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Febrile Seizures

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Febrile Seizures
Janet L. Patterson, MD; Stephanie A. Carapetian, MD; Joseph R. Hageman, MD; and Kent R. Kelly, MD

Abstract CM E EDUCATIONAL OBJECTIVES

Janet L. Patterson, MD, is Assistant Pro-
Febrile seizures are the most common form of childhood seizures, affecting 2%
fessor of Clinical Pediatrics, Division of Child
to 5% of children. They are considered benign and self-limiting, however, a febrile
Development, University of Illinois College
seizure is a terrifying event for most parents, and is one of the most common causes of Medicine at Peoria. Stephanie A. Cara-
of trips to the emergency room. petian, MD, is a pediatric neurology fellow,
A febrile seizure is an event in infancy or childhood, usually occurring between 3 Division of Pediatric Neurology, University
months and 5 years of age, associated with fever but without evidence of intracranial of Washington. Joseph R. Hageman, MD, is
infection or defined cause. This definition excludes seizures with fever in children Senior Clinical Educator, Pritzker School of
who have had a prior afebrile seizure. In 2011, The American Academy of Pediatrics Medicine, University of Chicago, Depart-
(AAP) published a clinical practice guideline defining a febrile seizure as a seizure ment of Pediatrics, NorthShore University
accompanied by fever (temperature 100.4F or 38C by any method), without cen- Health System. Kent R. Kelly, MD, is Clinical
tral nervous system infection, that occurs in infants and children 6 through 60 months Assistant Professor, Pritzker School of Medi-
cine, University of Chicago, Department of
of age. Febrile seizures are further classified as simple or complex. This article re-
Pediatrics, NorthShore University Health
views the evaluation, management, and prognosis of simple and complex seizures,
System.
including febrile status epilepticus.
Address correspondence to: Janet L. Pat-
terson, MD; University of Illinois College of
Medicine, Peoria, University Child Develop-
ment, 507 E. Armstrong Peoria, IL 61603;
email: patters@uicomp.uic.edu.
Disclosure: The authors have no relevant
financial relationships to disclose.
doi: 10.3928/00904481-20131122-09
Shutterstock

