Epilepsy - Wikipedia

Epilepsy is a group of non-communicable neurological disorders characterized by recurrent epileptic seizures. ... Epileptic seizures can vary from brief and ... Epilepsy FromWikipedia,thefreeencyclopedia Jumptonavigation Jumptosearch Groupofneurologicaldisorderscausingseizures "Epilepsia"and"Epileptic"redirecthere.Forthejournal,seeEpilepsia(journal).Forthecomics,seeEpileptic(comics). MedicalconditionEpilepsyOthernamesSeizuredisorderGeneralized3 Hzspike-and-wavedischargesonanelectroencephalogramSpecialtyNeurologySymptomsPeriodsofvigorousshaking,nearlyundetectablespells[1]DurationLongterm[1]CausesUnknown,braininjury,stroke,braintumors,infectionsofthebrain,birthdefects[1][2][3]DiagnosticmethodElectroencephalogram,rulingoutotherpossiblecauses[4]DifferentialdiagnosisFainting,alcoholwithdrawal,electrolyteproblems[4]TreatmentMedication,surgery,neurostimulation,dietarychanges[5][6]PrognosisControllablein69%[7]Frequency39million/0.5%(2015)[8]Deaths125,000(2015)[9] Epilepsyisagroupofnon-communicableneurologicaldisorderscharacterizedbyrecurrentepilepticseizures.[10][11][12]Epilepticseizurescanvaryfrombriefandnearlyundetectableperiodstolongperiodsofvigorousshakingduetoabnormalelectricalactivityinthebrain.[1]Theseepisodescanresultinphysicalinjuries,eitherdirectlysuchasbrokenbonesorthroughcausingaccidents.[1]Inepilepsy,seizurestendtorecurandmayhavenoimmediateunderlyingcause.[10]Isolatedseizuresthatareprovokedbyaspecificcausesuchaspoisoningarenotdeemedtorepresentepilepsy.[13]Peoplewithepilepsymaybetreateddifferentlyinvariousareasoftheworldandexperiencevaryingdegreesofsocialstigmaduetotheircondition.[1] Theunderlyingmechanismofepilepticseizuresisexcessiveandabnormalneuronalactivityinthecortexofthebrain[13]whichcanbeobservedintheelectroencephalogram(EEG)ofanindividual.Thereasonthisoccursinmostcasesofepilepsyisunknown(idiopathic);[1]somecasesoccurastheresultofbraininjury,stroke,braintumors,infectionsofthebrain,orbirthdefectsthroughaprocessknownasepileptogenesis.[1][2][3]Knowngeneticmutationsaredirectlylinkedtoasmallproportionofcases.[4][14]Thediagnosisinvolvesrulingoutotherconditionsthatmightcausesimilarsymptoms,suchasfainting,anddeterminingifanothercauseofseizuresispresent,suchasalcoholwithdrawalorelectrolyteproblems.[4]Thismaybepartlydonebyimagingthebrainandperformingbloodtests.[4]Epilepsycanoftenbeconfirmedwithanelectroencephalogram(EEG),butanormaltestdoesnotruleoutthecondition.[4] Epilepsythatoccursasaresultofotherissuesmaybepreventable.[1]Seizuresarecontrollablewithmedicationinabout69%ofcases;[7]inexpensiveanti-seizuremedicationsareoftenavailable.[1]Inthosewhoseseizuresdonotrespondtomedication;surgery,neurostimulationordietarychangesmaythenbeconsidered.[12][5][6]Notallcasesofepilepsyarelifelong,andmanypeopleimprovetothepointthattreatmentisnolongerneeded.[1] Asof2020[update],about50 millionpeoplehaveepilepsy.[12]Nearly80%ofcasesoccurinthedevelopingworld.[1]In2015,itresultedin125,000deaths,anincreasefrom112,000in1990.[9][15]Epilepsyismorecommoninolderpeople.[16][17]Inthedevelopedworld,onsetofnewcasesoccursmostfrequentlyinbabiesandtheelderly.[18]Inthedevelopingworld,onsetismorecommoninolderchildrenandyoungadultsduetodifferencesinthefrequencyoftheunderlyingcauses.[19]About5–10%ofpeoplewillhaveanunprovokedseizurebytheageof80,[20]withthechanceofexperiencingasecondseizurerisingtobetween40%and50%.[21]Inmanyareasoftheworld,thosewithepilepsyeitherhaverestrictionsplacedontheirabilitytodriveorarenotpermittedtodriveuntiltheyarefreeofseizuresforaspecificlengthoftime.[22]ThewordepilepsyisfromAncientGreekἐπιλαμβάνειν,"toseize,possess,orafflict".[23] Contents 1Signsandsymptoms 1.1Seizures 1.2Post-ictal 1.3Psychosocial 2Causes 2.1Genetics 2.2Acquired 3Mechanism 3.1Epilepsy 3.2Seizures 4Diagnosis 4.1Definition 4.2Classification 4.3Syndromes 4.4Tests 4.5Differentialdiagnosis 5Prevention 6Complication 7Management 7.1Firstaid 7.2Medications 7.3Surgery 7.4Diet 7.5Other 7.6Inpregnancy 7.7Alternativemedicine 8Prognosis 8.1Mortality 9Epidemiology 10History 11Societyandculture 11.1Stigma 11.2Economics 11.3Vehicles 11.4Supportorganizations 12Research 12.1Seizurepredictionandmodeling 12.2Potentialfuturetherapies 13Otheranimals 14References 15Furtherreading 16Externallinks Signsandsymptoms[edit] Astillimageofageneralizedseizure Abitetothetipofthetongueduetoaseizure Epilepsyischaracterizedbyalong-termriskofrecurrentepilepticseizures.[24]Theseseizuresmaypresentinseveralwaysdependingonthepartsofthebraininvolvedandtheperson'sage.[24][25] Seizures[edit] Mainarticle:Epilepticseizure Themostcommontype(60%)ofseizuresareconvulsivewhichinvolveinvoluntarymusclecontractions.[25]Ofthese,one-thirdbeginasgeneralizedseizuresfromthestart,affectingbothhemispheresofthebrainandimpairingconsciousness.[25]Two-thirdsbeginasfocalseizures(whichaffectonehemisphereofthebrain)whichmayprogresstogeneralizedseizures.[25]Theremaining40%ofseizuresarenon-convulsive.Anexampleofthistypeistheabsenceseizure,whichpresentsasadecreasedlevelofconsciousnessandusuallylastsabout10seconds.[2][26] Certainexperiences,knownasaurasoftenprecedefocalseizures.[27]Theseizurescanincludesensory(visual,hearing,orsmell),psychic,autonomic,andmotorphenomenadependingonwhichpartofthebrainisinvolved.[2]MusclejerksmaystartinaspecificmusclegroupandspreadtosurroundingmusclegroupsinwhichcaseitisknownasaJacksonianmarch.[28]Automatismsmayoccur,whicharenon-consciouslygeneratedactivitiesandmostlysimplerepetitivemovementslikesmackingthelipsormorecomplexactivitiessuchasattemptstopickupsomething.[28] Therearesixmaintypesofgeneralizedseizures:tonic-clonic,tonic,clonic,myoclonic,absence,andatonicseizures.[29]Theyallinvolvelossofconsciousnessandtypicallyhappenwithoutwarning. Tonic-clonicseizuresoccurwithacontractionofthelimbsfollowedbytheirextensionandarchingofthebackwhichlasts10–30 seconds(thetonicphase).Acrymaybeheardduetocontractionofthechestmuscles,followedbyashakingofthelimbsinunison(clonicphase).Tonicseizuresproduceconstantcontractionsofthemuscles.Apersonoftenturnsblueasbreathingisstopped.Inclonicseizuresthereisshakingofthelimbsinunison.Aftertheshakinghasstoppeditmaytake10–30 minutesforthepersontoreturntonormal;thisperiodiscalledthe"postictalstate"or"postictalphase."Lossofbowelorbladdercontrolmayoccurduringaseizure.[30]Peopleexperiencingaseizuremaybitetheirtongue,eitherthetiporonthesides;[31]intonic-clonicseizure,bitestothesidesaremorecommon.[31]Tonguebitesarealsorelativelycommoninpsychogenicnon-epilepticseizures.[31] Myoclonicseizuresinvolveverybriefspasmsofmusclesineitherafewareasorallover.[32][33]Thesesometimescausethepersontofall,whichcancauseinjury.[32]Absenceseizurescanbesubtlewithonlyaslightturnoftheheadoreyeblinkingwithimpairedconsciousness;[2]typically,thepersondoesnotfalloverandreturnstonormalrightafteritends.[2]Atonicseizuresinvolvelosingmuscleactivityforgreaterthanonesecond,[28]typicallyoccurringonbothsidesofthebody.[28]Rarerseizuretypescancauseinvoluntaryunnaturallaughter(gelastic),crying(dyscrastic),ormorecomplexexperiencessuchasdéjàvu.[33] About6%ofthosewithepilepsyhaveseizuresthatareoftentriggeredbyspecificeventsandareknownasreflexseizures.[34]Thosewithreflexepilepsyhaveseizuresthatareonlytriggeredbyspecificstimuli.[35]Commontriggersincludeflashinglightsandsuddennoises.[34]Incertaintypesofepilepsy,seizureshappenmoreoftenduringsleep,[36]andinothertypestheyoccuralmostonlywhensleeping.