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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." It does not exclude children with prior
neurological impairment and neither provides specific temperature criteria nor
defines a "seizure."

Febrile seizures are usually benign but can cause considerable parental anxiety.
Recent studies have defined a group of patients at higher risk for febrile seizures
and a group likely to have recurrence of febrile seizures.

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

For related CME activities, see CME/CE - Neonatal Emergencies and CME/CE -
Commonly Administered Vaccines and Associated Illnesses.

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 1,
that, by increasing neuronal excitability, may link fever and seizure activity.
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.

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).
Complex febrile seizures may indicate a more serious disease process, such as
meningitis, abscess, or encephalitis. 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.
Genetics: 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.

Frequency

United States

Between 2% and 5% of children have febrile seizures by their fifth birthday. About
one third of these patients have at least one recurrence.

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, 0.35% for Hong Kong, and 0.5-1.5% for China.

Mortality/Morbidity

Febrile seizures are usually benign.


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.

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.

CLINICAL
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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.

Physical

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.

Causes

Risk factors for developing febrile seizures



o Family history of febrile seizures
o High temperature
o Parental report of developmental delay
o Neonatal discharge at an age greater than 28 days (suggesting
perinatal illness requiring hospitalization)
o Daycare attendance
o Presence of 2 of these risk factors increases the probability of a
first febrile seizure to about 30%.
o Maternal alcohol intake and smoking during pregnancy has a 2-fold
increased risk.
o 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.

o Risk factors for recurrent febrile seizures include the following:
o
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
o 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.

DIFFERENTIALS
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Epidural and Subdural Infections


Epidural Hematoma
Meningitis
Pediatrics, Bacteremia and Sepsis
Pediatrics, Fever
Pediatrics, Meningitis and Encephalitis
Pediatrics, Status Epilepticus

WORKUP
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Lab Studies

Routine laboratory studies usually are not indicated 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.
Patients with febrile seizures have an incidence of bacteremia similar to
patients with fever alone.

Imaging Studies

A CT scan usually is not necessary 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.1 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.

Other Tests
An electroencephalogram (EEG) usually is not necessary in the routine
evaluation of a child with a first simple febrile seizure.

Procedures

Lumbar puncture

o Controversy exists regarding the need for a lumbar puncture in a
child presenting with a simple febrile seizure.
o 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.
o Several reviews of the medical literature report less than 5%
incidence of meningitis in children presenting with seizures and
fever.
o Risk factors for meningitis in patients presenting with seizure and
fever include the following:
o
A physician visit within 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
o 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.

TREATMENT
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Prehospital Care

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.

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.
Parental anxiety needs to be addressed.
MEDICATION
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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.

Drug Category: Antipyretics

Antipyretics should be used in patients who appear uncomfortable secondary to


fever. Antipyretics do not appear to prevent recurrence of febrile seizures.
Drug Name Acetaminophen (Tylenol)
Reduces fever by acting directly on
hypothalamic heat-regulating centers,
Description
which increases dissipation of body heat
via vasodilation and sweating.
325-650 mg PO/PR q4-6h; not to exceed
Adult Dose
4 g/d
10-15 mg/kg PO/PR q4-6h; not to exceed
Pediatric Dose
5 doses/d or 2.6 g/d
Contraindications Documented hypersensitivity; liver failure
Rifampin can reduce analgesic effects of
acetaminophen; coadministration with
Interactions barbiturates, carbamazepine, hydantoins,
and isoniazid may increase
hepatotoxicity
B - Fetal risk not confirmed in studies in
Pregnancy humans but has been shown in some
studies in animals
Hepatotoxicity possible in chronic
alcoholics following various dose levels;
severe or recurrent pain or high or
continued fever may indicate a serious
Precautions illness; contained in many OTC products
and combined use with these products
may result in toxicity due to cumulative
doses exceeding recommended
maximum daily dose
Drug Name Ibuprofen (Advil, Motrin)
One of the few NSAIDs indicated for
Description reduction of fever. Inhibits the formation
of prostaglandins.
200-400 mg PO q4-6h while symptoms
Adult Dose
persist; not to exceed 3.2 g/d
5-10 mg/kg/dose PO q6-8h prn; not to
Pediatric Dose
exceed 40 mg/kg/d or 2.4 g/d
Documented hypersensitivity; peptic
ulcer disease, recent GI bleeding or
Contraindications
perforation, renal insufficiency, high risk
of bleeding
Interactions Coadministration with aspirin increases
risk of inducing serious NSAID-related
adverse effects; probenecid may
increase concentrations and, possibly,
toxicity of NSAIDs; may decrease effect
of hydralazine, captopril, and beta-
blockers; may decrease diuretic effects
of furosemide and thiazides; monitor PT
closely (instruct patients to watch for
signs of bleeding); may increase risk of
methotrexate toxicity; phenytoin levels
may be increased when administered
concurrently
B - Fetal risk not confirmed in studies in
humans but has been shown in some
Pregnancy studies in animals
D - Fetal risk shown in humans; use only
if benefits outweigh risk to fetus
Caution in congestive heart failure,
hypertension, and decreased renal and
Precautions hepatic function; caution in
anticoagulation abnormalities or during
anticoagulant therapy

Drug Category: Anticonvulsant agents

Prophylactic treatment with an anticonvulsant agent may be considered for


subsequent fever episodes.

