Practice Essentials

Pediatric febrile seizures, which represent the most common childhood

seizure disorder, exist only in association with an elevated temperature.
Evidence suggests, however, that they have little connection with cognitive
function, so the prognosis for normal neurologic function is excellent in
children with febrile seizures. [1]
Epidemiologic studies have led to the division of febrile seizures into 3
groups, as follows:
Simple febrile seizures
Complex febrile seizures
Symptomatic febrile seizures

Essential update: Starting MMR/MMRV vaccination earlier may reduce

seizure risk
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 measles-
mumps-rubella (MMR) or measles-mumps-rubella-varicella (MMRV)
vaccine beyond the age of 15 months may more than double the risk of
postvaccination seizures in the second year of life. [2, 3]
In infants, there was no association between vaccination timing and
postvaccination seizures. [3] In the second year of life, however, the incident
rate ratio (IRR) for seizures within 7-10 days was 2.65 (95% confidence
interval [CI], 1.99-3.55) after first MMR doses at 12-15 months of age,
compared with 6.53 (95% CI, 3.15-13.53) after first MMR doses at 16-23
months. For the MMRV vaccine, the IRR for seizures was 4.95 (95% CI,
3.68-6.66) after first doses at 12-15 months, compared with 9.80 (95% CI,
4.35-22.06) for first doses at 16-23 months.
Signs and symptoms
Simple febrile seizure
The setting is fever in a child aged 6 months to 5 years
The single seizure is generalized and lasts less than 15 minutes
The child is otherwise neurologically healthy and without neurologic
abnormality by examination or by developmental history
Fever (and seizure) is not caused by meningitis, encephalitis, or any
other illness affecting the brain
The seizure is described as either a generalized clonic or a generalized
tonic-clonic seizure
Complex febrile seizure
Age, neurologic status before the illness, and fever are the same as for
simple febrile seizure
This seizure is either focal or prolonged (ie, >15 min), or multiple
seizures occur in close succession
Symptomatic febrile seizure
 Age and fever are the same as for simple febrile seizure
The child has a preexisting neurologic abnormality or acute illness
See Clinical Presentation for more detail.
Diagnosis
No specific laboratory studies are indicated for a simple febrile seizure.
Physicians should instead focus on diagnosing the cause of fever. Other
laboratory tests may be indicated by the nature of the underlying febrile
illness. For example, a child with severe diarrhea may benefit from blood
studies for electrolytes.
With regard to lumbar puncture, the following should be kept in mind:
Strongly consider lumbar puncture in children younger than 12 months,
because the signs and symptoms of bacterial meningitis may be
minimal or absent in this age group
Lumbar puncture should be considered in children aged 12-18 months,
because clinical signs and symptoms of bacterial meningitis may be
subtle in this age group
In children older than 18 months, the decision to perform lumbar
puncture rests on the clinical suspicion of meningitis
See Workup for more detail.
Management
On the basis of risk/benefit analysis, neither long-term nor intermittent
anticonvulsant therapy is indicated for children who have experienced 1 or
more simple febrile seizures.
If, however, preventing subsequent febrile seizures is essential, oral
diazepam would be the treatment of choice. It can reduce the risk of febrile
seizure recurrence and, because it is intermittent, probably has the fewest
adverse effects.[4]
See Treatment and Medication for more detail.

Background
Febrile seizures are the most common seizure disorder in childhood. Since
early in the 20th century, people have debated about whether these
children would benefit from daily anticonvulsant therapy. Epidemiologic
studies have led to the division of febrile seizures into 3 groups, as follows:
simple febrile seizures, complex febrile seizures, and symptomatic febrile
seizures.
Simple febrile seizure
See the list below:
The setting is fever in a child aged 6 months to 5 years.
The single seizure is generalized and lasts less than 15 minutes.
 The child is otherwise neurologically healthy and without neurological
abnormality by examination or by developmental history.
Fever (and seizure) is not caused by meningitis, encephalitis, or other
illness affecting the brain.
Complex febrile seizure
See the list below:
Age, neurological status before the illness, and fever are the same as
for simple febrile seizure.
This seizure is either focal or prolonged (ie, >15 min), or multiple
seizures occur in close succession.
Symptomatic febrile seizure
See the list below:
Age and fever are the same as for simple febrile seizure.
The child has a preexisting neurological abnormality or acute illness.

Pathophysiology
This is a unique form of epilepsy that occurs in early childhood and only in
association with an elevation of temperature. The underlying
pathophysiology is unknown, but genetic predisposition clearly contributes
to the occurrence of this disorder. [5]

Frequency
United States
Febrile seizures occur in 2-5% of children aged 6 months to 5 years in
industrialized countries. Among children with febrile seizures, about 70-75%
have only simple febrile seizures, another 20-25% have complex febrile
seizures, and about 5% have symptomatic febrile seizures.

Mortality/Morbidity
See the list below:
Children with a previous simple febrile seizure are at increased risk of
recurrent febrile seizures; this occurs in approximately one third of
cases.
Children younger than 12 months at the time of their first simple febrile
seizure have a 50% probability of having a second seizure. After 12
months, the probability decreases to 30%.
 Children who have simple febrile seizures are at an increased risk for
epilepsy. The rate of epilepsy by age 25 years is approximately 2.4%,
which is about twice the risk in the general population.
The literature does not support the hypothesis that simple febrile
seizures lower intelligence (ie, cause a learning disability) or are
associated with increased mortality [6] .
Sex
Males have a slightly (but definite) higher incidence of febrile seizures.
Age
Simple febrile seizures occur most commonly in children aged 6 months to
5 years.

