Febrile Seizures

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Background

Febrile seizures are the most common type of seizures observed in the pediatric age group.

Although described by the ancient Greeks, it was not until this 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."[1] 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".[2]

For other information, see Medscape's Pediatrics Specialty page.

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 infection, otitis media, 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.[3] 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.[4, 5]

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).[6] 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. Shigella gastroenteritis also has been associated with febrile seizures. One study suggests a relationship between recurrent febrile seizures and influenza A.[7, 8]

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.[9]

While 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.[10, 11, 12]

Epidemiology

Frequency

United States

Between 2% and 5% of children have febrile seizures by their fifth birthday.[13]

International

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,[14] 0.35% for Hong Kong, and 0.5-1.5% for China.[15]

Mortality/Morbidity

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.[16]

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.[17, 18]

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.

History

Physical

Causes

Risk factors for developing febrile seizures are as follows[13, 19, 20, 21] :

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.[22] Risk factors for recurrent febrile seizures include the following[23, 24] :

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.[25] 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.[26]

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 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.[27, 28]

Laboratory Studies

In children under the age of 5 with complex febrile seizures, over one-third of experienced pediatric emergency physicians would do extensive workup, nearly half would admit, but variability exists in the approach to optimal management of patients with CFS. Past studies support more aggressive workup for patients under the age of 18 months, but future prospective studies on this subject are warranted.[29]

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.

Electrolytes assessments are rarely helpful in the evaluation of febrile seizures.[6]

Patients with febrile seizures have an incidence of bacteremia similar to patients with fever alone.[30]

Imaging Studies

A CT scan should not be performed in the evaluation of a child with a first simple febrile seizure.

A CT scan should be considered in patients with complex febrile seizures. However, a study by Teng et al analyzed data in 71 children with first complex febrile seizure.[31] Fifty-one (72%) had a single complex feature (20 focal, 22 multiple, and 9 prolonged), and 20 (28%) had multiple complex features. None of the 71 patients (1-sided 95% confidence interval, 4%) had intracranial pathologic conditions that required emergency neurosurgical or medical intervention. Forty-six had normal acute scans; the rest were normal on clinical follow up without a scan. The confidence interval means that this study cannot exclude a risk of intracranial pathology of 4% or less.

Kimia et al reported a retrospective cohort review in children presenting with first complex febrile seizure (CFS). Of 526 subjects with CFS, 268 had emergent head imaging: 4 had a clinically significant finding; 2 had intracranial hemorrhage; 1 had acute disseminated encephalomyelitis; and 1 patient had focal cerebral edema (1.5%; 95% CI, 0.5-4%). Assigning low risk to patients not imaged and not returning to the emergency department within a week of the original visit, the risk of intracranial pathology was 4 (0.8%; 95% CI, 0.2-2.1%). Three of these 4 patients had other obvious findings (nystagmus, emesis, and altered mental status; persistent hemiparesis; bruises suggestive of inflicted injury). In the absence of other sign and symptoms, patients presenting with CFS are at very low risk for intracranial pathology.[32]

Other Tests

An electroencephalogram (EEG) is not necessary in the routine evaluation of a child with a simple febrile seizure. In a prospective study, Nordli et al recruited 199 children with febrile status epilepticus (severe type of complex febrile seizure) within 72 hours of presentation. Of these, 45.2 % had an abnormal EEG with focal slowing and attenuation seen maximally over the temporal areas in almost all cases and were highly associated with MRI evidence of hippocampal injury.[33]

Procedures

Lumbar puncture

Controversy exists regarding the need for a lumbar puncture in a child presenting with a simple febrile seizure. Lumbar puncture is not needed for young children with first simple febrile seizure.[34]

Certainly, meningitis can present with a seizure, although the seizure usually is not the only sign of meningitis. Patients who have a first-time febrile seizure and do not have a rapidly improving mental status (short postictal period) should be evaluated for meningitis.

Several reviews of the medical literature report less than 5% incidence of meningitis in children presenting with seizures and fever.

