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Epilepsy

Generalized3Hzspikeandwavedischargesonanelectroencephalogram

Classificationandexternalresources

ICD10 G40(http://apps.who.int/classifications/icd10/browse/2015/en#/G40)G41(http://apps.who.int/classifications/icd10/browse/2015/en#/G41)

ICD9 345(http://www.icd9data.com/getICD9Code.ashx?icd9=345)

DiseasesDB 4366(http://www.diseasesdatabase.com/ddb4366.htm)

MedlinePlus 000694(http://www.nlm.nih.gov/medlineplus/ency/article/000694.htm)

eMedicine neuro/415(http://www.emedicine.com/neuro/topic415.htm)

MeSH D004827(https://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&term=D004827)

EpilepsyFromWikipedia,thefreeencyclopedia

Epilepsy(fromtheAncientGreekverbmeaning"toseize,possess,orafflict")[1]isagroupofneurologicaldisorderscharacterizedbyepilepticseizures.[2][3]Epilepticseizuresareepisodesthatcanvaryfrombriefandnearlyundetectabletolongperiodsofvigorousshaking.[4]Inepilepsy,seizurestendtorecur,andhavenoimmediateunderlyingcause[2]whileseizuresthatoccurduetoaspecificcausearenotdeemedtorepresentepilepsy.[5]

Thecauseofmostcasesofepilepsyisunknown,althoughsomepeopledevelopepilepsyastheresultofbraininjury,stroke,braintumor,anddrugandalcoholmisuse.Geneticmutationsarelinkedtoasmallproportionofthedisease.[6]Epilepticseizuresaretheresultofexcessiveandabnormalcorticalnervecellactivityinthebrain.[5]Thediagnosistypicallyinvolvesrulingoutotherconditionsthatmightcausesimilarsymptomssuchasfainting.Additionally,makingthediagnosisinvolvesdeterminingifanyothercauseofseizuresispresentsuchasalcoholwithdrawalorelectrolyteproblems.[6]Thismaybedonebyimagingthebrainandperformingbloodtests.[6]Epilepsycanoftenbeconfirmedwithanelectroencephalogram(EEG)butanormaltestdoesnotruleoutthecondition.[6]

Seizuresarecontrollablewithmedicationinabout70%ofcases.[7]Inthosewhoseseizuresdonotrespondtomedication,surgery,neurostimulationordietarychangesmaybeconsidered.Notallcasesofepilepsyarelifelong,andmanypeopleimprovetothepointthatmedicationisnolongerneeded.

About1%ofpeopleworldwide(65million)haveepilepsy,[8]andnearly80%ofcasesoccurindevelopingcountries.[4]In2013itresultedin116,000deathsupfrom111,000deathsin1990.[9]

Epilepsybecomesmorecommonaspeopleage.[10][11]Inthedevelopedworld,onsetofnewcasesoccursmostfrequentlyininfantsandtheelderly[12]inthedevelopingworldthisisinolderchildrenandyoung



adults,[13]duetodifferencesinthefrequencyoftheunderlyingcauses.About510%ofallpeoplewillhaveanunprovokedseizurebytheageof80,[14]andthechanceofexperiencingasecondseizureisbetween40and50%.[15]Inmanyareasoftheworldthosewithepilepsyeitherhaverestrictionsplacedontheirabilitytodriveorarenotpermittedtodrive,[16]butmostareabletoreturntodrivingafteraperiodoftimewithoutseizures.

Contents

1Signsandsymptoms1.1Seizures1.2Postictal1.3Psychosocial

2Causes2.1Genetics2.2Acquired

3Pathophysiology3.1Epilepsy3.2Seizures

4Diagnosis4.1Definition4.2Classification4.3Syndromes4.4Tests4.5Differentialdiagnosis

5Prevention6Management

6.1Firstaid6.2Medications6.3Surgery6.4Other6.5Alternativemedicine

7Prognosis7.1Mortality

8Epidemiology9History10Societyandculture

10.1Stigma10.2Economics10.3Vehicles



Aninstructionalvideoaboutepilepticseizures

Abitetothetipofthetongueduetoaseizure

10.4Supportorganizations11Research12Otheranimals13References14Furtherreading15Externallinks

Signsandsymptoms

Epilepsyischaracterizedbyalongtermriskofrecurrentseizures.[17]Theseseizuresmaypresentinseveralwaysdependingonthepartofthebraininvolvedandtheperson'sage.[17][18]

Seizures

Themostcommontype(60%)ofseizuresareconvulsive.[18]Ofthese,onethirdbeginasgeneralizedseizuresfromthestart,affectingbothhemispheresofthebrain.[18]Twothirdsbeginaspartialseizures(whichaffectonehemisphereofthebrain)whichmaythenprogresstogeneralizedseizures.[18]Theremaining40%ofseizuresarenonconvulsive.Anexampleofthistypeistheabsenceseizure,whichpresentsasadecreasedlevelofconsciousnessandusuallylastsabout10seconds.[19][20]

Partialseizuresareoftenprecededbycertainexperiences,knownasanaura.[21]Thesemayincludesensory(visual,hearingorsmell),psychic,autonomic,ormotorphenomena.[19]JerkingactivitymaystartinaspecificmusclegroupandspreadtosurroundingmusclegroupsinwhichcaseitisknownasaJacksonianmarch.[22]Automatismsmayoccurthesearenonconsciouslygeneratedactivitiesandmostlysimplerepetitivemovementslikesmackingofthelipsormorecomplexactivitiessuchasattemptstopicksomethingup.[22]

Therearesixmaintypesofgeneralizedseizures:tonicclonic,tonic,clonic,myoclonic,absence,andatonicseizures.[23]Theyallinvolvelossofconsciousnessandtypicallyhappenwithoutwarning.