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F
ebrile seizures are the most com-
mon form of childhood seizures,
affecting 2% to 5% of children.
They are considered benign and self-
limiting, however, a febrile seizure is a
terrifying event for most parents, and is
one of the most common causes of trips
to the emergency room
CHARACTERISTICS AND
CLASSIFICATION
Febrile seizures are classified as
simple or complex based on duration,
physical characteristics, and recurrence
patterns (Table 1). A self-limited, short
(< 15 minutes), generalized, tonic-clon-
ic seizure that does not recur within the
same illness and is not associated with
post-ictal pathology is classified as a
simple febrile seizure (SFS). Febrile
seizures that do not meet all criteria for
SFS are classified as complex febrile
seizures (CFS). A prolonged febrile
seizure (PFS) is a complex seizure that
lasts longer than 15 minutes, and a fe-
brile seizure that continues longer than
30 minutes is classified as febrile status
epilepticus (FSE).5 FSE accounts for 5%
to 9% of all febrile seizures6,7 and 25%
of all episodes of status epilepticus oc-
curring in children.8,9 In the second year
of life, two-thirds of all cases of status
epilepticus are FSE.10 FSE is considered
a medical emergency.
Despite the common belief that fe-
brile seizures occur with rise in tem-
perature, there is no evidence to support
this. Febrile seizures usually develop in
the first 24 hours of the illness,8,11 with
21% of children manifesting a seizure
within an hour of fever onset.11 The fe-
ver associated with febrile seizures is
typically higher than in children with
similar fever-related illness who do not
experience a seizure,1 and the height
of the fever is often at least 39C at the
time of the seizure.11 The seizure itself
is the first sign of febrile illness in 25%
to 50% of cases, and seizures that occur
3 or more days after the onset of fever
250 | Healio.com/Pediatrics
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should be considered unlikely to be a fe-
brile seizure.11
INCIDENCE
In the United States and Western Eu-
rope, 2% to 5% of all children experi-
ence a febrile seizure. The incidence
varies in other parts of the world; for
example, 5% to 10% in India, 8.8% in
Japan, and 14% in Guam.8 The first fe-
brile seizure occurs commonly between
6 months and 3 years of age, with the
peak incidence at 18 months.1,11 They
are complex in 9% to 35% of cases, and
the incidence in boys is slightly higher
than in girls.
RISK FACTORS
The two most consistently identified
risk factors for developing febrile sei-
zures are the height of the temperature
and a positive family history in first-de-
gree relatives.8,11,12
Higher temperatures are associated
with a higher likelihood of having a
febrile seizure.11,12 The risk for febrile
seizures increases with the number of
relatives who have a history of febrile
seizures.1,8 Sibling studies identify a risk
of 10% to 45%.8,13
Other identified risk factors are a
neonatal nursery stay of greater than 28
days, developmental delay, and day care
attendance.2,14,15
PATHOGENESIS
Febrile seizures are strongly age-
specific, and mechanisms of seizure de-
velopment are related to the identified
risk factors, environment (fever) and ge-
netics. Animal models have shown that
brain hyperthermia can lead to seizures
in all species of rats and mice. Certain
strains have different seizure - threshold
temperatures, implying genetic influ-
ences on susceptibility.16
Several gene loci have been implicat-
ed in familial febrile seizures, including
genes that code for GABAA receptors
and interleukins. SCN1A gene muta-
tions are responsible for a spectrum of
seizure disorders that often present ini-
tially as a febrile seizure. This spectrum
of disorders ranges from SFS to general-
ized epilepsy with febrile seizures plus
(GEFS+), and at the severe end, Dravet
syndrome (or severe myoclonic epilepsy
in infancy).17,18 Various mechanisms
have been proposed in the pathogen-
esis of febrile seizures, including tem-
perature sensitive ion channels altering
neuronal function, and inflammatory
processes promoting secretion of cyto-
kines (known to increase neuronal excit-
ability).11,16 Specific infectious etiolo-
gies have been associated with febrile
seizures, such as human herpes simplex
virus-6 (roseola infantum), accounting
for as much as 20% of children present-
ing with first febrile seizures, shigella
gastroenteritis, and influenza A.19-21 Im-
munizations, such as diphtheria-tetanus-
pertussis and measles-mumps-rubella,
are associated with significantly elevat-
ed risks of febrile seizures.22 It is unclear
whether the association of infections and
immunizations are related to the height
of the fever or some other unidentified
factor.11
EVALUATION/MANAGEMENT
Simple Febrile Seizures
Children with SFS tend to present to
the ER for medical care after resolution
of the seizure. They may be post-ictal
and appear irritable, confused, or lethar-
gic. Gradual return to a normal level of
alertness occurs within 1 hour, and there
are no focal deficits. Transient hemipare-
sis (Todds paralysis) has been described
with SFS but should always raise suspi-
cion of focality and, therefore, complex
classification.23
The medical history should include
duration of fever, potential illness expo-
sure, and recent antibiotic use. Neuro-
developmental delay, possible metabolic
disturbance, history of prior seizures,
and other potential causes of seizures,
such as trauma or accidental ingestion,
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should also be considered. TABLE 1.
The diagnostic evaluation of a child
with an SFS should clarify whether the Classification of Febrile Seizures
child actually had a seizure and focus on
Simple Febrile Seizure Complex Febrile Seizure
identifying the source of fever. The 2011
AAP clinical practice guideline recom- (all criteria must be met) (one or more of the following)
mendations state, meningitis should be
Prolonged febrile seizure
considered in the differential diagnosis
(> 15 minutes)
in any child with fever, and a lumbar Short (< 15 minutes) Febrile status epilepticus
puncture (LP) should be performed if Duration Self - limiting (> 30 minutes)
there are any signs or symptoms of con-
cern (level B evidence). Level D evi- Focal onset or features
dence supports consideration of an LP Clonic and/or tonic
in the evaluation of a younger child (6 Loss of muscle tone
to 12 months), a child who is underim- Focal progressing to general
munized, of questionable vaccination Phenotype Generalized tonic-clonic Head/eye deviation to one side
status, or on prior antibiotics. Further
investigations such as blood studies, Recurrence within the same
imaging studies, or EEGs are not nec- Recurrence Frequency No recurrence in 24 hours febrile illness
essary, unless there are specific indica-
tions for concern based on the history Prior Neurologic Diagnosis None Present
and physical findings.4
The AAP guidelines were based on Present (unilateral paralysis,
retrospective analyses of the risk for Post-ictal Pathology None somnolence)