[37] Post-ictal[edit] Aftertheactiveportionofaseizure(theictalstate)thereistypicallyaperiodofrecoveryduringwhichthereisconfusion,referredtoasthepostictalperiod,beforeanormallevelofconsciousnessreturns.[27]Itusuallylasts3to15minutes[38]butmaylastforhours.[39]Othercommonsymptomsincludefeelingtired,headache,difficultyspeaking,andabnormalbehavior.[39]Psychosisafteraseizureisrelativelycommon,occurringin6–10%ofpeople.[40]Oftenpeopledonotrememberwhathappenedduringthistime.[39]Localizedweakness,knownasTodd'sparalysis,mayalsooccurafterafocalseizure.Itwouldtypicallylastforsecondstominutesbutmayrarelylastforadayortwo.[41] Psychosocial[edit] Epilepsycanhaveadverseeffectsonsocialandpsychologicalwell-being.[25]Theseeffectsmayincludesocialisolation,stigmatization,ordisability.[25]Theymayresultinlowereducationalachievementandworseemploymentoutcomes.[25]Learningdisabilitiesarecommoninthosewiththecondition,andespeciallyamongchildrenwithepilepsy.[25]Thestigmaofepilepsycanalsoaffectthefamiliesofthosewiththedisorder.[30] Certaindisordersoccurmoreofteninpeoplewithepilepsy,dependingpartlyontheepilepsysyndromepresent.Theseincludedepression,anxiety,obsessive–compulsivedisorder(OCD),[42]andmigraine.[43]Attentiondeficithyperactivitydisorder(ADHD)affectsthreetofivetimesmorechildrenwithepilepsythanchildrenwithoutthecondition.[44]ADHDandepilepsyhavesignificantconsequencesonachild'sbehavioral,learning,andsocialdevelopment.[45]Epilepsyisalsomorecommoninchildrenwithautism.[46] Causes[edit] Seealso:Causesofseizures Epilepsycanhavebothgeneticandacquiredcauses,withtheinteractionofthesefactorsinmanycases.[47]Establishedacquiredcausesincludeseriousbraintrauma,stroke,tumours,andbrainproblemsresultingfromapreviousinfection.[47]Inabout60%ofcases,thecauseisunknown.[25][30]Epilepsiescausedbygenetic,congenital,ordevelopmentalconditionsaremorecommonamongyoungerpeople,whilebraintumorsandstrokesaremorelikelyinolderpeople.[25] Seizuresmayalsooccurasaconsequenceofotherhealthproblems;[29]iftheyoccurrightaroundaspecificcause,suchasastroke,headinjury,toxicingestion,ormetabolicproblem,theyareknownasacutesymptomaticseizuresandareinthebroaderclassificationofseizure-relateddisordersratherthanepilepsyitself.[48][49] Genetics[edit] Geneticsisbelievedtobeinvolvedinthemajorityofcases,eitherdirectlyorindirectly.[14]Someepilepsiesareduetoasinglegenedefect(1–2%);mostareduetotheinteractionofmultiplegenesandenvironmentalfactors.[14]Eachofthesinglegenedefectsisrare,withmorethan200inalldescribed.[50]Mostgenesinvolvedaffectionchannels,eitherdirectlyorindirectly.[47]Theseincludegenesforionchannelsthemselves,enzymes,GABA,andGprotein-coupledreceptors.[32] Inidenticaltwins,ifoneisaffected,thereisa50–60%chancethattheotherwillalsobeaffected.[14]Innon-identicaltwins,theriskis15%.[14]Theserisksaregreaterinthosewithgeneralizedratherthanfocalseizures.[14]Ifbothtwinsareaffected,mostofthetimetheyhavethesameepilepticsyndrome(70–90%).[14]Othercloserelativesofapersonwithepilepsyhaveariskfivetimesthatofthegeneralpopulation.[51]Between1and10%ofthosewithDownsyndromeand90%ofthosewithAngelmansyndromehaveepilepsy.[51] Acquired[edit] Epilepsymayoccurasaresultofseveralotherconditions,includingtumors,strokes,headtrauma,previousinfectionsofthecentralnervoussystem,geneticabnormalities,andasaresultofbraindamagearoundthetimeofbirth.[29][30]Ofthosewithbraintumors,almost30%haveepilepsy,makingthemthecauseofabout4%ofcases.[51]Theriskisgreatestfortumorsinthetemporallobeandthosethatgrowslowly.[51]Othermasslesionssuchascerebralcavernousmalformationsandarteriovenousmalformationshaverisksashighas40–60%.[51]Ofthosewhohavehadastroke,2–4%developepilepsy.[51]IntheUnitedKingdom,strokesaccountfor15%ofcasesandtheyarebelievedtobethecausein30%oftheelderly.[25][51]Between6and20%ofepilepsyisbelievedtobeduetoheadtrauma.[51]Mildbraininjuryincreasestheriskabouttwo-foldwhileseverebraininjuryincreasestheriskseven-fold.[51]Inthosewhohaveexperiencedahigh-poweredgunshotwoundtothehead,theriskisabout50%.[51] Someevidencelinksepilepsyandceliacdiseaseandnon-celiacglutensensitivity,whileotherevidencedoesnot.Thereappearstobeaspecificsyndromethatincludescoeliacdisease,epilepsy,andcalcificationsinthebrain.[52][53]A2012reviewestimatesthatbetween1%and6%ofpeoplewithepilepsyhavecoeliacdiseasewhile1%ofthegeneralpopulationhasthecondition.[53] Theriskofepilepsyfollowingmeningitisislessthan10%;itmorecommonlycausesseizuresduringtheinfectionitself.[51]Inherpessimplexencephalitistheriskofaseizureisaround50%[51]withahighriskofepilepsyfollowing(upto25%).[54][55]Aformofaninfectionwiththeporktapeworm(cysticercosis),inthebrain,isknownasneurocysticercosis,andisthecauseofuptohalfofepilepsycasesinareasoftheworldwheretheparasiteiscommon.[51]Epilepsymayalsooccurafterotherbraininfectionssuchascerebralmalaria,toxoplasmosis,andtoxocariasis.[51]Chronicalcoholuseincreasestheriskofepilepsy:thosewhodrinksixunitsofalcoholperdayhavea2.5-foldincreaseinrisk.[51]OtherrisksincludeAlzheimer'sdisease,multiplesclerosis,tuberoussclerosis,andautoimmuneencephalitis.[51]Gettingvaccinateddoesnotincreasetheriskofepilepsy.[51]Malnutritionisariskfactorseenmostlyinthedevelopingworld,althoughitisunclearhoweverifitisadirectcauseoranassociation.[19]Peoplewithcerebralpalsyhaveanincreasedriskofepilepsy,withhalfofpeoplewithspasticquadriplegiaandspastichemiplegiahavingthedisease.[56] Mechanism[edit] Normallybrainelectricalactivityisnon-synchronous,aslargenumbersofneuronsdonotnormallyfireatthesametime,butratherfireinorderassignalstravelthroughoutthebrain.[2]Neuronactivityisregulatedbyvariousfactorsbothwithinthecellandthecellularenvironment.Factorswithintheneuronincludethetype,numberanddistributionofionchannels,changestoreceptorsandchangesofgeneexpression.[57]Factorsaroundtheneuronincludeionconcentrations,synapticplasticityandregulationoftransmitterbreakdownbyglialcells.[57][58] Epilepsy[edit] Theexactmechanismforepilepsyisunknown,[59]butalittleisknownaboutitscellularandnetworkmechanisms.However,itisunknownunderwhichcircumstancesthebrainshiftsintotheactivityofaseizurewithitsexcessivesynchronization.[60][61]ChangesinMicroRNAs(miRNAs)levelsseemstoplayaleadingrole.MicroRNAs(miRNAs)areafamilyofsmallnon-codingRNAsthatcontroltheexpressionlevelsofmultipleproteinsbydecreasingmRNAstabilityandtranslation,andcouldthereforebekeyregulatorymechanismsandtherapeutictargetsinepilepsy[62] Inepilepsy,theresistanceofexcitatoryneuronstofireduringthisperiodisdecreased.[2]Thismayoccurduetochangesinionchannelsorinhibitoryneuronsnotfunctioningproperly.[2]Thisthenresultsinaspecificareafromwhichseizuresmaydevelop,knownasa"seizurefocus".[2]Anothermechanismofepilepsymaybetheup-regulationofexcitatorycircuitsordown-regulationofinhibitorycircuitsfollowinganinjurytothebrain.[2][3]Thesesecondaryepilepsiesoccurthroughprocessesknownasepileptogenesis.[2][3]Failureoftheblood–brainbarriermayalsobeacausalmechanismasitwouldallowsubstancesinthebloodtoenterthebrain.[63] Seizures[edit] Thereisevidencethatepilepticseizuresareusuallynotarandomevent.Seizuresareoftenbroughtonbyfactors(alsoknownastriggers)suchasstress,excessivealcoholuse,flickeringlight,oralackofsleep,amongothers.Thetermseizurethresholdisusedtoindicatetheamountofstimulusnecessarytobringaboutaseizure,thisseizurethresholdisloweredinepilepsy.[60] Inepilepticseizuresagroupofneuronsbeginfiringinanabnormal,excessive,[25]andsynchronizedmanner.