BASICS
DESCRIPTION
- By definition, febrile seizures occur in pediatric patients aged 6 months to 5 years with fever ≥100.4 ‚ °F (38 ‚ °C). Evidence of an underlying neurologic abnormality, metabolic condition, or intracranial infection excludes this diagnosis.
- Distinguished as simple or complex based on multiple criteria (1):
- Simple (65 " “90%; must meet all criteria)
- Generalized clonic or tonic " “clonic seizure activity without focal features
- Duration <15 minutes
- Does not recur within 24 hours
- Resolves spontaneously
- No history of previous afebrile seizure or seizure disorder
- Complex (20 " “30%; only one criterion must be met)
- Partial seizure, focal activity
- Duration >15 minutes
- Recurs within 24 hours
EPIDEMIOLOGY
Incidence
- Approximately 500,000 febrile seizures occur in the United States annually.
- Most occur in children 6 months to 3 years old; only 6 " “15% occur in patients ≥4 years
- Peak incidence is 18 months of age.
- Risk of recurrence is 30 " “50% (2).
- Follows a bimodal seasonal pattern that mirrors peaks of febrile respiratory (November to January) and gastrointestinal infections (June to August).
Prevalence
- 2 " “5% of children in United States and Western Europe have at least one febrile seizure.
- Cumulative incidence varies in other populations (0.5 " “14%), with higher prevalence in Asia (3).
ETIOLOGY AND PATHOPHYSIOLOGY
A variety of mechanisms have been proposed: ‚
- A lower baseline seizure threshold in the age group affected by febrile seizures.
- Familial genotypes may result in lower seizure thresholds.
- Fever may alter ion channel activity, resulting in increased circuit excitability.
- Cytokines released secondary to infection, specifically interleukin (IL)-1 Ž ˛, increase neuronal activity.
Genetics
- Evidence for genetic association:
- Greater concordance in monozygotic than dizygotic twins
- Risk of febrile seizure with a previously affected sibling is increased.
- Having two affected parents doubles a child 's risk of febrile seizure.
- Positive family history can be seen in 25 " “40% of cases (4).
- Several rare familial epileptic syndromes present with febrile seizure.
RISK FACTORS
- Family history of febrile seizures; risk increases with the number of affected first-degree relatives.
- Any condition causing fever
- Recent vaccination
- As febrile seizures are a benign entity, the benefits of vaccination outweigh the risk.
- Risk increases after the administration of all measles-containing vaccines; peak incidence occurs 7 to 10 days after vaccination.
- Risk increases on the day of DTaP-IPV-Hib combination vaccine administration, as fever rate increases by 70% compared to giving them separately.
- Absolute vaccination-associated risk is very low.
- Prenatal exposure to alcohol and tobacco, iron deficiency anemia, daycare attendance, developmental delay, premature birth, and prolonged NICU stay
- Children with iron deficiency anemia may have increased risk for febrile seizures. Consider checking for anemia if the history suggests a risk for iron deficiency (5)[C].
GENERAL PREVENTION
Prevention is not usually indicated given the benign nature of this condition, lack of effective interventions, and side effects of prophylactic medications. ‚
COMMONLY ASSOCIATED CONDITIONS
- Viral infections: Frequently implicated pathogens include human herpesvirus 6, influenza, parainfluenza, adenovirus, and respiratory syncytial virus (RSV).
- Bacterial infections: Frequently associated infections include otitis media, pharyngitis, urinary tract infection (UTI), pneumonia, and gastroenteritis.
DIAGNOSIS
HISTORY
- History of present illness:
- Description of seizure:
- Febrile seizures are generalized with clonic or tonic " “clonic activity.
- Absence, myoclonic, atonic, and focal seizures are atypical of febrile seizures and warrant further evaluation.
- Seizure duration
- Presence of postictal state (consistent with febrile seizure)
- Number of seizures in previous 24 hours
- Lethargy, irritability, or decreased level of consciousness as reported by the caretaker
- Symptoms of underlying infection
- Symptoms concerning for neurologic deficits
- Past medical history:
- Existing conditions, including developmental delay, cerebral palsy, and metabolic disorders
- Recent antibiotic course
- History of febrile seizures
- History of afebrile seizures or seizure disorder
- History of head injury
- Vaccination status, recent immunization
- Family history: febrile seizures, afebrile seizures, epilepsy, metabolic disorders, and other neurologic conditions
- Social history: factors concerning for child abuse
PHYSICAL EXAM
- Vital signs should be stable and consistent with intercurrent febrile illness; unstable vital signs or toxic appearance warrant further evaluation.
- Identify the presence or absence of focal deficits on a complete neurologic exam.
- Assess for signs of meningitis, including decreased level of consciousness, irritability, meningeal signs, bulging fontanelle, papilledema, and petechiae.
- Identify cause of fever.
