JPediatr(RioJ).2015;91(6):512---514
www.jped.com.br
EDITORIAL
Epidemiology
of
febrile
seizures
and
epilepsy:
a
call
for
action
夽
,
夽夽
Epidemiologia
das
convulsões
febris
e
epilepsia:
um
apelo
à
ac
¸ão
Pierre-Marie
Preux
a,b,
Voa
Ratsimbazafy
a,b,c,
Jeremy
Jost
a,b,c,∗aINSERM,UMR1094,TropicalNeuroepidemiology,Limoges,France
bUniversitédeLimoges,UMR1094,TropicalNeuroepidemiology,InstituteofNeuroepidemiologyandTropicalNeurology,
CNRSFR3503GEIST,Limoges,France
cDepartmentofPharmacy,CentreHospitalierUniversitaireLimoges(CHULimoges),Limoges,France
Seizures triggered by fever, qualified as febrile seizures, havebeenfordecadesamajorissueforchildrenin devel-oped countries and more so in resource-limited settings. Approximately 2---5% of children are affected by this kind ofseizure.Manystudies aimedtodescribe,measure,and analyzeseveralhypotheses,includingtheassessmentofthe physiopathologicalmechanisms,epidemiologicalindicators, care management,and theirimpacton theirlater neuro-logicalimpairments,suchasepilepsy,butmanyunknowns remain.
InthisissueofJornaldePediatria,Dalbemetal.1report
apopulation-basedcross-sectional study conductedinthe
cityofBarradoBugresinBraziltoassesstheprevalenceof
benignfebrileseizuresduringchildhood.Themainoutcome
was a prevalence of 6.4/1000 habitants (95% confidence
interval[CI],3.8---10.1),whichismuchlowerthantheresults
reportedin twostudies also performed in Brazil, ranging
from13.9to16.0/1000,2,3butwithintheliteraturerange,
from 3.5/1000 in an Arab population4 to 17.0/1000 in a
ruralnorth Americanpopulation.5Oneof thestrengthsof
DOIoforiginalarticle:
http://dx.doi.org/10.1016/j.jped.2015.01.005
夽 Pleasecitethisarticleas:PreuxP-M,RatsimbazafyV,JostJ.
Epidemiologyoffebrileseizuresandepilepsy:acallforaction.J Pediatr(RioJ).2015;91:512---4.
夽夽
SeepaperbyDalbemetal.inpages529---34.
∗Correspondingauthor.
E-mail:jostjeremy@gmail.com(J.Jost).
theirstudywasthatalmostallthepediatricpopulation in
thestudyareawasincluded.Severalhypotheseswere
dis-cussed toexplain this lowerresult. The authors reported
aselectionbiasandalackofstandardized method,which
did not allow for comparisons between studies. In
addi-tion to these divergences, it is admitted that interview
and/orquestionnairesurveyshavelowerlevelofevidence,
especiallyinthiscase.Febrileseizureswithmotor
manifes-tationswerethemostidentified,leadingtoasub-selection
ofprevalentcases,generating aninformationbias.
There-fore,theselectionphaseofthepresentstudyusedahistory
of febrile seizure to identify cases, which could lead to
a recall bias. Nevertheless,these studies areessential to
increment epidemiological data. Among 12 of the main
studiesassessingfebrileseizuresworldwide,onlyfive
mea-sured the prevalence; patient recruitment methods were
widely different andtherewasno homogeneity regarding
data recorded. These variations in results are not
neces-sarily an irremediable resultof methodological problems,
but morefrequently thanexpectedit couldberelatedto
population features (age, sex-ratio, genetic factors,
ori-gins,environmentalimpacts,etc.),differentetiologies(e.g.
heterogeneityofprevalenceofinfectiousdiseases),and/or
unknownfactors.Asanexampleandformatterof
compar-ison,Yemadjeetal.6 have investigatedthedifferences in
prevalenceofepilepsyintropicalregions.Theirconclusions
corroborate the abovementioned assumptions, enhanced
by the stigmatization of people with epilepsy, leading to
an underestimatingofprevalence,eveninwell-conducted
studies.
http://dx.doi.org/10.1016/j.jped.2015.08.003
Epidemiologyoffebrileseizuresandepilepsy 513
A febrileseizureis aconvulsionin achild triggeredby
afever,oftenoccurringinfamilies,andmostoftenin
chil-drenbetweenagesof9monthsand5yearsaccordingtothe
NationalInstitutesofHealth(NIH).
