21/2/23, 19:08 Treatment and prognosis of febrile seizures - UpToDate

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Treatment and prognosis of febrile seizures

Author: John J Millichap, MD, FAAP, FAAN
Section Editor: Douglas R Nordli, Jr, MD
Deputy Editor: John F Dashe, MD, PhD

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Jan 2023. | This topic last updated: Dec 21, 2022.

INTRODUCTION

Febrile seizures are the most common neurologic disorder of infants and young children, occurring in
2 to 4 percent of children younger than five years of age. They are an age-dependent phenomenon
with a strong genetic predisposition. While often frightening to parents, caregivers, and witnesses,
febrile seizures are a mostly benign occurrence and are associated with a low risk for future epilepsy.
Approximately one-third of children will have recurrent febrile seizures during early childhood, and the
risk is increased in association with certain clinical features, including young age, low fever, family
history of febrile seizures, and abnormal development at the time of first seizure.

Febrile seizures are described as being simple or complex. Simple febrile seizures are the most
common type and are characterized by a single generalized seizure lasting less than 10 to 15
minutes. Complex febrile seizures include those that are focal, prolonged, or recurrent within a 24-
hour period. (See "Clinical features and evaluation of febrile seizures".)

While simple febrile seizures have typically spontaneously resolved by the time the child is evaluated
and do not need to be treated, prolonged seizures may require abortive treatment with
benzodiazepines in the ambulance or in the emergency department. Prophylactic antiseizure
medications can decrease the risk of recurrent febrile seizures, but given the benign nature of most
seizures, the risks of side effects generally outweigh the benefits.

This topic will review the treatment and prognosis of febrile seizures, including febrile status
epilepticus. Management of afebrile seizures and epilepsy in infants and children are discussed
separately. (See "Seizures and epilepsy in children: Initial treatment and monitoring".)

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INITIAL ASSESSMENT

The initial evaluation of children with seizure in the setting of fever must distinguish febrile seizure
from alternative and more serious etiologies such as central nervous system infection. This can be
accomplished with a thorough history and physical examination in most cases, along with
neuroimaging and lumbar puncture in selected circumstances. Children with focal or prolonged febrile
seizures may require more extensive evaluation than those with simple febrile seizures, particularly at
the time of the first seizure. Therapies discussed below assume that such etiologies have been ruled
out and that the diagnosis of febrile seizure has been established. (See "Clinical features and
evaluation of febrile seizures".)

ACUTE MANAGEMENT

Emergency rescue therapy — The majority of febrile seizures have ended spontaneously by the
time the child is first evaluated, and the child is rapidly returning to a normal baseline. In such cases,
active treatment with benzodiazepines is not necessary. Fever should be treated symptomatically with
antipyretics.

As with afebrile seizures, febrile seizures that continue for more than five minutes should be treated.
Intravenous benzodiazepines (diazepam 0.1 to 0.2 mg/kg or lorazepam 0.05 to 0.1 mg/kg) are
effective in aborting seizure in many cases. If the seizure persists, an additional dose may be given.
The child's respiratory and circulatory status should be monitored carefully and an advanced airway
intervention (eg, bag-mask ventilation, laryngeal mask airway, definitive artificial airway) undertaken if
the ventilatory status becomes inadequate. (See "Basic airway management in children" and
"Emergency endotracheal intubation in children".)

The efficacy and safety of intravenous benzodiazepines as first-line agents for the treatment of
seizures in children has been demonstrated in several randomized trials, primarily in children with
afebrile seizures or status epilepticus. A 2018 meta-analysis concluded that intravenous lorazepam
was as effective as intravenous diazepam and that both were associated with similar rates of
respiratory depression [1]. In a randomized trial of 273 children with status epilepticus, intravenous
lorazepam and intravenous diazepam had similar efficacy, but lorazepam-treated children were more
likely to be sedated (67 versus 50 percent) [2]. Rates of intubation were similar (16 to 17 percent).
(See "Management of convulsive status epilepticus in children", section on 'Benzodiazepine efficacy
and pharmacokinetics'.)