Tonicclonicseizurespresentwithacontractionofthelimbsfollowedbytheirextensionalongwitharchingofthebackwhichlasts1030seconds(thetonicphase).Acrymaybeheardduetocontractionofthechestmuscles.Thisisthenfollowedbyashakingofthelimbsinunison(clonicphase).Tonicseizuresproduceconstantcontractionsofthemuscles.Apersonoftenturnsblueasbreathingisstopped.Inclonicseizuresthereisshakingofthelimbsinunison.Aftertheshakinghasstoppeditmaytake1030minutesforthepersontoreturntonormalthisperiodiscalledthe"postictalstate"or"postictal



phase".Lossofbowelorbladdercontrolmayoccurduringaseizure.[4]Thetonguemaybebittenateitherthetiporonthesidesduringaseizure.[24]Intonicclonicseizure,bitestothesidesaremorecommon.[24]Tonguebitesarealsorelativelycommoninpsychogenicnonepilepticseizures.[24]

Myoclonicseizuresinvolvespasmsofmusclesineitherafewareasorallover.[25]Absenceseizurescanbesubtlewithonlyaslightturnoftheheadoreyeblinking.[19]Thepersondoesnotfalloverandreturnstonormalrightafteritends.[19]Atonicseizuresinvolvethelossofmuscleactivityforgreaterthanonesecond.[22]Thistypicallyoccursonbothsidesofthebody.[22]

About6%ofthosewithepilepsyhaveseizuresthatareoftentriggeredbyspecificeventsandareknownasreflexseizures.[26]Thosewithreflexepilepsyhaveseizuresthatareonlytriggeredbyspecificstimuli.[27]Commontriggersincludeflashinglightsandsuddennoises.[26]Incertaintypesofepilepsy,seizureshappenmoreoftenduringsleep,[28]andinothertypestheyoccuralmostonlywhensleeping.[29]

Postictal

Aftertheactiveportionofaseizure,thereistypicallyaperiodofconfusionreferredtoasthepostictalperiodbeforeanormallevelofconsciousnessreturns.[21]Thisusuallylasts3to15minutes[30]butmaylastforhours.[31]Othercommonsymptomsincludefeelingtired,headache,difficultyspeaking,andabnormalbehavior.[31]Psychosisafteraseizureisrelativelycommon,occurringin610%ofpeople.[32]

Oftenpeopledonotrememberwhathappenedduringthistime.[31]Localizedweakness,knownasTodd'sparalysis,mayalsooccurafterapartialseizure.Whenitoccursittypicallylastsforsecondstominutesbutmayrarelylastforadayortwo.[33]

Psychosocial

Epilepsycanhaveadverseeffectsonsocialandpsychologicalwellbeing.[18]Theseeffectsmayincludesocialisolation,stigmatization,ordisability.[18]Theymayresultinlowereducationalachievementandworseemploymentoutcomes.[18]Learningdifficultiesarecommoninthosewiththecondition,andespeciallyamongchildrenwithepilepsy.[18]Thestigmaofepilepsycanalsoaffectthefamiliesofthosewiththedisease.[4]

Certaindisordersoccurmoreofteninpeoplewithepilepsy,dependingpartlyontheepilepsysyndromepresent.Theseincludedepression,anxietydisorders,andmigraines.[34]Attentiondeficithyperactivitydisorderaffectsthreetofivetimesmorechildrenwithepilepsythanchildreninthegeneralpopulation.[35]ADHDandepilepsyhavesignificantconsequencesonachild'sbehavioral,learning,andsocialdevelopment.[36]Epilepsyisalsomorecommoninthosewithautism.[37]

Causes

Epilepsycanhavebothgeneticandacquiredcauses,withinteractionofthesefactorsinmanycases.[38]Establishedacquiredcausesincludeseriousbraintrauma,stroke,tumoursandproblemsinthebrainasaresultofapreviousinfective.[38]Inabout60%ofcasesthecauseisunknown.[4][18]Epilepsiescausedbygenetic,congenital,ordevelopmentalconditionsaremorecommonamongyoungerpeople,whilebraintumorsandstrokesaremorelikelyinolderpeople.[18]



Seizuresmayalsooccurasaconsequenceofotherhealthproblems[23]iftheyoccurrightaroundaspecificcause,suchasastroke,headinjury,toxicingestionormetabolicproblem,theyareknownasacutesymptomaticseizuresandareinthebroaderclassificationofseizurerelateddisordersratherthanepilepsyitself.[8][39]

Genetics

Geneticsisbelievedtobeinvolvedinthemajorityofcases,eitherdirectlyorindirectly.[40]Someepilepsiesareduetoasinglegenedefect(12%)mostareduetotheinteractionofmultiplegenesandenvironmentalfactors.[40]Eachofthesinglegenedefectsisrare,withmorethan200inalldescribed.[41]

Mostgenesinvolvedaffectionchannels,eitherdirectlyorindirectly.[38]Theseincludegenesforionchannelsthemselves,enzymes,GABA,andGproteincoupledreceptors.[25]

Inidenticaltwins,ifoneisaffectedthereisa5060%chancethattheotherwillalsobeaffected.[40]Innonidenticaltwinstheriskis15%.[40]Theserisksaregreaterinthosewithgeneralizedratherthanpartialseizures.[40]Ifbothtwinsareaffected,mostofthetimetheyhavethesameepilepticsyndrome(7090%).[40]Othercloserelativesofapersonwithepilepsyhaveariskfivetimesthatofthegeneralpopulation.[42]Between1and10%ofthosewithDownsyndromeand90%ofthosewithAngelmansyndromehaveepilepsy.[42]

Acquired

Epilepsymayoccurasaresultofanumberofotherconditionsincludingtumors,strokes,headtrauma,previousinfectionsofthecentralnervoussystem,geneticabnormalities,andasaresultofbraindamagearoundthetimeofbirth.[4][23]Ofthosewithbraintumors,almost30%haveepilepsy,makingthemthecauseofabout4%ofcases.[42]Theriskisgreatestfortumorsinthetemporallobeandthosethatgrowslowly.[42]Othermasslesionssuchascerebralcavernousmalformationsandarteriovenousmalformationshaverisksashighas4060%.[42]Ofthosewhohavehadastroke,24%developepilepsy.[42]IntheUnitedKingdomstrokesaccountfor15%ofcasesanditisbelievedtobethecausein30%oftheelderly.[18][42]Between6and20%ofepilepsyisbelievedtobeduetoheadtrauma.[42]Mildbraininjuryincreasestheriskabouttwofoldwhileseverebraininjuryincreasestherisksevenfold.[42]

Inthosewhohaveexperiencedahighpoweredgunshotwoundtothehead,theriskisabout50%.[42]