- Assess thoroughly for manifestations of child abuse with a careful skin exam, inspection and palpation for occult trauma, and retinal exam if possible.
DIFFERENTIAL DIAGNOSIS
- Seizures due to an etiology other than febrile seizure:
- Meningitis, encephalitis
- Primary epilepsy
- Neonatal seizure
- Dravet syndrome
- Intracranial mass
- Nonaccidental trauma
- Electrolyte abnormality
- Hypoglycemia
- Metabolic disorder
- Conditions presenting similarly to seizure:
- Rigors
- Crying
- Benign myoclonus of infancy
- Breath-holding spell
- Choking episode
- Tic disorder
- Parasomnia
- Arrhythmia
- Metabolic disorder
- Dystonic reaction
DIAGNOSTIC TESTS & INTERPRETATION
- Routine laboratory tests are not recommended to identify an underlying cause of a simple febrile seizure (1)[C].
- Rates of UTI in children with simple febrile seizures and in febrile children without seizure are comparable; consider obtaining urinalysis for susceptible patients (2)[B].
- Blood glucose if the patient is convulsing or is obtunded on presentation (2)[B].
- Lumbar puncture
- In studies of patients with simple febrile seizures conducted since the initiation of routine infant vaccination against Haemophilus influenzae, rates of acute bacterial meningitis were very low (0 " “0.8%).
- Seizure is unlikely to be the only presenting symptom of meningitis. Symptoms indicating increased likelihood of meningitis include toxic appearance, altered level of consciousness, meningeal signs, focal neurologic deficits, bulging fontanelle, and petechiae.
- Cases of bacterial meningitis in children with febrile seizures who return to baseline or in the absence of other signs or symptoms are rare (6).
- Recommendations:
- Lumbar puncture should be performed in a child with fever and seizure if meningeal signs are present or if there is concern for meningitis or other intracranial pathology based on history and exam (7)[B].
- In infants aged 6 to 12 months, consider lumbar puncture if the child has not been vaccinated against H. influenzae or Streptococcus pneumoniae according to schedule (7)[C].
- Consider lumbar puncture for children with fever and seizure who have recently been treated with antibiotics, as antibiotics may mask meningeal signs and symptoms (7)[C].
- The yield of lumbar puncture in children with complex febrile seizure is very low; however, some recommend considering a lumbar puncture in these patients (6)[B].
- Neuroimaging is not routinely recommended for the purposes of identifying the cause of a simple febrile seizure (7)[B].
- Studies have demonstrated limited use of emergent imaging in patients who meet criteria for complex febrile seizure based on multiple episodes in 24 hours; however, imaging may be indicated for focal findings or concerning history or exam. There are no current guidelines regarding imaging with complex febrile seizures (8)[B].
Diagnostic Procedures/Other
- EEG is not recommended in neurologically normal children presenting with simple febrile seizure (7)[B].
- There is mixed evidence for use of EEG after complex febrile seizures; some recommend outpatient EEG on follow-up.
TREATMENT
GENERAL MEASURES
- Acute seizure management
- Airway: Position the patient laterally, suction secretions, and place a nasopharyngeal airway if necessary.
- Breathing: Administer oxygen for cyanosis; consider bag-mask ventilation or intubation for inadequate ventilation.
- Circulation: Establish IV access if first-line buccal or nasal midazolam is not effective.
- Antipyretics are helpful for patient comfort but do not prevent seizure recurrence during the initial febrile episode (1)[A].
- Provide supportive care and treat underlying infection if necessary.
MEDICATION
First Line
Treat seizures of ≥5 minutes duration with anticonvulsants: ‚
- Buccal midazolam 0.5 mg/kg or nasal midazolam 0.2 mg/kg (3)
- IV or IM lorazepam 0.1 mg/kg
Second Line
Rectal diazepam is less effective and more commonly associated with respiratory depression than first-line treatments (1)[B]. ‚
ISSUES FOR REFERRAL
Simple febrile seizures do not require referral to a pediatric neurologist. ‚
INPATIENT CONSIDERATIONS
Admission Criteria/Initial Stabilization
- Unstable vital signs
- Concerning findings on history or physical exam
- Prolonged seizure requiring anticonvulsants
- Persistent change in mental status
- Inpatient management of underlying condition is required.
ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
- Anticonvulsant prophylaxis during subsequent febrile episodes (1)[B]:
- The American Academy of Pediatrics recommends against prophylaxis with anticonvulsants due to an unacceptable risk " “benefit ratio.
- Phenobarbital is effective but can have serious side effects, including lowering IQ.
- Prophylaxis with valproic acid may be effective but can cause hepatotoxicity and/or hyperammonemia.
- Prophylaxis with phenytoin and carbamazepine is ineffective.
- Oral and rectal diazepam are effective but are not recommended due to the benign nature of febrile seizures.
- Antipyretic prophylaxis during subsequent febrile episodes (1)[A]:
- No study has demonstrated that fever management will prevent recurrence.