When intravenous access is unavailable or cannot be achieved, buccal midazolam is an effective

alternative [1]; a typical dose is 0.2 mg/kg, maximum dose 10 mg. Intranasal lorazepam is also an
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option. A systematic review and meta-analysis of 18 trials including 2199 children concluded that
buccal or intranasal antiseizure medications were as effective as intravenous antiseizure medications
in treating status epilepticus, but there was only low-quality evidence comparing buccal midazolam
with rectal diazepam [1]. Respiratory complications requiring assisted ventilation are similar,
regardless of administration route. (See "Seizures and epilepsy in children: Refractory seizures",
section on 'Home rescue therapy (transmucosal antiseizure medications)'.)

Febrile status epilepticus — Patients with prolonged or repetitive seizures despite initial

benzodiazepine administration (ie, febrile status epilepticus) should be treated promptly with
additional antiseizure medications, as are other patients with status epilepticus. The most commonly
used drug in this setting is fosphenytoin (20 mg phenytoin equivalents [PE]/kg intravenously). Efforts
should be made to lower fever with antipyretics and a cooling blanket. The management of status
epilepticus in children is discussed in more detail separately. (See "Management of convulsive status
epilepticus in children" and "Fever in infants and children: Pathophysiology and management",
section on 'Management of fever'.)

Febrile status epilepticus rarely stops spontaneously and often requires more than one medication to
control [3,4]. It is more common in young children and is focal in two-thirds of cases [3,5]. In a
prospective cohort study of 119 children presenting with prolonged febrile seizures (>30 minutes), 70
percent of children required more than one antiseizure medication, and delays in antiseizure
medication administration were associated with longer seizure duration [3]. Important clinical clues
that a seizure has ended include the presence of closed eyes and a deep breath. Children with
persistently open and deviated eyes may still be seizing, even if convulsive motor activity has
stopped. (See "Clinical features and evaluation of febrile seizures", section on 'Febrile status
epilepticus'.)

Prehospital treatment — Treatment of prolonged seizures by paramedics with either intramuscular

midazolam or intravenous lorazepam appears to be safe and effective in children with status
epilepticus [6], and limited data support out-of-hospital treatment for prolonged febrile seizures as well
[5]. The ability of emergency medical services (EMS) to administer antiseizure medications varies by
region, however. (See "Management of convulsive status epilepticus in children", section on
'Prehospital treatment'.)

In a prospective study of children presenting to the emergency department with prolonged febrile
seizure (>15 minutes), 11 percent of those receiving rectal diazepam in the ambulance responded,
compared with 58 percent of patients treated with intravenous diazepam [5]. In a larger prospective
study, earlier onset of treatment was associated with shorter total seizure duration of febrile status
epilepticus and better outcomes [3]. Similarly in the United Kingdom, an epidemiological study

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strongly supported prehospital treatment with buccal midazolam as a widely used but unlicensed
option in the community [7].

DISCHARGE DISPOSITION

Most children with simple febrile seizures do not require hospital admission and can be discharged
safely to home once they have returned to a normal baseline and parents and caregivers have been
educated about the risk of recurrent febrile seizures. (See 'Recurrent febrile seizures' below.)

Children with focal or prolonged seizures may require a more extended period of observation,
particularly if there is delayed recovery to baseline or postictal focality. The normal duration of the
postictal phase is not well defined, but available studies suggest that return to cognitive baseline
typically occurs within five minutes [8]. Failure to return to cognitive baseline within five minutes or the
presence of focal postictal weakness (Todd paralysis) would constitute delayed recovery. A Todd
paralysis may last up to 24 hours.

In addition, children with focal or prolonged seizures are at higher risk of having multiple seizures
within the index illness. In a retrospective study of 228 presenting to an emergency department with
febrile seizure, the cumulative probability of early recurrence was 9 percent within 6 hours, 13 percent
within 12 hours, and 16 percent within 24 hours [9]. Ninety percent of recurrences occurred within the
first 24 hours. Risk factors for early recurrence were focal seizure and prolonged seizure (>15
minutes).

Additional factors to consider when deciding whether to admit a child include the confidence with
which outpatient follow-up can be arranged (for focal or prolonged seizures), comfort level of the
parents or caregivers, and severity of the underlying febrile illness (eg, hydration status, ability to take
oral fluids).