bacterial meningitis presenting as a SFS

with no other symptoms of meningitis.
In a 20-year review of 503 consecutive
children with bacterial meningitis, no
child presented solely with an SFS.24
A more recent study of 6- to 18-month-
old children presenting with a first SFS
found no cases of bacterial meningitis.25
Complex Febrile Seizures
CFS are heterogeneous in presenta-
tion, and no national practice guidelines
are established. A survey of 353 pedi-
atric emergency providers identified
significant variability in the evaluation
of children with CFS.26 One-third of fe-
brile status epilepticus (FSE) cases are
unrecognized in the ER.5,6 In a prospec-
tive study of 60 children presenting with
prolonged febrile seizure (PFS), 70%
went into FSE, irrespective of wheth-
er treatment was administered in the
field.10 Treatment of an ongoing seizure
consists of airway maintenance, oxygen,
supportive care, and anticonvulsants.
Rectal diazepam has been used at home
and in the ER with dosing of 0.25 mg/kg
to 0.5 mg/kg.15
CFS and FSE are more frequently as-
sociated with meningitis than SFS.24,27
CNS infections are unlikely, however,
unless there are accompanying clini-
cal findings, such as decreased level of
consciousness, meningeal signs, or toxic
appearance.25,28 An LP is frequently un-
necessary unless the patient is under the
age of 12 months (limiting confidence in
physical exam), displays signs of CNS
infection, or does not return to baseline
mental status.29 About one in four chil-
dren with meningitis present with a sei-
zure,15 and bacterial meningitis occurs
in up to 18% of children with CFS.27
Imaging studies are not indicated in
most well-appearing children with first
CFS.29 In a recent review of children
with a first CFS, no child had intracra-
nial pathology.30 High resolution brain
MRI should be considered in the follow
up of focal, PFS, and FSE due to the as-
sociation of FSE with hippocampal in-
jury, mesial temporal sclerosis, and tem-
poral lobe epilepsy.5,31,32
An EEG is not usually indicated for
evaluations of CFS with the exception of
FSE. EEG may be considered in follow-
up if there are recurrences without fever
or evidence of developmental delay or
neurologic deficits.33
A prospective, multicenter study
(Consequences of Prolonged Febrile
Seizures in Childhood, or FEBSTAT)
was initiated to examine the associa-
tion between PFS, FSE, and the devel-
opment of hippocampal sclerosis. The
FEBSTAT study followed children aged
1 month to 6 years who presented with
an episode of FES, documenting peri-
odic imaging and EEGs.5 The FEBSTAT
study findings identified 90 of 119 EEGs
obtained in the first 72 hours after FSE
as abnormal, with focal slowing or atten-
uation primarily over the temporal area.
These preliminary findings (currently at

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the 5-year mark) were highly associated
with MRI evidence of acute hippocam-
pal injury and may indicate a marker for
injury associated with FSE.5
PROGNOSIS
Recurrence Risk
One in three children with a febrile
seizure will have another, and age (< 15
months) appears to be the most consis-
tent risk factor associated with recur-
rence.1,8 If recurrence occurs, half will
recur within the first year and 90% will
occur within 2 years.8 Other associated
factors include epilepsy or febrile sei-
zures in first-degree relatives, first CFS,
and day care exposure. As the number
of risk factors increase, the recurrence
risk increases;34 the presence of three or
more risk factors is associated with 80%
to 100% recurrence. Higher recurrence
risk has also been associated with sei-
zures that occur at lower-peak tempera-
tures or within an hour of fever onset.35
Epilepsy Risk
Although children with febrile sei-
zures are at increased risk of develop-
ing epilepsy compared to healthy con-
trols,36,37 most children with febrile
seizures (97%) will never develop epi-
lepsy.1
Risk factors for developing epilepsy
following SFS is 1% to 2.4% (compared
to 0.5% in the general population) and
4% to 6% following CFS.36 The Nation-
al Cooperative Perinatal project identi-
fied idiopathic or genetic epilepsy in a
first-degree relatives, abnormal neurode-
velopmental status prior to seizure onset,
and CFS as independent risk factors.37
Population-based studies identified ce-
rebral palsy, low apgar score, PFS, focal
seizures, and recurrent febrile seizures
with increased epilepsy risk.38
PFS have been associated with in-
creased risk of recurrent febrile seizures,
epilepsy, and FSE.10 Hersdorffer7 noted
that defining PFS at 10 minutes or great-
er, instead of 15, is associated with prior
252 | Healio.com/Pediatrics
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TABLE 2.
Talking Points
Simple Febrile Seizure
(not harmful / does not cause
General information death or brain damage)
One-third have recurrence
Increased risk if child:
Has family history of
seizures
Is < 12 months
Recurrence Has temperature < 102
Important action points:
Remain calm
Place child on his / her side
to prevent choking.
Do not put anything in
the childs mouth or try to
restrain
Call 911 if seizure lasts
Management longer than 5 minutes.
Most children never develop
epilepsy. Risk is slightly high-
Epilepsy Risk er than risk for all children.
No higher risk of learning dif-
Learning Risk ficulties or decreased IQ
Prophylaxis Not indicated
FSE = febrile status epilepticus; PFS = prolonged febrile seizure ; SFS = simple febrile seizure.
Data from Leung and Robson WL,11 and Vestergaard et al38
developmental delay and younger age at
first seizure.
MORTALITY AND MORBIDITY
Population-based studies have shown
no association between any type of fe-
brile seizure, including FSE, and the
later development of neurological defi-
cits or impaired cognitive functioning.39
Children with febrile seizures do not
have a higher risk of mortality.11
Complex Febrile Seizure
(not harmful / does not cause death
or brain damage)
One-third have recurrence
Increased risk if child:
Has family history of seizures
Is < 12 months
Has temperature < 102
Has PFS
Important action points:
Remain calm
Place child on his / her side to
prevent choking.
Do not put anything in the childs
mouth or try to restrain
Call 911 if seizure lasts longer
than 5 minutes
Most children never develop
epilepsy.
Higher epilepsy risk than SFS if
child has:
Prior neurodevelop-mental
abnormality,
Positive family history
Onset prior to 1 year of age
Learning risk is associated with
familial seizure disorders
Rarely indicated (identified syn-
drome, PFS or FSE)
PREVENTION
There is no evidence to support the
use of antipyretics for the prevention of
recurrent seizures, although they may be
helpful in relieving the discomfort of a
febrile child.15
Although studies have shown effi-
cacy in reducing the recurrence rate of
febrile seizures by treating with con-
tinuous antiepileptic therapy, both the
Royal College of Pediatrics and Child
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TABLE 3.

