Juliann M. Paolicchi, MA, MD

DESCRIPTION

• Febrile seizures (FSs) are seizures that occur in infancy or childhood, typically between 3 months and 5 years, associated with fever, but without evidence of intracranial infection or defined cause. FSs are distinct from epilepsy, which is characterized by recurrent nonfebrile seizures.
• Simple FS: Single, brief (<15 minutes), generalized seizures during fever (rise or fall) in developmentally/neurologically normal children
• Complex FS: Duration >15 minutes, focal features or postictal focal weakness, or recur within 24 hours
• Febrile status epilepticus (FSE): Continuous or intermittent seizures without neurologic recovery for a period of 30 minutes or longer.
• Febrile seizure syndrome (FSS): Genetic epilepsy with FSs plus: FSs with generalized tonic–clonic seizures, complex partial seizures, and absence seizures. Strong family history of similar seizures.

EPIDEMIOLOGY

Incidence/Prevalence

• Most FSs are simple (65%). The most frequent complex feature is focality, followed by recurrence and prolonged duration. FSE accounts for only 5% of all FSs, but accounts for 25% of all childhood status epilepticus and more than two-thirds of status epilepticus in the second year of life.
• Age: FSs occur in 2–5% of all children <5 years of age. 90% occur between 6 months and 3 years, with the peak period between 12 and 18 months. 4% occur before 6 months, and 6% occur after age 3 years.
• Sex: Slightly more frequently in boys.

RISK FACTORS

• Family history of seizures, FS, FSS.
• Previous neurologic injury, stroke, hemorrhage, infection
• Recent immunizations: On the same day as diptheria/tetanus/pertiussis vaccination, and 8–14 days after measles/mumps/rubella vaccination

Genetics

• Inheritance: Multifactorial in most cases. Children with a positive family history of FS are more likely to experience FS and to have recurrences. At least, five different genetic loci have been identified.
• FSS: Multiple genes identified including SCN1A, SCN1B, and GABA(A) gamma 2 subunit genes.

GENERAL PREVENTION

• Since the seizure typically occurs early in the onset of the FS, and is often the first presenting sign, prevention is not effective. Children with a history of recurrent FS can be treated with diazepam (see below).
• Adherence to vaccination schedules in infancy and childhood can reduce the incidence and severity of febrile illnesses.

Etiology/Pathophysiology

Pathogenesis is likely multifactorial based on genetic predisposition, maturity of brain development, proconvulsant fever-induced factors (i.e. interleukin-1-beta), temperature sensitive neuronal ion channels, and fever-induced hyperventilation and alkalosis.

COMMONLY ASSOCIATED CONDITIONS

Any fever-inducing childhood infection; most frequently, upper respiratory infections, otitis media, roseola infantum, tonsillitis, and gastroenteritis and Herpesvirus-6 (exanthema subitum or roseola) are associated with FS.

HISTORY

• FS often occur early in the course of a febrile illness. The majority of events are brief (<15 minutes).
  • Tonic-clonic seizures are most common seizure type, but partial features can be present. A typical seizure involves a cry, loss of consciousness, and tonic posture. Breath-holding or circumoral cyanosis may be observed, along with vomiting and incontinence. Focality may be observed during the clonic phase. Postictal lethargy or sleep is common.
• Previous history of seizures, febrile or afebrile, neurologic or developmental abnormality
• Presence of neurologic and developmental abnormality increases risk of subsequent epilepsy. Previous afebrile seizures suggest a seizure precipitated by fever rather than FS.
• Diagnosis of FS after 6 years should be one of the exclusions.
• Precipitating factors: Degree and duration of fever, length and symptoms of preceding illness, recent history of head trauma, possibility of ingestion of toxic substance: Low fever, ingestion, head trauma, or prolonged illness before seizure suggest cause other than fever alone.
• Past medical history: Gestation, birth, general health, growth and development, and current medications. Birth complications and developmental delay may increase risk of epilepsy, but not of FS.
• Family history: Both febrile and afebrile seizures can be hereditary. A family history of FS is typically present.
  • Neurologic findings: Recent onset of headaches, vomiting not in the setting of GI illness, lethargy, weakness, sensory deficits, or changes in vision, behavior, balance, or gait suggest underlying brain pathology or infection and the need for neuroimaging and/or lumbar puncture