Theriskofepilepsyfollowingmeningitisislessthan10%thatdiseasemorecommonlycausesseizuresduringtheinfectionitself.[42]Inherpessimplexencephalitistheriskofaseizureisaround50%[42]withahighriskofepilepsyfollowing(upto25%).[43][44]Infectionwiththeporktapeworm,whichcanresultinneurocysticercosis,isthecauseofuptohalfofepilepsycasesinareasoftheworldwheretheparasiteiscommon.[42]Epilepsymayalsooccurafterotherbraininfectionssuchascerebralmalaria,toxoplasmosis,andtoxocariasis.[42]Chronicalcoholuseincreasestheriskofepilepsy:thosewhodrinksixunitsofalcoholperdayhaveatwoandahalffoldincreaseinrisk.[42]OtherrisksincludeAlzheimer'sdisease,multiplesclerosis,tuberoussclerosis,andautoimmuneencephalitis.[42]Gettingvaccinateddoesnotincreasetheriskofepilepsy.[42]Malnutritionisariskfactorseenmostlyinthedevelopingworld,althoughitisunclearhoweverifitisadirectcauseoranassociation.[13]

Pathophysiology



Normallybrainelectricalactivityisnonsynchronous.[19]Itsactivityisregulatedbyvariousfactorsbothwithintheneuronandthecellularenvironment.Factorswithintheneuronincludethetype,numberanddistributionofionchannels,changestoreceptorsandchangesofgeneexpression.[45]Factorsaroundtheneuronincludeionconcentrations,synapticplasticityandregulationoftransmitterbreakdownbyglialcells.[45][46]

Epilepsy

Theexactmechanismofepilepsyitselfisunknown.[47]Alittle,however,isknownaboutboththecellularandnetworkmechanismsofepilepsy.However,itisunknownunderwhichcircumstancesthebrainshiftsintotheactivityofaseizurewithitsexcessivesynchronization.[48][49]

Inepilepsytheresistanceofexcitatoryneuronstofireduringthisperiodisdecreased.[19]Thismayoccurduetochangesinionchannelsorinhibitoryneuronsnotfunctioningproperly.[19]Thisthenresultsinaspecificareafromwhichseizuresmaydevelop,knownasa"seizurefocus".[19]Anothermechanismofepilepsymaybetheupregulationofexcitatorycircuitsordownregulationofinhibitorycircuitsfollowinganinjurytothebrain.[19][50]Thesesecondaryepilepsiesoccurthroughprocessesknownasepileptogenesis.[19][50]Failureofthebloodbrainbarriermayalsobeacausalmechanismasitwouldallowsubstancesinthebloodtoenterthebrain.[51]

Seizures

Thereisevidencethatepilepticseizureareusuallynotarandomevent.Seizuresareoftenbroughtonbyfactorssuchaslackofsleep,stressorflickeringlightamongothers.Thetermseizurethresholdisusedtoindicatetheamountofstimulusnecessarytobringaboutaseizure.Seizurethresholdisloweredinepilepsy.[48]

Inepilepticseizuresagroupofneuronsbeginfiringinanabnormal,excessive,[18]andsynchronizedmanner.[19]Thisresultsinawaveofdepolarizationknownasaparoxysmaldepolarizingshift.[52]

Normally,afteranexcitatoryneuronfiresitbecomesmoreresistanttofiringforaperiodoftime.[19]Thisisdueinparttotheeffectofinhibitoryneurons,electricalchangeswithintheexcitatoryneuron,andthenegativeeffectsofadenosine.[19]

Partialseizuresbegininonehemisphereofthebrainwhilegeneralizedseizuresbegininbothhemispheres.[23]Sometypesofseizuresmaychangebrainstructure,whileothersappeartohavelittleeffect.[53]Gliosis,neuronalloss,andatrophyofspecificareasofthebrainarelinkedtoepilepsybutitisunclearifepilepsycausesthesechangesorifthesechangesresultinepilepsy.[53]

Diagnosis

Thediagnosisofepilepsyistypicallymadebasedonthedescriptionoftheseizureandtheunderlyingcause.[18]Anelectroencephalogramandneuroimagingarealsousuallypartoftheworkup.[18]Whilefiguringoutaspecificepilepticsyndromeisoftenattempted,itisnotalwayspossible.[18]VideoandEEGmonitoringmaybeusefulindifficultcases.[54]

Definition



AnEEGcanaidinlocatingthefocusoftheepilepticseizure.

Epilepsyisadiseaseofthebraindefinedbyanyofthefollowingconditions:[3]

1. Atleasttwounprovoked(orreflex)seizuresoccurringgreaterthan24hoursapart2. Oneunprovoked(orreflex)seizureandaprobabilityoffurtherseizuressimilartothe

generalrecurrencerisk(atleast60%)aftertwounprovokedseizures,occurringoverthenext10years

3. Diagnosisofanepilepsysyndrome

Furthermoreepilepsyisconsideredtoberesolvedforindividualswhohadanagedependentepilepsysyndromebutarenowpastthethatageorthosewhohaveremainedseizurefreeforthelast10years,withnoseizuremedicinesforthelast5years.[3]

This2014definitionoftheInternationalLeagueAgainstEpilepsy[3]isarefinementoftheir2005definitionwhichwas"adisorderofthebraincharacterizedbyanenduringpredispositiontogenerateepilepticseizuresandbytheneurobiologic,cognitive,psychological,andsocialconsequencesofthiscondition.Thedefinitionofepilepsyrequirestheoccurrenceofatleastoneepilepticseizure."[55][56]

Itisthereforepossibletooutgrowepilepsyortoundergotreatmentthatcausestheepilepsytoberesolved.Resolutionofepilepsyunfortunatelydoesnotguaranteethatitwillnotreturn.Inthedefinition,epilepsyisnowcalledadisease,ratherthanadisorder.ThiswasadecisionoftheexecutivecommitteeoftheILAE,takenbecausetheword"disorder,"whileperhapshavinglessstigmathandoes"disease,"alsodoesnotexpressthedegreeofseriousnessthatepilepsydeserves.[3]

Thedefinitionispracticalinnatureandisdesignedforclinicaluse.Researchers,statisticallymindedepidemiologistsandotherspecializedgroupsmaychoosetousetheolderdefinitionoradefinitionoftheirowndevising.TheILAEconsidersdoingsoisperfectlyallowable,solongasitisclearwhatdefinitionisbeingused.[3]

Classification



Incontrasttotheclassificationofseizureswhichfocusesonwhathappensduringaseizure,theclassificationofepilepsiesfocusesontheunderlyingcauses.Whenapersonisadmittedtohospitalafteranepilepticseizurethediagnosticworkupresultspreferablyintheseizureitselfbeingclassified(e.g.tonicclonic)andintheunderlyingdiseasebeingidentified(e.g.hippocampalsclerosis).[54]Thenameofthediagnosisfinallymadedependsontheavailablediagnosticresultsandtheapplieddefinitionsandclassifications(ofseizuresandepilepsies)anditsrespectiveterminology.

