Clin Evid (Online). 2008; 2008: 0324.

Published online 2008 May 22.

PMCID: PMC2907951

Febrile seizures
Leena D Mewasingh, Consultant Paediatric Neurologist
Author information Copyright and License information

Abstract
Introduction
Simple febrile seizures are generalised in onset, last less than 15 minutes, and do not occur
more than once in 24 hours. Complex seizures are longer lasting, have focal symptoms, and
can recur within 24 hours. This review only deals with simple febrile seizures. About 2-5% of
children in the USA and Western Europe, and 6-9% of infants and children in Japan, will
have experienced at least one febrile seizure by the age of 5 years. Simple febrile seizures
may slightly increase the risk of developing epilepsy, but have no known adverse effects on
behaviour, scholastic performance, or neurocognition.

Methods and outcomes

We conducted a systematic review and aimed to answer the following clinical questions:
What are the effects of treatments given during episodes of fever in children with one or more
previous simple febrile seizures? What are the effects of long-term (daily, for more than 1
month) anticonvulsant treatment in children with a history of simple febrile seizures? What
are the effects of treatments on reducing the risk of subsequent epilepsy in children with a
history of simple febrile seizures? We searched: Medline, Embase, The Cochrane Library and
other important databases up to August 2007 (BMJ Clinical Evidence reviews are updated
periodically, please check our website for the most up-to-date version of this review). We
included harms alerts from relevant organisations such as the US Food and Drug
Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency
(MHRA).

Results
We found 19 systematic reviews, RCTs, or observational studies that met our inclusion
criteria. We performed a GRADE evaluation of the quality of evidence for interventions.

Conclusions
In this systematic review we present information relating to the effectiveness and safety of
the following interventions: anticonvulsants (intermittent or continuous), and antipyretic
treatments (physical antipyretic measures, paracetamol, ibuprofen).
Go to:

Key Points
Febrile seizures are defined as events in infancy or childhood usually occurring between 3
months and 5 years of age associated with a fever, but without evidence of intracranial
infection, or defined cause for the seizure.

Simple febrile seizures are generalised in onset, last less than 15 minutes, and do not
occur more than once in 24 hours. Complex seizures are longer lasting, have focal
symptoms, and can recur within 24 hours. This review only deals with simple febrile
seizures.
About 2-5% of children in the USA and Western Europe, and 6-9% of infants and
children in Japan will have experienced at least one febrile seizure by age 5 years.
Simple febrile seizures may slightly increase the risk of developing epilepsy, but have
no known adverse effects on behaviour, 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 is associated with adverse effects: for example,
phenobarbital is associated with cognitive impairments and behavioural adverse effects,
including hyperactivity, irritability, and 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.

About this condition

Definition
Febrile seizures are divided into three types: simple febrile seizures, complex febrile seizures,
and febrile status epilepticus. This review focuses on children with simple febrile seizures.
The National Institutes of Health (NIH) definition of a febrile seizure is "an event in infancy
or childhood usually occurring between 3 months and 5 years of age associated with a fever,
but without evidence of intracranial infection or defined cause for their seizure",[1] after
having excluded children with previous afebrile seizures. Another definition from the
International League Against Epilepsy (ILAE) is that of "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".[2] In working practice, the
lower age limit for febrile seizures is generally taken to be 6 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 generalised
seizure, often tonic-clonic, lasting less than 15 minutes in duration, which does not occur
more than once in 24 hours, and is followed by full recovery within 1 hour. Treatment for the
actual seizure is generally not indicated, given the short duration. In over 80% of children the
duration of the febrile seizure is less than 10 minutes, and in only about 9% of children do
they last longer than 15 minutes.[3] Often, by the time the child presents to 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 characterised by any of the following features: greater than 15 minutes in duration,
focal symptoms, recurrence within 24 hours, and not followed by full consciousness within 1
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, as 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 management of simple febrile seizures.

Incidence/ Prevalence
About 2-5% of children in the USA and Western Europe, and 6-9% of infants and children in
Japan, will have experienced at least one febrile seizure, simple or complex, by the age of 5
years. Elsewhere the incidence varies, being 5-10% in India, and as high as 14% in Guam.[2]
There are no specific data available for simple febrile seizures.