Management of Febrile Seizures

SFS (Simple)
Short (< 15 minutes), self-limiting, CFS (Complex) PFS/FSE (Prolonged)
Diagnostic Criteria tonic/clonic generalized, non-recurrent Does not meet criteria for simple >15 minutes
Comfort measures Comfort Measures Treat with antiepileptic
Observe post-ictal state Monitor post-ictal state Monitor post-ictal state
Acute Management Investigate etiology of fever Investigate etiology of fever Investigate etiology of fever
Consider LP if:
Consider LP if: S/X of meningitis
Consider LP: S/X of meningitis Non-return to baseline status
S/X of meningitis Non-return to baseline status Concern for exam reliability
LP Concern for exam reliability Concern for exam reliability
NI
NI unless S/X of space occupying NI unless concern for ongoing
EEG NI lesion or bleed seizure

NI unless s/x of space occupying

Imaging (CT) NI NI lesion or bleed

Labs NI NI NI
Follow-Up Management Parental Education/Support Parental Education/Support Parental Education/Support
NI routinely, consider if:
> 1 complex feature
Abnormal neurodevelopmental
status
EEG NI History of family epilepsy Indicated

Imaging (MRI) NI NI Indicated

Consider acute intermittent

Prophylaxis NI NI therapy
Note: NI (not implicated) implies based on seizure alone.

CFS = complex febrile seizure; CT = computed tomography; EEG = electroencephalogram; FSE = febrile status epilepticus; LP = lumbar puncture; MRI = magnetic resonance imaging; PFS = prolonged
febrile seizure; SFS = S/X = symptoms/signs.

Data from American Academy of Pediatrics4 and Patel and Vidaurre29

Health and the AAP do not recommend
the use of prophylactic oral antiepileptic
medication in children with either SFS
or CFS due to significant associated side
effects.1,23
EDUCATION
Despite the benign nature and excel-
lent prognosis of febrile seizures, they
are a cause of high anxiety among par-
ents. When a seizure is first witnessed,
parents may think that the child is dying,
and parental reactions to febrile seizures
include anxiety in reference to recur-
rence and fear of subsequent develop-
ment of epilepsy, physical disabilities,
mental retardation, and learning dys-
function. In light of the high incidence
of recurrence, parents need specific
information on appropriate first aid
techniques and reassurance that febrile
seizures are not associated with death,
development of neurological deficits, or
impaired cognitive functioning. (Table
2)
SUMMARY
In conclusion, febrile seizures are a
common, benign disorder occurring in
children between 6 months and 3 years
of age, and most children have an ex-
cellent outcome with no long-term se-
quelae. Identifying the source of fever

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and parental education are the mainstays
of management for children with SFS.
Balancing the avoidance of unnecessary
diagnostic and therapeutic interventions
with practical approaches to long-term
follow-up for CFS is crucial. The rec-
ognition, treatment, and prevention of
FSE, as well as the understanding of
long-term outcomes, will guide future
management of PFS (Table 3).
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