Febrile seizures

Marvin A Fishman, MD , Douglas R Nordli, Jr, MD , April F Eichler, MD, MPH

All topics are updated as new evidence becomes available and our peer review
process is complete.
Literature review current through: Mar 2013. | This topic last updated: Nov 16, 2012.
INTRODUCTION febrile seizures are a common cause of convulsions in young
children. They occur in 2 to 4 percent of children younger than five years of age, but
the incidence is as high as 15 percent in some populations. This incidence has been
attributed to closer living arrangements among family members making detection
more likely, but racial and geographic variations may also be important.
The generally accepted criteria for febrile seizures include:

A convulsion associated with an elevated temperature greater than 38C

A child younger than six years of age
No central nervous system infection or inflammation
No acute systemic metabolic abnormality that may produce convulsions
No history of previous afebrile seizures

Febrile convulsions are divided into two categories, simple (benign), or complex,
based upon clinical features. Simple febrile seizures are the most common and are
characterized by seizures that last less than 15 minutes, have no focal features, and,
if they occur in a series, the total duration is less than 30 minutes. Complex febrile
seizures are characterized by episodes that last more than 15 minutes, have focal
features or postictal paresis, and occur in a series with a total duration greater than
30 minutes [ 1,2 ].
ETIOLOGY AND PATHOGENESIS It is not known how or why seizures are
generated in response to fever; it may be that fever-induced factors (eg, interleukin1beta) are proconvulsant in individuals who are susceptible based upon the stage of
brain development and genetic susceptibility [ 3,4 ]. Certain ion channels in the brain
are temperature sensitive and may generate fever-associated synchronized neuronal
activity [ 5,6 ]. There is also evidence to suggest that hyperthermia-induced
hyperventilation and alkalosis may play a role [ 7 ].
Infections Febrile seizures can occur during both viral and bacterial infections. In
one hospital based study, the incidence of febrile seizures was similar with influenza,
adenovirus, and parainfluenza infections (6 to 18 percent), and somewhat less
common with respiratory syncytial virus and rotavirus (4 to 5 percent) [ 8 ]. No
specific virus was associated with risk of complex febrile seizures or later recurrence.
Other studies have reported higher rates of febrile seizures (up to 36 percent in the
12 to 15 month age group) in primary human herpesvirus (HHV)-6 infections and also
a higher rate of complex features, recurrence, and febrile status epilepticus [ 9-11 ].
(See "Human herpesvirus 6 infection in children: Clinical manifestations; diagnosis;
and treatment", section on 'Acute febrile illness' and 'Febrile status epilepticus' below.)
Immunizations The risk of febrile seizures is increased after administration of
diphtheria, tetanus toxoid, and whole-cell pertussis (DTP) and measles, mumps, and
rubella (MMR) vaccine. (See "Standard immunizations for children and adolescents" .)
In a large cohort study, febrile seizures were significantly increased on the day of DTP

vaccination and 8 to 14 days following MMR vaccination (adjusted relative risks 5.7
and 2.83, respectively) [ 12 ]. The risk for subsequent seizures or
neurodevelopmental disabilities was comparable in children with febrile seizures
whether or not they were associated with vaccination; however, because
immunization and the clinical onset of neurodevelopmental syndromes occur in early
childhood, there may be a perception that the vaccination is causative [ 13 ].
Predisposing factors Susceptibility to febrile seizures has been linked with
abnormalities in neurotransmitters. However, whether observed abnormalities were
primary events or were secondary to the convulsions is unclear. As an example, the
cerebrospinal fluid (CSF) concentration of gamma-aminobutyric acid (GABA), an
inhibitory transmitter, was reduced in one series of children who were studied after
their first or second febrile seizure; the samples were obtained after the convulsion
and, thus, may be the effect rather than the cause of the seizure [ 14 ]. Furthermore,
low CSF GABA was not confirmed in other studies of children with febrile seizures
[ 15 ].
CSF neopterin concentrations may be elevated in children with febrile seizures [ 16 ].
Because neopterin is secreted by activated macrophages, this observation suggests
immune activation within the central nervous system [ 16 ].
Iron insufficiency may play a role in pathogenesis. In a prospective study of 150
children, mean ferritin levels were significantly lower in children with a first febrile
seizure than in matched controls with febrile illness but no convulsions (29.5 versus
53.3 mcg/L) [ 17 ]. Plasma ferritin levels 30 mcg/L occurred in a significantly greater
proportion of children with seizures than controls (65 versus 32 percent). Further
studies will be required to confirm this preliminary finding.
Genetic susceptibility Genetic and familial factors appear to be important factors
in the expression of febrile convulsions and the subsequent development of epilepsy in
some children [ 2,18 ]. Among first-degree relatives of children with febrile seizures,
10 to 20 percent of parents and siblings also have had or will have febrile seizures. In
addition, monozygotic twins have a much higher concordance rate than do dizygotic
twins, in whom the rate is similar to that of other siblings.
Susceptibility to febrile seizures has been linked to several genetic loci in different
families, including the long arm of chromosome 8q13-21 (FEB1) [ 19 ], chromosome
19p (FEB2) [ 20,21 ], chromosome 2q23-24 (FEB3) [ 22 ], chromosome 5q14-15
(FEB4) [ 23,24 ], chromosome 6q22-q24 (FEB5) [ 25 ], chromosome 6q16.3-22.31
[ 26 ], chromosome 21q22 [ 27 ], and perhaps chromosome 18p11.2 [ 28 ]. The trait
is transmitted in an autosomal dominant fashion. However, susceptibility genes have
not been identified in most patients with febrile seizures [ 3 ].
Genetic factors are also believed to be important in nonmendelian forms of febrile
seizures. One study suggests that common polymorphism in a sodium channel gene
(splice site variant SCN1A) is a common risk factor for febrile seizures [ 29 ].
However, this finding was not replicated in a follow-up study [ 30 ].
A syndrome of generalized epilepsy with febrile seizures plus (GEFS+) also has been
described [ 31-33 ]. The most common phenotype consists of children who had
seizures with fever in early childhood that, unlike typical febrile seizures, continued
beyond six years of age or were associated with afebrile tonic clonic seizures as well

