Practice Essentials
Febrile seizures are the most common type of seizures observed in the pediatric age group. Febrile seizures are categorized into the following two types [1, 2] :
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Simple febrile seizures (which are generalized, last < 15 minutes, and do not recur within 24 hours)
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Complex febrile seizures (which are prolonged, recur more than once in 24 hours, or are focal)
Complex febrile seizures may indicate a more serious disease process, such as meningitis, abscess, or encephalitis.
Signs and symptoms
The underlying cause of the fever should be sought. A careful physical examination often reveals otitis media, pharyngitis, or a viral exanthem.
See Presentation for more detail.
Diagnosis
Laboratory studies
Routine laboratory studies usually are not indicated for febrile seizure unless they are performed as part of a search for the source of a fever.
Imaging studies
A computed tomography (CT) scan should not be performed in the evaluation of a child with a first simple febrile seizure; however, CT should be considered in patients with complex febrile seizures.
See Workup for more detail.
Management
Patients with active seizures should be treated with airway management, high-flow oxygen, supportive care, and anticonvulsants as necessary.
Patients who are postictal should receive supportive care and antipyretics as appropriate.
See Treatment and Medication for more detail.
Background
Although described by the ancient Greeks, it was not until the 20th century that febrile seizures were recognized as a distinct syndrome separate from epilepsy. In 1980, a consensus conference held by the National Institutes of Health described a febrile seizure as, "An event in infancy or childhood usually occurring between three months and five years of age, associated with fever, but without evidence of intracranial infection or defined cause." [3] It does not exclude children with prior neurological impairment and neither provides specific temperature criteria nor defines a "seizure." Another definition from the International League Against Epilepsy (ILAE) is "a seizure occurring in childhood after 1 month of age associated with a febrile illness not caused by an infection of the central nervous system (CNS), without previous neonatal seizures or a previous unprovoked seizure, and not meeting the criteria for other acute symptomatic seizures." [4]
Pathophysiology
Febrile seizures occur in young children at a time in their development when the seizure threshold is low. This is a time when young children are susceptible to frequent childhood infections such as upper respiratory tract infection, otitis media, and viral syndrome, and they respond with comparably higher temperatures. Animal studies suggest a possible role of endogenous pyrogens, such as interleukin 1beta, that, by increasing neuronal excitability, may link fever and seizure activity. [5] Preliminary studies in children appear to support the hypothesis that the cytokine network is activated and may have a role in the pathogenesis of febrile seizures, but the precise clinical and pathological significance of these observations is not yet clear. [6, 7]
Febrile seizures are divided into 2 types: simple febrile seizures (which are generalized, last < 15 min and do not recur within 24 h) and complex febrile seizures (which are prolonged, recur more than once in 24 h, or are focal). [1] Complex febrile seizures may indicate a more serious disease process, such as meningitis, abscess, or encephalitis. Febrile status epilepticus, a severe type of complex febrile seizure, is defined as single seizure or series of seizures without interim recovery lasting at least 30 minutes.
Viral illnesses are the predominant cause of febrile seizures. Recent literature documented the presence of human herpes simplex virus 6 (HHSV-6) as the etiologic agent in roseola in about 20% of a group of patients presenting with their first febrile seizures. Other viruses that have been commonly implicated in febrile seizures are influenza viruses, adenoviruses, and parainfluenza viruses. [2] Shigella gastroenteritis also has been associated with febrile seizures. One study suggests a relationship between recurrent febrile seizures and influenza A. [8, 9]
Febrile seizures tend to occur in families. In a child with febrile seizure, the risk of febrile seizure is 10% for the sibling and almost 50% for the sibling if a parent has febrile seizures as well. Although clear evidence exists for a genetic basis of febrile seizures, the mode of inheritance is unclear. [10]
Whereas polygenic inheritance is likely, a small number of families are identified with an autosomal dominant pattern of inheritance of febrile seizures, leading to the description of a "febrile seizure susceptibility trait" with an autosomal dominant pattern of inheritance with reduced penetrance. Although the exact molecular mechanisms of febrile seizures are yet to be understood, underlying mutations have been found in genes encoding the sodium channel and the gamma amino-butyric acid A receptor. [11, 12, 13]
Etiology
Risk factors for developing febrile seizures are as follows [14, 15, 16, 17] :
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Family history of febrile seizures
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High temperature
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Parental report of developmental delay
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Neonatal discharge at an age greater than 28 days (suggesting perinatal illness requiring hospitalization)
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Daycare attendance
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Presence of 2 of these risk factors - Increases the probability of a first febrile seizure to about 30%
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Maternal alcohol intake and smoking during pregnancy - Two-fold increased risk
Interestingly, no data support the theory that a rapid rise in temperature is a cause of febrile seizures.
