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.

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 39C 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

The type of seizure (generalized or focal) and its duration should be

described to help differentiate between simple and complex febrile seizures.
Focus on the history of fever, duration of fever, and potential exposures to
illness.
A history of the cause of fever (eg, viral illnesses, gastroenteritis) should be
elucidated.
Recent antibiotic use is particularly important because partially treated
meningitis must be considered.
A history of seizures, neurologic problems, developmental delay, or other
potential causes of seizure (eg, trauma, ingestion) should be sought.

The underlying cause for the fever should be sought.

A careful physical examination often reveals otitis media, pharyngitis, or a

viral exanthem.
Serial evaluations of the patient's neurologic status are essential.
Check for meningeal signs as well as for signs of trauma or toxic ingestion.
Risk factors for developing febrile seizures are as follows:[13, 19, 20, 21]

Family history of febrile seizures

High temperature
Parental report of developmental delay
Neonatal discharge at an age greater than 28 days (suggesting perinatal
illness requiring hospitalization)
Daycare attendance
Presence of 2 of these risk factors - Increases the probability of a first
febrile seizure to about 30%
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.[22] Risk factors for recurrent febrile seizures include the
following[23, 24] :

Young age at time of first febrile seizure

Relatively low fever at time of first seizure
Family history of a febrile seizure in a first-degree relative
Brief duration between fever onset and initial seizure
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.[25] In a Danish study, DTaP-IPVHib 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], 2.8612.65), 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 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.[
Epidural and Subdural Infections
Epidural Hematoma
Meningitis
Pediatrics, Bacteremia and Sepsis
Pediatrics, Fever
Pediatrics, Meningitis and Encephalitis
Pediatrics, Status Epilepticus
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.

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.
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.[

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:

A visit to a healthcare setting within the previous 48 hours

Seizure activity at the time of arrival in the ED
Focal seizure, suspicious physical examination findings (eg, rash,
petechiae) cyanosis, hypotension, or grunting
Abnormal neurologic examination
Pretreatment with antibiotics, as it can mask signs and symptoms of
meningitis

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.

Prehospital Care

Patients with active seizures should be treated with airway management,

high-flow oxygen, supportive care, and anticonvulsants as necessary. Acute
treatment such as rectal diazepam (0.5 mg/kg) and buccal 0.4-0.5 mg/kg) or
intranasal (0.2 mg/kg) are effective and can be given at home for a seizure
lasting longer than 5 minutes.[38, 39, 40]
Patients who are postictal should receive supportive care and antipyretics
as appropriate.
Emergency Department Care

Patients presenting with status epilepticus should be treated with airway

management and anticonvulsants as necessary.
Patients presenting with history and physical examination findings
consistent with a simple febrile seizure should have frequent neurologic
examinations to monitor mental status.
Other causes of seizure should be ruled out.
The cause of the febrile illness should be sought and treated.
Antipyretics should be considered. Acetaminophen (Tylenol) and ibuprofen
(Motrin) are often used.
Parental anxiety and fear that their child may die or will develop brain
damage needs to be addressed with reassurance and education.
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,
Class Summary

Antipyretics should be used in patients who appear uncomfortable secondary

to fever. Antipyretics do not appear to prevent recurrence of febrile seizures.

Acetaminophen (Tylenol)

Reduces fever by acting directly on hypothalamic heat-regulating centers,

which increases dissipation of body heat via vasodilation and sweating.
<12 years: 10-15 mg/kg PO q4-6hr PRN; not to exceed 2.6 g/day (5 doses/24
hours)

>12 years: 40-60 mg/kg/day PO divided q6hr PRN; not to exceed 3.75 g/day
(5 doses/24 hours)

Potential toxic dose <6 years: 200 mg/kg

Ibuprofen (Advil, Motrin)

One of the few NSAIDs indicated for reduction of fever. Inhibits the formation
of prostaglandins.
Fever

6 months to 12 years

<102.5 degrees F: 5-10 mg/kg/dose PO q6-8hr; not to exceed 40 mg/kg/day

102.5 degrees F: 10 mg/kg/dose q6-8hr; not to exceed 40 mg/kg/day

Pain

4-10 mg/kg/dose PO q6-8hr

Juvenile Idiopathic Arthritis

30-50 mg/kg/24hr PO divided q8hr; not to exceed 2.4 g/day

Patent Ductus Arteriosus

See ibuprofen IV drug monograph

Cystic Fibrosis (Off-label)

<4 years: Safety and efficacy not established

4 years: PO administration q12hr, adjusted to maintain serum levels of 50100 mcg/mL; may slow disease progression in younger patients with mild
lung disease
Dosing Considerations

Potential toxic dose in children <6 years: 200 mg/kg

Anticonvulsant agents
Class Summary

Prophylactic treatment with an anticonvulsant agent may be considered for

subsequent fever episodes.
View full drug information
Diazepam (Valium, Diastat)

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.
View full drug information
Lorazepam (Ativan)

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.
Further Inpatient Care

The decision to admit should be individualized, but admission usually is not

necessary for patients with febrile seizure.
Most patients should be observed in the ED until awake and alert.
Conditions requiring admission of the patient include the following:
More than 1 seizure within 24 hours
Unstable clinical status
Lethargy beyond the postictal period
Uncertain home situation

Unclear follow-up care

Further Outpatient Care

Arrange for medical reevaluation of discharged patients and parental

education in a follow-up appointment within 24-48 hours.
Inpatient & Outpatient Medications

Discharge medications include antipyretics and, if indicated, antibiotics

(eg, otitis media, pneumonia).
Prophylactic use of antipyretics and sedatives/anticonvulsants for possible
recurrence of febrile seizure has not shown to be effective.
Regular or sporadic administration of antipyretics during febrile illness is
generally safe, but no study has shown them to be effective in reducing
recurrence of febrile seizures.[41, 42] Acetaminophen and ibuprofen are no
better than placebo for preventing recurrences of febrile seizures .[43]
Phenobarbital and valproic acid can be given daily and are effective, but
they are associated with multiple adverse effects. Carbamazepine and
phenytoin are not effective in preventing recurrent febrile seizures. Citing a
preponderance of harm over benefit, the 2008 Clinical Practice Guideline for
the Long-Term Management of the Child with Simple Febrile Seizures
recommends neither continuous nor intermittent use of anticonvulsants for
children with one or more simple febrile seizures.[42]
Some studies report that diazepam, given orally or rectally every 8
hours during febrile illnesses, is effective in preventing recurrence of febrile
seizures.[44, 45] . However, these benzodiazepines can cause lethargy,
drowsiness, and ataxia, and sedation could mask an evolving central nervous
system infection. The AAP guideline released in 2008 does not recommend
prophylactic use of diazepam as the risk outweighs the benefits.
Deterrence/Prevention

Given a more established role of influenza A in the etiology of febrile

seizure, both acute and recurrent, vaccination against influenza A in the flu
season may have a role in preventing development of both acute and
recurrent febrile seizures.[8]

Prognosis

Simple febrile seizures may slightly increase the risk of developing

epilepsy,[46] 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.[13, 47, 48, 49]
A strong association exists between febrile status epilepticus or febrile
seizures characterized by focal symptoms and later development of temporal
lobe epilepsy.[46, 50]
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.[51]
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.
For excellent patient education resources