TheInternationalLeagueAgainstEpilepsy(ILAE)providedaclassificationoftheepilepsiesandepilepticsyndromesin1989asfollows:[57]

1. Localizationrelatedepilepsiesandsyndromes1. Unknowncause(e.g.benignchildhoodepilepsywithcentrotemporalspikes)2. Symptomatic/cryptogenic(e.g.temporallobeepilepsy)

2. Generalized1. Unknowncause(e.g.childhoodabsenceepilepsy)2. Cryptogenicorsymptomatic(e.g.LennoxGastautsyndrome)3. Symptomatic(e.g.earlyinfantileepilepticencephalopathywithsuppressionburst)

3. Epilepsiesandsyndromesundeterminedwhetherpartialorgeneralized1. Withbothgeneralizedandpartialseizures(e.g.epilepsywithcontinuousspike

wavesduringslowwavesleep)

4. Specialsyndromes(withsituationrelatedseizures)[57]

Thisclassificationwaswidelyacceptedbuthasalsobeencriticizedmainlybecausetheunderlyingcausesofepilepsy(whichareamajordeterminantofclinicalcourseandprognosis)werenotcoveredindetail.[58]In2010theILAECommissionforClassificationoftheEpilepsiesaddressedthisissueanddividedepilepsiesintothreecategories(genetic,structural/metabolic,unknowncause)[59]thatwererefinedintheir2011recommendationintofourcategoriesandanumberofsubcategoriesreflectingrecenttechnologicandscientificadvances.[60]

1. Unknowncause(mostlygeneticorpresumedgeneticorigin)1. Pureepilepsiesduetosinglegenedisorders2. Pureepilepsieswithcomplexinheritance

2. Symptomatic(associatedwithgrossanatomicorpathologicabnormalities)1. Mostlygeneticordevelopmentalcausation

1. Childhoodepilepsysyndromes2. Progressivemyoclonicepilepsies3. Neurocutaneoussyndromes4. Otherneurologicsinglegenedisorders5. Disordersofchromosomefunction6. Developmentalanomaliesofcerebralstructure



2. Mostlyacquiredcauses1. Hippocampalsclerosis2. Perinatalandinfantilecauses3. Cerebraltrauma,tumororinfection4. Cerebrovasculardisorders5. Cerebralimmunologicdisorders6. Degenerativeandotherneurologicconditions

3. Provoked(aspecificsystemicorenvironmentalfactoristhepredominantcauseoftheseizures)

1. Provokingfactors2. Reflexepilepsies

4. Crytogenic(presumedsymptomaticnatureinwhichthecausehasnotbeenidentified)[60]

Syndromes

Casesofepilepsymaybeorganizedintoepilepsysyndromesbythespecificfeaturesthatarepresent.Thesefeaturesincludetheagethatseizurebegin,theseizuretypes,EEGfindings,amongothers.Identifyinganepilepsysyndromeisusefulasithelpsdeterminetheunderlyingcausesaswellaswhatantiseizuremedicationshouldbetried.[61][23]

Theabilitytocategorizeacaseofepilepsyintoaspecificsyndromeoccursmoreoftenwithchildrensincetheonsetofseizuresiscommonlyearly.[39]Lessseriousexamplesarebenignrolandicepilepsy(2.8per100,000),childhoodabsenceepilepsy(0.8per100,000)andjuvenilemyoclonicepilepsy(0.7per100,000).[39]Severesyndromeswithdiffusebraindysfunctioncaused,atleastpartly,bysomeaspectofepilepsy,arealsoreferredtoasepilepticencephalopathies.Theseareassociatedwithfrequentseizuresthatareresistanttotreatmentandseverecognitivedysfunction,forinstanceLennoxGastautsyndromeandWestsyndrome.[62]Geneticsisbelievedtoplayanimportantroleinepilepsiesbyanumberofmechanisms.Simpleandcomplexmodesofinheritancehavebeenidentifiedforsomeofthem.However,extensivescreeninghavefailedtoidentifymanysinglegenevariantsoflargeeffect.[63]Morerecentexomeandgenomesequencingstudieshavebeguntorevealanumberofdenovogenemutationsthatareresponsibleforsomeepilepticencephalopathies,includingCHD2andSYNGAP1[64][65][66]andDMN1,GABBR2,FASNandRYR3,[67]

Syndromesinwhichcausesarenotclearlyidentifiedaredifficulttomatchwithcategoriesofthecurrentclassificationofepilepsy.Categorizationforthesecaseswasmadesomewhatarbitrarily.[60]Theidiopathic(unknowncause)categoryofthe2011classificationincludessyndromesinwhichthegeneralclinicalfeaturesand/oragespecificitystronglypointtoapresumedgeneticcause.[60]Somechildhoodepilepsysyndromesareincludedintheunknowncausecategoryinwhichthecauseispresumedgenetic,forinstancebenignrolandicepilepsy.Othersareincludedinsymptomaticdespiteapresumedgeneticcause(inatleastinsomecases),forinstanceLennoxGastautsyndrome.[60]Clinicalsyndromesinwhichepilepsyisnotthemainfeature(e.g.Angelmansyndrome)werecategorizedsymptomaticbutitwasarguedtoincludethesewithinthecategoryidiopathic.[60]Classificationofepilepsiesandparticularlyofepilepsysyndromeswillchangewithadvancesinresearch.



