11/17/2016

EpilepsyandSeizures:PracticeEssentials,Background,Pathophysiology

Thissiteisintendedforhealthcareprofessionals

EpilepsyandSeizures
Updated:Jul12,2016
Author:DavidYKo,MDChiefEditor:SelimRBenbadis,MDmore...

OVERVIEW

PracticeEssentials
Epilepsyisdefinedasabraindisordercharacterizedbyanenduringpredispositiontogenerate
epilepticseizuresandbytheneurobiologic,cognitive,psychological,andsocialconsequencesofthis
condition.[1]

Signsandsymptoms
Theclinicalsignsandsymptomsofseizuresdependonthelocationoftheepilepticdischargesinthe
cerebralcortexandtheextentandpatternofthepropagationoftheepilepticdischargeinthebrain.A
keyfeatureofepilepticseizuresistheirstereotypicnature.
Questionsthathelpclarifythetypeofseizureincludethefollowing:
Wasanywarningnotedbeforethespell?Ifso,whatkindofwarningoccurred?
Whatdidthepatientdoduringthespell?
Wasthepatientabletorelatetotheenvironmentduringthespelland/ordoesthepatienthave
recollectionofthespell?
Howdidthepatientfeelafterthespell?Howlongdidittakeforthepatienttogetbackto
baselinecondition?
Howlongdidthespelllast?
Howfrequentdothespellsoccur?
Areanyprecipitantsassociatedwiththespells?
Hasthepatientshownanyresponsetotherapyforthespells?
SeeClinicalPresentationformoredetail.

Diagnosis
Thediagnosisofepilepticseizuresismadebyanalyzingthepatient'sdetailedclinicalhistoryandby
performingancillarytestsforconfirmation.Physicalexaminationhelpsinthediagnosisofspecific
epilepticsyndromesthatcauseabnormalfindings,suchasdermatologicabnormalities(eg,patients
withintractablegeneralizedtonicclonicseizuresforyearsarelikelytohaveinjuriesrequiring
stitches).
Testing
Potentiallyusefullaboratorytestsforpatientswithsuspectedepilepticseizuresincludethefollowing:

http://emedicine.medscape.com/article/1184846overview

1/25

11/17/2016

EpilepsyandSeizures:PracticeEssentials,Background,Pathophysiology

Prolactinlevelsobtainedshortlyafteraseizuretoassesstheetiology(epilepticvsnonepileptic)
ofaspelllevelsaretypicallyelevated3or4foldandmorelikelytooccurwithgeneralized
tonicclonicseizuresthanwithotherseizuretypeshowever,theconsiderablevariabilityof
prolactinlevelshasprecludedtheirroutineclinicaluse
Serumlevelsofanticonvulsantagentstodeterminebaselinelevels,potentialtoxicity,lackof
efficacy,treatmentnoncompliance,and/orautoinductionorpharmacokineticchange
CSFexaminationinpatientswithobtundationorinpatientsinwhommeningitisorencephalitisis
suspected
Imagingstudies
Thefollowing2imagingstudiesmustbeperformedafteraseizure:
Neuroimagingevaluation(eg,MRI,CTscanning)
EEG
TheclinicaldiagnosiscanbeconfirmedbyabnormalitiesontheinterictalEEG,butthese
abnormalitiescouldbepresentinotherwisehealthyindividuals,andtheirabsencedoesnotexclude
thediagnosisofepilepsy.
VideoEEGmonitoringisthestandardtestforclassifyingthetypeofseizureorsyndromeorto
diagnosepseudoseizures(ie,toestablishadefinitivediagnosisofspellswithimpairmentof
consciousness).Thistechniqueisalsousedtocharacterizethetypeofseizureandepileptic
syndrometooptimizepharmacologictreatmentandforpresurgicalworkup.
SeeWorkupformoredetail.

Management
Pharmacotherapy
Thegoaloftreatmentistoachieveaseizurefreestatuswithoutadverseeffects.Monotherapyis
important,becauseitdecreasesthelikelihoodofadverseeffectsandavoidsdruginteractions.
Standardofcareforasingle,unprovokedseizureisavoidanceoftypicalprecipitants(eg,alcohol,
sleepdeprivation).Noanticonvulsantsarerecommendedunlessthepatienthasriskfactorsfor
recurrence.
Specialsituationsthatrequiretreatmentincludethefollowing:
Recurrentunprovokedseizures:Themainstayoftherapyisananticonvulsantifapatienthas
hadmorethan1seizure,administrationofananticonvulsantisrecommended
HavinganabnormalsleepdeprivedEEGthatincludesepileptiformabnormalitiesandfocal
slowing,diffusebackgroundslowing,andintermittentdiffuseintermixedslowing
Selectionofananticonvulsantmedicationdependsonanaccuratediagnosisoftheepileptic
syndrome.Althoughsomeanticonvulsants(eg,lamotrigine,topiramate,valproicacid,zonisamide)
havemultiplemechanismsofaction,andsome(eg,phenytoin,carbamazepine,ethosuximide)have
onlyoneknownmechanismofaction,anticonvulsantagentscanbedividedintolargegroupsbased
ontheirmechanisms,asfollows:
Blockersofrepetitiveactivationofthesodiumchannel:Phenytoin,carbamazepine,
oxcarbazepine,lamotrigine,topiramate
Enhancerofslowinactivationofthesodiumchannel:Lacosamide,rufinamide
http://emedicine.medscape.com/article/1184846overview

