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IndianPediatrics200138:733740

FebrileSeizures
PratibhaD.Singhi,M.Srinivas
From the Division of Pediatric Neurology and Neuro Developmental Unit, Department of Pediatrics,
PGIMER,Chandigarh160012,India.
Correspondece to: Dr. Pratibha D. Singhi, Chief, Neurology and Neuro Developmental Unit, Department of
Pediatrics,PGIMER,Chandigarh160012,India.
Email:medinst@pgi.chd.nic.in
Febrile seizures are the most frequent neurologic disorder in children. There have been a number of
controversiesregardingtheirmanagement,recurrenceriskandlongtermoutcome.RecentlytheAmerican
AcademyofPediatrics(AAP)hassetguidelinesformanagementofsimplefebrileseizuresinchildhood(l).
Thisarticleprovidesanupdateonthecurrentstatusandmanagementpracticesoffebrileseizures.
Definitions
Febrile seizures are defined as an event in neurologically healthy infants and children between 6 months
and 5 years of age, associated with fever >38C rectal temperature but without evidence of intracranial
infection as a defined cause and with no history of prior afebrile seizures(2). Febrile seizures are to be
distinguishedfromepilepsywhichischaracterizedbyrecurrentnonfebrileseizures.Allseizureswithfever
are not febrile seizures. Convulsions in children with fever due to pyogenic meningitis, hypernatremic
dehydration or other metabolic disorders are not included. Generally, febrile seizures occur during early
phaseofrisingtemperatureandareuncommonafter24hoursofonsetoffever(3).
Simplefebrileseizuresaregeneralizedseizures,lastinglessthan15min,notrecurringwithin24hours,and
withnopostictalneurologicalabnormalities.
Complex febrile seizures are focal, prolonged or recurrent within 24 hours or associated with postictal
neurological abnormalities including Todd paresis. These seizures constitute around 15% of febrile
seizures.
Febrilestatusisseizuredurationof30min.ormore,eitheronelonglastingoraseriesofshorterseizures
withoutregainingconsciousnessinterictally.
Incidence
Febrile seizures occur in 34% of children under the age of 5 years(3). Usually, they do not occur beyond
theageof5yearsimplyingaspecificvulnerabilityofyoungchildrentofeverasaprecipitant.Themedium
ageofoccurrenceis1822months(4).
Ithasbeenrecognizedthatthereissignificantgeneticcomponentforsusceptibilitytofebrileseizures.Two
putative febrile seizure (FS) loci, FEB1 (chromosome 8q13q2l) and FEB2 (chromosome 19P) have been
mapped.Furthermore,amutationinthevoltagegatedsodium(Na+)channelbetasubunitgene(SCN1B)at
chromosome19ql3.1wasidentifiedinafamilywithclinicalsubset,termedgeneralizedepilepsywithfebrile
seizuresplussyndrome(GEFS(+)).Studieshavealsolinkedthesusceptibilityoffebrileseizurestoagene
on chromosome 5ql4ql5 (FEB4)(5).The risk of another child having febrile seizure is one in five with one
affectedsiblingandoneinthreeifbothparentsandapreviouschildhavehadfebrileseizures(6).
RiskFactorsforRecurrenceofFebrileSeizures