as other seizure types. The epilepsy typically remits by mid-adolescence, but can
persist into adulthood. This disorder is usually autosomal dominantly inherited. Family
members who inherit the mutation may only have nonfebrile seizures [ 34 ].
Among different families with GEFS+, a variety of gene loci and mutations have been
identified, including chromosome 19q with mutations in the beta-1-subunit of the
neuronal sodium channel [ 31,32,34,35 ], chromosome 2q with mutations in the
alpha-1-subunit of the neuronal sodium channel [ 28,36-40 ], chromosome 8p23-p21
[ 41 ] and a mutation in the gamma-2 subunit of the GABA-A receptor [ 42-44 ]. A
mutation in the last gene has also been identified in a family with febrile seizures
without associated epilepsy [ 45 ].
These observations link febrile seizures with afebrile seizures in some families in an
autosomal dominant fashion. In addition, previous studies have shown that siblings
and parents of patients with febrile seizures have a 4 to 10 percent incidence of
epilepsy.
Hippocampal lesions Another approach linking febrile seizures and epilepsy was
suggested from an evaluation of two families with familial febrile convulsions [ 46 ].
Magnetic resonance imaging (MRI) was performed in family members who had no
seizures, febrile convulsions only, and febrile convulsions with the subsequent
development of temporal lobe epilepsy. All subjects with febrile convulsions who did
not develop epilepsy and six clinically unaffected relatives showed asymmetry in the
size of the hippocampi. In addition to a difference in the size between the right and
left hippocampi were changes in the internal architecture of the hippocampal bodies.
The authors concluded that a subtle preexisting hippocampal malformation that was
present may facilitate febrile convulsions and contribute to the development of
subsequent hippocampal sclerosis, which was seen in the patients who developed
temporal lobe epilepsy. (See 'Subsequent temporal lobe epilepsy' below.)
Furthermore, the hippocampal malformation did not appear to be a consequence of
the febrile convulsions and, therefore, may have been a predisposing factor associated
with the development of epilepsy. Developmental abnormalities of the hippocampus,
including hippocampal malrotation, have also been reported in 10.5 percent of
children presenting with febrile status epilepticus [ 47 ]. (See 'Febrile status
epilepticus' below.)
In another study, the effect of prolonged febrile seizures was evaluated in the
immature rat [ 48 ]. Prolonged hyperthermia-induced seizures did not lead to
spontaneous seizures in adult rats. However, the experimental animals, but not
control animals, developed hippocampal seizures after systemic administration of a
low dose of kainate, a chemical convulsant, indicative of a reduced seizure threshold.
An analogous situation may exist in humans. Individuals predisposed to developing
epilepsy, by a variety of factors, may become symptomatic in later years after having
their thresholds modified by febrile seizures in infancy.
CLINICAL FEATURES Febrile seizures occur in children between the ages of six
months and six years, with the majority occurring in children between 12 to 18
months of age. Febrile seizures have been reported in children over six years of age,
but in older children, febrile seizures should be considered a diagnosis of exclusion, as
they are more likely than younger children with febrile seizures to have subsequent
afebrile seizures [ 49 ].