Tests

Anelectroencephalogram(EEG)canassistinshowingbrainactivitysuggestiveofanincreasedriskofseizures.Itisonlyrecommendedforthosewhoarelikelytohavehadanepilepticseizureonthebasisofsymptoms.Inthediagnosisofepilepsy,electroencephalographymayhelpdistinguishthetypeofseizureorsyndromepresent.Inchildrenitistypicallyonlyneededafterasecondseizure.Itcannotbeusedtoruleoutthediagnosis,andmaybefalselypositiveinthosewithoutthedisease.IncertainsituationsitmaybeusefultoperformtheEEGwhiletheaffectedindividualissleepingorsleepdeprived.[54]

DiagnosticimagingbyCTscanandMRIisrecommendedafterafirstnonfebrileseizuretodetectstructuralproblemsinandaroundthebrain.[54]MRIisgenerallyabetterimagingtestexceptwhenbleedingissuspected,forwhichCTismoresensitiveandmoreeasilyavailable.[14]Ifsomeoneattendstheemergencyroomwithaseizurebutreturnstonormalquickly,imagingtestsmaybedoneatalaterpoint.[14]Ifapersonhasapreviousdiagnosisofepilepsywithpreviousimaging,repeatingtheimagingisusuallynotneededeveniftherearesubsequentseizures.[54]

Foradults,thetestingofelectrolyte,bloodglucoseandcalciumlevelsisimportanttoruleoutproblemswiththeseascauses.[54]Anelectrocardiogramcanruleoutproblemswiththerhythmoftheheart.[54]Alumbarpuncturemaybeusefultodiagnoseacentralnervoussysteminfectionbutisnotroutinelyneeded.[14]Inchildrenadditionaltestsmayberequiredsuchasurinebiochemistryandbloodtestinglookingformetabolicdisorders.[54][68]

Ahighbloodprolactinlevelwithinthefirst20minutesfollowingaseizuremaybeusefultoconfirmanepilepticseizureasopposedtopsychogenicnonepilepticseizure.[69][70]Serumprolactinlevelislessusefulfordetectingpartialseizures.[71]Ifitisnormalanepilepticseizureisstillpossible[70]andaserumprolactindoesnotseparateepilepticseizuresfromsyncope.[72]Itisnotrecommendedasaroutinepartofthediagnosisofepilepsy.[54]

Differentialdiagnosis

Diagnosisofepilepsycanbedifficult.Anumberofotherconditionsmaypresentverysimilarsignsandsymptomstoseizures,includingsyncope,hyperventilation,migraines,narcolepsy,panicattacksandpsychogenicnonepilepticseizures(PNES).[73][74]Inparticularasyncopecanbeaccompaniedbyashortepisodeofconvulsions.[75]Nocturnalfrontallobeepilepsy,oftenmisdiagnosedasnightmares,wasconsideredtobeaparasomniabutlateridentifiedtobeepileptic.[76]Attacksofthemovementdisorderparoxysmaldyskinesiamaybetakenforepilepticseizures.[77]Thecauseofadropattackcanbe,amongmanyothers,anatonicseizure.[74]

Childrenmayhavebehaviorsthatareeasilymistakenforepilepticseizuresbutarenot.Theseincludebreathholdingspells,bedwetting,nightterrors,ticsandshudderattacks.[74]Gastroesophagealrefluxmaycausearchingofthebackandtwistingoftheheadtothesideininfants,whichmaybemistakenfortonicclonicseizures.[74]

Misdiagnosisisfrequent(occurringinabout5to30%ofcases).[18]Differentstudiesshowedthatinmanycasesseizurelikeattacksinapparenttreatmentresistantepilepsyhaveacardiovascularcause.[75][78]Approximately20%ofthepeopleseenatepilepsyclinicshavePNES[14]andofthosewho



havePNESabout10%alsohaveepilepsy[79]separatingthetwobasedontheseizureepisodealonewithoutfurthertestingisoftendifficult.[79]

Prevention

Whilemanycasesarenotpreventable,effortstoreduceheadinjuries,providegoodcarearoundthetimeofbirth,andreduceenvironmentalparasitessuchastheporktapewormmaybeeffective.[4]EffortsinonepartofCentralAmericatodecreaseratesofporktapewormresultedina50%decreaseinnewcasesofepilepsy.[13]

Management

Epilepsyisusuallytreatedwithdailymedicationonceasecondseizurehasoccurred,[18][54]butforthoseathighrisk,medicationmaybestartedafterthefirstseizure.[54]Insomecases,aspecialdiet,theimplantationofaneurostimulator,orneurosurgerymayberequired.

Firstaid

Rollingapersonwithanactivetonicclonicseizureontotheirsideandintotherecoverypositionhelpspreventfluidsfromgettingintothelungs.[80]Puttingfingers,abiteblockortonguedepressorinthemouthisnotrecommendedasitmightmakethepersonvomitorresultintherescuerbeingbitten.[21][80]

Effortsshouldbetakentopreventfurtherselfinjury.[21]Spinalprecautionsaregenerallynotneeded.[80]

Ifaseizurelastslongerthan5minutesoriftherearemorethantwoseizuresinanhourwithoutareturntoanormallevelofconsciousnessbetweenthem,itisconsideredamedicalemergencyknownasstatusepilepticus.[54][81]Thismayrequiremedicalhelptokeeptheairwayopenandprotected[54]anasopharyngealairwaymaybeusefulforthis.[80]Athometherecommendedinitialmedicationforseizureofalongdurationismidazolamplacedinthemouth.[82]Diazepammayalsobeusedrectally.[82]

Inhospital,intravenouslorazepamispreferred.[54]Iftwodosesofbenzodiazepinesarenoteffective,othermedicationssuchasphenytoinarerecommended.[54]Convulsivestatusepilepticusthatdoesnotrespondtoinitialtreatmenttypicallyrequiresadmissiontotheintensivecareunitandtreatmentwithstrongeragentssuchasthiopentoneorpropofol.[54]

Medications

Themainstaytreatmentofepilepsyisanticonvulsantmedications,possiblyfortheperson'sentirelife.[18]Thechoiceofanticonvulsantisbasedonseizuretype,epilepsysyndrome,othermedicationsused,otherhealthproblems,andtheperson'sageandlifestyle.[82]Asinglemedicationisrecommendedinitially[83]

ifthisisnoteffective,switchingtoasingleothermedicationisrecommended.[54]Twomedicationsatonceisrecommendedonlyifasinglemedicationdoesnotwork.[54]Inabouthalf,thefirstagentiseffectiveasecondsingleagenthelpsinabout13%andathirdortwoagentsatthesametimemayhelpanadditional4%.[84]About30%ofpeoplecontinuetohaveseizuresdespiteanticonvulsanttreatment.[7]



