Febrile seizures are an age-related phenomenon and occur in children between the ages of 6 months and 6 years. The reason that febrile seizures occur only in infants and young children is unclear, as are the mechanism whereby fever induces the seizure.

Febrile seizures occur during both bacterial and viral infections and may occur more frequently in patients with illnesses that are accompanied by severe constitutional symptoms. One study found that infection with human herpesvirus 6 accounted for approximately one-third of the first-time febrile seizures in children 2 years old or younger. These children are more likely to have clusters of seizures and long-lasting partial seizures with postictal paralysis. Attempts have been made to link susceptibility to febrile seizures with abnormalities of neurotransmitters. The concentration of gamma-aminobutyric acid (GABA), an inhibitory transmitter, was found to be reduced in the cerebrospinal fluid (CSF) of children who were studied after their first or second febrile seizure. No correlation was found between the duration of the seizure and the concentration of GABA; however, because the samples were obtained after the convulsion occurred, the abnormality possibly was a secondary phenomenon rather than a primary event.

Genetic factors appear to be important in the expression of the condition. An increased incidence of febrile seizures exists among first-degree relatives—10% to 20% of parents and siblings—of children with febrile seizures. The concordance rate for febrile seizures in monozygotic twins is much higher than that in dizygotic twins, in whom the rate is similar to that of other siblings. A complex segregation analysis of febrile seizures occurring in more than 450 families during a 30-year period was completed. Different models explained the rate of occurrence based on the frequency of febrile convulsions in the proband. In children who had a single febrile convulsion, a polygenic (common familial environment) model was most appropriate. If the proband had experienced multiple febrile convulsions, however, the most consistent model was that of a single major locus with nearly dominant seizure susceptibility.

A relationship between febrile seizures and an increased incidence of epilepsy in families of the proband appears to exist. Siblings and parents of patients with febrile seizures have a 4% to 10% incidence of epilepsy. Moreover, siblings of patients with epilepsy are at increased risk for having febrile seizures.

Recently, several autosomal dominant genetic syndromes that increase the susceptability to febrile seizures have been identified. The loci are found on 8q13-21, 19p, 19q, 2q23-24, and 5q14-15.

Generalized epilepsy with febrile seizures plus (GEPS+) is a newly identified autosomal dominant syndrome. The phenotype in families consists of children who have febrile seizures that persist beyond 6 years of age and may have afebrile tonic-clonic as well as other seizure types. Some families have had an association between myoclonic epilepsy, as well as partial seizures, and atonic seizures beginning between 1 and 4 years of age. Several genes have been identified, and they all involve sodium channel mutations. Families with the GEFS+ phenotype who have evidence of GABA receptor dysfunction also have been described. Mutations in the same receptor have been found in families with childhood absence epilepsy and febrile seizures. This finding suggests that the mutation has age-dependent effects and involves different neuronal networks because the ages of onset and the physiologic features of the seizure types are different.

Most febrile seizures are simple. Prolonged convulsions occur in fewer than 10% of children with febrile seizures, and focal features are seen in fewer than 5%. Generalized seizures mainly are clonic, but both atonic and tonic episodes have been noted. Involvement of the facial and respiratory muscles is noted frequently. Complex febrile seizures occur as the initial convulsion in most children who experience them. An initial simple febrile seizure can be followed by a subsequent complex febrile seizure, however, and vice versa. Children usually have significantly elevated body temperatures, but approximately 25% of febrile convulsions occur in children whose temperatures are between 38° and 39°C. Children who have repeated febrile seizures do not always experience them with the same degree of fever. In addition, these seizures do not occur every time the child has a temperature elevation similar to the one associated with the preceding febrile seizure. Most febrile seizures occur on the first day of illness, and, in some children, they are the first sign of the accompanying infection.

The main concern in evaluating an infant or child with a febrile convulsion is the possible presence of underlying meningitis or
encephalitis. A thorough evaluation by an experienced clinician almost always detects the child with meningitis. If the only indication for performing a lumbar puncture is a febrile seizure, meningitis is found in fewer than 1% of patients. Fewer than one-half of these patients have bacterial meningitis. In children who have meningitis presenting with seizures, as many as 40% (particularly younger infants) may not have meningeal signs. They may have other symptoms and findings, however, that strongly suggest the presence of meningitis. Thus, a diagnosis of bacterial meningitis based solely on a routine evaluation of CSF after a febrile seizure is exceedingly rare.

Seizures usually are distinguished easily from other types of involuntary movements occurring in sick infants. Chills usually consist of fine, rhythmic oscillatory movements about a joint and are not clonic in nature. They rarely involve facial or respiratory muscles. Moreover, chills are not accompanied by loss of consciousness, which does occur during a generalized seizure.

An underlying metabolic disorder presenting as a seizure in a febrile child rarely is detected. A careful review of the history usually provides other clues suggesting the likelihood of an underlying problem.

The routine performance of lumbar punctures in all children with febrile seizures does not seem warranted. Children who may be considered candidates for examination of the CSF include young infants, children whose febrile seizures occur after the second day of illness, cases in which the clinician is unsure of his or her judgment regarding the presence or absence of meningitis, and situations in which the patient cannot be observed. The American Academy of Pediatrics recommends that after the first seizure with fever in infants younger than 12 months of age, performing a lumbar puncture should be considered strongly. The routine performance of skull radiography in children with febrile seizures is useless. If imaging of the brain is indicated by abnormal head size, by an abnormal neurologic examination (especially with focal features), or by signs or symptoms of increased intracranial pressure, computed tomography or magnetic resonance imaging should be performed. Measurement of serum electrolytes, blood sugar, calcium, and urea nitrogen concentrations are of very low yield and need not be performed routinely. These tests should be done when indicated by the results of the history or physical examination. Patients with significant vomiting, diarrhea, and abnormal fluid intake may be suspected of having acute metabolic disturbances, and routine serum chemistry testing should be performed in these children. The routine use of electroencephalography in all children with febrile seizures is not warranted. A tracing obtained within 1 week of the seizure is abnormal in at least one-third of these children. Febrile convulsions of long duration or with focal features increase the likelihood that abnormalities will be found. Abnormal electroencephalographic results do not identify children in whom epilepsy subsequently will develop and should not be used as the basis for deciding which children need anticonvulsant therapy.