Simple febrile seizures are the most common type encountered in children.
Generalized seizures are mainly clonic, but other forms include atonic and tonic spells.
The facial and respiratory muscles are commonly involved.
Complex febrile seizures (focal features, longer than 15 minutes or multiple episodes
within 24 hours) are unusual; prolonged convulsions occur in fewer than 10 percent
and focal features in fewer than 5 percent of children with febrile seizures. An initial
simple febrile seizure may be followed by complex seizures, but the majority of
children who develop complex febrile seizures do so with their first seizure. However,
an initial complex febrile seizure does not necessarily indicate that all subsequent
seizures will be complex. In one study of 158 children with a first febrile seizure,
prolonged seizures (>10 minutes) occurred in 18 percent and were associated with
developmental delay and younger age at first seizure [ 50 ]. The findings of this study
suggest that 10 rather than 15 minutes might be a more appropriate criterion for
complex febrile seizure, particularly for purposes of prognosis.
Some patients present in febrile status epilepticus, ie, continuous seizures or
intermittent seizures without neurologic recovery, either lasting for a period of 30
minutes or longer. (See 'Febrile status epilepticus' below.)
The majority of children have their febrile seizures on the first day of illness and, in
some cases, it is the first manifestation that the child is ill. The degree of fever
associated with febrile convulsions is variable, and approximately 25 percent of events
occur when the temperature is between 38C and 39C. They are often seen as the
temperature is increasing rapidly but may develop as the fever is declining. Recurrent
febrile seizures do not necessarily occur with the same degree of fever as the first
episode and do not occur every time the child has a fever.
DIFFERENTIAL DIAGNOSIS Involuntary movements can occur in sick children
and be confused with seizures. Shaking chills are usually readily distinguished from
seizures. Chills are common and are characterized by fine rhythmic oscillatory
movements about a joint. They rarely involve facial or respiratory muscles, which
frequently occur during febrile seizures. In addition, chills usually involve both sides of
the body simultaneously and are not associated with loss of consciousness, in contrast
to children with generalized seizures. Thus, bilateral manifestations without apparent
unconsciousness strongly suggest that the movements are not convulsive.
An underlying metabolic disorder presenting as a seizure in a febrile child is rare. In
such children, the history and physical examination yield clues of an underlying
problem. Infants with a history of vomiting, diarrhea, and altered fluid intake may
have electrolyte abnormalities (eg, hypernatremia, hyponatremia) that can lead to
seizures.
Meningitis and encephalitis are the main concerns in a child presenting with fever and
seizures. A thorough evaluation by an experienced clinician almost always will detect
the child with meningitis. Although as many as 40 percent, particularly younger
infants, who have seizures as an initial manifestation of meningitis do not have
meningeal signs, they have other symptoms and findings that strongly suggest the
correct diagnosis.
It is exceedingly rare for bacterial meningitis to be detected on the basis of doing a
"routine" evaluation of the CSF after a febrile seizure. When the only indication for

performing a lumbar puncture is the seizure, meningitis will be found in less than 1
percent of patients and less than one-half of these will have bacterial meningitis
[ 51 ].
Children with status epilepticus (SE) and fever are more likely to have bacterial
meningitis than those with a short seizure. Meningitis must be considered as a
diagnostic possibility in children with SE and fever (see 'Febrile status
epilepticus' below).
The emergent evaluation and management of the child with suspected meningitis is
discussed separately. (See "Clinical features and diagnosis of acute bacterial
meningitis in children older than one month of age", section on 'Evaluation' .)
DIAGNOSTIC EVALUATION Diagnostic testing is unnecessary in most patients
with simple febrile seizures [ 52 ].
Lumbar puncture The need for a lumbar puncture (LP) with CSF examination to
exclude meningitis or encephalitis in children with a febrile seizure is uncertain. A
retrospective cohort review of 704 patients aged 6 to 18 months who presented with a
first simple febrile seizure revealed that 38 percent underwent LP [ 53 ]. There were
no diagnoses of bacterial meningitis made in children in whom this was not otherwise
suspected clinically; leukocytosis was present in 3.8 percent. CSF cultures revealed no
pathogens, but in 10 cases (3.8 percent) a contaminant grew. A separate study in
children with complex febrile seizures revealed similar findings [ 54 ].
While routine performance of LP in all children with febrile convulsions does not seem
warranted, the American Academy of Pediatrics (AAP) recommendations regarding the
performance of LP in the setting of febrile seizures are the following [ 55 ]:

LP should be performed when there are meningeal signs or symptoms or other

clinical features that suggest a possible meningitis or intracranial infection.
LP should be considered in infants between 6 and 12 months if the
immunization status for Haemophilus influenzae type B or Streptococcus
pneumoniae is deficient or undetermined.
LP should be considered when the patient is on antibiotics because antibiotic
treatment can mask the signs and symptoms of meningitis.