[2]Thisresultsinawaveofdepolarizationknownasaparoxysmaldepolarizingshift.[64]Normally,afteranexcitatoryneuronfiresitbecomesmoreresistanttofiringforaperiodoftime.[2]Thisisdueinparttotheeffectofinhibitoryneurons,electricalchangeswithintheexcitatoryneuron,andthenegativeeffectsofadenosine.[2] Focalseizuresbegininoneareaofthebrainwhilegeneralizedseizuresbegininbothhemispheres.[29]Sometypesofseizuresmaychangebrainstructure,whileothersappeartohavelittleeffect.[65]Gliosis,neuronalloss,andatrophyofspecificareasofthebrainarelinkedtoepilepsybutitisunclearifepilepsycausesthesechangesorifthesechangesresultinepilepsy.[65] Theseizurescanbedescribedondifferentscales,fromthecellularlevel[66]tothewholebrain.[67]Theseareseveralconcomitantfactor,whichondifferentscalecan"drive"thebraintopathologicalstatesandtriggeraseizure. Diagnosis[edit] AnEEGcanaidinlocatingthefocusoftheepilepticseizure. Thediagnosisofepilepsyistypicallymadebasedonobservationoftheseizureonsetandtheunderlyingcause.[25]Anelectroencephalogram(EEG)tolookforabnormalpatternsofbrainwavesandneuroimaging(CTscanorMRI)tolookatthestructureofthebrainarealsousuallypartoftheinitialinvestigations.[25]Whilefiguringoutaspecificepilepticsyndromeisoftenattempted,itisnotalwayspossible.[25]VideoandEEGmonitoringmaybeusefulindifficultcases.[68] Definition[edit] Epilepsyisadisorderofthebraindefinedbyanyofthefollowingconditions:[11] Atleasttwounprovoked(orreflex)seizuresoccurringmorethan24hoursapart Oneunprovoked(orreflex)seizureandaprobabilityoffurtherseizuressimilartothegeneralrecurrencerisk(atleast60%)aftertwounprovokedseizures,occurringoverthenext10years Diagnosisofanepilepsysyndrome Furthermore,epilepsyisconsideredtoberesolvedforindividualswhohadanage-dependentepilepsysyndromebutarenowpastthatageorthosewhohaveremainedseizure-freeforthelast10years,withnoseizuremedicinesforthelast5years.[11] This2014definitionoftheInternationalLeagueAgainstEpilepsy[11]isaclarificationoftheILAE2005conceptualdefinition,accordingtowhichepilepsyis"adisorderofthebraincharacterizedbyanenduringpredispositiontogenerateepilepticseizuresandbytheneurobiologic,cognitive,psychological,andsocialconsequencesofthiscondition.Thedefinitionofepilepsyrequirestheoccurrenceofatleastoneepilepticseizure."[13][69] Itis,therefore,possibletooutgrowepilepsyortoundergotreatmentthatcausesepilepsytoberesolved,butwithnoguaranteethatitwillnotreturn.Inthedefinition,epilepsyisnowcalledadisease,ratherthanadisorder.ThiswasadecisionoftheexecutivecommitteeoftheILAE,takenbecausetheword"disorder,"whileperhapshavinglessstigmathandoes"disease,"alsodoesnotexpressthedegreeofseriousnessthatepilepsydeserves.[11] Thedefinitionispracticalinnatureandisdesignedforclinicaluse.Inparticular,itaimstoclarifywhenan"enduringpredisposition"accordingtothe2005conceptualdefinitionispresent.Researchers,statisticallymindedepidemiologists,andotherspecializedgroupsmaychoosetousetheolderdefinitionoradefinitionoftheirowndevising.TheILAEconsidersdoingsoisperfectlyallowable,solongasitisclearwhatdefinitionisbeingused.[11] Classification[edit] Revisedoperationalschemeofseizureclassification,ILAE,2017 Incontrasttotheclassificationofseizureswhichfocusesonwhathappensduringaseizure,theclassificationofepilepsiesfocusesontheunderlyingcauses.Whenapersonisadmittedtohospitalafteranepilepticseizurethediagnosticworkupresultspreferablyintheseizureitselfbeingclassified(e.g.tonic-clonic)andintheunderlyingdiseasebeingidentified(e.g.hippocampalsclerosis).[68]Thenameofthediagnosisfinallymadedependsontheavailablediagnosticresultsandtheapplieddefinitionsandclassifications(ofseizuresandepilepsies)anditsrespectiveterminology. TheInternationalLeagueAgainstEpilepsy(ILAE)providedaclassificationoftheepilepsiesandepilepticsyndromesin1989asfollows:[70] Localization-relatedepilepsiesandsyndromes Unknowncause(e.g.benignchildhoodepilepsywithcentrotemporalspikes) Symptomatic/cryptogenic(e.g.temporallobeepilepsy) Generalized Unknowncause(e.g.childhoodabsenceepilepsy) Cryptogenicorsymptomatic(e.g.Lennox-Gastautsyndrome) Symptomatic(e.g.earlyinfantileepilepticencephalopathywithburstsuppression) Epilepsiesandsyndromesundeterminedwhetherfocalorgeneralized Withbothgeneralizedandfocalseizures(e.g.epilepsywithcontinuousspike-wavesduringslowwavesleep) Specialsyndromes(withsituation-relatedseizures) Thisclassificationwaswidelyacceptedbuthasalsobeencriticizedmainlybecausetheunderlyingcausesofepilepsy(whichareamajordeterminantofclinicalcourseandprognosis)werenotcoveredindetail.[71]In2010theILAECommissionforClassificationoftheEpilepsiesaddressedthisissueanddividedepilepsiesintothreecategories(genetic,structural/metabolic,unknowncause)[72]thatwererefinedintheir2011recommendationintofourcategoriesandanumberofsubcategoriesreflectingrecenttechnologicandscientificadvances.[73] Unknowncause(mostlygeneticorpresumedgeneticorigin) Pureepilepsiesduetosinglegenedisorders Pureepilepsieswithcomplexinheritance Symptomatic(associatedwithgrossanatomicorpathologicabnormalities) Mostlygeneticordevelopmentalcausation Childhoodepilepsysyndromes Progressivemyoclonicepilepsies Neurocutaneoussyndromes Otherneurologicsinglegenedisorders Disordersofchromosomefunction Developmentalanomaliesofcerebralstructure Mostlyacquiredcauses Hippocampalsclerosis Perinatalandinfantilecauses Cerebraltrauma,tumororinfection Cerebrovasculardisorders Cerebralimmunologicdisorders Degenerativeandotherneurologicconditions Provoked(aspecificsystemicorenvironmentalfactoristhepredominantcauseoftheseizures) Provokingfactors Reflexepilepsies Cryptogenic(presumedsymptomaticnatureinwhichthecausehasnotbeenidentified)[73] Arevised,operationalclassificationofseizuretypeshasbeenintroducedbytheILAE.[74]Itallowsmoreclearlyunderstoodtermsandclearlydefinesfocalandgeneralizedonsetdichotomy,whenpossible,evenwithoutobservingtheseizuresbasedondescriptionbypatientorobservers.[75]Theessentialchangesinterminologyarethat"partial"iscalled"focal"withawarenessusedasaclassifierforfocalseizures-basedondescriptionfocalseizuresarenowdefinedasbehavioralarrest,automatisms,cognitive,autonomic,emotionalorhyperkineticvariantswhileatonic,myoclonic,clonic,infantilespasms,andtonicseizuresmaybeeitherfocalorgeneralizedbasedontheironset.Severaltermsthatwerenotclearorconsistentindescriptionwereremovedsuchasdyscognitive,psychic,simpleandcomplexpartial,while"secondarilygeneralized"isreplacedbyaclearerterm"focaltobilateraltonicclonicseizure".Newseizuretypesnowbelievedtobegeneralizedareeyelidmyoclonia,myoclonicatonic,myoclonicabsence,andmyoclonictonicclonic.Sometimesitispossibletoclassifyseizuresasfocalorgeneralizedbasedonpresentingfeatureseventhoughonsetinnotknown.Thissystemisbasedonthe1981seizureclassificationmodifiedin2010andprincipallyisthesamewithanefforttoimprovetheflexibilityandclarityofusetounderstandseizurestypesbetterinkeepingwithcurrentknowledge. Syndromes[edit] Mainarticle:Epilepsysyndromes Casesofepilepsymaybeorganizedintoepilepsysyndromesbythespecificfeaturesthatarepresent.Thesefeaturesincludetheagethatseizurebegin,theseizuretypes,EEGfindings,amongothers.Identifyinganepilepsysyndromeisusefulasithelpsdeterminetheunderlyingcausesaswellaswhatanti-seizuremedicationshouldbetried.[29][76] Theabilitytocategorizeacaseofepilepsyintoaspecificsyndromeoccursmoreoftenwithchildrensincetheonsetofseizuresiscommonlyearly.[49]Lessseriousexamplesarebenignrolandicepilepsy(2.8per100,000),childhoodabsenceepilepsy(0.8per100,000)andjuvenilemyoclonicepilepsy(0.7per100,000).