Most febrile seizures occur in the first 24h of an
ill-ness,and thefever has an unexpected importantweight;
bodytemperatureover than38.3◦Cincreasestherisk
fac-torcomparetolowerfeverthan38.3◦C.Majorupperairway
infections such as ear infections, cold or viral infections
represent the main triggering factors. Mostoften, febrile
seizure has spontaneous resolution and does not require
any drugtreatment. In somecases, whenthe durationof
theseizureexceeds5min,infusionoflorazepamor
midazo-lamcanavoidconvulsions.Ifthereisnoresolution,febrile
seizureshouldbeconsideredasstatusepilepticusandthe
managementshouldfollowthecorrespondingmedical
pro-tocol. Inthis regard,phenobarbital is proposedin several
guidelines. Farwellet al.7 reportedin 1990 that a
treat-mentusingphenobarbital(versusplacebo)canbeworsein
thecareoffebrileseizures,andiatrogeniccognitive
impair-mentshavebeenobserved.Thisoutcomecouldbeexplained
bythefundamentalpharmacologicaleffectthisdrug,which
is anticonvulsant with a hypnotic side effect, having any
effectonthefever.
Themostfrequentevolutionisnomoreseizureseverbut
thereisa15---70% riskof recurrenceinthefirsttwoyears
aftertheinitialfebrileseizure.Inthisarticle,onlyonecase
(5.5%)among18 had morethan oneseizure;and another
one(5.5%)athirdseizure.Predictorsofrecurrenceare
com-monlyage atonset(higherrisk forchild whoexperienced
febrileseizurebefore18months),temperature(lowfever
is curiously more likely linked with recurrence than high
fever),andapositivefamilyhistoryoffebrileseizures.8,9
As well as unprovoked seizure and epilepsy, provoked
seizures are quite common in resource-limited countries
under tropical areas mainly due to high rates of central
nervoussystem (CNS)infections suchascerebral malaria,
tuberculosis, schistosomiasis, HIV, and most often
neuro-cysticercosis (NCC). The last burden has been frequently
associated with a high risk of epilepsy impairment, but
arising an afebrile seizure. It is noteworthy that febrile
seizureshouldbedistinguishedasseizureoccurringduring
anintracranialinfectionoraseveremetabolicdisturbance.
Infact,febrileseizurehasbeenrecognizedasadistinct
syn-drome separated from epilepsy.The International League
AgainstEpilepsy(ILAE)defineditasaseizureoccurringin
childhood after 1 month of age associated witha febrile
illness not caused by a CNS infection, without previous
neonatalseizuresorprevious unprovokedseizure,andnot
meetingthecriteriaforotheracutesymptomaticseizures.
Nevertheless,althoughadivergenceoforiginexists,the
sig-nificantlinkbetweenbothaffectionsisthatfebrileseizure
representsanimportantriskfactorfordevelopingepilepsy.
Infectiousepilepsyisoneofthemainetiologiesdescribed
in several studies. Bhalla et al.10 described in 2011 with
genetic,braintumors, andhead traumacases, that
cere-bralinfectionshaveasignificantweightintheworldburden
of epilepsy. As mentioned above, NCC is highly
associ-ated withepilepsy(30%to50% ofall epilepsyinendemic
zones)andSouthAmericaisdeeplyimpactedbythispublic
health issue, aswell asAsiaand Africa.Mac etal.11
con-ducted a literature review of epidemiology, etiology, and
clinical management of epilepsy in Asia, which was
pub-lished in 2007. They reported that main causes were
dominated by head injury,birth trauma, and intracranial
infections, such as NCC or meningoencephalitis.
Further-more,theirarticle highlighted thelack of methodological
andpowerfulstudiesundertakeninthosecountries,which
would strengthen the body of evidence. The same issues
were raised in a sub-Saharan Africa conducted by Preux
and Druet-Cabanac, published in 2005,12 as well as in a
reviewandupdatebyBa-Diopetal.in2014.13Themainrisk
factorsforepilepsyinthatareaoftheworldwerefamily
his-toryofseizures,previousfebrileseizures,perinataltrauma,
head injury, and CNS infections, such as NCC. They
con-firmedthatfebrileseizureswerecommonlyassociatedwith
epileptic seizures among the pediatric population (6---38%
ofpatientswithepilepsyhadahistoryoffebrileseizures).