Anticonvulsants

Thereareanumberofmedicationsavailable.Phenytoin,carbamazepineandvalproateappeartobeequallyeffectiveinbothpartialandgeneralizedseizures.[85][86]Controlledreleasecarbamazepineappearstoworkaswellasimmediatereleasecarbamazepine,andmayhavefewersideeffects.[87]IntheUnitedKingdom,carbamazepineorlamotriginearerecommendedasfirstlinetreatmentforpartialseizures,withlevetiracetamandvalproateassecondlineduetoissuesofcostandsideeffects.[54]

Valproateisrecommendedfirstlineforgeneralizedseizureswithlamotriginebeingsecondline.[54]Inthosewithabsenceseizures,ethosuximideorvalproatearerecommendedvalproateisparticularlyeffectiveinmyoclonicseizuresandtonicoratonicseizures.[54]Ifseizuresarewellcontrolledonaparticulartreatment,itisnotusuallynecessarytoroutinelycheckthemedicationlevelsintheblood.[54]

Theleastexpensiveanticonvulsantisphenobarbitalataround$5USDayear.[13]TheWorldHealthOrganizationgivesitafirstlinerecommendationinthedevelopingworldanditiscommonlyusedthere.[88][89]Accesshowevermaybedifficultassomecountrieslabelitasacontrolleddrug.[13]

Adverseeffectsfrommedicationsarereportedin10to90%ofpeople,dependingonhowandfromwhomthedataiscollected.[90]Mostadverseeffectsaredoserelatedandmild.[90]Someexamplesincludemoodchanges,sleepiness,oranunsteadinessingait.[90]Certainmedicationshavesideeffectsthatarenotrelatedtodosesuchasrashes,livertoxicity,orsuppressionofthebonemarrow.[90]Uptoaquarterofpeoplestoptreatmentduetoadverseeffects.[90]Somemedicationsareassociatedwithbirthdefectswhenusedinpregnancy.[54]Valproateisofparticularconcern,especiallyduringthefirsttrimester.[91]Despitethis,treatmentisoftencontinuedonceeffective,becausetheriskofuntreatedepilepsyisbelievedtobegreaterthantheriskofthemedications.[91]

Slowlystoppingmedicationsmaybereasonableinsomepeoplewhodonothaveaseizurefortwotofouryearshowever,aroundathirdofpeoplehavearecurrence,mostoftenduringthefirstsixmonths.[54][92]Stoppingispossibleinabout70%ofchildrenand60%ofadults.[4]

Surgery

Epilepsysurgerymaybeanoptionforpeoplewithpartialseizuresthatremainaproblemdespiteothertreatments.[93]Theseothertreatmentsincludeatleastatrialoftwoorthreemedications.[94]Thegoalofsurgeryistotalcontrolofseizures[95]andthismaybeachievedin6070%ofcases.[94]Commonproceduresincludecuttingoutthehippocampusviaananteriortemporalloberesection,removaloftumors,andremovingpartsoftheneocortex.[94]Someproceduressuchasacorpuscallosotomyareattemptedinanefforttodecreasethenumberofseizuresratherthancurethecondition.[94]Followingsurgery,medicationsmaybeslowlywithdrawninmanycases.[94]

Neurostimulationmaybeanotheroptioninthosewhoarenotcandidatesforsurgery.[54]Threetypeshavebeenshowntobeeffectiveinthosewhodonotrespondtomedications:vagusnervestimulation,anteriorthalamicstimulation,andclosedloopresponsivestimulation.[96]



Disabilityadjustedlifeyearforepilepsyper100,000inhabitantsin2004. nodata

275

Other

Aketogenicdiet(highfat,lowcarbohydrate,adequateprotein)appearstodecreasethenumberofseizuresbyhalfinabout3040%ofchildren.[97]Itisareasonableoptioninthosewhohaveepilepsythatisnotimprovedwithmedicationsandforwhomsurgeryisnotanoption.[97]About10%stayonthedietforafewyearsduetoissuesofeffectivenessandtolerability.[97]Sideeffectsincludestomachandintestinalproblemsin30%,andtherearelongtermconcernsofheartdisease.[97]Lessradicaldietsareeasiertotolerateandmaybeeffective.[97]Itisunclearwhythisdietworks.[98]Exercisehasbeenproposedaspossiblyusefulforpreventingseizures[99]withsomedatatosupportthisclaim.[100]

Avoidancetherapyconsistsofminimizingoreliminatingtriggers.Forexample,inthosewhoaresensitivetolight,usingasmalltelevision,avoidingvideogamesorwearingdarkglassesmaybeuseful.[101]OperantbasedbiofeedbackbasedontheEEGwaveshassomesupportinthosewhodonotrespondtomedications.[102]Psychologicalmethodsshouldnot,however,beusedtoreplacemedications.[54]Somedogs,alsoreferredtoasseizuredogs,mayhelpduringorafteraseizure.[103][104]

Itisnotclearifdogshavetheabilitytopredictseizuresbeforetheyoccur.[105]

Alternativemedicine

Alternativemedicine,includingacupuncture,[106]psychologicalinterventions,[107]routinevitamins,[108]

andyoga,[109]havenoreliableevidencetosupporttheiruseinepilepsy.Theuseofcannabisisnotsupportedbytheevidence.[110]Melatoninisinsufficientlysupportedbyevidence.[111]

Prognosis

Epilepsycannotusuallybecured,butmedicationcancontrolseizureseffectivelyinabout70%ofcases.[7]Ofthosewithgeneralizedseizures,morethan80%canbewellcontrolledwithmedicationswhilethisistrueinonly50%ofpeoplewithpartialseizures.[96]Onepredictoroflongtermoutcomeisthenumberofseizuresthatoccurinthefirstsixmonths.[18]Otherfactorsincreasingtheriskofapooroutcomeincludelittleresponsetotheinitialtreatment,generalizedseizures,afamilyhistoryofepilepsy,psychiatricproblems,andwavesontheEEGrepresentinggeneralizedepileptiformactivity.[112]Inthedevelopingworld75%ofpeopleareeitheruntreatedornotappropriatelytreated.[4]InAfrica90%donotgettreatment.[4]Thisispartlyrelatedtoappropriatemedicationsnotbeingavailableorbeingtooexpensive.[4]