The determinants for recurrent febrile seizures and for later epilepsy are different.The average recurrence
rate after a first febrile seizure is 3040% but this is dependent on complex interplay between the genetic
andenvironmentalfactors.Recurrenceriskisrelatedtovariousriskfactors,whichmayincludethetypeof
treatment.Onestudyfoundatotaloffiveriskfactorsforrecurrentfebrileseizureswhennoprophylaxiswas
given(7).Inorderofpredictivepoweritincludedyoungageatonset (<15 months), epilepsy in first degree
relative, febrile seizures in first degree relatives, many subsequent febrile episodes and a first complex
febrile seizure. The higher the number of risk factors, the higher the recurrence rate and vice versa.
Untreatedchildrenwithnoriskfactorshaveaverylowrecurrencerate(10%)childrenwithoneortworisks
haveanintermediaterisk(2550%)andthosewith3ormorefactorshaveaveryhighrecurrencerate(50
100%). In a similar group of children with febrile seizures, given intermittent diazepam prophylaxis at the
time of fever, all risk groups had a low recurrence rate (12%). This intermittent prophylaxis reduced
recurrenceriskinthosewithoneormorerisks.Thehighertherecurrencerisk,thebettertheseizurecontrol
duringprophylaxis(7).Ametaanalysisof14studies foundmainly2factorsassociatedwithrecurrenceof
febrile seizures: (i) younger age of onset, and (ii) family history of febrile seizures(8). Subsequently, two
more factors have been associated: (i) lower temperature at the time of febrile seizure(9) and shorter
duration of temperature before the onset of seizure(10). In another metaanalysis by Offringa et al. young
age at onset (<12 months), a history of febrile or unprovoked seizure in first degree relative and a rectal
temperature less than 40C at the time of febrile seizure were associated with a significantly increased
recurrencerate(11).
Ageofonsetisperhapsthesinglestrongestandmostconsistentpredictorofrecurrentfebrileseizures:the
younger the child, the greater the risk (50% in <1 year old versus 20% in >3 years old)(4). The higher
recurrenceriskassociatedwithearlyageatonsetmayindicateincreasedvulnerabilitytofebrileseizureor
may simply be a function of greater remaining risk period available in which to have a recurrence. The
younger the child at second or third febrile seizure, the higher the likelihood of further recurrences. The
association between complex febrile seizures and recurrences though seen in some studies(7) has not
been consistently proven(8,11,12). However, in children with recurrent febrile seizures, complex features
tendtorepeat(12).Therecurrencehazardishighest in the first 6 to 12 months after an initial seizure(11).
TheimportantriskfactorsaresummarizedinTableI.
The most crucial risk factors for febrile status include young age at onset, family history of unprovoked
seizure and an initial partial febrile seizure(11,12). Risk factors for the first febrile seizure comprise the
heightofthetemperatureandfamilyhistoryoffebrileseizure(13).
RiskofEpilepsy(TableII)
Populationbasedstudieshaveshownthattheriskofepilepsyafterfebrileconvulsionvaries from 22.5%.
Ahistoryoffebrileconvulsionsispresentin10 to15%ofpeoplewithepilepsyorunprovokedseizure(14),
several times higher than the 2 to 4% seen in the general population.Among children with febrile seizure
threefactorshavebeenwellestablishedaspredictorsoflaterepilepsy(15):(i)Afamilyhistoryofepilepsy,
(ii)Preexistingneurologicordevelopmentalabnormalitiesand(iii)Complex febrile seizures, each complex
featureoffebrileseizuresisanindependentpredictoroflaterafebrileseizures.
TableIRiskFactorsforRecurrenceofaFebrileSeizure

1.Youngageatonset(<15months)
2.Epilepsyinfirstdegreerelative
3.Febrileseizuresinfirstdegreerelative
4.Manypreviousepisodesoffebrileseizures
5.Firstcomplexfebrileseizure?

TableIIRiskFactorsforEpilepsyAfteraFebrileSeizure

Afamilyhistoryofepilepsy
Preexistingneurologicordevelopmentalabnormalities
Complexpartialseizures,eachcomplexfeatureisanindependentpredictoroflaterafebrileseizure.