PHYSICAL EXAM

• Vital signs:
  • Degree of fever
  • Tachycardia or hypotension (suggests sepsis)
  • Tachypnea (suggests respiratory infection)
  • Head circumference
  • Signs of head trauma or possible abuse: Retinal hemorrhages and evidence of intracranial hypertension such as bulging fontanelle should be noted on HEENT exam.
  • Meningitis: Nuchal rigidity. ALERT: Not a reliable sign in infants, esp. <6 months of age.
• Careful neurologic examination: Specific attention should be directed to mental status and presence of focal abnormalities of motor strength, tone, or sensation.

DIAGNOSTIC TESTS AND INTERPRETATION

Lab

Initial Lab Tests

• Routine laboratory testing not necessary after a simple FS if child appears well.
• Additional laboratory analysis dependent on history, presentation and examination of the child, and as needed for diagnosis of the fever. Can include CBC, electrolytes, calcium, glucose, and toxicology screen.

ALERT

Imaging

• Urgent CT: Reserved for infants and children presenting with fever and seizures in whom the diagnosis of acute neurologic event/infection is suspect.
• MRI: Reserved for children with:
  • Complex (focal or prolonged) FS
  • Focal neurologic deficits, even transitory, after seizure
  • Focal abnormality on EEG
• Should be done after febrile illness has resolved, except if indicated for workup of febrile illness.

Diagnostic Procedures/Other

• EEG: Not routinely indicated after simple FS. Should be performed on children who are neurologically abnormal, experience complex FS, or have prolonged postictal encephalopathy.
• Lumbar Puncture: Indicated when history or examination suggests CNS infection. Special considerations:
  • children under 6 months of age with any new-onset FS
  • older child who appear toxic, have clinical signs suggesting CNS infection, have a prolonged postictal encephalopathy
  • LP may be indicated for children with new onset FS who have been pretreated with antibiotics.

DIFFERENTIAL DIAGNOSIS

• Non-epileptic imitators of seizures: i.e., chills or rigor due to fever in a child with illness
• Underlying CNS injury/illness presenting with seizure and fever, i.e.
  • CNS infection
    • Anoxia/Stroke/Hemorrhage
    • Trauma
    • Intoxication
    • Metabolic encephalopathy
    • Neurodegenerative disorder
    • Brain lesion or tumor
    • Neurocutaneous syndromes
    • Epileptic conditions
    • Previous history of afebrile seizures
    • Certain neurogenetic conditions present with seizures in the setting of high fevers, i.e., Angelman's and Dravet's syndrome.
    • Previous brain injury (stroke, CNS infection, hemorrhage, birth asphyxia, cerebral palsy)

MEDICATION

First Line

• Primary therapy is abortive. Rectal diazepam, 0.3–0.5 mg/kg, can be administered if seizure persists for >5 minutes.
• Focality and a prolonged FS, >10 minutes, are more likely to have recurrence. Therapy with abortive medication should be considered with the first incidence of FS.
  • Oral administration of diazepam, 0.3 mg/kg q8h, during febrile illnesses reduces risk of recurrent FS; however, causes sedation, and is typically useful only for children with a history of recurrent FS within an illness.

Second Line

Antiepileptic medications that have evidence of efficacy in recurrent FS include phenobarbital, valproate, and primidone limiting side effects occur in 40% of patients. Phenytoin and carbamazepine are ineffective as prophylaxis. There are limited data to support the use levetiracetam for FS.

ADDITIONAL TREATMENT

General Measures

• Treatment of a single FS is not indicated
  • Antiepileptic medication is typically reserved for diagnosis of established epilepsy. Anti-epileptic medication does not prevent the subsequent development of epilepsy. Abortive therapy is recommended in children with complex FS, and recurrent simple FS.
  • Treatment with antipyretics does not significantly affect the recurrence rate of FS.