RECURRENT FEBRILE SEIZURES

Children with febrile seizures are at risk for developing recurrent febrile seizures with future illnesses
during early childhood.

Risk factors for recurrence — The overall recurrence rate is approximately 30 to 35 percent [10,11].
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 [12]. A major
factor influencing the recurrence rate is the age of the infant at the time of the first seizure.

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A prospective cohort study of 428 children with a first febrile seizure defined other features and
factors influencing recurrences [10]. 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 [13]. Four factors in the
prospective cohort study increased the recurrence risk [10]:

● 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 [14].

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 [11,13-16]. 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 [10,14]. 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) [17].

Provision of home benzodiazepines — In children with a history of prolonged febrile seizure,

including febrile status epilepticus (FSE), diazepam rectal gel (0.5 mg/kg) can be administered by
parents or caregivers at home if the episode lasts longer than five minutes [18]. Parents and
caregivers can be taught to safely give the medication at home, and one dose administered rectally
will not lead to respiratory depression.

Where available, midazolam nasal spray is an alternative to rectal diazepam for home use. A
comparison of midazolam nasal spray and rectal diazepam solution for residential treatment of
seizure exacerbations found that midazolam was equal in efficacy to diazepam, and drowsiness
occurred in more than 50 percent of administrations for both drugs [19]. The majority of patients and
caregivers preferred the nasal spray to rectal formulations.

Factors helpful in predicting future prolonged febrile seizures are focality and history of prolonged
febrile seizure, including FSE [20]. There appears to be a strong correlation between focality and
prolonged duration of both first and recurrent febrile seizures [18]. In children with recurrent febrile
seizures, those with long duration (defined as lasting longer than 10 minutes) tend to have similar
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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 [10]. This is a group of children for whom rectal therapy at
the time of occurrence should be strongly considered.

Role of preventive therapy — Prophylactic antiseizure medications can decrease the risk of

recurrent febrile seizures, but given the benign nature of most seizures, the risks of side effects
generally outweigh the benefits [16,21,22]. Use of antipyretics at the first sign of fever does not
prevent recurrent febrile seizures.

Antiseizure therapy — Children with febrile seizures are at increased risk for recurrent febrile
seizures as well as the development of afebrile seizures, suggesting a role for prophylactic treatment
with chronic antiseizure medications. However, given the benign nature of recurrent febrile seizures,
there is general consensus that risks of antiseizure medication treatment outweigh potential benefits
for most patients [21,23].

The effectiveness of antiseizure medications was evaluated in a meta-analysis of studies for the
prevention of recurrent febrile seizures [24]. While treatment with phenobarbital 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 up to 30 percent of children
[24-27]. The use of chronic antiseizure medications or the prevention of recurrent febrile seizures is
not associated with a reduced risk of epilepsy [16,21].

A clinical practice guideline developed by the Committee on Quality Improvement, Subcommittee on

Febrile Seizures of the American Academy of Pediatrics concludes that neither continuous nor
intermittent anticonvulsive therapy is recommended for children with one or more simple febrile
seizures, based on the risks and benefits of effective therapies [21]. The guideline also recognizes
that recurrent episodes of febrile seizures can create anxiety in some parents, caregivers, and
affected children and as such, appropriate educational and emotional support should be provided.

This guideline does not address children with complex febrile seizures in whom the risk of future
afebrile seizures is higher than in those with simple febrile seizures. In some children, a febrile
seizure may represent the first presentation of epilepsy. Treatment decisions in such cases should be
individualized based upon underlying risk factors, but there is no evidence that supports treatment in
any one subset of patients. However, careful clinical history and review of the electroencephalogram
(EEG) in cases of complex febrile seizures or febrile status epilepticus may reveal characteristics of
an underlying epilepsy syndrome or risk factors for later development of temporal lobe epilepsy, such
as acute focal slowing on EEG or subsequent mesial temporal sclerosis on magnetic resonance
imaging (MRI) [28,29]. The benefits of antiseizure medication therapy may outweigh risks in such

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cases, particularly if caregiver concern about recurrent seizures is high and the risks of antiseizure
medication therapy are carefully considered.