About one third of all children with a first febrile seizure experience recurrent seizures. [18] Risk factors for recurrent febrile seizures include the following [19, 20] :
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Young age at time of first febrile seizure
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Relatively low fever at time of first seizure
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Family history of a febrile seizure in a first-degree relative
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Brief duration between fever onset and initial seizure
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Multiple initial febrile seizures during same episode
Patients with all 4 risk factors have greater than 70% chance of recurrence. Patients with no risk factors have less than a 20% chance of recurrence.
Regarding vaccination and risk of febrile seizures, Administration of the first dose of MMRV vaccine at age 12-15 months carries a slight increase risk of febrile seizure (0.05%, approximately 1 in 2000), from day 5 through 12 following receipt of the vaccine. However, the risk is not higher in older children receiving the second dose of MMRV. [21] A study by Macartney et al evaluated the risk of febrile seizures after a second dose of MMRV vaccine at 18 months. The study reported no increased risk of febrile seizures (RI, 1.08; 95% CI, 0.55-2.13) in the 5 to 12 days following MMRV vaccine given as the second MCV to toddlers. [22]
In a Danish study, DTaP-IPV-Hib vaccination was associated with an increased risk of febrile seizures on the day of first and second vaccinations, although the absolute risk was small. A higher risk for febrile seizures was found on the day of first vaccination (hazard ratio [HR], 6.02; 95% confidence interval [CI], 2.86-12.65), as well as on the day of the second vaccination (HR, 3.94; 95% CI, 2.18-7.10), but higher risk was not seen on the day of the third vaccination (HR, 1.07; 95% CI, 0.73-1.57) when compared with the reference group. Vaccination with DTaP IPV-Hib was not associated with an increased risk of epilepsy. [23]
In a case-series analysis of a cohort of 323,247 US children born from 2004 to 2008, Hambidge et al found that delaying the first dose of MMR or MMRV vaccine beyond the age of 15 months may more than double the risk of postvaccination seizures in the second year of life. [24, 25]
A study by Duffy et al sought to determine whether concomitant administration of trivalent inactivated influenza vaccine (IIV3) with other vaccines affects the febrile seizure risk. The study found that the administration of IIV3 on the same day as either pneumococcal conjugate vaccine or a diphtheria-tetanus-acellular-pertussis-containing vaccine was associated with a greater risk of febrile seizure than when IIV3 was given on a separate day. However, the absolute risk of postvaccination febrile seizure with these vaccine combinations was small. [26, 27]
Epidemiology
United States statistics
Between 2% and 5% of children have febrile seizures by their fifth birthday. [14]
International statistics
A similar rate of febrile seizures is found in Western Europe. The incidence elsewhere in the world varies between 5% and 10% for India, 8.8% for Japan, 14% for Guam, [28] 0.35% for Hong Kong, and 0.5-1.5% for China. [29]
Race-, sex-, and age-related demographics
Race
Febrile seizures occur in all races.
Sex
Some studies demonstrate a slight male predominance.
Age
By definition, febrile seizures occur in children aged 3 months to 5 years. The highest incidence of febrile seizures has been reported in children aged 12-18 months. [30]
Prognosis
Simple febrile seizures may slightly increase the risk of developing epilepsy, [31] but they have no adverse effects on behavior, scholastic performance, or neurocognition. The risk of developing epilepsy is increased further in children with a history of complex febrile seizures. [14, 32, 33, 34]
A strong association exists between febrile status epilepticus or febrile seizures characterized by focal symptoms and later development of temporal lobe epilepsy. [31, 35]
Children with febrile seizures have a slightly higher incidence of epilepsy compared with the general population (2% vs 1%).
Risk factors for epilepsy later in life include complex febrile seizure, family history of epilepsy or neurologic abnormality, and developmental delay. Patients with 2 risk factors have up to a 10% chance of developing afebrile seizures. [36]
Morbidity/mortality
Children with simple febrile seizures do not have increased mortality risk. However, seizures that were complex, occurred before age 1 year, or were triggered by a temperature of less than 39°C were associated with a 2-fold increased mortality rate during the first 2 years after seizure occurrence. [37]
Children with febrile seizures have a slightly higher incidence of epilepsy compared with the general population (2% vs 1%). [38] Risk factors for epilepsy later in life include complex febrile seizure, family history of epilepsy or neurologic abnormality, and developmental delay. Patients with 2 risk factors have up to a 10% chance of developing afebrile seizures. [39, 40]
Patient Education
Parents should be taught what to do if their child has another seizure.
The parent should be advised to call for assistance if the seizure lasts longer than 10 minutes or if the postictal period lasts longer than 30 minutes.
Parents should be counseled on the benign nature of febrile seizures.
Parents should be reassured that simple febrile seizures do not lead to neurologic problems or developmental delay.