[49]Severesyndromeswithdiffusebraindysfunctioncaused,atleastpartly,bysomeaspectofepilepsy,arealsoreferredtoasdevelopmentalandepilepticencephalopathies.Theseareassociatedwithfrequentseizuresthatareresistanttotreatmentandcognitivedysfunction,forinstanceLennox–Gastautsyndrome(1-2%ofallpersonswithepilepsy),[77]Dravetsyndrome(1:15000-40000worldwide[78]),andWestsyndrome(1-9:100000[79]).[80]Geneticsisbelievedtoplayanimportantroleinepilepsiesbyanumberofmechanisms.Simpleandcomplexmodesofinheritancehavebeenidentifiedforsomeofthem.However,extensivescreeninghavefailedtoidentifymanysinglegenevariantsoflargeeffect.[81]Morerecentexomeandgenomesequencingstudieshavebeguntorevealanumberofdenovogenemutationsthatareresponsibleforsomeepilepticencephalopathies,includingCHD2andSYNGAP1[82][83][84]andDNM1,GABBR2,FASNandRYR3.[85] Syndromesinwhichcausesarenotclearlyidentifiedaredifficulttomatchwithcategoriesofthecurrentclassificationofepilepsy.Categorizationforthesecaseswasmadesomewhatarbitrarily.[73]Theidiopathic(unknowncause)categoryofthe2011classificationincludessyndromesinwhichthegeneralclinicalfeaturesand/oragespecificitystronglypointtoapresumedgeneticcause.[73]Somechildhoodepilepsysyndromesareincludedintheunknowncausecategoryinwhichthecauseispresumedgenetic,forinstancebenignrolandicepilepsy.Othersareincludedinsymptomaticdespiteapresumedgeneticcause(inatleastinsomecases),forinstanceLennox-Gastautsyndrome.[73]Clinicalsyndromesinwhichepilepsyisnotthemainfeature(e.g.Angelmansyndrome)werecategorizedsymptomaticbutitwasarguedtoincludethesewithinthecategoryidiopathic.[73]Classificationofepilepsiesandparticularlyofepilepsysyndromeswillchangewithadvancesinresearch. Tests[edit] Anelectroencephalogram(EEG)canassistinshowingbrainactivitysuggestiveofanincreasedriskofseizures.Itisonlyrecommendedforthosewhoarelikelytohavehadanepilepticseizureonthebasisofsymptoms.Inthediagnosisofepilepsy,electroencephalographymayhelpdistinguishthetypeofseizureorsyndromepresent.[86]Inchildrenitistypicallyonlyneededafterasecondseizureunlessspecifiedbyaspecialist.Itcannotbeusedtoruleoutthediagnosisandmaybefalselypositiveinthosewithoutthedisease.[86]IncertainsituationsitmaybeusefultoperformtheEEGwhiletheaffectedindividualissleepingorsleepdeprived.[68] DiagnosticimagingbyCTscanandMRIisrecommendedafterafirstnon-febrileseizuretodetectstructuralproblemsinandaroundthebrain.[68]MRIisgenerallyabetterimagingtestexceptwhenbleedingissuspected,forwhichCTismoresensitiveandmoreeasilyavailable.[20]Ifsomeoneattendstheemergencyroomwithaseizurebutreturnstonormalquickly,imagingtestsmaybedoneatalaterpoint.[20]Ifapersonhasapreviousdiagnosisofepilepsywithpreviousimaging,repeatingtheimagingisusuallynotneededeveniftherearesubsequentseizures.[68][87] Foradults,thetestingofelectrolyte,bloodglucoseandcalciumlevelsisimportanttoruleoutproblemswiththeseascauses.[68]Anelectrocardiogramcanruleoutproblemswiththerhythmoftheheart.[68]Alumbarpuncturemaybeusefultodiagnoseacentralnervoussysteminfectionbutisnotroutinelyneeded.[20]Inchildrenadditionaltestsmayberequiredsuchasurinebiochemistryandbloodtestinglookingformetabolicdisorders.[68][88]TogetherwithEEGandneuroimaging,genetictestingisbecomingoneofthemostimportantdiagnostictechniqueforepilepsy,asadiagnosismightbeachievedinarelevantproportionofcaseswithsevereepilepsies,bothinchildrenandadults.[89]Forthosewithnegativegenetictesting,insomeitmightbeimportanttorepeatorre-analyzepreviousgeneticstudiesafter2–3years.[90] Ahighbloodprolactinlevelwithinthefirst20minutesfollowingaseizuremaybeusefultohelpconfirmanepilepticseizureasopposedtopsychogenicnon-epilepticseizure.[91][92]Serumprolactinlevelislessusefulfordetectingfocalseizures.[93]Ifitisnormalanepilepticseizureisstillpossible[92]andaserumprolactindoesnotseparateepilepticseizuresfromsyncope.[94]Itisnotrecommendedasaroutinepartofthediagnosisofepilepsy.[68] Differentialdiagnosis[edit] Diagnosisofepilepsycanbedifficult.Anumberofotherconditionsmaypresentverysimilarsignsandsymptomstoseizures,includingsyncope,hyperventilation,migraines,narcolepsy,panicattacksandpsychogenicnon-epilepticseizures(PNES).[95][96]Inparticularasyncopecanbeaccompaniedbyashortepisodeofconvulsions.[97]Nocturnalfrontallobeepilepsy,oftenmisdiagnosedasnightmares,wasconsideredtobeaparasomniabutlateridentifiedtobeanepilepsysyndrome.[98]Attacksofthemovementdisorderparoxysmaldyskinesiamaybetakenforepilepticseizures.[99]Thecauseofadropattackcanbe,amongmanyothers,anatonicseizure.[96] Childrenmayhavebehaviorsthatareeasilymistakenforepilepticseizuresbutarenot.Theseincludebreath-holdingspells,bedwetting,nightterrors,ticsandshudderattacks.[96]Gastroesophagealrefluxmaycausearchingofthebackandtwistingoftheheadtothesideininfants,whichmaybemistakenfortonic-clonicseizures.[96] Misdiagnosisisfrequent(occurringinabout5to30%ofcases).[25]Differentstudiesshowedthatinmanycasesseizure-likeattacksinapparenttreatment-resistantepilepsyhaveacardiovascularcause.[97][100]Approximately20%ofthepeopleseenatepilepsyclinicshavePNES[20]andofthosewhohavePNESabout10%alsohaveepilepsy;[101]separatingthetwobasedontheseizureepisodealonewithoutfurthertestingisoftendifficult.[101] Prevention[edit] Whilemanycasesarenotpreventable,effortstoreduceheadinjuries,providegoodcarearoundthetimeofbirth,andreduceenvironmentalparasitessuchastheporktapewormmaybeeffective.[30]EffortsinonepartofCentralAmericatodecreaseratesofporktapewormresultedina50%decreaseinnewcasesofepilepsy.[19] Complication[edit] Epilepsycanbedangerouswhenseizureoccursatcertaintimes.Thepossibilityofdrowningandhavingcaraccidentishigher.Itisalsodangerouswhenseizureoccursduringpregnancy.Certainanti-epilepticmedicationsincreasetheriskofbirthdefects.Itisalsofoundthatpeoplewithepilepsyaremorelikelytohavepsychologicalproblems.[102]Othercomplicationsincludeaspirationpneumoniaanddifficultylearning.[103] Management[edit] Wristbandsorbraceletsdenotingtheirconditionareoccasionallywornbyepilepticsshouldtheyneedmedicalassistance. Epilepsyisusuallytreatedwithdailymedicationonceasecondseizurehasoccurred,[25][68]whilemedicationmaybestartedafterthefirstseizureinthoseathighriskforsubsequentseizures.[68]Supportingpeople'sselfmanagementoftheirconditionmaybeuseful.[104]Indrug-resistantcasesdifferentmanagementoptionsmaybelookedatincludingaspecialdiet,theimplantationofaneurostimulator,orneurosurgery. Firstaid[edit] Rollingpeoplewithanactivetonic-clonicseizureontotheirsideandintotherecoverypositionhelpspreventfluidsfromgettingintothelungs.[105]Puttingfingers,abiteblockortonguedepressorinthemouthisnotrecommendedasitmightmakethepersonvomitorresultintherescuerbeingbitten.[27][105]Effortsshouldbetakentopreventfurtherself-injury.[27]Spinalprecautionsaregenerallynotneeded.[105] Ifaseizurelastslongerthan5 minutesoriftherearemorethantwoseizuresinanhourwithoutareturntoanormallevelofconsciousnessbetweenthem,itisconsideredamedicalemergencyknownasstatusepilepticus.[68][106]Thismayrequiremedicalhelptokeeptheairwayopenandprotected;[68]anasopharyngealairwaymaybeusefulforthis.[105]Athometherecommendedinitialmedicationforseizureofalongdurationismidazolamplacedinthemouth.[107]Diazepammayalsobeusedrectally.[107]Inhospital,intravenouslorazepamispreferred.[68]Iftwodosesofbenzodiazepinesarenoteffective,othermedicationssuchasphenytoinarerecommended.