Febrile seizures (FS) are the most common type of convulsion among pediatric patients. The prevalence of FS varies between different populations, affecting, for example, an estimated 2%–5% of European and North American children and 6%–9% of children from Japan. In a large registry-based study of febrile seizures in children born in Denmark between 1977 and 2004, 50% experienced their first febrile seizure between 6 and 18 months of age, and 93% before the age of 48 months.¹

Febrile seizures are classified as either simple or complex in nature. Simple FS are defined as short (<15 minutes), generalized tonic, clonic, or tonic–clonic seizures that occur during the course of a febrile illness^2,3,4; approximately 80%–90% of FS are simple febrile convulsions.⁵ Complex FS consist of either focal or generalized seizures that are prolonged (>15 minutes) or recurrent over a 24-hour period. Febrile seizures that persist for longer than 30 minutes or that involve multiple shorter seizures without return to a baseline level of consciousness are termed febrile status epilepticus.⁶

Febrile seizures, whether simple or complex, generally occur in the context of an illness that causes a fever of at least 38.0°C.³ FS tend to be seen in conjunction with common infections, such as upper respiratory tract infections, otitis media, and gastrointestinal disorders; however, there is no specific infectious agent connected to febrile seizures. FS associated with fevers secondary to immunizations are also common. In this setting, the seizure typically occurs within 48 hours after administration of the immunization.⁷ Most often, both simple and complex FS occur early in the course of an illness or during the initial rise in body temperature, but the seizure may also precede the onset of fever.

In addition to fever, FS are precipitated by other environmental and/or genetic factors that remain largely unidentified. Vestergaard and Christensen¹ observed that low birth weight and short gestational ages were significant risk factors for FS; however, there was no association between birth weight, birth order, or 1- or 5-minute Apgar scores and an increased risk for FS in a study of disease-discordant twins.⁸ Moreover, prenatal exposure to other common insults, such as maternal smoking, alcohol or coffee consumption, and stress, appear to have little to no effect on the incidence of FS.¹

Twin and family studies reveal that genetic factors play an important role in FS, and that there are different modes of inheritance. Large pedigrees with recurrent FS are often consistent with a model of autosomal dominant inheritance with reduced penetrance, although the majority of cases are likely due to more complex, polygenic inheritance. Genetic linkage analysis of FS families points to at least 10 loci that are suspected of harboring FS genes (reviewed in⁹), yet there has been little progress toward identifying the actual disease-causing genes.

Ion channels play an important role in the regulation of neuronal excitability, and altered ion channel function is responsible for a range of epilepsy subtypes, several of which include FS. Over 600 mutations in the voltage-gated sodium channel (VGSC) gene SCN1A^10,11 have been linked to disorders such as genetic (generalized) epilepsy with febrile seizures plus (GEFS+)^12,13,14 and Dravet syndrome (DS),^15,16,17 in which FS are common. A SCN1A mutation was also found in a large, multigenerational pedigree affected by simple FS,¹⁸ raising the possibility that altered SCN1A function may be responsible for some isolated cases of simple FS, as well. Interestingly, mice with SCN1A mutations are more susceptible to FS.^19,20

GEFS+ is also caused by mutations in the sodium channel β1 subunit, SCN1B^21,22 and two GABA_A receptor genes, GABRG2 and GABRD,^23,24,25,26 suggesting that these genes, too, may contribute to some cases of simple FS. Notably, mutations in the VGSC gene, SCN9A, which is traditionally considered a peripheral sodium channel, were recently found in 5 out of 92 unrelated FS patients.²⁷

The rate of temperature increase used to be considered a causative factor in febrile seizure generation, but this is no longer believed to be true. Although the etiology of FS is not fully understood, there are several known contributing factors. Fever is known to cause an immune response mediated by the release of proinflammatory cytokines, such as interleukin (IL)1β, which can enhance neuronal excitability, in part by augmenting glutamate receptor function.²⁸ Mice that lack the IL-1β receptor exhibit increased thresholds to experimentally induced FS, supporting a role for IL-1β in seizure generation.²⁹ Proinflammatory cytokines, which include IL-1β, IL-6, IL-10, and tumor necrosis factor alpha, are also elevated in patients with febrile seizures.³⁰ Febrile seizure induction experiments in immature rat pups also reveal a link between hyperthermia-induced hyperventilation and alkalosis in febrile seizure generation (reviewed in³¹); however, whether this holds true for human FS remains unclear.

The evaluation and treatment of a febrile seizure depends largely on the patient’s history and clinical presentation (FIG. 17–1). The first steps in evaluating a child with a febrile seizure are obtaining a detailed history and performing a physical examination. The American Academy of Pediatrics has established guidelines for children presenting with their first febrile seizure. As detailed in Table 17–1, the recommendation for a child 18 months or older who presents with a simple febrile seizure and is clinically stable, with no focal abnormalities, is that extensive diagnostic investigations, including routine electroencephalogram and neuroimaging, are unnecessary. Furthermore, patients with a single, simple febrile seizure do not require hospital admission.² Children younger than 18 months who present with a febrile seizure, on the other hand, should be observed for 24 hours and may require a lumbar puncture (LP), as the signs and symptoms of meningitis may not be obvious in this population.³²

A child who presents with a complex febrile seizure demands a more rigorous evaluation. The American Academy of Pediatrics recommends routine laboratory investigations and neuroimaging with computed tomography or magnetic resonance imaging for patients presenting with a complex febrile seizure. A LP should also be performed to evaluate the cerebrospinal fluid for evidence of meningitis.