Febrile seizures

Why and at what age do children have febrile seizures?

Febrile seizures result from a combination of genetic and environmental factors.2 Of children with febrile seizures, 24% have a family history of febrile seizures and 4% have a family history of epilepsy.3 Although polygenic inheritance is usual, a small number of families exist in whom the inheritance of febrile seizures is autosomal dominant, and several chromosomal loci and a few genes have been identified.4 Mutations in sodium channel and γ-aminobutyric acid A receptor genes have been identified in children with febrile seizures,^{w3 w4} suggesting that genes coding for ion channels are likely to underlie the syndrome.

Febrile seizures are defined as occurring between 6 months and 6 years of age.5 The median age of onset is 18 months, and half of children present between 12 and 30 months.3

What is the relation of the fever to the seizure?

The fever associated with a febrile seizure is usually defined by a temperature of at least 38°C.3 No evidence exists that febrile seizures are more likely to occur with the maximal rate of temperature rise, although this is often quoted.6 Febrile seizures may occur before the fever is apparent and early or late in the course of a febrile illness.^w5

An entity of afebrile convulsions in young children with mild gastroenteritis is increasingly recognised. This disorder was initially observed in Asian countries, but white children from the United Kingdom have recently been reported with the condition.^w6 Whether the racial differences are caused by underlying genetic or environmental factors or relate to under-recognition is unclear. A large case series found that these children present with clusters of generalised or focal seizures with and without fever over several days in the setting of viral gastroenteritis.7 ^w6 Children do well without recurrence of seizures and have normal development. Compared with children with febrile seizures, these children have less of a family history of seizures, a lower recurrence rate, and more clustering of attacks.7 ^w6

Features and duration of febrile seizures

Febrile seizures are predominantly brief, generalised tonic-clonic seizures, and 4-16% have focal features according to epidemiological studies.1 8 9 More recently, febrile myoclonic seizures have been recognised.10 Febrile myoclonus has a similar age of onset to convulsive febrile seizures and is associated with a family history of febrile seizures.10

In 87% of children, the duration of the febrile seizure is less than 10 minutes; seizures last more than 15 minutes in 9% of children.11 Febrile status epilepticus (>30 minutes' duration) occurs in 5% children and is more likely to have focal features.11 A prolonged febrile seizure is a risk factor for further prolonged attacks.11

When do febrile seizures recur?

Thirty per cent of children have recurrent febrile seizures during subsequent illnesses.3 Risk factors for recurrence (as distinct from risk of a first febrile seizure) include onset before 18 months, lower temperature close to 38°C, shorter duration of fever (<1 hour) before the seizure, and a family history of febrile seizures.12 13 ^{w7 w8} (table 1⇓). Of children who have all these risk factors, 76% will have a recurrence of febrile seizure compared with 4% without risk factors.12

What is the risk of epilepsy occurring?

The vast majority of children who present with febrile seizures do not develop epilepsy. Febrile seizures are classified as simple or complex; complex febrile seizures are associated with an increased risk of epilepsy. Complex febrile seizures are defined by at least one of the following features: duration longer than 15 minutes, multiple seizures within 24 hours, and focal features.1 These features are absent in simple febrile seizures, which make up 75% of attacks.9

Large prospective cohort studies of children have identified other risk factors for epilepsy, including neurological abnormality, a family history of epilepsy, and short duration of fever (<1 hour) before the seizure (table 1⇑).1 8 11 Children with no risk factors have a 2.4% chance of developing afebrile seizures by 25 years compared with 1.4% for the general population.9 Children with a history of at least one complex feature, a neurological abnormality, and a family history have a 10% risk of developing epilepsy by the age of 7.1 Prolonged febrile seizures increase the incidence of epilepsy to 21%.^w9 For children with all three features of a complex febrile seizure, the risk increases to 49%.9

The relation of epilepsy to seizures with fever is complex; three different scenarios deserve consideration. The first is where the seizure with fever is essentially the onset of the epilepsy syndrome. The best example is severe myoclonic epilepsy of infancy (or Dravet syndrome), in which infants classically present with febrile status epilepticus at around 6 months. The syndromic diagnosis is not initially apparent until the infant later develops afebrile seizures. Another example is the syndrome of “febrile seizures plus,” in which seizures with fever persist beyond the age of 5 years or afebrile seizures also occur. By definition, these children have epilepsy and do not fit the definition of febrile seizures, but they carry a similarly good prognosis.^w10

In the second scenario, a period of freedom from seizures follows febrile seizures before the development of a specific epilepsy syndrome such as childhood absence epilepsy. In the third scenario, the child has previously had afebrile seizures and has a diagnosis of epilepsy and then subsequently presents with seizures with fever. These seizures are triggered by fever; these are not febrile seizures but may be confused with them.

Are febrile seizures and hippocampal sclerosis related?

A highly controversial area is whether prolonged febrile seizures cause hippocampal sclerosis and intractable temporal lobe epilepsy. Video-electroencephalograph controlled studies of immature rats show that prolonged seizures induced by fever lead to hippocampal damage and spontaneous temporal lobe epilepsy.14 Human studies also show that prolonged seizures with fever are associated with hippocampal sclerosis.15 16 17 The hippocampus is hypothesised to be abnormal before the seizure with fever, predisposing the child to prolonged seizures and subsequent development of hippocampal sclerosis.16 17 The association of prolonged febrile seizures and hippocampal sclerosis is uncommon. For example, a prospective 12 year study of 24 children with prolonged febrile seizures found no hippocampal sclerosis.^w11 Population studies show no increase in temporal lobe epilepsy in children with complex febrile seizures.1 ^{w9 w11} Given the rarity of hippocampal sclerosis, temporal lobe epilepsy, and febrile status epilepticus, the number of subjects needed to show an effect with epidemiological techniques is beyond the limits of published series.^w12

Do febrile seizures affect cognition and behaviour?

Febrile seizures have an excellent outcome; population studies show normal intellect and behaviour, even for children with complex febrile seizures.^{w9 w13 w14} Recent population based prospective case controlled studies from Taiwan found that children who had febrile seizures did at least as well as, if not better than, controls on measures of intelligence, academic achievement, behaviour, and working memory.18

What investigations should be done?

The investigations done on a child with fever should be directed by the degree of illness and the suspected underlying infection. The fact that a child also has a simple febrile seizure in the illness should not modify this approach (table 2⇓).

Management

Parents may become extremely anxious when their child has febrile seizures, and many think their child is dying.^w24 Concern about the child's future can lead to family stress that interferes with daily family life, such as the child sleeping in the parents' bed.^w25 Reassurance that the child will not die and education (verbally, in writing, and through support groups) about the cause and prognosis of this disorder can alleviate the anxiety and let the family return to normal life.^w26

Summary

Febrile seizures are a common benign disorder with an excellent outcome. Exclusion of central nervous system infection such as meningitis and encephalitis is important, particularly in a child with febrile status epilepticus. Education and reassurance remains the mainstay of management for families faced with these frightening attacks.