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Clinical Evidence Concise

Febrile Seizures
LEENA D. MEWASINGH, Imperial College NHS Trust, London, United Kingdom

Am Fam Physician. 2008 Nov 15;78(10):1199-1200.

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Febrile seizures are defined as events in infancy or childhood that usually occur between three
months and five years of age and are associated with a fever, but without evidence of intracranial
infection or a defined cause for the seizure.

• Simple febrile seizures are generalized in onset, last less than 15 minutes, and do not
occur more than once in 24 hours. Complex seizures last longer, have focal symptoms, and can
recur within 24 hours. This review only deals with simple febrile seizures.
• Approximately 2 to 5 percent of children in the United States and Western Europe, and 6
to 9 percent of infants and children in Japan, will have experienced at least one febrile seizure
by five years of age.
• Simple febrile seizures may slightly increase the risk of developing epilepsy, but have no
known adverse effects on behavior, scholastic performance, or neurocognition.
We do not know whether antipyretics are useful in treating episodes of fever to prevent seizure
recurrence in children with one or more previous simple febrile seizures.
• Intermittent anticonvulsants used in treating episodes of fever to prevent seizure
recurrence in children are associated with adverse effects, including hyperactivity; irritability;
and difficulties with speech, activity level, or sleep.
Continuous anticonvulsant treatment may be effective for reducing recurrence in children with
a history of simple febrile seizures, but it is associated with adverse effects. For example,
phenobarbital is associated with cognitive impairments and behavioral adverse effects (e.g.,
hyperactivity, irritability, aggressiveness).
• Anticonvulsants do not appear to reduce the risk of epilepsy up to 12 years later in
children with a history of simple febrile seizures.

Definition
Febrile seizures are divided into three types: simple febrile seizures, complex febrile seizures, and
febrile status epilepticus. The National Institutes of Health define a febrile seizure as “an event in
infancy or childhood usually occurring between three months and five years of age associated
with a fever, but without evidence of intracranial infection or defined cause for the seizure,” after
having excluded children with previous afebrile seizures. Another definition, from the
International League Against Epilepsy, is “a seizure occurring in childhood after one month of
age associated with a febrile illness not caused by an infection of the central nervous system,
without previous neonatal seizures or a previous unprovoked seizure, and not meeting the criteria
for other acute symptomatic seizures.”

Clinical Questions

In working practice, the lower age limit for febrile seizures is generally considered to be six
months, given concerns regarding the possibility of an underlying serious, but treatable, infection
in younger infants masquerading as a febrile seizure (e.g., meningitis). A simple febrile seizure is
a generalized seizure, often tonic-clonic, lasting less than 15 minutes in duration that does not
occur more than once in 24 hours, and is followed by full recovery within one hour.

Treatment for the actual seizure is generally not indicated, given the short duration. In over 80
percent of children, the duration of the febrile seizure is less than 10 minutes, and in only about 9
percent of children do they last longer than 15 minutes. Often, by the time the child presents to a
hospital, the seizure has already stopped. A febrile seizure may also be the presenting sign of a
fever episode.

This review does not include children experiencing complex febrile seizures, which are
characterized by any of the following features: longer than 15 minutes in duration, focal
symptoms, recurrence within 24 hours, and not followed by full consciousness within one hour.
Investigations, including neuroimaging and lumbar puncture, are often warranted. Also excluded
from this review are children experiencing febrile status epilepticus, which lasts longer than 30
minutes and requires treatment.

Addressing parental anxiety forms a key part of the management of simple febrile seizures,
because parents' (unspoken) worry with a first seizure is that their child might have died.
However, there is little in the medical literature about this aspect of education and reassurance in
the management of simple febrile seizures.

Etiology
Although the exact cause of simple febrile seizures is unknown, it is thought to be multifactorial,
with genetic and environmental factors having been shown to contribute to its pathogenesis.
Increasingly, a genetic predisposition is recognized, with febrile seizures occurring in families.
However, the exact mode of inheritance is not known and seems to vary between families.
Although polygenic inheritance is likely, there is a small number of families 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.

In addition, mutations in several genes have been found that account for enhanced susceptibility
to febrile seizures. A familial epilepsy syndrome exists (generalized epilepsy with febrile seizures
plus [GEFS+]), in which patients can have classic febrile seizures, febrile seizures that persist
beyond five years (hence, the “FS+”), or epilepsy. Similar genetic factors have been identified
that are involved in both febrile seizures and GEFS+.

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-aminobutyric
acid A receptor. Both of these channels are also associated with another early epilepsy syndrome,
severe myoclonic epilepsy of infancy, which often begins with prolonged febrile seizure (either
complex febrile seizure or febrile status) with subsequent seizures precipitated by fever.

With regard to risk factors, febrile seizures are more frequent in children attending day care
centers, and in those with a first- or second-degree relative with a history of febrile seizures. The
risk of another child having febrile seizures is one in five if one sibling is affected, and one in
three if both parents and a previous child have had febrile seizures. Other risk factors associated
with an increased rate of febrile seizure recurrence include young age at onset (younger than 12
months), history of simple or complex febrile seizures, and body temperature at onset of less than
40°C. Among these, age at onset seems the most constant predictive factor, with 50 percent of
children younger than 12 months and 30 percent of children older than 12 months presenting with
a recurrent febrile seizure. Positive family history of epilepsy is not consistently associated with
an increased recurrence of simple febrile seizures.

Prognosis
The risk of developing epilepsy is increased in children with a history of complex febrile seizures.
A strong association exists between febrile status epilepticus or febrile seizures characterized by
focal symptoms and later development of temporal lobe epilepsy.

EDITOR'S NOTE: Paracetamol is available as acetaminophen in the United States.


SEARCH DATE: August 2007
Author disclosure: Leena D. Mewasingh has been reimbursed by the pharmaceutical
companies Janssen-Cilag and UCB Pharma for attending congresses and meetings
on epilepsy.
Adapted with permission from Mewasingh LD. Febrile seizures. Clin Evid Handbook. June
2008:91–93. Please visit http://www.clinicalevidence.bmj.com for full text and references.
This is one in a series of chapters excerpted from the Clinical Evidence Handbook,
published by the BMJ Publishing Group, London, U.K. The medical information
contained herein is the most accurate available at the date of publication. More
updated and comprehensive information on this topic may be available in future print
editions of the Clinical Evidence Handbook, as well as online at
http://www.clinicalevidence.bmj.com (subscription required). Those who receive a
complimentary print copy of the Clinical Evidence Handbook from United Health
Foundation can gain complimentary online access by registering on the Web site using
the ISBN number of their book.

Clinical Questions
What are the effects of treatments given during episodes of fever in children with one or more previous simple febrile seizures?

Unknown
Antipyretic
effectiveness
treatments (physical antipyretic measures, paracetamol, ibuprofen)

Likely
Anticonvulsants
to be ineffective
(intermittent)
or harmful

What are the effects of long-term (daily, longer than one month) anticonvulsant treatment in children with a history of simple febrile seizures?

Trade-off
Anticonvulsants
between(continuous)
benefits and harms

What are the effects of treatments on reducing the risk of subsequent epilepsy in children with a history of simple febrile seizures?

Unlikely
Anticonvulsants
to be beneficial
(intermittent and continuous)

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