Inmalaria-endemic areas,mostacuteseizures arecaused
bymalaria, butwhethertheyarefebrileseizuresoracute
symptomaticseizuresisunclear.Somestudieshaveassessed
thelink betweenepilepsy andcerebral malaria (CM) asa
consequencemostlyinsub-SaharanAfrica.InGabon,a
case-controlstudyobservedanadjustedoddsratioof3.9([95%CI,
1.7---89.0],p=0.001)todevelopepilepsyafterCM.An
addi-tionalrisk factor wasfebrile convulsions (aOR=9.2, [95%
CI,4.0---21.1],p<0.0001).14 Anexposed-nonexposedstudy
carried out in Mali reported a relative risk of 14.3 ([95%
CI,1.6---132.0], p=0.01) adjusted on age and duration of
follow-uptodevelopepilepsyafteraCM.15Inthesameway,
seizures triggered by malaria infections couldresult from
feveronly(andthenfebrileseizures),butconvulsionscould
alsooccurwithoutfeverinmalaria.16Theauthorsassumed
thatinterleukinsinvolvedininflammatoryreactioncouldbe
involvedin the association betweenseizures withCMand
sequelarepilepsy,the sameinterleukinsthat areinvolved
inthegenerationoffebrileseizuresandepileptogenesis.
Assessingtheepidemiologyofillnessisadutytofurther
medicineknowledge;however,everydiseasecanhave
vari-ationsin expression and etiologydue tomany knownand
unknownfactors.Thispostulateemphasizestheimportance
of performing studies in various countries, areas (rural,
urban),andpopulationstocollectasmuchusefuland
rele-vantdataaspossible.AsexampleofNCC,whichisendemic
inmanyregionswherepigsareraisedincludingLatin
Amer-ica,Africa,andAsia,butmoreoftenapublichealthissuein
resources-limitedsettingshasbeen quite assess.Fornow,
asidefromthe epidemiologicaldata thathave been
mea-sured, new research approaches have been pointed out,
suchashumanNCC,whichoffersopportunitytounderstand
basicmechanismsofseizures.17TofocusonLatinAmerica,
Brazil does not have the same health concerns than low
andmiddle-income countries (LMICs). However,
neurolog-icalaffections such asepilepsyare not insignificant.In a
cross-sectionalevaluationofneurologicaldiseasesinarural
regionofBrazil,themostcommongroupsofdiseaseswere
headache(32.2%)andepilepsy(16.3%).18Butincontrastof
tropicalandsub-tropicalareas,tropicaldiseases(including
malaria)wereobservedinalowerproportionthanexpected
inthisstudy,eventhough Brazilis acountrythat present
mostofthemaintropicaldiseasesaccordingtoWHO.Each
oftheseelementshighlightsthedifficultiesandthedanger
togeneralizea resultinallsituations, mainlydue to
514 PreuxP-Metal.
studyrequiresseveralfeaturesthatarenoteasilyreachable
underallcircumstances. Bharuchaetal.19 raised
method-ological difficulties in the conduction of epidemiological
studiesinLMICs.Tospecify,LMICsfaceregulatoryissuesand
lackof infrastructure(lack ofcensusdata,lack ofa
well-developedhealthcaresystem,etc.),withawidevarietyof
differentkeyfeatures(perceptionofthedisease,language,
migratorypatterns, etc.)dependingof regionalconditions
andenvironmentalfactors.Medicaltoolsfrequentlyusedin
primarystudies,suchasthequestionnairetoidentifycases
intheDalbemstudy,mustbeadaptedtolocalconditionsand
validatedinordertogiverelevantandmeaningfuldata.Only
withuniformandcomparablemethodology,primarystudies
canprovideusabledatafor systematicreviewsand
meta-analyses.Theserecommendationsareevenmoreimportant
forpublichealthissues,asepilepsyremainsoneofthemajor
neglecteddiseases.Indeed,approximately70millionpeople
worldwidemayhaveepilepsy,andnearly80%ofthemlivein
resource-limitedcountries.In2011,Thurman etal.20 have
definedstandards(operationaldefinitions,methods,useful
analysis,etc.)forthesestudies,takingintoaccountthe
vari-abilityof country resourcesand differentstudy purposes.
Each study,as that by Dalbem et al. in Brazil, shouldbe
supportedandencouragedtoprovideessentialinformation
neededforextendtheunderstandingofthedisease,to
pro-motepreventionandeffectivehealthcare,andtocontribute
forthedevelopmentofoperationalsupportprograms.
Conflicts
of
interest
Theauthorsdeclarenoconflictsofinterest.
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