Once a decision to perform an LP has been made, blood culture and serum glucose
testing should be performed concurrently.
LP should also be considered when febrile seizures occur after the second day of
illness, or when, based on history or examination, the clinician remains concerned
about possible central nervous system infection. Based on case series, but not
included in the AAP guidelines, febrile status epilepticus may be another possible
indication for lumbar puncture (see 'Febrile status epilepticus' below) [ 56-58 ].
A finding of pleocytosis in the CSF in a patient with a febrile seizure should be
considered a sign of infection until proven otherwise, indicating further evaluation with
cultures and in certain cases empiric antimicrobial therapy. While pleocytosis in the
CSF has been attributed to an epileptic seizure in some cases, this is rare in the
setting of febrile seizure and should be considered a diagnosis of exclusion [ 59 ].
Other tests A complete blood count and measurement of serum electrolytes
[ 60 ], blood sugar, calcium, and urea nitrogen is of very low yield; these parameters

should be measured only when the patient has a history of vomiting, diarrhea, and
abnormal fluid intake, or when physical findings of dehydration or edema exist [ 55 ].
Neuroimaging with computed tomography (CT) or MRI is not required for children with
simple febrile seizures [ 55,58,61 ]. The incidence of intracranial pathology in children
presenting with complex febrile seizures also appears to be very low [ 62,63 ]. Urgent
neuroimaging (CT with contrast or MRI) should be done in children with abnormally
large heads, a persistently abnormal neurologic examination, particularly with focal
features, or signs and symptoms of increased intracranial pressure [ 58,61,62 ].
Routine electroencephalography (EEG) is not warranted, particularly in the setting of a
neurologically healthy child with a simple partial febrile seizure [ 55 ]. Abnormalities
are more likely to be found when the test is performed shortly after the seizure and
when convulsions are of long duration and have focal features. While some studies
suggest that certain abnormal EEG findings may be associated with the risk of
epilepsy, it should not be used as a basis for treatment decisions [ 64 ].
TREATMENT OPTIONS
General considerations Febrile seizures that continue for more than five minutes
should be treated. Airway, respiratory status, and circulatory status are continuously
assessed in patients with active seizures. Blood should be obtained for electrolytes
and glucose determination, if indicated. Antiepileptic drugs should be administered
intravenously, if possible, starting with a short-acting benzodiazepine such
as lorazepam (0.05 to 0.1 mg/kg). If the seizure persists, an additional dose may be
given. The child's respiratory status needs to be monitored carefully and intubation
undertaken if the ventilatory status becomes inadequate. (See "Emergent
endotracheal intubation in children".)
Persistence of the seizure is rare. When it does, the child can be treated
with fosphenytoin (15 to 20 mg/kg IV) (see 'Febrile status epilepticus' below). If
intravenous access is not possible or if the child is being treated at
home, diazepam rectal gel may be used (0.5 mg/kg). (See 'Recurrent febrile
seizures' below.)
The fever should be treated as the seizures are controlled. (See "Pathophysiology and
management of fever in infants and children", section on 'Management of fever' .)
Recurrent febrile seizures One strategy for the treatment of a recurrent febrile
seizure is the use of rectal diazepam gel if the episode lasts longer than five minutes
[ 65]. Parents can be taught to safely give the medication at home, and one dose
administered rectally will not lead to respiratory depression.
One factor helpful in predicting a prolonged febrile seizure is focality. A strong
correlation appears to exist between focality and a prolonged duration of both first
and recurrent febrile seizures [ 66 ]. In children with recurrent febrile seizures, those
with long duration, defined as lasting longer than 10 minutes, tend to have similar
features in repeat episodes. Similarly, children who have multiple risk factors for
recurrent febrile seizures (focal onset, multiple seizures during the episode) and have
a prolonged febrile seizure often have prolonged recurrent febrile seizures [ 66 ]. This
may be a group of children for whom rectal therapy at the time of occurrence should
be strongly considered.