Antipyretics — For children who have had febrile seizures, treatment with antipyretics at the time of
a febrile illness may allay discomfort and reduce the recurrence of febrile seizures during the same
fever episode [30], but it does not appear to affect the recurrence rate of febrile seizures in
subsequent fever episodes [21,24,27].

An open-label trial from Japan found that acetaminophen reduced febrile seizure recurrence during
the same fever episode [30]. The trial enrolled over 400 children who presented to the hospital with
febrile seizures and randomly assigned them to acetaminophen (10 mg/kg by suppository every six
hours until 24 hours after febrile seizure onset if temperature remained >38.0° C) or to no antipyretic
treatment. The rate of febrile seizure recurrence during the same fever episode was lower in the
group assigned to rectal acetaminophen compared with the group assigned to no antipyretics (9
versus 24 percent). There were no serious adverse events related to acetaminophen.

However, antipyretic treatment does not appear to affect the recurrence rate of febrile seizures in
subsequent fever episodes. A 2013 systematic review and meta-analysis that included three
randomized controlled trials in 540 patients with febrile seizure also concluded that antipyretics
(acetaminophen, ibuprofen, or diclofenac) were ineffective in reducing the rate of recurrent febrile
seizures, compared with placebo [31]. The risk of recurrent febrile seizure was 23 percent in the
antipyretics group and 24 percent in the placebo group during a one to two-year follow-up period.

There are several potential physiologic reasons why antipyretics may not prevent febrile seizures.
Antipyretics facilitate heat loss but do not retard temperature elevation or lower the threshold
convulsive temperature during the initial stage of fever that triggers a seizure [32]. Heat production is
not inhibited by antipyretics, but heat dissipation is augmented by increased peripheral blood flow and
sweating [33].

Both acetaminophen and barbiturates cause a fall in body temperature by depression of the central
temperature regulatory mechanism. Phenobarbital inhibits heat production during the pyrogenic stage
of the fever, whereas acetaminophen facilitates heat loss at the height of the fever or during its
defervescence. The mechanism whereby phenobarbital reduces febrile seizure recurrence may be
related to both an antipyretic and anticonvulsant effect [32].

The role of antipyretics in the management of fever in children is discussed separately. (See "Fever in
infants and children: Pathophysiology and management", section on 'Management of fever'.)

PROGNOSIS
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The prognosis for children with febrile seizures is favorable. While early reports had suggested that
febrile seizures were associated with an increased risk of 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 [34]. Furthermore, the increased risk in those
patients is explained, at least in part, by preexisting neurologic abnormalities and subsequent
epilepsy. In six cases of sudden unexplained death in toddlers with febrile seizures, hippocampal
abnormalities were identified in one of three with available autopsy [35]. Inheritance was autosomal
dominant. The interval from the last febrile seizure to death ranged from three weeks to six months.

Neurologic outcomes — Neurologic sequelae, including new neurologic deficits, intellectual

impairment, and behavioral disorder, are rare following febrile seizures. In a case-control study in
which 159 children with febrile seizures were compared with 142 controls, performance on measures
of cognition, motor ability, and adaptive behavior were similar at one month after a first febrile seizure
and one year later [36].

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 a small study, face recognition memory was impaired after prolonged
febrile seizures, and the deficit was linked to the size of the hippocampi when tested one year later
[37].

In general, population-based studies do not corroborate anecdotal reports of neurologic

complications. In the National Collaborative Perinatal Project (NCPP), 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 [15]. Similar findings were noted in a population-based study of 381 children with febrile
convulsions in the United Kingdom [38]. The children were assessed when they were 10 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
seizures, whether simple, complex, or recurrent, compared with a controlled cohort. There was also
no difference in behavior between the two groups. Finally, among 18,000 Danish conscripts aged 18
to 20 years old, there was no association found between febrile seizures and cognitive function [39].

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 approximately
1 to 2 percent, only slightly above that of the general population [40]. For children with complex febrile
seizures, an abnormal developmental history, or a family history of epilepsy, the risk is closer to 5 to
10 percent.
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Epidemiologic studies have identified risk factors for epilepsy among children with febrile seizures:

● In the NCPP, 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) [40].

● In Rochester, Minnesota, 687 children with a history of febrile seizures were observed into
adulthood [41]. 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
[42]. 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.