Issues for Referral

Neurologic referral indicated for children in whom underlying CNS illness is suspected from history, presentation or examination, or if history reveals previous afebrile seizures.

COMPLEMENTARY AND ALTERNATIVE THERAPIES

Routine vaccination reduces the occurrence of childhood febrile illnesses.

IN-PATIENT CONSIDERATIONS

Initial Stabilization

If abortive therapy is ineffective, initiate status epilepticus protocol for children.

Admission Criteria

Admission indicated for FSE, seizures induced by CNS infection or lesion, frequent recurrent FS, persistent postictal encephalopathy, and children whose underlying source of fever warrants admission.

FOLLOW-UP RECOMMENDATIONS

Patient Monitoring

The majority of children with FS can have adequate follow-up with their primary care provider. Neurologic follow-up is indicated for the development of afebrile seizures.

PATIENT EDUCATION

• Web site: http://www.epilepsy.com
• Parents/caregivers of children with FS should be counseled regarding treatment of subsequent seizures including placement of the child supine with head turned to avoid aspiration with nothing in the mouth. Abortive therapy should be initiated at 5 minutes of seizure activity and EMT services should be activated. Instruct to administer rectal diazepam for prolonged or serial seizures.
• Children with recurrent seizures of any kind should receive the following precautions: Not to swim or bathe unattended, sleep in a top bunk bed, or climb to high places. They should wear a helmet when biking or using any wheeled toy.

PROGNOSIS

• Recurrent FS occur in 30% of children with FS, and 50% of children with recurrence have a third FS. Four predictors of occurrence are young age at onset, FS in a first degree relative, low precipitating fever, and short duration between fever onset and seizure. The risk factors are cumulative: 70% with 4 factors, 20% with none.
• Age of presentation is the strongest predictor of recurrence: 50–60% of infants <12 months have recurrence. Of recurrences, 90% occur within 2 years, 75% within 1 year, and 50% within 6 months.
• The risk of children with FS developing epilepsy is 2%, compared to 1% in the general population.
• Risk factors for the development of epilepsy include: Focal, prolonged, and recurrent seizures. The risk factors are cumulative: 25% higher risk in children with 3 factors compared to none.
• No evidence that occasional FS or even FSE causes subsequent neurologic/cognitive deficits.

COMPLICATIONS

FS can present or recur as FSE. If seizure activity persists after an initial abortive therapy is administered, the protocol for status epilepticus in children needs to be initiated.

• Annegars JF, Hauser WA, Shirts SB, Kurland LT. Factors prognostic of unprovoked seizures after febrile convulsions. NEJM 1987;316:493.
• Baumann RJ, Duffner PK. Treatment of children with simple febrile seizures: The AAP practice parameter. American Academy of Pediatrics. Pediatr Neurol 2000;23:11–17.
• Berg AT, Shinnar S, Hauser WA, et al. A prospective study of recurrent febrile seizures. Pediatrics 1978;61:720.
• Subcommittee on Febrile Seizures. Neurodiagnostic evaluation of the child with a simple febrile seizure. Pediatrics 2011;127:389.
• Strengell T, Uhari M, Tarkka R, et al. Antipyretic agents for preventing recurrences of febrile seizures: Randomized controlled trial. Arch Pediatr Med 2009;163:799.

SEE-ALSO

NIH Febrile Seizures Fact Sheet: http://www.ninds.nih.gov/disorders/febrile_seizures/detail_febrile_seizures.htm

ICD9

• 780.31 Febrile convulsions (simple), unspecified
• 780.39 Other convulsions

• FS is common in children <5 years, and unlikely to result in subsequent neurologic injury or epilepsy.
• The diagnosis is focused on evaluation for other neurologic conditions, such as CNS infection/injury that may present as a seizure in the setting of fever.
• Rectal diazepam is an effective abortive agent for recurrent and prolonged FS. Anti-epileptic medication should be reserved for children with epilepsy.