high as 49%. Mortality is not increased in children with febrile seizures who are neurologically normal.
Simple febrile seizures have not been associated with, nor do they lead to, mental retardation, low IQ, poor school achievement, or behavioral problems. Most studies have also failed to demonstrate any cognitive or behavioral consequences of complex febrile seizures, although some differences have been reported. In children with prolonged febrile convulsions, nonverbal intelligence measures may be slightly lower compared with children with simple febrile seizures and normal controls. Children with complex febrile seizures are also more likely to require special schooling than those with simple febrile seizures.
Whether prolonged febrile seizures cause mesial temporal sclerosis and refractory partial seizures is controversial. Large prospective studies have failed to find an association, but experience in adult epilepsy surgical centers suggests otherwise because many adults with mesial temporal sclerosis have had a prolonged febrile convulsion as a child. Furthermore, magnetic resonance imaging (MRI) in some children with prolonged febrile seizures has shown acute changes in the mesial temporal region that progress over time to mesial temporal sclerosis. There is accumulating evidence that febrile status epilepticus may have long-term consequences. This issue is currently being studied in the United States in a prospective multicenter research effort. The first phase consists of identifying the patients and biomarkers and the next phase will identify who ultimately develops mesial temporal sclerosis.
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