● Long-term risk of developing epilepsy in a median 21-year follow-up UK study of 181 infants
with a first febrile seizure was 6 percent [43]. The risk of developing epilepsy decreased with
time.

● 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 [43]. 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.

● A prospective study of 501 children with a first febrile seizure found a 5.4 percent risk of
occurrence of epilepsy during a 30-month follow-up period. Significant prognostic markers for
subsequent epilepsy included a family history of epilepsy (especially maternal), complex febrile
seizure, focal febrile seizure, Todd's paresis, short fever duration before the seizure, late onset
of febrile seizure (>3 years old), and multiple febrile seizure recurrences. Multiple febrile
seizures increased the risk of epilepsy 10 times [44].

Electroencephalogram and risk of epilepsy — While electroencephalogram (EEG) is not useful in

determining the risk of recurrent febrile seizures, it is often performed in the outpatient setting to
identify children at increased risk for future epilepsy, in combination with other risk factors.

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The evidence to support the utility of EEG in this setting is mixed, however. In one small study, 25
percent of children (9 of 36) with epileptiform discharges on EEG after febrile seizure developed
epilepsy, compared with 2 percent of controls with a normal EEG [45]. The rate of recurrent febrile
seizures was similar (33 and 26 percent, respectively). In a larger study that included 154 children
with a first complex febrile seizure who underwent EEG, 13 percent of children developed epilepsy
with a minimum of two years of follow up [46]. Epileptiform EEGs were noted in 20 percent of those
who developed epilepsy and 13 percent of those who did not, resulting in a positive predictive value
of only 15 percent.

If the decision is made to obtain an EEG, the optimal timing is also uncertain. 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. Transient slow wave abnormality up to 10 days after recovery
from a febrile seizure is reported in 50 percent of patients [47]. Multiple seizures within 24 hours are
predictive of abnormal EEG, and abnormalities are more common in children with complex than
simple febrile seizures (43 versus 28 percent) [48]. Some studies suggest that certain abnormal EEG
findings may be more strongly associated with the risk of epilepsy than others, but the EEG alone
should not be used as a basis for treatment decisions [49].

Focal EEG slowing or attenuation on an EEG obtained within 72 hours of febrile status epilepticus is
a potential biomarker for later development of epilepsy, and such changes are highly associated with
MRI evidence of acute hippocampal injury [28]. (See 'Febrile status epilepticus' below.)

Subsequent temporal lobe epilepsy — Although a variety of seizure types follow febrile seizures,
whether prolonged febrile seizures 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 [50]. In addition, studies
assessing hippocampal volume in adults with epilepsy have found an association between a smaller
hippocampus and a history of febrile seizures [51,52]. Data are conflicting as to whether a correlation
exists between the duration of epilepsy and a reduction in hippocampal volume [53]. Hippocampal
abnormalities have also been associated with familial febrile seizures [54].

The possibility of hippocampal injury induced by febrile seizures was assessed by MRI in infants who
had had complex febrile seizures [55]. Abnormalities were found in the children with focal and
prolonged complex febrile seizures but not in those with generalized febrile seizures. 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 [56,57]. 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 characteristics of hippocampal sclerosis were more common
in adults with a history of febrile seizures in childhood than those without [58]. Although these
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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 seizures
and their characteristics [59]. Febrile seizures 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 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 seizures.

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 [50]. 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 — Febrile status epilepticus (FSE) is a subset of complex febrile seizures,
and as such is associated with an increased risk of recurrent febrile seizures, as well as future
afebrile seizures. However, the magnitude of the elevation in risk is not well-defined.

Clinical follow–up of a large prospective cohort of children with febrile status epilepticus (FEBSTAT) is
in progress [4]. Children with febrile status epilepticus are more likely to have hippocampal imaging
abnormalities at the time of presentation compared with those with simple febrile seizures, including
abnormal hippocampal T2 hyperintensity in 11.5 percent and developmental abnormalities of the
hippocampus in 10.5 percent [4,29]. The majority of children with abnormal hippocampal T2
hyperintensity at baseline had evidence of decreased hippocampal volume one year later, but the
implications of this finding in terms of long-term seizure risk are not yet known [60]. Compared with
children with a first simple febrile seizure, children with FSE are also at an increased risk for
subsequent FSE, particularly those with a baseline MRI abnormality [20].