PROGNOSIS The prognosis for children with febrile seizures is favorable. While
early reports had suggested that febrile seizures were associated with sudden death,
the results from a large population-based study indicate that the small excess in
mortality among children with febrile seizures is restricted to those with complex
febrile seizures. Furthermore, the increased risk in those patients is explained, at least
in part, by pre-existing neurologic abnormalities and subsequent epilepsy [ 67 ].
Recurrent febrile seizures Children with febrile seizures are at risk for
developing recurrent febrile seizures. The overall recurrence rate is approximately 30
to 35 percent [68,69 ]. However, the values vary with age from as high as 50 to 65
percent in children who are younger than one year of age at the time of the first
seizure to as low as 20 percent in older children [ 70 ]. A major factor influencing the
recurrence rate is the age of the infant at the time of the first seizure.
A prospective cohort study of 428 children with a first febrile seizure defined other
features and factors influencing recurrences [ 68 ]. Approximately one-third of the
children had at least one recurrence, 17 percent had one recurrence, 9 percent had
two recurrences, and approximately 6 percent had three or more recurrences. The
majority of recurrences (50 to 75 percent) took place within one year of the initial
seizure and almost all occurred within two years [ 71 ]. Four factors in the prospective
cohort study increased the recurrence risk [ 68 ]:

Young age at onset

History of febrile seizures in a first-degree relative
Low degree of fever while in the emergency department
Brief duration between the onset of fever and the initial seizure

Children who had all four factors were much more likely to have a recurrent febrile
seizure than were those with none (70 versus 20 percent). Complex features were
not associated with the risk of recurrence. These findings were confirmed in another
prospective study [ 72 ].
Other factors identified in different studies have been abnormal development before
the first febrile seizure, a history of afebrile seizures in parents and siblings,
recurrence of seizures within the same illness, and the number of subsequent febrile
illnesses [ 69,71-73 ]. Among children who have had one recurrence, younger age at
the time of the first recurrence and a family history of epilepsy are predictors of
subsequent recurrences [ 68,72 ]. Another risk factor is an unprovoked seizure after a
febrile seizure; such children are at substantial risk for further seizures with fever
(rate ratio 3.47 after adjusting for the above risk factors, p = 0.0015) [ 74 ].
Neurologic sequelae Neurologic sequelae, including new neurologic deficits,
intellectual impairment, and behavioral disorder, are rare following febrile convulsions.
Most reports documenting neurologic complications have been anecdotal and derived
from biased populations consisting of children assessed in hospitals or clinics; in some
cases, they may reflect preexisting abnormalities. When new deficits were reported,
they occurred only after complex or prolonged febrile seizures.
In general, population-based studies do not corroborate anecdotal reports of
neurologic complications. In the National Collaborative Perinatal Project,
approximately 5 percent of children had febrile seizures lasting longer than 30

minutes. None of these children sustained permanent motor deficits and none had
impaired mental development unless they developed afebrile seizures [ 73 ]. Similar
findings were noted in a population-based study of 381 children with febrile
convulsions in the United Kingdom [ 75 ]. The children were assessed when they were
ten years old, and children who had neurologic and developmental problems prior to
the first febrile seizure were excluded. No difference was found in measurements of
academic progress in children with febrile convulsions, whether simple, complex, or
recurrent, compared to a controlled cohort. There was also no difference in behavior
between the two groups. Finally, among 18 thousand Danish conscripts aged 18 to 20
years, there was no association found between febrile seizures and cognitive function
[ 76 ].
Subsequent epilepsy Epilepsy occurs more frequently in children who have had
febrile seizures than in the general population. In a normal child with a simple febrile
seizure, the risk is only slightly above that of the general population [ 77 ].
Epidemiologic studies have identified risk factors for epilepsy among children with
febrile seizures:

In the National Collaborative Perinatal Project, children with abnormal

neurologic development and whose first seizure was complex (focal, multiple,
or longer than 15 minutes) had a 9.2 percent incidence of afebrile seizures by
seven years of age; a risk 18 times higher than that in children with no history
of febrile seizures (0.5 percent) and more than eight times higher than that in
normal children with a noncomplex first febrile seizure (1.1 percent) [ 77 ].
In Rochester, Minnesota, 687 children with a history of febrile seizures were
observed into adulthood [ 78 ]. Three risk factors for developing epilepsy were
identified: focal seizures, prolonged seizures, and repeated episodes within 24
hours during the same illness. The risk of developing epilepsy was 2.4, 6 to 8,
17 to 22, and 49 percent in children with no, one, two, or three of these risk
factors, respectively.
A population-based study in Denmark also followed children with febrile
seizures into adulthood [ 79 ]. The cumulative incidence of epilepsy was 6.9
percent at 23 years, and the relative risk associated with febrile seizures was
5.4. The risk of epilepsy was higher in those with a family history of epilepsy,
cerebral palsy, or low Apgar scores at five minutes.
Another cohort study of 181 children with febrile seizure found that the risk of
epilepsy was highest in the first five years and appeared to decrease over time
[ 80 ]. Overall, individuals aged 15 to 19 years with a history of febrile seizure
appeared to have a similar risk of epilepsy compared with controls, however
subgroups of children with febrile seizures who might be at higher risk of
epilepsy were not compared.