[68]Convulsivestatusepilepticusthatdoesnotrespondtoinitialtreatmenttypicallyrequiresadmissiontotheintensivecareunitandtreatmentwithstrongeragentssuchasthiopentoneorpropofol.[68] Medications[edit] Anticonvulsants Themainstaytreatmentofepilepsyisanticonvulsantmedications,possiblyfortheperson'sentirelife.[12][25]Thechoiceofanticonvulsantisbasedonseizuretype,epilepsysyndrome,othermedicationsused,otherhealthproblems,andtheperson'sageandlifestyle.[107]Asinglemedicationisrecommendedinitially;[108]ifthisisnoteffective,switchingtoasingleothermedicationisrecommended.[68]Twomedicationsatonceisrecommendedonlyifasinglemedicationdoesnotwork.[68]Inabouthalf,thefirstagentiseffective;asecondsingleagenthelpsinabout13%andathirdortwoagentsatthesametimemayhelpanadditional4%.[109]About30%ofpeoplecontinuetohaveseizuresdespiteanticonvulsanttreatment.[7] Thereareanumberofmedicationsavailableincludingphenytoin,carbamazepineandvalproate.Evidencesuggeststhatphenytoin,carbamazepine,andvalproatemaybeequallyeffectiveinbothfocalandgeneralizedseizures.[110][111]Controlledreleasecarbamazepineappearstoworkaswellasimmediatereleasecarbamazepine,andmayhavefewersideeffects.[112]Recently,Nuxvomica[113]andCicutavirosa[114]havebeenshowntoproducesignificantanti-epilepticeffectsandnosideeffects.Thiscouldprovetobeveryhelpfulforalargesegmentofpopulation.IntheUnitedKingdom,carbamazepineorlamotriginearerecommendedasfirst-linetreatmentforfocalseizures,withlevetiracetamandvalproateassecond-lineduetoissuesofcostandsideeffects.[68]Valproateisrecommendedfirst-lineforgeneralizedseizureswithlamotriginebeingsecond-line.[68]Inthosewithabsenceseizures,ethosuximideorvalproatearerecommended;valproateisparticularlyeffectiveinmyoclonicseizuresandtonicoratonicseizures.[68]Ifseizuresarewell-controlledonaparticulartreatment,itisnotusuallynecessarytoroutinelycheckthemedicationlevelsintheblood.[68] TheleastexpensiveanticonvulsantisphenobarbitalataroundUS$5ayear.[19]TheWorldHealthOrganizationgivesitafirst-linerecommendationinthedevelopingworldanditiscommonlyusedthere.[115][116]Accesshowevermaybedifficultassomecountrieslabelitasacontrolleddrug.[19] Adverseeffectsfrommedicationsarereportedin10to90%ofpeople,dependingonhowandfromwhomthedataiscollected.[117]Mostadverseeffectsaredose-relatedandmild.[117]Someexamplesincludemoodchanges,sleepiness,oranunsteadinessingait.[117]Certainmedicationshavesideeffectsthatarenotrelatedtodosesuchasrashes,livertoxicity,orsuppressionofthebonemarrow.[117]Uptoaquarterofpeoplestoptreatmentduetoadverseeffects.[117]Somemedicationsareassociatedwithbirthdefectswhenusedinpregnancy.[68]Manyofthecommonusedmedications,suchasvalproate,phenytoin,carbamazepine,phenobarbital,andgabapentinhavebeenreportedtocauseincreasedriskofbirthdefects,[118]especiallywhenusedduringthefirsttrimester.[119]Despitethis,treatmentisoftencontinuedonceeffective,becausetheriskofuntreatedepilepsyisbelievedtobegreaterthantheriskofthemedications.[119]Amongtheantiepilepticmedications,[120]levetiracetamandlamotrigineseemtocarrythelowestriskofcausingbirthdefects.[118] Slowlystoppingmedicationsmaybereasonableinsomepeoplewhodonothaveaseizurefortwotofouryears;however,aroundathirdofpeoplehavearecurrence,mostoftenduringthefirstsixmonths.[68][121]Stoppingispossibleinabout70%ofchildrenand60%ofadults.[30]Measuringmedicationlevelsisnotgenerallyneededinthosewhoseseizuresarewellcontrolled.[87] Surgery[edit] Epilepsysurgerymaybeanoptionforpeoplewithfocalseizuresthatremainaproblemdespiteothertreatments.[122][123]Theseothertreatmentsincludeatleastatrialoftwoorthreemedications.[124]Thegoalofsurgeryistotalcontrolofseizures[125]andthismaybeachievedin60–70%ofcases.[124]Commonproceduresincludecuttingoutthehippocampusviaananteriortemporalloberesection,removaloftumors,andremovingpartsoftheneocortex.[124]Someproceduressuchasacorpuscallosotomyareattemptedinanefforttodecreasethenumberofseizuresratherthancurethecondition.[124]Followingsurgery,medicationsmaybeslowlywithdrawninmanycases.[124][122] Neurostimulationmaybeanotheroptioninthosewhoarenotcandidatesforsurgery.[68]Threetypeshavebeenusedinthosewhodonotrespondtomedications:vagusnervestimulation,anteriorthalamicstimulation,andclosed-loopresponsivestimulation.[5][126][127] Diet[edit] Thereispromisingevidencethataketogenicdiet(high-fat,low-carbohydrate,adequate-protein)decreasesthenumberofseizuresandeliminatesseizuresinsome;however,furtherresearchisnecessary.[6]Itisareasonableoptioninthosewhohaveepilepsythatisnotimprovedwithmedicationsandforwhomsurgeryisnotanoption.[6]About10%stayonthedietforafewyearsduetoissuesofeffectivenessandtolerability.[6]Sideeffectsincludestomachandintestinalproblemsin30%,andtherearelong-termconcernsaboutheartdisease.[6]Lessradicaldietsareeasiertotolerateandmaybeeffective.[6]Itisunclearwhythisdietworks.[128]Inpeoplewithcoeliacdiseaseornon-celiacglutensensitivityandoccipitalcalcifications,agluten-freedietmaydecreasethefrequencyofseizures.[53] Other[edit] Avoidancetherapyconsistsofminimizingoreliminatingtriggers.Forexample,thosewhoaresensitivetolightmayhavesuccesswithusingasmalltelevision,avoidingvideogames,orwearingdarkglasses.[129]Operant-basedbiofeedbackbasedontheEEGwaveshassomesupportinthosewhodonotrespondtomedications.[130]Psychologicalmethodsshouldnot,however,beusedtoreplacemedications.[68] Exercisehasbeenproposedaspossiblyusefulforpreventingseizures,[131]withsomedatatosupportthisclaim.[132]Somedogs,commonlyreferredtoasseizuredogs,mayhelpduringorafteraseizure.[133][134]Itisnotclearifdogshavetheabilitytopredictseizuresbeforetheyoccur.[135] Thereismoderate-qualityevidencesupportingtheuseofpsychologicalinterventionsalongwithothertreatmentsinepilepsy.[136]Thiscanimprovequalityoflife,enhanceemotionalwellbeing,andreducefatigueinadultsandadolescents.[136]Psychologicalinterventionsmayalsoimproveseizurecontrolforsomeindividualsbypromotingself-managementandadherence.[136] Asanadd-ontherapyinthosewhoarenotwellcontrolledwithothermedications,cannabidiolappearstobeusefulinsomechildren.[137][138]In2018theFDAapprovedthisproductforLennox–GastautsyndromeandDravetsyndrome.[139] Thereareafewstudiesontheuseofdexamethasoneforthesuccessfultreatmentofdrug-resistantseizuresinbothadultsandchildren[140] Inpregnancy[edit] Inwomenofchildbearingage,useofantiepilepticdrugsisamajorconcernbalancingpossiblesideeffectsonthefetusagainstriskfromuncontrolledseizures.UseofAEDsentailteratogeniceffectsincludingintrauterinegrowthretardation,majorcongenitalmalformationsanddevelopmental(neurocognitive)andbehavioralissues,thatneedtobediscussedwiththepatientatthetimeofstartingtheAEDsandbeforetheyplanpregnancy.[141]Mostwomenwithepilepsyreceivesafeandeffectivetreatmentandhavenormalchildren,howeverrisksexist.TheInternationalLeagueAgainstEpilepsycreatedataskforceonwomenandepilepsywhichpublishedconsensusrecommendationstoguidetherapydecisionsuntilmoredefinitiveevidenceisavailableinthefuture.[141] Alternativemedicine[edit] Alternativemedicine,includingacupuncture,[142]routinevitamins,[143]andyoga,[144]havenoreliableevidencetosupporttheiruseinepilepsy.Melatonin,asof2016[update],isinsufficientlysupportedbyevidence.[145]Thetrialswereofpoormethodologicalqualityanditwasnotpossibletodrawanydefinitiveconclusions.[145] Severalsupplements(withvariedreliabilitiesofevidence)havebeenreportedtobehelpfulfordrug-resistantepilepsy.Theseincludehigh-doseOmega-3,berberine,Manukahoney,ReishiandLion'sManemushrooms,curcumin,[146]vitaminE,coenzymeQ-10,andresveratrol.Thereasonthesecanwork(intheory)isthattheyreduceinflammationoroxidativestress,twoofthemajormechanismcontributingtoepilepsy.