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Another study followed 44 children with FSE, most of whom were identified prospectively [61]. 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 status, show focal slowing in one-third [62], a finding that has been associated with a
higher risk of epilepsy in some studies. (See 'Electroencephalogram and risk of epilepsy' above.)

SOCIETY GUIDELINE LINKS

Links to society and government-sponsored guidelines from selected countries and regions around
the world are provided separately. (See "Society guideline links: Seizures and epilepsy in children".)

INFORMATION FOR PATIENTS

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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, easy-to-read
materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more
detailed. These articles are written at the 10th to 12th 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 topic (see "Patient education: Febrile seizures (The Basics)")

● Beyond the Basics topic (see "Patient education: Febrile seizures (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

● Description – 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
five years of age and do not have epilepsy, central nervous system infection or inflammation, or
other triggers for seizures. (See "Clinical features and evaluation of febrile seizures", section on
'Definitions'.)

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● Initial evaluation – The initial evaluation must distinguish febrile seizure from alternative and
more serious etiologies such as central nervous system infection. In most cases, this can be
accomplished with a thorough history and physical examination, as discussed in detail
separately. (See "Clinical features and evaluation of febrile seizures", section on 'Diagnostic
evaluation'.)

● Acute management – Fever should be treated symptomatically with antipyretics. (See 'Acute
management' above.)

• Seizure ended – The majority of febrile seizures have ended spontaneously by the time the
child is first evaluated, and the child is rapidly returning to a normal baseline. In such cases,
active treatment with benzodiazepines is not necessary. (See 'Emergency rescue therapy'
above.)

• Seizure prolonged or ongoing – In children with febrile seizures that continue for more
than five minutes, we recommend treatment with intravenous (IV) benzodiazepines
(diazepam 0.1 to 0.2 mg/kg or lorazepam 0.05 to 0.1 mg/kg) (Grade 1B). Buccal midazolam
(0.2 mg/kg, maximum 10 mg) is an alternative when IV access is unavailable. Patients with
continued seizures despite initial benzodiazepine administration (ie, febrile status
epilepticus) should be treated promptly with additional antiseizure medications, as are other
patients with status epilepticus. (See 'Emergency rescue therapy' above and 'Febrile status
epilepticus' above.)

• Disposition – Most children with simple febrile seizures do not require hospital admission
and can be discharged safely to home once they have returned to a normal baseline and
parents and caregivers have been educated about the risk of recurrent febrile seizures.
Children with focal or prolonged seizures may require a more extended period of
observation, particularly if there is delayed recovery to baseline or focal postictal weakness.
(See 'Discharge disposition' above.)

● Recurrent febrile seizures

• Risk factors – 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. (See 'Risk factors for
recurrence' above.)

• Home benzodiazepines – In children with a history of prolonged febrile seizure,

benzodiazepines (eg, diazepam rectal gel 0.5 mg/kg) can be administered at home by

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parents or caregivers if the seizure lasts longer than five minutes. (See 'Provision of home
benzodiazepines' above.)

• Limited role of antiseizure prophylaxis

- For simple febrile seizures – We suggest not treating patients with simple febrile
seizures with antiseizure medication therapy (Grade 2B). While antiseizure medications
may decrease the risk of recurrent febrile seizures, the prevention of febrile seizures is
generally not considered worth the potential adverse effects of treatment. The available
evidence suggests that the use of chronic antiseizure medications does not reduce the
risk of epilepsy. (See 'Role of preventive therapy' above.)

- For complex febrile seizures – The use of antiseizure medication prophylaxis in

children with complex febrile seizures is individualized based upon underlying risk
factors. (See 'Antiseizure therapy' above.)

● Risk of 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. Children with complex febrile seizures, an
abnormal developmental history, or a family history of epilepsy have an increased risk. (See
'Subsequent epilepsy' above.)

ACKNOWLEDGMENT

The UpToDate editorial staff acknowledges J Gordon Millichap, MD, FRCP, who contributed to an
earlier version of this topic review.

Use of UpToDate is subject to the Terms of Use.

Topic 96573 Version 33.0

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