TypeofEpilepsy
Differenttypesofseizures(generalizedtonicclonic,absence,complexpartial)mayoccurinthosechildren
whodevelopepilepsyafterpreviousfebrileseizures.Inrarecasesmultiplefebrilerecurrencesarefollowed
by severe myoclonic epilepsy(16). Contrary to earlier belief, only a small proportion of children with febrile
seizures go on to develop temporal lobe epilepsy(17). The relationship between febrile seizures in
childhood,complexpartialseizures,temporallobeepilepsyandmesialtemporalsclerosis in particular has
long been assumed based upon associations seen among these and other factors in adults as well as
children, largely with refractory epilepsy. While one study had shown strong association between prior
febrile seizures and temporal but not extra temporal lobe epilepsy(14) another noted that there is no
evidence that prior febrile seizures were associated with complex partial seizures, localizationrelated
epilepsy,orspecificallywithtemporallobeepilepsyorwithhippocampalatrophyorotherpotentiallyrelated
findings in the temporal lobe(18). In selected families, prolonged febrile seizures were found to have a
strong association with temporal lobe epilepsy(19). Thus, the relationship between febrile seizures and
mesialtemporalsclerosisistilldateinconclusive.Mesialtemporalsclerosishasbeenreportedbothbefore
and after febrile seizures.There is evidence demonstrating that mesial temporal sclerosis is both a result
andacauseofseizures(20).
IntellectualandMotorFunctions
Thereisnoevidencethatsimplefebrileseizurescauseanystructuraldamagetothebrainorthatchildren
with simple febrile seizures are at risk for cognitive decline. Population based studies have shown that
febrile seizures in early childhood do not have adverse effects on behavior, scholastic performance and
neurocognitiveattention(21).
ManagementofaChildWithFebrileSeizure
(a)DuringtheSeizure
Any child with a febrile seizure needs to be managed as for any other seizure, with airway
management, a semi prone position to decrease the risk of aspiration, monitoring of vital
signs and other supportive care. Seizure should be terminated with IV diazepam or
lorazepam. Rectal diazepam (0.5 mg/kg) has also been found to be safe and effective. It is
completelyabsorbedandanticonvulsantplasmaconcentrationsareobtainedwithin24 min.,
almostasrapidlyasanintravenousdose.Wherereadyrectalpreparations are not available,
the undiluted intravenous preparation is sucked in a small syringe and given through a
Polythene tube which is gently inserted 4 to 5 cm into the anus after lubricating with
lignocainejelly.Thismethodhasbeenfoundtobeeffectiveinacuteseizurecontrolinfebrile
andafebrileseizuresathomeandinahospitalsetting(22).
Rectal,oralorIVlorazepam(23),rectalclonazepam(24),nasalmidazolam(25)andotherdrugs
have also been used in acute seizure control but to a lesser extent. Lorazepam appears to
beaseffectiveasdiazepaminseizurecontrolandhasamoreprotracteddurationofaction.
In a preliminary study, midazolam by nasal route demonstrated effective seizure control in
children with epilepsy(25). Recent studies have shown that midazolam (0.2 mg/kg) given
intranasallyisassafeandaseffectiveasdiazepamgiven intravenously in the management
offebrileseizuresinchildren(26).
(b)Hospitalization
Thedecisiontoadmitshouldbeindividualizedbutadmissionisusuallynotnecessary.Most
childrenshouldbeobserveduntiltheyareawakeandalert.Children,especially those with a
first febrile seizure, should be hospitalized if any of the following are present: (i) Lethargy
beyond postictal state (ii) Unstable clinical status (iii) Age <18 months (iv) Complex
features (v) Uncertain home situation (vi) Unclear follow up. It must be remembered that a
historyofpreviousfebrileconvulsiondoesnotruleoutpossibilityofmeningitis.Anychildwith
theslightestsuspicionofmeningitisshouldbeadmittedandinvestigated.
(c)Investigations

Theinvestigationsare oriented towards finding the cause of fever and to rule out meningitis.
Fever is most often due to viral infections of upper respiratory tract, acute otitis media,
infectionsofurinarytract,gastrointestinaltractandfebrilereactionsaftervaccinations(27).A
good clinical examination is necessary to determine the focus of fever, and investigations
wouldbeindicatedaccordingly.Serumelectrolytes,bloodglucose,calcium, magnesium and
bloodcountsarenotroutinelyneeded.
(d)LumbarPuncture(LP)
LP is not routinely performed in children with fever and first seizure. It is however, indicated
wheneveradoubtofmeningitisexists.Riskfactorsformeningitis in patients presenting with
feverandseizureare(28):(i)Abnormalneurologicalexamination,especiallymeningeal signs
(ii) Focal seizure, suspicious physical findings (rash or petechiae, cyanosis, hypotension,
grunt,etc.(iii)Aphysicianseenwithin48hoursoffeverand(iv)Ongoingseizure activity at
the time of arrival in the hospital. Used in combination, these risk factors are very helpful in
identifyingchildrenwithmeningitisandtheirnegativepredictivevaluewas100%(28).
TheAAPstrongly recommends LP in patients under 12 months of age presenting with fever
andseizurebecausemeningealsignsmaybeminimalorabsentinthisagegroup.LPistobe
consideredinpatients12to18monthsofage(29)assymptomsandsignsofmeningitismay
be subtle. Symptoms and signs of meninigitis may also be masked in children with febrile
seizures who have received antibiotics, hence LP is warranted in such cases also(29). The
spinal fluid findings may be normal in early meningitis thus a negative spinal tap does not
eliminatetheneedforcarefulfollowup.
(e)EEG
AnEEGisnotnecessaryintheroutineevaluationofachildwithafirstsimplefebrile seizure.
ThereportedincidenceofparoxysmalEEGabnormalitiesinchildrenwithFSvarywidelyfrom
2 to 86%. The first reason for this variability is related to differences used for subject
selection by different authors. Second the criteria used in different studies to define
paroxysmal discharges are different. Some authors dont confine their definition of
paroxysmalactivitytospikesorspikewavesandincludephantomspikewaves,highvoltage
slow waves burst and so on. Third the timing of EEG has to be taken into consideration as
generally detection of epileptic discharges is unusual within the first postictal week and is
alsodifficultinearlychildhoodbeforetheageof3years(30).
Abnormal EEGs do not reliably predict the development of epilepsy or recurrence of febrile
seizures. Considering the wide variability and the poor prediction, EEG has no role in the
management of a patient with simple febrile seizure. The yield of postictal EEG in children
with complex febrile seizures is low, and similar to that in children with simple febrile
seizures. Routine EEG in neurologically normal children with complex febrile seizures is not
indicated(31).
(f)Neuroimaging
Neither CT nor MRI head has any role in the management of a child with simple febrile
seizure.
(g)TreatmentofFever
Antipyreticsarenoteffectiveinpreventingrecurrentfebrileseizures,butareusefulin making
thechildmorecomfortable(32).
LongTermManagement
Theprimarygoaloflongtermmanagementoffebrileseizureistopreventrecurrences.Treatment options
include: (a) prolonged daily prophylaxis with phenobarbitone or valproate and (b) intermittent prophylaxis
withdiazepamorotherbenzodiazepines.