[147] Prognosis[edit] Deathsduetoepilepsypermillionpersonsin2012  0–7  8–10  11–13  14–17  18–21  22–28  29–37  38–67  68–100  101–232 Epilepsycannotusuallybecured,butmedicationcancontrolseizureseffectivelyinabout70%ofcases.[7]Ofthosewithgeneralizedseizures,morethan80%canbewellcontrolledwithmedicationswhilethisistrueinonly50%ofpeoplewithfocalseizures.[5]Onepredictoroflong-termoutcomeisthenumberofseizuresthatoccurinthefirstsixmonths.[25]Otherfactorsincreasingtheriskofapooroutcomeincludelittleresponsetotheinitialtreatment,generalizedseizures,afamilyhistoryofepilepsy,psychiatricproblems,andwavesontheEEGrepresentinggeneralizedepileptiformactivity.[148]Inthedevelopingworld,75%ofpeopleareeitheruntreatedornotappropriatelytreated.[30]InAfrica,90%donotgettreatment.[30]Thisispartlyrelatedtoappropriatemedicationsnotbeingavailableorbeingtooexpensive.[30] Mortality[edit] Peoplewithepilepsyareatanincreasedriskofdeath.[149]Thisincreaseisbetween1.6and4.1foldgreaterthanthatofthegeneralpopulation.[150]Thegreatestincreaseinmortalityfromepilepsyisamongtheelderly.[150]Thosewithepilepsyduetoanunknowncausehavelittleincreasedrisk.[150] Mortalityisoftenrelatedto:theunderlyingcauseoftheseizures,statusepilepticus,suicide,trauma,andsuddenunexpecteddeathinepilepsy(SUDEP).[149]Deathfromstatusepilepticusisprimarilyduetoanunderlyingproblemratherthanmissingdosesofmedications.[149]Theriskofsuicideisbetween2and6timeshigherinthosewithepilepsy;[151][152]thecauseofthisisunclear.[151]SUDEPappearstobepartlyrelatedtothefrequencyofgeneralizedtonic-clonicseizures[153]andaccountsforabout15%ofepilepsy-relateddeaths;[148]itisunclearhowtodecreaseitsrisk.[153] IntheUnitedKingdom,itisestimatedthat40–60%ofdeathsarepossiblypreventable.[25]Inthedevelopingworld,manydeathsareduetountreatedepilepsyleadingtofallsorstatusepilepticus.[19] Epidemiology[edit] Epilepsyisoneofthemostcommonseriousneurologicaldisorders[154]affectingabout39 millionpeopleasof2015[update].[8]Itaffects1%ofthepopulationbyage20and3%ofthepopulationbyage75.[17]Itismorecommoninmalesthanfemaleswiththeoveralldifferencebeingsmall.[19][49]Mostofthosewiththedisorder(80%)areinlowincomepopulations[155]orthedevelopingworld.[30] Theestimatedprevalenceofactiveepilepsy(asof2012[update])isintherange3–10per1,000,withactiveepilepsydefinedassomeonewithepilepsywhohashadaleastoneunprovokedseizureinthelastfiveyears.[49][156]Epilepsybeginseachyearin40–70per100,000indevelopedcountriesand80–140per100,000indevelopingcountries.[30]Povertyisariskandincludesbothbeingfromapoorcountryandbeingpoorrelativetootherswithinone'scountry.[19]Inthedevelopedworldepilepsymostcommonlystartseitherintheyoungorintheold.[19]Inthedevelopingworlditsonsetismorecommoninolderchildrenandyoungadultsduetothehigherratesoftraumaandinfectiousdiseases.[19]Indevelopedcountriesthenumberofcasesayearhasdecreasedinchildrenandincreasedamongtheelderlybetweenthe1970sand2003.[156]Thishasbeenattributedpartlytobettersurvivalfollowingstrokesintheelderly.[49] History[edit] Seealso:OntheSacredDisease Hippocrates,17thcenturyengravingbyPeterPaulRubensofanantiquebust Theoldestmedicalrecordsshowthatepilepsyhasbeenaffectingpeopleatleastsincethebeginningofrecordedhistory.[157]Throughoutancienthistory,thediseasewasthoughttobeaspiritualcondition.[157]Theworld'soldestdescriptionofanepilepticseizurecomesfromatextinAkkadian(alanguageusedinancientMesopotamia)andwaswrittenaround2000BC.[23]Thepersondescribedinthetextwasdiagnosedasbeingundertheinfluenceofamoongod,andunderwentanexorcism.[23]EpilepticseizuresarelistedintheCodeofHammurabi(c. 1790BC)asreasonforwhichapurchasedslavemaybereturnedforarefund,[23]andtheEdwinSmithPapyrus(c. 1700BC)describescasesofindividualswithepilepticconvulsions.[23] TheoldestknowndetailedrecordofthediseaseitselfisintheSakikku,aBabyloniancuneiformmedicaltextfrom1067–1046BC.[157]Thistextgivessignsandsymptoms,detailstreatmentandlikelyoutcomes,[23]anddescribesmanyfeaturesofthedifferentseizuretypes.[157]AstheBabylonianshadnobiomedicalunderstandingofthenatureofdisease,theyattributedtheseizurestopossessionbyevilspiritsandcalledfortreatingtheconditionthroughspiritualmeans.[157]Around900BC,PunarvasuAtreyadescribedepilepsyaslossofconsciousness;[158]thisdefinitionwascarriedforwardintotheAyurvedictextofCharakaSamhita(about400BC).[159] TheancientGreekshadcontradictoryviewsofthedisease.Theythoughtofepilepsyasaformofspiritualpossession,butalsoassociatedtheconditionwithgeniusandthedivine.Oneofthenamestheygavetoitwasthesacreddisease(ἠἱερὰνόσος).[23][160]EpilepsyappearswithinGreekmythology:itisassociatedwiththeMoongoddessesSeleneandArtemis,whoafflictedthosewhoupsetthem.TheGreeksthoughtthatimportantfiguressuchasJuliusCaesarandHerculeshadthedisease.[23]ThenotableexceptiontothisdivineandspiritualviewwasthatoftheschoolofHippocrates.InthefifthcenturyBC,Hippocratesrejectedtheideathatthediseasewascausedbyspirits.InhislandmarkworkOntheSacredDisease,heproposedthatepilepsywasnotdivineinoriginandinsteadwasamedicallytreatableproblemoriginatinginthebrain.[23][157]Heaccusedthoseofattributingasacredcausetothediseaseofspreadingignorancethroughabeliefinsuperstitiousmagic.[23]Hippocratesproposedthathereditywasimportantasacause,describedworseoutcomesifthediseasepresentsatanearlyage,andmadenoteofthephysicalcharacteristicsaswellasthesocialshameassociatedwithit.[23]Insteadofreferringtoitasthesacreddisease,heusedthetermgreatdisease,givingrisetothemoderntermgrandmal,usedfortonic–clonicseizures.[23]Despitehisworkdetailingthephysicaloriginsofthedisease,hisviewwasnotacceptedatthetime.[157]Evilspiritscontinuedtobeblameduntilatleastthe17thcentury.[157] InAncientRomepeopledidnoteatordrinkwiththesamepotteryasthatusedbysomeonewhowasaffected.[161]Peopleofthetimewouldspitontheirchestbelievingthatthiswouldkeeptheproblemfromaffectingthem.[161]AccordingtoApuleiusandotherancientphysicians,inordertodetectepilepsy,itwascommontolightapieceofgagates,whosesmokewouldtriggertheseizure.[162]Occasionallyaspinningpotter'swheelwasused,perhapsareferencetophotosensitiveepilepsy.[163] Inmostcultures,personswithepilepsyhavebeenstigmatized,shunned,orevenimprisoned.Aslateasinthesecondhalfofthe20thcentury,inTanzaniaandotherpartsofAfricaepilepsywasassociatedwithpossessionbyevilspirits,witchcraft,orpoisoningandwasbelievedbymanytobecontagious.[164]IntheSalpêtrière,thebirthplaceofmodernneurology,Jean-MartinCharcotfoundpeoplewithepilepsysidebysidewiththementallyill,thosewithchronicsyphilis,andthecriminallyinsane.[165]InancientRome,epilepsywasknownasthemorbuscomitialis('diseaseoftheassemblyhall')andwasseenasacursefromthegods.InnorthernItaly,epilepsywasoncetraditionallyknownasSaintValentine'smalady.[166] Inthemid-19thcentury,thefirsteffectiveanti-seizuremedication,bromide,wasintroduced.[117]Thefirstmoderntreatment,phenobarbital,wasdevelopedin1912,withphenytoincomingintousein1938.[167] Societyandculture[edit] Seealso:Listofpeoplewithepilepsy Stigma[edit] Stigmaiscommonlyexperienced,aroundtheworld,bythosewithepilepsy.[168]Itcanaffectpeopleeconomically,sociallyandculturally.[168]InIndiaandChina,epilepsymaybeusedasjustificationtodenymarriage.[30]Peopleinsomeareasstillbelievethosewithepilepsytobecursed.[19]InpartsofAfrica,suchasTanzaniaandUganda,epilepsyisclaimedtobeassociatedwithpossessionbyevilspirits,witchcraft,orpoisoningandisincorrectlybelievedbymanytobecontagious.