Subsequent temporal lobe epilepsy Although a variety of seizure types follow

febrile convulsions, whether prolonged febrile convulsions lead to the development of
temporal lobe epilepsy is controversial. Reports of patients with refractory temporal
lobe epilepsy considered for surgery often find an association with febrile convulsions
in infancy, particularly prolonged seizures [ 81 ]. In addition, studies assessing
hippocampal volume in adults with epilepsy have found an association between a
smaller hippocampus and a history of febrile seizures [ 82,83 ]. Data are conflicting as
to whether a correlation exists between the duration of epilepsy and a reduction in
hippocampal volume [ 84 ]. As noted above, hippocampal abnormalities have also
been associated with familial febrile seizures [ 46 ]. (See 'Hippocampal
lesions' above.)

The possibility of hippocampal injury induced by febrile seizures was assessed by MRI
in infants who had had complex febrile seizures [ 85 ]. Abnormalities were found in
the children with focal and prolonged complex febrile seizures but not in those with
generalized febrile convulsions. In a few children who had significantly longer
seizures, MRI suggested acute edema of the hippocampus, a finding noted in other
case series as well [ 86-88 ]. Follow-up imaging studies in these children may show
hippocampal atrophy or abnormal apparent diffusion coefficient measurements.
Another study found that hippocampal atrophy and other MRI characteristic of
hippocampal sclerosis were more common in adults with a history of febrile seizures in
childhood than those without [ 89 ]. Although these observations suggest acute injury
to the hippocampus during a febrile seizure, the possibility of preexisting lesions
leading to susceptibility to injury is not excluded.
Studies based mainly upon imaging results and patients being considered for epilepsy
surgery suggest an association between febrile seizures and temporal lobe epilepsy.
Some clinical studies reached a similar conclusion. In one, patients presenting to an
epilepsy clinic because of a previous diagnosis of epilepsy or recent onset of seizures
were prospectively questioned about febrile convulsions and their characteristics
[ 90 ]. Febrile convulsions were reported by 13.2 percent of the patients. Temporal
lobe epilepsy was more likely to be preceded by febrile convulsions than by other
types of epilepsy (25.2 percent versus 5.6 percent, respectively). Prolonged duration
was the most common feature of the complex febrile seizure associated with temporal
lobe epilepsy, although patients with generalized epilepsy were more likely to have
had simple febrile convulsions.
However, carefully performed community-based epidemiologic studies have not been
able to confirm this association. In one, the characteristics of epilepsy were evaluated
in 524 children who were one year of age or older at the onset of epilepsy [ 81 ].
Febrile seizures were present in 14 percent of the patients. Complex febrile seizures
were associated with a younger age at onset of the epilepsy, but there was no specific
association with localization-related forms of epilepsy. No evidence that focal or
prolonged febrile seizures were associated with temporal lobe epilepsy was found;
three children had hippocampal atrophy demonstrated on their initial MRI, but none
had a history of febrile seizures.
In summary, febrile seizures do not appear to cause temporal lobe epilepsy. The
association may represent an inherent susceptibility in some children who are
predisposed to prolonged febrile seizures and epilepsy simultaneously.
FEBRILE STATUS EPILEPTICUS A prolonged febrile seizure (febrile status
epilepticus [FSE]) is a concern for both physicians and parents. A multicenter
prospective cohort study described the characteristics of prolonged (>30 minutes)
febrile seizures in 119 children, aged one month through five years [ 11,91 ]. The
following findings were noted:

The median duration was 68 minutes

The seizures were convulsive in all but one child
The seizures were continuous in 52 percent and intermittent in 48 percent
Two-thirds of seizures were partial
This was the first febrile seizure in 76 percent of children
Primary or reactivated HHV-6B infection was found in 32 percent of children