ContinuousProphylaxis
Phenobarbitaliseffectiveinpreventingtherecurrenceofsimplefebrileseizures(33).Inacontrolleddouble
blindstudy,dailytherapywithPhenobarbitalreducedtherateofsubsequentfebrileseizurefrom25per100
subjects/years to 5 per 100 subjects/year(34). The adverse effects include behavioral problems such as
hyperactivity and hypersensitivity reactions. Longterm phenobarbital treatment appears to influence
cognitionandbehavior,alargepriceforpreventionofbenigncondition.
Valproateisaseffectiveasphenobarbitoneinpreventingrecurrent,simplefebrileseizures. In randomized,
controlled studies, only 4% of children taking valproate as opposed to 35% of control subjects had a
subsequent febrile seizure(35). Drawbacks to therapy with valproate include its rare association with fatal
hepatotoxicity,thrombocytopenia,weightlossandgain,gastrointestinaldisturbancesandpancreatitis.
Neither Phenobarbital or Valproate is effective in reducing the risk of epilepsy in children with febrile
seizure.
IntermittentDiazepamProphylaxis
Diazepam administered intermittently either rectally as suppositories, or solution or orally at the onset of
fever has been shown to be effective in preventing recurrence of febrile seizures(36). By either route,
generallyadoseof0.3to0.5mg/kg(max10mg)isusedandrepeatedevery812hoursif temperature is
38C or more. A maximum of 45 doses are given per illness. Intermittent clobazam (1mg/kg/day) given
orallyhasalsobeenfoundtobeusefulinpreventingfebrileseizurerecurrences(37).A potential drawback
to intermittent medication is that seizure could occur before fever is noticed. Adverse effects of oral
diazepam include lethargy, drowsiness and ataxia(36). The sedation associated with this therapy could
maskevolvingsignsofmeningitis.Itmusthoweverberememberedthatthistherapydoesnotdecreasethe
incidenceoflaterepilepsyinchildrenwithfebrileseizures(38).
PatientEducation
This perhaps is the most important (and often neglected) aspect of management of febrile seizures. As
seizures in their child can be very frightening for the parents they should be counselled properly with
particularemphasison:(i)Thebenignnatureofthefebrileseizures(ii)Thatfebrileseizuresdonotleadto
neurological problems or developmental delay (iii) What they should do immediately if their child has
another seizure (iv)A doctor should be consulted if the seizure lasts for more than 15 min. or if the post
ictaldrowsinesspersistsformorethan30min.
Conclusions
Febrile seizures in children are benign events that do not have any long term neurological sequalae, and
neitherlongtermdailyphenobarbitonenorintermittentdiazepamhaveanyroleinthemanagementofthese
childrenwithsimplefebrileseizures(39).Appropriateeducationandemotionalsupportshouldbeprovidedto
parents.Insituationswheresevereparentalanxietyisassociatedwithfebrileseizures,intermittenttherapy
may be advised continuous antiepileptic therapy is rarely used. Recent epidemiologic studies have also
confirmedthatthevastmajorityofchildrenwithfebrileseizureshaveabenignprognosisandanormallong
termoutcome(40,41).
Contributors: PD conceptualized and drafted the manuscript, she will act as the guarantor. SM helped in
literaturereviewanddrafting.
Funding:None.
Competinginterests:Nonestated.
KeyMessages
Febrile Seizures are generally benign events and do not cause lasting intellectual or
neurologicdamage.
EEGandneuroimagingarenotindicatedintheusualevaluationoffebrileseizure.

Antiepileptic therapy (Phenobarbitone/Valproate), either intermittent or continuous, can

preventrecurrencesoffebrileseizurebutdoesnotpreventsubsequentepilepsy.
Mostchildrenwithfebrileseizuresdonotrequireantiepileptictherapyincasesofsevere
parentalanxietyand/ormultiplerecurrences,intermittenttherapymaybeadvised.

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