- Ibuprofen and acetaminophen are no more effective than placebo in preventing recurrence.
PATIENT EDUCATION
There is frequently a high degree of parental anxiety associated with febrile seizures. Suggested anticipatory guidance: ‚
- Febrile seizures do not cause brain damage and are associated with a low risk for sequelae.
- Parents should be reassured after a simple febrile seizure that there is no negative impact on intellect, behavior, or risk of death (1)[B].
- Parents should be prepared for a high probability of recurrence.
- If seizure recurs, position the child safely and do not intervene inappropriately.
- Time the seizure; call rescue if the child turns blue, has difficulty breathing, or the seizure lasts >5 minutes.
- If the seizure spontaneously resolves in <5 minutes and the child is well but sleepy, seek immediate attention, but calling rescue is not necessary.
PROGNOSIS
- Recurrence:
- Estimates of recurrence rates vary (30 " “50%).
- Factors associated with seizure recurrence include age <12 months at time of first episode, first-degree relative with history of febrile seizure, and history of complex febrile seizures.
- Intellectual and behavioral outcomes (2)
- Febrile seizures do not impact IQ, behavioral abnormalities, academic performance, or neurocognitive inattention.
- Outcomes in children with single and multiple febrile seizures are similar.
- Subsequent development of epilepsy (2)
- Risk of epilepsy after a simple partial seizure is approximately 1% compared to the general population.
- Risk is 2.4% in those with multiple simple febrile seizures, age <12 months at time of initial episode and a family history of epilepsy.
- Factors associated with increased risk include presenting with complex febrile seizure, family history of epilepsy or febrile seizures, cerebral palsy, developmental delay, low birth weight, and prematurity.
- Mortality (2):
- A slight increase in mortality is attributable in part to underlying neurodevelopmental abnormalities and to the subsequent development of epilepsy.
- There is not an increased risk for SIDS in siblings of children who have febrile seizures.
COMPLICATIONS
Seizure-related injury, aspiration pneumonia, side effects of prescribed medications or diagnostic procedures, and subsequent parental perception of the child as being vulnerable, especially during subsequent fevers. ‚
REFERENCES
11 Graves ‚ RC, Oehler ‚ K, Tingle ‚ LE. Febrile seizures: risks, evaluation, and prognosis. Am Fam Physician. 2012;85(2):149 " “153.22 Steering Committee on Quality Improvement and Management, Subcommittee on Febrile Seizures American Academy of Pediatrics. Febrile seizures: clinical practice guideline for the long-term management of the child with simple febrile seizures. Pediatrics. 2008;121(6):1281 " “1286.33 Farrell ‚ K, Goldman ‚ R. The management of febrile seizures. B C Med J. 2011;53(6):268 " “273.44 Syndi Seinfeld ‚ D, Pellock ‚ J. Recent research on febrile seizures: a review. J Neurol Neurophysiol. 2013;4(165):19519.55 King ‚ D, King ‚ A. Question 2: should children who have a febrile seizure be screened for iron deficiency? Arch Dis Child. 2014;99(10):960 " “964.66 Najaf-Zadeh ‚ A, Dubos ‚ F, Hue ‚ V, et al. Risk of bacterial meningitis in young children with a first seizure in the context of fever: a systematic review and meta-analysis. PLoS One. 2013;8(1):e55270.77 Subcommittee on Febrile ‚ Seizures, American Academy of ‚ Pediatrics. Neurodiagnostic evaluation of the child with a simple febrile seizure. Pediatrics. 2011;127(2):389 " “394.88 Kimia ‚ A, Ben-Joseph ‚ EP, Rudloe ‚ T, et al. Yield of lumbar puncture among children who present with their first complex febrile seizure. Pediatrics. 2010;126(1):62 " “69.
CODES
ICD10
- R56.00 Simple febrile convulsions
- R56.01 Complex febrile convulsions
- G40.901 Epilepsy, unsp, not intractable, with status epilepticus
ICD9
- 780.31 Febrile convulsions (simple), unspecified
- 780.32 Complex febrile convulsions
- 345.3 Grand mal status
SNOMED
- 432354000 Simple febrile seizure
- 433083002 Complex febrile seizure
- 41497008 Febrile convulsion (finding)
CLINICAL PEARLS
- Febrile seizures are generally benign, and families can be reassured that children are at low risk of death, subsequent development of epilepsy, and learning or behavioral abnormalities.
- History and physical exam are important tools in identifying children presenting with febrile seizure who may be at greater risk for meningitis or other intracranial pathology.
- For simple febrile seizures, routine labs, lumbar puncture, neuroimaging studies, and EEG are not recommended in the absence of clinical suspicion of serious underlying pathology.
- Prophylaxis with anticonvulsants or antipyretics during subsequent febrile episodes is not recommended due to their lack of effectiveness and the risk of medication-associated side effects.