Hom and Medwid, in an evidence-based review, examined the risk of bacterial meningitis as diagnosed by lumbar puncture in children presenting to the emergency department with a simple febrile seizure. The study population consisted of fully immunized children aged 6-18 months with an unremarkable history and normal physical examination. Of 461 children, 150 enrolled for febrile seizure underwent lumbar puncture to rule out meningitis. The rate of bacterial meningitis was 0% (95% CI, 0-3%).[35] Fletcher and Sharieff also determine that acute bacterial meningitis (ABM) is rare in patients presenting with a first complex febrile seizure. Patients presenting only with 2 short febrile seizures within 24 hours may be less likely to have ABM, and may not require lumbar puncture without other clinical symptoms of neurological disease.[36]

Risk factors for meningitis in patients presenting with seizure and fever include the following:

In 1996, the American Academy of Pediatrics (AAP) recommended that a lumbar puncture be strongly considered in patients younger than 12 months presenting with fever and seizure.[2] The AAP also recommended that a lumbar puncture be considered in patients aged 12-18 months. A lumber puncture is not routinely necessary in patients older than 18 months. This recommendation is conservative, but it takes into account the difficulty in recognizing meningitis in infants and young children and the range of experience in the evaluation of pediatric patients among healthcare providers.

In 2011, the AAP revised this guideline. It no longer recommends routine lumbar puncture in well-appearing, fully immunized children who present with a simple febrile seizure and makes lumbar puncture an option in infants age 6-12 months who are deficient in Haemophilus influenzae or Streptococcus pneumoniae immunizations or when immunization status cannot be established.[37]

Prehospital Care

Emergency Department Care

Medication Summary

Patients presenting in status epilepticus can be treated with routine seizure medications, including benzodiazepines, phenytoin, and phenobarbital. For further discussion on the treatment of seizures, see Pediatrics, Status Epilepticus.

Acetaminophen (Tylenol)

Clinical Context:  Reduces fever by acting directly on hypothalamic heat-regulating centers, which increases dissipation of body heat via vasodilation and sweating.

Ibuprofen (Advil, Motrin)

Clinical Context:  One of the few NSAIDs indicated for reduction of fever. Inhibits the formation of prostaglandins.

Class Summary

Antipyretics should be used in patients who appear uncomfortable secondary to fever. Antipyretics do not appear to prevent recurrence of febrile seizures.

Diazepam (Valium, Diastat)

Clinical Context:  Can decrease number of subsequent febrile seizures when given with each febrile episode. Modulates postsynaptic effects of GABA-A transmission, resulting in an increase in presynaptic inhibition. Appears to act on part of the limbic system, the thalamus, and hypothalamus, to induce a calming effect. Also has been found to be an effective adjunct for the relief of skeletal muscle spasm caused by upper motor neuron disorders.

Rapidly distributes to other body fat stores. Twenty minutes after initial IV infusion, serum concentration drops to 20% of Cmax.

Individualize dosage and increase cautiously to avoid adverse effects. Available as IV, PO, and PR dosage forms.

Lorazepam (Ativan)

Clinical Context:  Sedative hypnotic with short onset of effects and relatively long half-life.

By increasing the action of gamma-aminobutyric acid (GABA), which is a major inhibitory neurotransmitter in the brain, may depress all levels of CNS, including limbic and reticular formation.

Important to monitor patient's blood pressure after administering dose. Adjust as necessary.

Class Summary

Prophylactic treatment with an anticonvulsant agent may be considered for subsequent fever episodes.

Further Inpatient Care

Further Outpatient Care

Inpatient & Outpatient Medications

Deterrence/Prevention

Prognosis

Author

Nooruddin R Tejani, MD, Assistant Professor, Department of Emergency Medicine, SUNY Health Sciences Center Brooklyn; Director, Pediatric Emergency Medicine, Downstate Medical Center

Disclosure: Nothing to disclose.

Specialty Editors

Debra Slapper, MD, Southwest Washington Free Clinic System - Urgent Care

Disclosure: Nothing to disclose.

Mary L Windle, PharmD, Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Wayne Wolfram, MD, MPH, Professor, Department of Emergency Medicine, Mercy St Vincent Medical Center; Chairman, Pediatric Institutional Review Board, Mercy St Vincent Medical Center, Toledo, Ohio

Disclosure: Nothing to disclose.

John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center

Disclosure: Nothing to disclose.

Chief Editor

Richard G Bachur, MD, Associate Professor of Pediatrics, Harvard Medical School; Associate Chief and Fellowship Director, Attending Physician, Division of Emergency Medicine, Children's Hospital of Boston

Disclosure: Nothing to disclose.

Additional Contributors

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author, William T Zempsky, MD, to the development and writing of this article.

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