[164][19]Before1971intheUnitedKingdom,epilepsywasconsideredgroundsfortheannulmentofmarriage.[30]Thestigmamayresultinsomepeoplewithepilepsydenyingthattheyhaveeverhadseizures.[49] Economics[edit] SeizuresresultindirecteconomiccostsofaboutonebilliondollarsintheUnitedStates.[20]EpilepsyresultedineconomiccostsinEuropeofaround15.5 billioneurosin2004.[25]InIndiaepilepsyisestimatedtoresultincostsofUS$1.7 billionor0.5%oftheGDP.[30]Itisthecauseofabout1%ofemergencydepartmentvisits(2%foremergencydepartmentsforchildren)intheUnitedStates.[169] Vehicles[edit] Seealso:Epilepsyanddriving Thosewithepilepsyareatabouttwicetheriskofbeinginvolvedinamotorvehicularcollisionandthusinmanyareasoftheworldarenotallowedtodriveoronlyabletodriveifcertainconditionsaremet.[22]Diagnosticdelayhasbeensuggestedtobeacauseofsomepotentiallyavoidablemotorvehiclecollisionssinceatleastonestudyshowedthatmostmotorvehicleaccidentsoccurredinthosewithundiagnosednonmotorseizuresasopposedtothosewithmotorseizuresatepilepsyonset.[170]Insomeplacesphysiciansarerequiredbylawtoreportifapersonhashadaseizuretothelicensingbodywhileinotherstherequirementisonlythattheyencouragethepersoninquestiontoreportithimself.[22]CountriesthatrequirephysicianreportingincludeSweden,Austria,DenmarkandSpain.[22]CountriesthatrequiretheindividualtoreportincludetheUKandNewZealand,andphysiciansmayreportiftheybelievetheindividualhasnotalready.[22]InCanada,theUnitedStatesandAustraliatherequirementsaroundreportingvarybyprovinceorstate.[22]Ifseizuresarewellcontrolledmostfeelallowingdrivingisreasonable.[171]Theamountoftimeapersonmustbefreefromseizuresbeforehecandrivevariesbycountry.[171]Manycountriesrequireonetothreeyearswithoutseizures.[171]IntheUnitedStatesthetimeneededwithoutaseizureisdeterminedbyeachstateandisbetweenthreemonthsandoneyear.[171] Thosewithepilepsyorseizuresaretypicallydeniedapilotlicense.[172]InCanadaifanindividualhashadnomorethanoneseizure,theymaybeconsideredafterfiveyearsforalimitedlicenseifallothertestingisnormal.[173]Thosewithfebrileseizuresanddrugrelatedseizuresmayalsobeconsidered.[173]IntheUnitedStates,theFederalAviationAdministrationdoesnotallowthosewithepilepsytogetacommercialpilotlicense.[174]Rarely,exceptionscanbemadeforpersonswhohavehadanisolatedseizureorfebrileseizuresandhaveremainedfreeofseizuresintoadulthoodwithoutmedication.[175]IntheUnitedKingdom,afullnationalprivatepilotlicenserequiresthesamestandardsasaprofessionaldriver'slicense.[176]Thisrequiresaperiodoftenyearswithoutseizureswhileoffmedications.[177]Thosewhodonotmeetthisrequirementmayacquirearestrictedlicenseiffreefromseizuresforfiveyears.[176] Supportorganizations[edit] Thereareorganizationsthatprovidesupportforpeopleandfamiliesaffectedbyepilepsy.TheOutoftheShadowscampaign,ajointeffortbytheWorldHealthOrganization,theInternationalLeagueAgainstEpilepsyandtheInternationalBureauforEpilepsy,provideshelpinternationally.[30]IntheUnitedStates,theEpilepsyFoundationisanationalorganizationthatworkstoincreasetheacceptanceofthosewiththedisorder,theirabilitytofunctioninsocietyandtopromoteresearchforacure.[178]TheEpilepsyFoundation,somehospitals,andsomeindividualsalsorunsupportgroupsintheUnitedStates.[179]InAustralia,theEpilepsyFoundationprovidessupport,deliverseducationandtrainingandfundsresearchforpeoplelivingwithepilepsy. InternationalEpilepsyDay(WorldEpilepsyDay)beganin2015andoccursonthesecondMondayinFebruary.[180][181] PurpleDay,adifferentworld-wideepilepsyawarenessdayforepilepsy,wasinitiatedbyanine-year-oldCanadiannamedCassidyMeganin2008,andiseveryyearonMarch26.[182] Research[edit] Seealso:Computationalmodelsinepilepsy Seizurepredictionandmodeling[edit] SeizurepredictionreferstoattemptstoforecastepilepticseizuresbasedontheEEGbeforetheyoccur.[183]Asof2011[update],noeffectivemechanismtopredictseizureshasbeendeveloped.[183]Kindling,whererepeatedexposurestoeventsthatcouldcauseseizureseventuallycausesseizuresmoreeasily,hasbeenusedtocreateanimalmodelsofepilepsy.[184]Oneofthehypothesespresentintheliteratureisbasedoninflammatorypathways.Studiessupportingthismechanismrevealedthatinflammatory,glycolipid,andoxidativefactorsarehigherinepilepsypatients,especiallythosewithgeneralizedepilepsy.[185] Potentialfuturetherapies[edit] Genetherapyisbeingstudiedinsometypesofepilepsy.[186]Medicationsthatalterimmunefunction,suchasintravenousimmunoglobulins,arepoorlysupportedbyevidence.[187]Noninvasivestereotacticradiosurgeryis,asof2012[update],beingcomparedtostandardsurgeryforcertaintypesofepilepsy.[188] Otheranimals[edit] Mainarticle:Epilepsyinanimals Epilepsyoccursinanumberofotheranimalsincludingdogsandcats;itisinfactthemostcommonbraindisorderindogs.[189]Itistypicallytreatedwithanticonvulsantssuchasphenobarbitalorbromideindogsandphenobarbitalincats.[189]Imepitoinisalsousedindogs.[190]Whilegeneralizedseizuresinhorsesarefairlyeasytodiagnose,itmaybemoredifficultinnon-generalizedseizuresandEEGsmaybeuseful.[191] References[edit] ^abcdefghijkl"EpilepsyFactsheet".WHO.February2016.Archivedfromtheoriginalon11March2016.Retrieved4March2016. ^abcdefghijklmnoHammerGD,McPheeSJ,eds.(2010)."7".Pathophysiologyofdisease :anintroductiontoclinicalmedicine(6th ed.).NewYork:McGraw-HillMedical.ISBN 978-0-07-162167-0. 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^MartindaleJL,GoldsteinJN,PallinDJ(February2011)."Emergencydepartmentseizureepidemiology".EmergencyMedicineClinicsofNorthAmerica.29(1):15–27.doi:10.1016/j.emc.2010.08.002.PMID 21109099. ^Pellinen,Jacob;Tafuro,Erica;Yang,Annie;Price,Dana;Friedman,Daniel;Holmes,Manisha;Barnard,Sarah;Detyniecki,Kamil;Hegde,Manu;Hixson,John;Haut,Sheryl(2020)."Focalnonmotorversusmotorseizures:Theimpactondiagnosticdelayinfocalepilepsy".Epilepsia.61(12):2643–2652.doi:10.1111/epi.16707.ISSN 1528-1167.PMID 33078409.S2CID 224811014. ^abcdEngelJ,PedleyTA,eds.(2008).Epilepsy :acomprehensivetextbook(2nd ed.).Philadelphia:WoltersKluwerHealth/LippincottWilliams&Wilkins.p. 2279.ISBN 978-0-7817-5777-5. ^BorR(2012).AviationMentalHealth:PsychologicalImplicationsforAirTransportation.AshgatePublishing.p. 148.ISBN 978-1-4094-8491-2. ^ab"SeizureDisorders".TransportCanada.GovernmentofCanada.Archivedfromtheoriginalon30December2013.Retrieved29December2013. 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^Aleem,MA(February2015)."Letter:WorldEpilepsyDay".Epilepsia.56(2):168.doi:10.1111/epi.12814.PMID 25404065.S2CID 11256074. ^Perucca,Emilio(February2015)."Commentary:WhyanInternationalEpilepsyDay?".Epilepsia.56(2):170–171.doi:10.1111/epi.12813.PMID 25403985. ^Carr,Flora(26March2018)."PeopleAreWearingPurpleTodayforEpilepsyAwarenessDay.Here'sWhatThatIs".Time.com.Retrieved18April2018. ^abCarneyPR,MyersS,GeyerJD(December2011)."Seizureprediction:methods".Epilepsy&Behavior.22Suppl1:S94–101.doi:10.1016/j.yebeh.2011.09.001.PMC 3233702.PMID 22078526. ^EngelJ,ed.