Aetiology/ Risk factors

While the exact cause of simple febrile seizures is unknown, it is thought to be multifactorial,
with both genetic and environmental factors having been shown to contribute to its
pathogenesis.[4] [5]Increasingly, a genetic predisposition is recognised, with febrile seizures
occurring in families. However, the exact mode of inheritance is not known, and seems to
vary between families. While 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.[6] [4] In addition, mutations in

several genes have been found that account for enhanced susceptibility to febrile seizures.[5]
[7] [8] [9] [10] [11]A familial epilepsy syndrome exists (Generalised Epilepsy with Febrile
Seizures Plus [GEFS+]), in which patients can have classical febrile seizures, febrile seizures
that persist beyond 5 years (hence FS+), and/or epilepsy. Similar genetic factors have been
identified that are involved in both febrile seizures and GEFS+.[5] [12] 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.[12] [13]Both of these channels are also associated with another early epilepsy
syndrome, Severe Myoclonic Epilepsy of Infancy (SMEI) which often begins with prolonged
febrile seizure (either complex febrile seizure or febrile status) with subsequent seizures
precipitated by fever.[12] With regards risk factors, febrile seizures are more frequent in
children attending day-care centres, and in those with a first- or second-degree relative with a
history of febrile seizures.[14] 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.[15] Other risk factors associated with an increased rate of febrile seizure recurrence
include young age at onset (less than 12 months), history of simple or complex febrile
seizures, and body temperature at onset of less than 40 C.[14] [16] Among these, age at
onset seems the most constant predictive factor, with 50% of children aged less than 12
months, and 30% of children aged more than 12 months, presenting with a recurrent febrile
seizure. Positive family history of epilepsy is not consistently associated with increased
simple febrile seizure recurrence.[16]

Prognosis
Simple febrile seizures may slightly increase the risk of developing epilepsy,[17] but have no
adverse effects on behaviour, scholastic performance, or neurocognition. The risk of
developing epilepsy is increased further in children with a history of complex febrile seizures.
[18] [19] [20] [21] A strong association exists between febrile status epilepticus or febrile
seizures characterised by focal symptoms and later development of temporal lobe epilepsy.
[17] [22]

Aims of intervention
To reduce febrile seizures and prevent recurrence, and to prevent the development of
epilepsy, with minimal adverse effects.

Outcomes
Febrile seizures; development of epilepsy; adverse effects of treatment.

Methods
BMJ Clinical Evidence search and appraisal August 2007. The following databases were used
to identify studies for this review: Medline 1966 to August 2007, Embase 1980 to August
2007, and The Cochrane Database of Systematic Reviews and Cochrane Central Register of
Controlled Clinical Trials 2007, Issue 3. Additional searches were carried out using these
websites: NHS Centre for Reviews and Dissemination (CRD) for Database of Abstracts of
Reviews of Effects (DARE) and Health Technology Assessment (HTA), Turning Research

into Practice (TRIP), and NICE. Abstracts of the studies retrieved from the initial search were
assessed by an information specialist. Selected studies were then sent to the author for
additional assessment, using pre-determined criteria to identify relevant studies. Study design
criteria for evaluation in this chapter were: published systematic reviews and RCTs in any
language, and containing more than 20 individuals of whom more than 80% were followed
up. There was no minimum length of follow-up required to include studies. We included all
studies described as "blinded", "open", "open label", or not blinded. We also searched for
cohort studies on specific harms of named interventions. In addition, we use a regular
surveillance protocol to capture harms alerts from organisations such as the FDA and the UK
Medicines and Healthcare products Regulatory Agency (MHRA), which are added to the
review as required. Some systematic reviews meta-analysed RCTs of children with both
simple febrile seizures and complex febrile seizures, and in some RCTs the type of febrile
seizure is unspecified; we have reported this throughout the text. We have performed a
GRADE evaluation of the quality of evidence for interventions included in this review