History
See the list below:
Children with simple febrile seizures are neurologically and
developmentally healthy before and after the seizure.
They do not experience a seizure in the absence of fever.
The seizure is described as either a generalized clonic or a generalized
tonic-clonic seizure.
o Signs of a focal seizure during the onset or in the postictal period
(eg, initial clonic movements of 1 limb or of the limbs on 1 side, a
weak limb postictally) would rule out a simple febrile seizure.
o Similarly, simple febrile seizure activity does not continue for more
than 15 minutes, although a postictal period of sleepiness or
confusion can extend beyond the 15-minute maximum.
Simple febrile seizures often occur with the initial temperature elevation
at the onset of illness. The seizure may be the first indication that the
child is ill. While no clear cutoff is known, a rectal temperature under
38C should raise concern that the event was not a simple febrile
seizure.

Physical
Physical examination findings reveal a neurologically and developmentally
healthy child. It is especially important that the child have no signs of
meningitis or encephalitis (eg, stiff neck or persistent mental status
changes).
Causes
Simple febrile seizures are considered a genetic disorder, but neither a
specific locus nor a specific pattern of inheritance has been described. The
mode of inheritance is likely to vary between families and may be
multifactorial.

Laboratory Studies
See the list below:
No specific studies are indicated for a simple febrile seizure.
Physicians should focus on diagnosing the cause of fever.
Other laboratory tests may be indicated by the nature of the underlying
febrile illness. For example, a child with severe diarrhea may benefit
from blood studies for electrolytes.

Imaging Studies
Neither computed tomography (CT) nor magnetic resonance imaging (MRI)
is indicated in patients with simple febrile seizures. A prospective study on
the outcomes of febrile status epilepticus (duration 30 minutes), named
the Consequences of Prolonged Febrile Seizures in Childhood or
FEBSTAT, has shown that febrile status epilepticus is more frequently
associated with hippocampal abnormality as compared to patients with
simple febrile seizure. [7]

Other Tests
EEG is not indicated in children with simple febrile seizures. Published
studies demonstrate that the vast majority of these children have a normal
EEG. In addition, some of those with an abnormal EEG have remained free
of seizures for the duration of their follow-up. On the other hand, some of
the children with a normal initial EEG have experienced 1 or more afebrile
seizures subsequent to the EEG. Finally, no evidence indicates that
beginning anticonvulsant therapy for a child with simple febrile seizures and
an abnormal EEG will alter the child's eventual outcome.

Procedures
See the list below:
Strongly consider lumbar puncture in children younger than 12 months,
because the signs and symptoms of bacterial meningitis may be
minimal or absent in this age group.
 Lumbar puncture should be considered in children aged 12-18 months,
because clinical signs and symptoms of bacterial meningitis may be
subtle in this age group.
In children older than 18 months, the decision to perform lumbar
puncture rests on the clinical suspicion of meningitis.

Medical Care
On the basis of risk/benefit analysis, neither long-term nor intermittent
anticonvulsant therapy is indicated for children who have experienced 1 or
more simple febrile seizures.
Continuous therapy with phenobarbital or valproate decreases the
occurrence of subsequent febrile seizures.
o Both therapies confer significant risks and potential adverse
effects, whereas additional simple febrile seizures have no proven
risk.
o These medications are not recommended, since the potential
benefits do not outweigh the potential risks.
No evidence suggests that any therapy administered after a first simple
seizure will reduce the risk of a subsequent afebrile seizure or the risk
of recurrent afebrile seizures (ie, epilepsy).
Oral diazepam can reduce the risk of subsequent febrile seizures.
Because it is intermittent, this therapy probably has the fewest adverse
effects. If preventing subsequent febrile seizures is essential, this
would be the treatment of choice.[4]
Although it does not prevent simple febrile seizures, antipyretic therapy
is desirable for other reasons, for instance comfort.
Febrile status epilepticus (duration 30 minutes) occurs in 5 to 9% of
children with first febrile seizure. Patients with febrile status epilepticus are
at greater risk for subsequent febrile status epilepticus. [8] Many
practitioners have prescribed rectal diazepam for patients with febrile
seizures, particularly those with febrile seizures lasting more than 5
minutes. There is some literature supporting the safety and efficacy towards
truncating the seizures. Following a review of 7 randomized studies,
investigators concluded that the benzodiazepine midazolam, administered
intranasally, is as safe and effective as intravenous or rectal diazepam in
the treatment of acute pediatric seizure emergencies. Results were based
on the administration of 0.2 mg/kg of intranasal midazolam versus 0.2-0.5
mg/kg of either intravenous (4 trials) or rectal (3 trials) diazepam, for the
treatment of seizure emergencies having an onset of action of less than 5
minutes. Patients in the study were aged 18 years or younger. The 3 types
of treatment produced only a few reports of respiratory depression. [9]
Medication Summary
On the basis of risk/benefit analysis, neither long-term nor intermittent
anticonvulsant therapy is indicated for children who have experienced 1 or
more simple febrile seizures. In unusual circumstances, oral diazepam can
be given with each fever.

Benzodiazepines
Class Summary
These agents have antiseizure activity and act rapidly in acute seizures.
Diazepam (Diastat Pediatric, Valium)
View full drug information
Oral diazepam can decrease number of subsequent febrile seizures when
given with each febrile episode. Many practitioners will prescribe rectal
diazepam, particularly to patients who have had prolonged febrile seizures,
in order to prevent future episodes of febrile status epilepticus. By
increasing activity of GABA, a major inhibitory neurotransmitter, depresses
all levels of CNS, including limbic and reticular formation.
A study reported in New England Journal of Medicine continued oral
diazepam therapy until child was afebrile for 24 h. However, this seems
excessive.

Prognosis
Prognosis for normal neurologic function is excellent.
About one third of children who experience a single simple febrile
seizure will have another.
The lifetime rate of epilepsy in these children is slightly above that of
the general population. [1]