(2008).Epilepsy:acomprehensivetextbook(2nd ed.).Philadelphia:WoltersKluwerHealth/LippincottWilliams&Wilkins.p. 426.ISBN 9780781757775. ^Kegler,Aline;Pascotini,EduardoT.;Caprara,AnaLetíciaFornari;Arend,Josi;Gabbi,Patricia;Duarte,MartaMMF.;Royes,LuizFernandoFreire;Fighera,MicheleRechia(February2021)."Relationshipbetweenseizuretype,metabolicprofile,andinflammatorymarkersinbloodsamplesofpatientswithepilepsy".EpilepticDisorders.23(1):74–84.doi:10.1684/epd.2021.1236.ISSN 1294-9361.PMID 33602662.S2CID 231962819. ^WalkerMC,SchorgeS,KullmannDM,WykesRC,HeeromaJH,MantoanL(September2013)."Genetherapyinstatusepilepticus"(PDF).Epilepsia.54Suppl6:43–5.doi:10.1111/epi.12275.PMID 24001071.S2CID 13942394. ^WalkerL,PirmohamedM,MarsonAG(June2013)."Immunomodulatoryinterventionsforfocalepilepsysyndromes".TheCochraneDatabaseofSystematicReviews.6(6):CD009945.doi:10.1002/14651858.CD009945.pub2.PMID 23803963. ^QuiggM,RolstonJ,BarbaroNM(January2012)."Radiosurgeryforepilepsy:clinicalexperienceandpotentialantiepilepticmechanisms".Epilepsia.53(1):7–15.doi:10.1111/j.1528-1167.2011.03339.x.PMC 3519388.PMID 22191545. ^abThomasWB(January2010)."Idiopathicepilepsyindogsandcats".TheVeterinaryClinicsofNorthAmerica.SmallAnimalPractice.40(1):161–79.doi:10.1016/j.cvsm.2009.09.004.PMID 19942062. ^RundfeldtC,LöscherW(January2014)."Thepharmacologyofimepitoin:thefirstpartialbenzodiazepinereceptoragonistdevelopedforthetreatmentofepilepsy".CNSDrugs.28(1):29–43.doi:10.1007/s40263-013-0129-z.PMID 24357084.S2CID 31627280. ^vanderReeM,WijnbergI(2012)."AreviewonepilepsyinthehorseandthepotentialofAmbulatoryEEGasadiagnostictool".TheVeterinaryQuarterly.32(3–4):159–67.doi:10.1080/01652176.2012.744496.PMID 23163553.S2CID 24726314. Furtherreading[edit] WorldHealthOrganization,DepartmentofMentalHealthandSubstanceAbuse,ProgrammeforNeurologicalDiseasesandNeuroscience;GlobalCampaignagainstEpilepsy;InternationalLeagueagainstEpilepsy(2005).Atlas,epilepsycareintheworld,2005(PDF).Geneva:ProgrammeforNeurologicalDiseasesandNeuroscience,DepartmentofMentalHealthandSubstanceAbuse,WorldHealthOrganization.ISBN 978-92-4-156303-1.{{citebook}}:CS1maint:multiplenames:authorslist(link) SchefferIE,BerkovicS,CapovillaG,ConnollyMB,FrenchJ,GuilhotoL,HirschE,JainS,MathernGW,MoshéSL,NordliDR,PeruccaE,TomsonT,WiebeS,ZhangYH,ZuberiSM(April2017)."ILAEclassificationoftheepilepsies:PositionpaperoftheILAECommissionforClassificationandTerminology".Epilepsia.58(4):512–521.doi:10.1111/epi.13709.PMC 5386840.PMID 28276062. Externallinks[edit] ClassificationDICD-10:G40-G41ICD-9-CM:345MeSH:D004827DiseasesDB:4366SNOMEDCT:84757009ExternalresourcesMedlinePlus:000694eMedicine:neuro/415 WikimediaCommonshasmediarelatedtoEpilepsy. WikiquotehasquotationsrelatedtoEpilepsy. EpilepsyatCurlie WorldHealthOrganizationfactsheet "EpilepsyBasics:AnOverviewforBehavioralHealthProviders".YouTube.EpilepsyFoundation.30May2019.Archivedfromtheoriginalon11December2021. "WhatToDoIfSomeoneHasASeizure-FirstAidTraining-StJohnAmbulance".YouTube.StJohnAmbulance.1February2017.Archivedfromtheoriginalon11December2021. vteDiseasesofthenervoussystem,primarilyCNSInflammationBrain Encephalitis Viralencephalitis Herpesviralencephalitis Limbicencephalitis Encephalitislethargica Cavernoussinusthrombosis Brainabscess Amoebic Brainandspinalcord Encephalomyelitis Acutedisseminated Meningitis Meningoencephalitis Brain/encephalopathyDegenerativeExtrapyramidalandmovementdisorders Basalgangliadisease Parkinsonism PD Postencephalitic NMS NBIA PKAN Tauopathy PSP Striatonigraldegeneration Hemiballismus HD OA Dyskinesia Dystonia Statusdystonicus Spasmodictorticollis Meige's Blepharospasm Athetosis Chorea Choreoathetosis Myoclonus Myoclonicepilepsy Akathisia Tremor Essentialtremor Intentiontremor Restlesslegs Stiff-person Dementia Tauopathy Alzheimer's Early-onset Primaryprogressiveaphasia Frontotemporaldementia/Frontotemporallobardegeneration Pick's Lewybodiesdementia Posteriorcorticalatrophy Vasculardementia Mitochondrialdisease Leighsyndrome Demyelinating Autoimmune Inflammatory Multiplesclerosis Formoredetailedcoverage,seeTemplate:DemyelinatingdiseasesofCNS Episodic/paroxysmalSeizuresandepilepsy Focal Generalised Statusepilepticus Formoredetailedcoverage,seeTemplate:Epilepsy Headache Migraine Cluster Tension Formoredetailedcoverage,seeTemplate:Headache Cerebrovascular TIA Stroke Formoredetailedcoverage,seeTemplate:Cerebrovasculardiseases Other Sleepdisorders Formoredetailedcoverage,seeTemplate:Sleep CSF Intracranialhypertension Hydrocephalus Normalpressurehydrocephalus Choroidplexuspapilloma Idiopathicintracranialhypertension Cerebraledema Intracranialhypotension Other Brainherniation Reyesyndrome Hepaticencephalopathy Toxicencephalopathy Hashimoto'sencephalopathy StaticEncephalopathy Both/eitherDegenerativeSA Friedreich'sataxia Ataxia–telangiectasia MND UMNonly: Primarylateralsclerosis Pseudobulbarpalsy Hereditaryspasticparaplegia LMNonly: Distalhereditarymotorneuronopathies Spinalmuscularatrophies SMA SMAX1 SMAX2 DSMA1 CongenitalDSMA Spinalmuscularatrophywithlowerextremitypredominance(SMALED) SMALED1 SMALED2A SMALED2B SMA-PCH SMA-PME Progressivemuscularatrophy Progressivebulbarpalsy Fazio–Londe Infantileprogressivebulbarpalsy both: Amyotrophiclateralsclerosis vteSeizuresandepilepsyBasics Seizuretypes Aura(warningsign) Postictalstate Epileptogenesis Neonatalseizure Epilepsyinchildren Management Anticonvulsants Investigations Electroencephalography Epileptologist Personalissues Epilepsyanddriving Epilepsyandemployment SeizuretypesFocal Seizures Simplepartial Complexpartial Gelasticseizure Epilepsy Temporallobeepilepsy Frontallobeepilepsy Rolandicepilepsy Nocturnalepilepsy Panayiotopoulossyndrome Vertiginousepilepsy Generalised Tonic–clonic Absenceseizure Atonicseizure Automatism Benignfamilialneonatalseizures Lennox–Gastautsyndrome Myoclonicastaticepilepsy Epilepticspasms Statusepilepticus Epilepsiapartialiscontinua Complexpartialstatusepilepticus Myoclonicepilepsy Progressivemyoclonusepilepsy Dentatorubral–pallidoluysianatrophy Unverricht–Lundborgdisease MERRFsyndrome Laforadisease Earlymyoclonicencephalopathy Juvenilemyoclonicepilepsy Non-epilepticseizure Febrileseizure Psychogenicnon-epilepticseizure Relateddisorders Suddenunexpecteddeathinepilepsy Todd'sparesis Landau–Kleffnersyndrome Epilepsyinanimals Organizations CitizensUnitedforResearchinEpilepsy(US) EpilepsyAction(UK) EpilepsyActionAustralia EpilepsyFoundation(US) EpilepsyOutlook(UK) EpilepsyResearchUK EpilepsySociety(UK) Authoritycontrol:Nationallibraries France(data) Ukraine Germany Israel UnitedStates CzechRepublic Croatia Sweden Retrievedfrom"https://en.wikipedia.org/w/index.php?title=Epilepsy&oldid=1096368638" Categories:EpilepsyDisorderscausingseizuresNeurologicaldisordersinchildrenHiddencategories:CS1errors:genericnameCS1:longvolumevalueCS1errors:missingperiodicalCS1maint:url-statusCS1maint:usesauthorsparameterCS1errors:missingtitleCS1errors:bareURLCS1errors:URLCS1maint:DOIinactiveasofFebruary2022ArticleswithshortdescriptionShortdescriptionisdifferentfromWikidataUsedmydatesfromJuly2020Articlescontainingpotentiallydatedstatementsfrom2020AllarticlescontainingpotentiallydatedstatementsArticlescontainingpotentiallydatedstatementsfrom2016Articlescontainingpotentiallydatedstatementsfrom2015Articlescontainingpotentiallydatedstatementsfrom2012Articlescontainingpotentiallydatedstatementsfrom2011CS1maint:multiplenames:authorslistCommonscategorylinkisonWikidataArticleswithCurlielinksArticleswithBNFidentifiersArticleswithEMUidentifiersArticleswithGNDidentifiersArticleswithJ9UidentifiersArticleswithLCCNidentifiersArticleswithNKCidentifiersArticleswithNSKidentifiersArticleswithSELIBRidentifiersGoodarticlesArticlescontainingvideoclipsWikipediamedicinearticlesreadytotranslate(full)Wikipedianeurologyarticlesreadytotranslate 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