Chart reviews suggested that status epilepticus was often not recognized by the
emergency department staff, perhaps contributing to the long duration of the
seizures.
The clinical setting in which FSE is not clearly different than shorter febrile seizures. In
the multicenter cohort described above, the median peak temperature was 103F
(39.4C), most patients had a defined viral or bacterial illness, and there was a higher
than expected family history of epilepsy [ 91 ].
In another series, patients with FSE were more likely to have a family history of
epilepsy than children who presented with briefer febrile seizures; they also had a
higher prevalence of baseline neurologic disease and a personal history of epilepsy
[ 92 ].
Some reports suggest that children with status epileptics and fever are more likely to
have bacterial meningitis than those with a short seizure. A group of 24 children with
status epilepticus in the setting of fever were identified over a six month period
through a British surveillance study of children with SE [ 56 ]. Lumbar puncture was
performed in nine patients, four of whom had findings characteristic of bacterial
meningitis. The incidence of bacterial meningitis in this report is quite high and may
be due, in part, to the small sample size. In another series 11 of 95 children with
status epilepticus and fever (11.6 percent) had acute bacterial meningitis [ 57 ]. Thus,
meningitis must be considered as a diagnostic possibility in children with presumed
FSE.
The distribution of seizure durations suggests that the longer a febrile seizure
continues the less likely is it to stop without treatment [ 91 ]. Patients with FSE should
be treated with anticonvulsant medication as are other patients with status epilepticus
and efforts should be made to lower fever using antipyretics and a cooling blanket.
(See"Management of status epilepticus in children" and "Pathophysiology and
management of fever in infants and children", section on 'Management of fever' .)
The long term consequences of FSE have not been defined. Clinical follow-up of the
above mentioned cohort is in progress [ 91 ]. The significance and predictive value of
MRI abnormalities in the hippocampus (abnormal T2 hyperintensity in 11.5 percent,
developmental abnormalities in 10.5 percent) found at the time of presentation with
FSE are being studied [ 47,91 ]. Another study followed 44 children with FSE, most of
whom were identified prospectively [ 93 ]. After a mean follow-up of 28 months, the
risk of recurrent seizures (febrile and afebrile) was increased only in those who had
prior neurologic abnormalities. This finding is similar to that seen in patients with
febrile seizures without status. Other case series have found that EEG studies,
performed within one week after FSE, show focal slowing in one-third [ 94 ]. While
some have found that this is associated with a higher risk of epilepsy, this association
has not been consistently reported and requires further study. (See 'Subsequent
epilepsy' above.)
ROLE OF PREVENTIVE THERAPY
Antiepileptic therapy Children with febrile seizures are at increased risk for
recurrent febrile as well as the development of afebrile seizures, suggesting a role for
prophylactic treatment with chronic antiepileptic medications (AEDs). However, given

the benign nature of recurrent febrile seizures, there is increasing consensus that risks
of AED treatment outweigh potential benefits for most patients [ 95-97 ].
The effectiveness of AEDs was evaluated in a meta-analysis of studies for the
prevention of recurrent febrile seizures [ 97 ]. While treatment
with phenobarbital , valproate , or intermittent oral or rectal diazepam was associated
with reduced risk of recurrent seizures in the short term (six months to two years),
this was also associated with a risk of adverse effects in 30 to 40 percent of children
[ 97-101 ].
There is no available evidence that the use of chronic AEDs or the prevention of
recurrent febrile seizures is associated with a reduced risk of epilepsy [ 96 ].
The Committee on Quality Improvement, Subcommittee on Febrile Seizures of the
AAP concluded that "Based on the risk and benefits of effective therapies, neither
continuous nor intermittent anticonvulsive therapy is recommended for children with
one or more simple febrile seizures [ 96 ]. The American Academy of Pediatrics
recognizes that recurrent episodes of febrile seizures can create anxiety in some
parents and their children and as such appropriate educational and emotional support
should be provided".
There is no data upon which to base a recommendation regarding AED prophylaxis in
children with complex febrile seizures [ 101 ]. Treatment in such cases is
individualized based upon underlying risk factors, but there is no evidence that
supports treatment in any one subset of patients.
Antipyresis For children who have had febrile seizures, treatment with
antipyretics at the time of a febrile illness may be helpful in overall management but
does not appear to affect the recurrence rate of febrile seizures [ 96,97,101-103 ]:

A study in which low dose acetaminophen or a placebo was administered for

fever failed to demonstrate a decrease in febrile seizures [ 103 ]. However, the
fact that the patients also received diazepam or a placebo and the fact that all
patients apparently received acetaminophen if temperature reached 40 C (104
F) makes the data difficult to interpret.
A systematic review of 12 trials (1,509 patients) of acetaminophen versus
placebo or sponging for treatment of fever concluded that there was
insufficient evidence to show whether or not acetaminophen influenced the risk
of febrile convulsions [ 102 ].
A subsequently published clinical trial randomly assigned 231 children with
febrile seizures to receive either rectal diclofenac or placebo at onset of a
subsequent febrile episode; patients were simultaneously randomized into one
of three subsequent treatment groups (oral placebo
versus acetaminophen versus ibuprofen ) to begin eight hours after initial
treatment [ 104 ]. In this study, antipyretics were not effective at lowering
body temperature or preventing the recurrence of febrile seizures (overall
incidence 23 percent).

