Febrile Seizures

Linda D. Leary

Douglas R. Nordli Jr.

Timothy A. Pedley

A febrile seizure is an event in infancy or childhood, usually occurring between 3 months and 5 years of age, associated with fever, but without evidence of an intracranial infection or defined cause (National Institutes of Health Consensus Conference, 1980). This definition excludes children who have had previous afebrile seizures.

Febrile seizures are the most common cause of convulsions in children: Between 2% and 5% of all children in the United States and Europe and 6% to 9% 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 twofold to threefold increased risk of seizures with fever. Based on studies of large families with simple febrile seizures, four genetic loci have been mapped. These loci are referred to as FEB1 (8q13-q21), FEB2 (19p), FEB3 (2q23-q24), and FEB4 (5q14-q15). Some families have a susceptibility to febrile seizures and later epilepsy, and these traits are inherited in an autosomal-dominant fashion. This has been termed generalized epilepsy febrile seizures plus (GEFS+). Mutations in the voltage-gated sodium channel ²-1 subunit gene (SCN1B; OMIM 600235) on chromosome 19q13 cause GEFS+ type 1; mutations in the SCN1A gene (OMIM 182389) on 2q24 cause GEFS+ type 2; and mutations in the GABRG2 gene (OMIM 137164) on 5q31.1-q33.1 cause GEFS+ type 3. Mutations in the SCN2A (OMIM 182390) gene cause febrile seizures associated with afebrile seizures. Owing to the overlap between the loci for FEB 3 and GEFS+ type 2, it is uncertain if FEB3 is a unique genetic locus for simple febrile seizures. The role of identified genes in sporadic febrile seizures remains to be determined.

CLINICAL MANIFESTATIONS

About two-thirds of febrile seizures occur early in the febrile illness (that is, within the first 24 hours). 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. 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.

DIAGNOSIS

Diagnosis is made by excluding other possible causes of the convulsion, such as meningitis, metabolic abnormalities, or structural brain lesions. Depending on the manifestations and the clinician’s experience, laboratory tests are not always necessary. Usually, a clinically identifiable illness such as otitis media, upper respiratory infection, or gastroenteritis is present. Fever after immunization may also trigger a febrile seizure. Any suspicion of meningitis, however, mandates lumbar puncture. The typical indicators of meningeal irritation, such as nuchal rigidity and the Brudzinski sign, are not reliable in young infants. Practice guidelines of the American Academy of Pediatrics (1996) recommend that lumbar puncture be strongly considered if the child is younger than 12 months of age or if the child has already been treated with antibiotics regardless of age. Lumbar puncture may be indicated in children between 12 and 18 months. If the seizure has focal features, or if the examination elicits focal neurologic abnormalities, brain imaging is necessary. EEG is not useful, because it does not provide information regarding either the risk for recurrence of febrile seizures or later development of epilepsy.

PROGNOSIS AND TREATMENT

About one-third of children with febrile seizures have more than one attack. Recurrence is highest in infants whose first febrile seizure occurred before the age of 1 year and in children with a family history of febrile seizures. Febrile seizures represent acute symptomatic or reactive seizures, and even when recurrent do not warrant the designation of epilepsy.

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%-3%), and if the febrile seizures are complex, there is a family history of afebrile seizures, or neurological abnormalities were detected before the first febrile convulsion (10%-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, 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.

Because most children with febrile seizures have no long-term consequences, prophylactic treatment using antiepileptic drugs should be avoided, even after two or three isolated convulsions. Although both phenobarbital and valproate are effective in reducing recurrence, evidence does not show that treatment alters the risk of later epilepsy. In addition, adverse drug effects occur in as many as 40% of infants and children treated with phenobarbital, and valproate carries a risk of idiosyncratic fatal hepatotoxicity and pancreatitis. Phenytoin and carbamazepine are ineffective.

If treatment is considered at all, it should be reserved for children with a high risk of developing epilepsy or a history of prolonged febrile seizures. A reasonable alternative to chronic drug therapy is intermittent treatment using rectal diazepam. Several studies have shown that rectal administration of diazepam during febrile illnesses is safe and as effective as phenobarbital in reducing seizure recurrence. Although oral diazepam has also been shown to be effective, as many as 30% of children experience adverse effects, including ataxia, lethargy, or irritability. Antipyretics may improve the child’s comfort during the febrile illness, but they have not been shown to be effective in preventing the recurrence of febrile convulsions.

Watching their child have a convulsion is a frightening experience for parents. The physician therefore must provide reassurance to dispel any myths the family may have, emphasizing in particular that febrile seizures are neither life threatening nor damaging to the brain. The American Academy of Pediatrics offers copies of its Guidelines and an information sheet for parents through its website (http://www.aap.org), and the Epilepsy Foundation website (http://www.epilepsyfoundation.org) provides information about febrile seizures.

Source : Merritt's Neurology, 11th Edition