Mortality

Peoplewithepilepsyareatanincreasedriskofdeath.[113]Thisincreaseisbetween1.6and4.1foldgreaterthanthatofthegeneralpopulation[114]andisoftenrelatedto:theunderlyingcauseoftheseizures,statusepilepticus,suicide,trauma,andsuddenunexpecteddeathinepilepsy(SUDEP).[113]Deathfromstatusepilepticusisprimarilyduetoanunderlyingproblemrather



thanmissingdosesofmedications.[113]Theriskofsuicideisincreasedbetweentwoandsixtimesinthosewithepilepsy.[115][116]Thecauseofthisisunclear.[115]SUDEPappearstobepartlyrelatedtothefrequencyofgeneralizedtonicclonicseizures[117]andaccountsforabout15%ofepilepsyrelateddeaths.[112]Itisunclearhowtodecreaseitsrisk.[117]Thegreatestincreaseinmortalityfromepilepsyisamongtheelderly.[114]Thosewithepilepsyduetoanunknowncausehavelittleincreasedrisk.[114]IntheUnitedKingdomitisestimatedthat4060%ofdeathsarepossiblypreventable.[18]Inthedevelopingworldmanydeathsareduetountreatedepilepsyleadingtofallsorstatusepilepticus.[13]

Epidemiology

Epilepsyisoneofthemostcommonseriousneurologicaldisorders[118]affectingabout65millionpeopleglobally.[8]Itaffects1%ofthepopulationbyage20and3%ofthepopulationbyage75.[11]Itismorecommoninmalesthanfemaleswiththeoveralldifferencebeingsmall.[13][39]Mostofthosewiththedisease(80%)areinthedevelopingworld.[4]

Thenumberofpeoplewhocurrentlyhaveactiveepilepsyisintherange510per1,000,withactiveepilepsydefinedassomeonewithepilepsywhohashadaleastoneseizureinthelastfiveyears.[39][119]Epilepsybeginseachyearin4070per100,000indevelopedcountriesand80140per100,000indevelopingcountries.[4]Povertyisariskandincludesbothbeingfromapoorcountryandbeingpoorrelativetootherswithinone'scountry.[13]Inthedevelopedworldepilepsymostcommonlystartseitherintheyoungorintheold.[13]Inthedevelopingworlditsonsetismorecommoninolderchildrenandyoungadultsduetothehigherratesoftraumaandinfectiousdiseases.[13]Indevelopedcountriesthenumberofcasesayearhasdecreasedinchildrenandincreasedamongtheelderlybetweenthe1970sand2003.[119]Thishasbeenattributedpartlytobettersurvivalfollowingstrokesintheelderly.[39]

History

Theoldestmedicalrecordsshowthatepilepsyhasbeenaffectingpeoplesincethebeginningofrecordedhistory.[120]Throughoutancienthistory,thedisorderwasthoughttobeaspiritualcondition.[120]Theworld'soldestdescriptionofanepilepticseizurecomesfromatextinAkkadian(alanguageusedinancientMesopotamia)andwaswrittenaround2000BC.[1][1]ThepersondescribedinthetextwasdiagnosedasbeingundertheinfluenceofaMoongod,andunderwentanexorcism.[1]EpilepticseizuresarelistedintheCodeofHammurabi(c.1790BC)asreasonforwhichapurchasedslavemaybereturnedforarefund,[1]andtheEdwinSmithPapyrus(c.1700BC)describescasesofindividualswithepilepticconvulsions.[1]

TheoldestknowndetailedrecordofthedisorderitselfisintheSakikku,aBabyloniancuneiformmedicaltextfrom10671046BC.[120]Thistextgivessignsandsymptoms,detailstreatmentandlikelyoutcomes,[1]anddescribesmanyfeaturesofthedifferentseizuretypes.[120]AstheBabylonianshadnobiomedicalunderstandingofthenatureofdisease,theyattributedtheseizurestopossessionbyevilspiritsandcalledfortreatingtheconditionthroughspiritualmeans.[120]Around900BC,PunarvasuAtreyadescribedepilepsyaslossofconsciousness[121]thisdefinitionwascarriedforwardintotheAyurvedictextofCharakaSamhita(about400BC).[122]



Hippocrates,17thcenturyengravingbyPeterPaulRubensofanantiquebust.

TheancientGreekshadcontradictoryviewsofthedisease.Theythoughtofepilepsyasaformofspiritualpossession,butalsoassociatedtheconditionwithgeniusandthedivine.Oneofthenamestheygavetoitwasthesacreddisease.[1][123]EpilepsyappearswithinGreekmythology:itisassociatedwiththeMoongoddessesSeleneandArtemis,whoafflictedthosewhoupsetthem.TheGreeksthoughtthatimportantfiguressuchasJuliusCaesarandHerculeshadthedisease.[1]ThenotableexceptiontothisdivineandspiritualviewwasthatoftheschoolofHippocrates.InthefifthcenturyBC,Hippocratesrejectedtheideathatthediseasewascausedbyspirits.InhislandmarkworkOntheSacredDisease,heproposedthatepilepsywasnotdivineinoriginandinsteadwasamedicallytreatableproblemoriginatinginthebrain.[1][120]Heaccusedthoseofattributingasacredcausetothediseaseofspreadingignorancethroughabeliefinsuperstitiousmagic.[1]Hippocratesproposedthathereditywasimportantasacause,describedworseoutcomesifthediseasepresentsatanearlyage,andmadenoteofthephysicalcharacteristicsaswellasthesocialshameassociatedwithit.[1]Insteadofreferringtoitasthesacreddisease,heusedthetermgreatdisease,givingrisetothemoderntermgrandmal,usedforgeneralizedseizures.[1]Despitehisworkdetailingthephysicaloriginsofthedisease,hisviewwasnotacceptedatthetime.[120]Evilspiritscontinuedtobeblameduntilatleastthe17thcentury.[120]