Drug Name Diazepam (Valium, Diastat)


Description 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.
Disease state not seen in adults; adult
Adult Dose dose for seizures is 5-15 mg IV q5min,
repeat prn; not to exceed 30 mg in 8 h
Oral: 0.33 mg/kg PO at the onset of
fever; continue q8h until child is afebrile
Rectal (round dose to 2.5, 5, 10, 15, or
20 mg/dose):
Pediatric Dose
2-5 years: 0.5 mg/kg PR
6-11 years: 0.3 mg/kg
May repeat rectal dose once after 4-12 h
if needed, not to exceed 20 mg/dose
Documented hypersensitivity; narrow-
angle glaucoma; reversal agents (eg,
flumazenil) contraindicated when
Contraindications
lorazepam used for life-threatening
conditions (eg, control of intracranial
pressure or status epilepticus)
Phenothiazines, barbiturates, alcohols,
Interactions and MAO inhibitors increase CNS toxicity
when administered concurrently
D - Fetal risk shown in humans; use only
Pregnancy
if benefits outweigh risk to fetus
Caution with other CNS depressants, low
Precautions albumin levels, or hepatic disease (may
increase toxicity)
Drug Name 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
Description
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.
Adult Dose Disease state not seen in adults; adult
dose is 4 mg/dose IV slowly over 2-5 min
and repeat in 10-15 min prn; cumulative
dose of 8 mg/d typically considered
maximum
1-10 mg/d PO/IV/IM divided bid/tid
Infants and children: 0.1 mg/kg IV slowly
over 2-5 min; repeat prn in 10-15 min at
0.05 mg/kg; not to exceed 4 mg/dose
Pediatric Dose
Adolescents: 0.07 mg/kg IV slowly over
2-5 min and repeat in 10-15 min prn; not
to exceed 4 mg/dose
Documented hypersensitivity; preexisting
CNS depression, hypotension, and
narrow-angle glaucoma; reversal agents
Contraindications (eg, flumazenil) contraindicated when
lorazepam used for life-threatening
conditions (eg, control of intracranial
pressure or status epilepticus)
Toxicity of benzodiazepines in CNS
increases when used concurrently with
Interactions
alcohol, phenothiazines, barbiturates,
and MAO inhibitors
D - Fetal risk shown in humans; use only
Pregnancy
if benefits outweigh risk to fetus
May lead to hypoventilation or apnea
Precautions (flumazenil contraindicated); caution in
renal or hepatic impairment

FOLLOW-UP
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Further Inpatient Care

The decision to admit should be individualized, but admission usually is


not necessary.
Most patients should be observed in the ED until awake and alert.
Conditions requiring admission of the patient include the following:

o More than 1 seizure within 24 hours
o Unstable clinical status
o Lethargy beyond the postictal period
o Uncertain home situation
o 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.

In/Out Patient Meds

Discharge medications include antipyretics and (if indicated) antibiotics.


Prophylaxis for possible recurrence of febrile seizures is controversial.

o No evidence indicates that antipyretics prevent the recurrence of
febrile seizures.
o 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.
o Some studies report that diazepam, given orally or rectally every 8
hours during febrile illnesses, is effective in preventing recurrence
of febrile seizures.
o Diazepam is associated with ataxia and lethargy; thus, it may make
the evaluation of the febrile child more difficult.
o Many clinicians believe that the risk of treating prophylactically for
febrile seizures outweighs the benefits.
o A decision to place a child on prophylactic medication should be
made in conjunction with the primary physician.

Deterrence/Prevention
Given a more established role of influenza A in the etiology of febrile
seizure, both acute and recurrent, there may, perhaps, be a role of
vaccination against influenza A in the flu season, to prevent development
of both acute and recurrent febrile seizures.3

Prognosis

Although commonly frightening to parents, febrile seizures are benign


events.
Recurrent febrile seizures occur in about one third of children having a first
febrile seizure.

o Risk factors for recurrent febrile seizures include young age at time
of first febrile seizure, relatively low fever at time of presentation
with first seizure, family history of a febrile seizure in a first-degree
relative, and brief duration between fever onset and initial seizure.
o Patients with all 4 risk factors have a greater than 70% chance of
recurrence. Patients with no risk factors have a less than 20%
chance of recurrence.
Children with a febrile seizure have a slight increase in the incidence of
epilepsy compared with the general population (1% vs 0.5%).

o Risk factors for epilepsy later in life include complex febrile seizure,
family history of epilepsy or neurologic abnormality, and
developmental delay.
o Patients with 2 risk factors have up to 10% chance of developing
afebrile seizures.

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, visit eMedicine's Brain and
Nervous System Center. Also, see eMedicine's patient education articles
Seizures and Fever and Seizures in Children.

MISCELLANEOUS
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Medical/Legal Pitfalls

Meningitis must be ruled out by clinical examination or by lumbar


puncture. This is more difficult when the patient is taking oral antibiotics at
the time of seizure.
Parents should be taught what to do if a seizure reoccurs.

REFERENCES
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