(See "Pathophysiology and management of fever in infants and children", section on

'Management of fever' .)
INFORMATION FOR PATIENTS UpToDate offers two types of patient education
materials, The Basics and Beyond the Basics. The Basics patient education pieces
are written in plain language, at the 5 th to 6 th grade reading level, and they answer

the four or five key questions a patient might have about a given condition. These
articles are best for patients who want a general overview and who prefer short, easyto-read materials. Beyond the Basics patient education pieces are longer, more
sophisticated, and more detailed. These articles are written at the 10 th to 12 th grade
reading level and are best for patients who want in-depth information and are
comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage
you to print or e-mail these topics to your patients. (You can also locate patient
education articles on a variety of subjects by searching on patient info and the
keyword(s) of interest.)

Basics topics (see "Patient information: Febrile seizures (The Basics)" )

Beyond the Basics topics (see "Patient information: Febrile seizures (Beyond
the Basics)" )

SUMMARY AND RECOMMENDATIONS Febrile seizures occur in children with

fever, usually in the setting of systemic bacterial or viral infection. Affected patients
are typically between the ages of six months and six years of age and do not have
epilepsy, central nervous system infection or inflammation, or other triggers for
seizures.

Febrile seizures occur in 2 to 4 percent of children younger than five years of

age, typically in the setting of infection or after an immunization. Genetic and
familial factors appear to be important in the genesis of febrile seizures.
(See 'Etiology and pathogenesis' above.)
Febrile seizures may be simple or complex: (See 'Clinical features' above.)
Simple febrile seizures are the most common and are characterized by seizures
that last less than 15 minutes, have no focal features, and, if they occur in a
series, the total duration is less than 30 minutes. These are mainly generalized
clonic seizures but may also be atonic or tonic in character.
Complex febrile seizures are characterized by episodes that last more than 15
minutes, have focal features or postictal paresis, and occur in a series with a
total duration greater than 30 minutes.
Febrile status epilepticus (FSE) lasts 30 minutes or longer, but otherwise
shares the characteristics of febrile seizures of shorter duration. The longer the
seizure continues, the less likely it is to stop without treatment. Patients with
FSE should be treated with antiepileptic medication as are other patients with
status epilepticus and efforts should be made to lower fever using antipyretics
and a cooling blanket. (See "Management of status epilepticus in
children" and 'Febrile status epilepticus' above and"Pathophysiology and
management of fever in infants and children", section on 'Management of
fever' .)
The need for a lumbar puncture (LP) with CSF examination to exclude
meningitis or encephalitis in children with a febrile seizure is uncertain
(See 'Lumbar puncture'above.).
LP should be performed when there are meningeal signs or symptoms or other
clinical features that suggest a possible meningitis or intracranial infection.
LP should be considered in infants between 6 and 12 months if the
immunization status for Haemophilus influenzae type B or Streptococcus
pneumoniae is deficient or undetermined.

LP should be considered when the patient is on antibiotics because antibiotic

treatment can mask the signs and symptoms of meningitis.
Other possible indications for LP include a presentation with febrile status
epilepticus, febrile seizures occurring after the second day of illness, or other
concerns for possible central nervous system infection.
Other laboratory testing, neuroimaging and electroencephalography are
required only in specific circumstances. (See 'Other tests' above.)
Children with febrile seizures are at risk for recurrent febrile seizures,
particularly if they have a young age of onset, a family history of febrile
seizures, brief latency between onset of fever and seizures, and a relatively low
fever. Epilepsy occurs somewhat more frequently in children who have had
febrile seizures than in the general population. (See 'Prognosis' above.)
We suggest NOT treating patients with simple febrile seizures with antiepileptic
drug (AED) therapy. While AEDs may decrease the risk of recurrent febrile
seizures, the prevention of these benign events and generally not considered
worth the potential adverse effects of treatment. There is no available evidence
that the use of chronic AEDs is associated with a reduced risk of epilepsy.
(See 'Role of preventive therapy' above.)
The use of AED prophylaxis in children with complex febrile seizures is
individualized based upon underlying risk factors. (See 'Antiepileptic
therapy' above.)
Treatment to lower fever does not appear to affect the recurrence rate of
febrile seizures. (See 'Antipyresis' above.)

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