Inmostcultures,personswithepilepsyhavebeenstigmatized,shunned,orevenimprisonedintheSalptrire,thebirthplaceofmodernneurology,JeanMartinCharcotfoundpeoplewithepilepsysidebysidewiththementallyill,thosewithchronicsyphilis,andthecriminallyinsane.[124]InancientRome,epilepsywasknownastheMorbusComitialis('diseaseoftheassemblyhall')andwasseenasacursefromthegods.InnorthernItaly,epilepsywasoncetraditionallyknownasSaintValentine'smalady.[125]

Inthemid1800sthefirsteffectiveantiseizuremedication,bromide,wasintroduced.[90]Thefirstmoderntreatment,phenobarbital,wasdevelopedin1912,withphenytoincomingintousein1938.[126]

Societyandculture

Stigma

Stigmaiscommonlyexperienced,aroundtheworld,bythosewithepilepsy.[127]Itcanaffectpeopleeconomically,sociallyandculturally.[127]InIndiaandChinaepilepsymaybeusedasjustificationtodenymarriage.[4]Peopleinsomeareasstillbelievethosewithepilepsytobecursed.[13]InTanzania,asinotherpartsofAfrica,epilepsyisassociatedwithpossessionbyevilspirits,witchcraft,orpoisoningandisbelievedbymanytobecontagious,[124]forwhichthereisnoevidence.[13]Before1970theUnitedKingdomhadlawswhichpreventedpeoplewithepilepsyfrommarrying.[4]Thestigmamayresultinsomepeoplewithepilepsydenyingthattheyhaveeverhadseizures.[39]

Economics



SeizuresresultindirecteconomiccostsofaboutonebilliondollarsintheUnitedStates.[14]EpilepsyresultedineconomiccostsinEuropeofaround15.5billionEurosin2004.[18]InIndiaepilepsyisestimatedtoresultincostsof1.7billionUSDor0.5%oftheGDP.[4]Itisthecauseofabout1%ofemergencydepartmentvisits(2%foremergencydepartmentsforchildren)intheUnitedStates.[128]

Vehicles

Thosewithepilepsyareatabouttwicetheriskofbeinginvolvedinamotorvehicularcollisionandthusinmanyareasoftheworldarenotallowedtodriveoronlyabletodriveifcertainconditionsaremet.[16]Insomeplacesphysiciansarerequiredbylawtoreportifapersonhashadaseizuretothelicensingbodywhileinotherstherequirementisonlythattheyencouragethepersoninquestiontoreportitthemselves.[16]CountriesthatrequirephysicianreportingincludeSweden,Austria,DenmarkandSpain.[16]CountriesthatrequiretheindividualtoreportincludetheUK,andNewZealandandthephysicianmayreportiftheybelievetheindividualhasnotalready.[16]InCanada,theUnitedStatesandAustraliatherequirementsaroundreportingvarybyprovinceorstate.[16]Ifseizuresarewellcontrolledmostfeelallowingdrivingisreasonable.[129]Theamountoftimeapersonmustbefreefromseizuresbeforetheycandrivevariesbycountry.[129]Manycountriesrequireonetothreeyearswithoutseizures.[129]IntheUnitedStatesthetimeneededwithoutaseizureisdeterminedbyeachstateandisbetweenthreemonthsandoneyear.[129]

Thosewithepilepsyorseizuresaretypicallydeniedapilotlicense.[130]InCanadaifanindividualhashadnomorethanoneseizure,theymaybeconsideredafterfiveyearsforalimitedlicenseifallothertestingisnormal.[131]Thosewithfebrileseizuresanddrugrelatedseizuresmayalsobeconsidered.[131]IntheUnitedStates,theFederalAviationAdministrationdoesnotallowthosewithepilepsytogetacommercialpilotlicense.[132]Rarely,exceptionscanbemadeforpersonswhohavehadanisolatedseizureorfebrileseizuresandhaveremainedfreeofseizuresintoadulthoodwithoutmedication.[133]IntheUnitedKingdom,afullnationalprivatepilotlicenserequiresthesamestandardsasaprofessionaldriver'slicense.[134]Thisrequiresaperiodoftenyearswithoutseizureswhileoffmedications.[135]Thosewhodonotmeetthisrequirementmayacquirearestrictedlicenseiffreefromseizuresforfiveyears.[134]

Supportorganizations

Thereareorganizationsthatprovidesupportforpeopleandfamiliesaffectedbyepilepsy.TheOutoftheShadowscampaign,ajointeffortbytheWorldHealthOrganization,theInternationalLeagueAgainstEpilepsyandtheInternationalBureauforEpilepsy,provideshelpinternationally.[4]TheJointEpilepsyCouncilservestheUKandIreland.[54]IntheUnitedStates,theEpilepsyFoundationisanationalorganizationthatworkstoincreasetheacceptanceofthosewiththedisease,theirabilitytofunctioninsocietyandtopromoteresearchforacure.[136]TheEpilepsyFoundation,somehospitals,andsomeindividualsalsorunsupportgroupsintheUnitedStates.[137]

Research



SeizurepredictionreferstoattemptstoforecastepilepticseizuresbasedontheEEGbeforetheyoccur.[138]Asof2011,noeffectivemechanismtopredictseizureshasbeendeveloped.[138]Kindling,whererepeatedexposurestoeventsthatcouldcauseseizureseventuallycausesseizuresmoreeasily,hasbeenusedtocreateanimalmodelsofepilepsy.[139]

Genetherapyisbeingstudiedinsometypesofepilepsy.[140]Medicationsthatalterimmunefunction,suchasintravenousimmunoglobulins,arepoorlysupportedbyevidence.[141]Noninvasivestereotacticradiosurgeryis,asof2012,beingcomparedtostandardsurgeryforcertaintypesofepilepsy.[142]

Otheranimals

Epilepsyoccursinanumberofotheranimalsincludingdogsandcatsandisthemostcommonbraindisorderindogs.[143]Itistypicallytreatedwithanticonvulsantssuchasphenobarbitalorbromideindogsandphenobarbitalincats.[144]Imepitoinisalsobeingusedindogs.[145]Whilegeneralizedseizuresinhorsesarefairlyeasytodiagnose,itmaybemoredifficultinnongeneralizedseizuresandEEGsmaybeuseful.[146]

References

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