2/25

11/17/2016

EpilepsyandSeizures:PracticeEssentials,Background,Pathophysiology

Gammaaminobutyricacid(GABA)Areceptorenhancers:Phenobarbital,benzodiazepines,
clobazam
NMDAreceptorblockers:Felbamate
AMPAreceptorblockers:Perampanel,topiramate
Tcalciumchannelblockers:Ethosuximide,valproate
NandLcalciumchannelblockers:Lamotrigine,topiramate,zonisamide,valproate
Hcurrentmodulators:Gabapentin,lamotrigine
Blockersofuniquebindingsites:Gabapentin,levetiracetam
Carbonicanhydraseinhibitors:Topiramate,zonisamide
Neuronalpotassiumchannel(KCNQ[Kv7])opener:Ezogabine
Nonpharmacologictherapy
Thefollowingare2nonpharmacologicmethodsinmanagingpatientswithseizures:
Aketogenicdiet
Vagalnervestimulation
Surgicaloptions
The2majorkindsofbrainsurgeryforepilepsyarepalliativeandpotentiallycurative.Theuseofa
vagalnervestimulator(VNS)forpalliativetherapyinpatientswithintractableatonicseizureshas
reducedtheneedforanteriorcallosotomy.Lobectomyandlesionectomyareamongseveralpossible
curativesurgeries.
SeeTreatmentandMedicationformoredetail.

Background
Epilepticseizuresareonlyonemanifestationofneurologicormetabolicdiseases.Epilepticseizures
havemanycauses,includingageneticpredispositionforcertaintypesofseizures,headtrauma,
stroke,braintumors,alcoholordrugwithdrawal,repeatedepisodesofmetabolicinsults,suchas
hypoglycemia,andotherconditions.Epilepsyisamedicaldisordermarkedbyrecurrent,unprovoked
seizures.Therefore,repeatedseizureswithanidentifiedprovocation(eg,alcoholwithdrawal)donot
constituteepilepsy.
AsproposedbytheInternationalLeagueAgainstEpilepsy(ILAE)andtheInternationalBureaufor
Epilepsy(IBE)in2005,epilepsyisdefinedasabraindisordercharacterizedbyanenduring
predispositiontogenerateepilepticseizuresandbytheneurobiologic,cognitive,psychological,and
socialconsequencesofthiscondition.[1]
Traditionally,thediagnosisofepilepsyrequirestheoccurrenceofatleast2unprovokedseizures.
Somecliniciansalsodiagnoseepilepsywhen1unprovokedseizureoccursinthesettingofa
predisposingcause,suchasafocalcorticalinjury,orageneralizedinterictaldischargeoccursthat
suggestsapersistentgeneticpredisposition.(SeeClinicalPresentation.)
Seizuresarethemanifestationofabnormalhypersynchronousorhyperexcitabledischargesofcortical
neurons.Theclinicalsignsorsymptomsofseizuresdependonthelocationoftheepilepticdischarges
inthecerebralcortexandtheextentandpatternofthepropagationoftheepilepticdischargeinthe
brain.Thus,seizuresymptomsarehighlyvariable,butformostpatientswith1focus,thesymptoms
areusuallyverystereotypic.
Itshouldnotbesurprisingthatseizuresareacommon,nonspecificmanifestationofneurologicinjury
anddisease,becausethemainfunctionofthebrainisthetransmissionofelectricalimpulses.The
http://emedicine.medscape.com/article/1184846overview

3/25

11/17/2016

EpilepsyandSeizures:PracticeEssentials,Background,Pathophysiology

lifetimelikelihoodofexperiencingatleast1epilepticseizureisabout9%,andthelifetimelikelihoodof
receivingadiagnosisofepilepsyisalmost3%.However,theprevalenceofactiveepilepsyisonly
about0.8%.(SeeEpidemiology.)
Thisarticlereviewstheclassifications,pathophysiology,clinicalmanifestations,andtreatmentof
epilepticseizuresandsomecommonepilepticsyndromes.(SeePathophysiology,Presentation,DDx,
andTreatment.)
Formoreinformationregardingseizuretypesandotherconditions,seethefollowingtopics:
AbsenceSeizures
ComplexPartialSeizures
GeneralizedTonicClonicSeizures
PsychogenicNonepilepticSeizures
PediatricFirstSeizure
EpilepsiaPartialisContinua
StatusEpilepticus
Preeclampsia
Eclampsia
Seethefollowingarticlesformoreinformationregardingepilepticsyndromesandepilepsytreatment:
BenignChildhoodEpilepsy
BenignNeonatalConvulsions
EEGinCommonEpilepsySyndromes
PediatricFebrileSeizures
NeonatalSeizures
FrontalLobeEpilepsy
TemporalLobeEpilepsy
JuvenileMyoclonicEpilepsy
LennoxGastautSyndrome
PosttraumaticEpilepsy
ReflexEpilepsy
VagusNerveStimulation
Women'sHealthandEpilepsy
PartialEpilepsies
PediatricStatusEpilepticus
MyoclonicEpilepsyBeginninginInfancyorEarlyChildhood

Historicalinformation
Epilepticseizureshavebeenrecognizedformillennia.Oneoftheearliestdescriptionsofasecondary
generalizedtonicclonicseizurewasrecordedover3000yearsagoinMesopotamia.Theseizurewas
attributedtothegodofthemoon.Epilepticseizuresweredescribedinotherancientcultures,
includingthoseofChina,Egypt,andIndia.AnancientEgyptianpapyrusdescribedaseizureinaman
whohadpreviousheadtrauma.
Hippocrateswrotethefirstbookaboutepilepsyalmost2500yearsago.Herejectedideasregarding
thedivineetiologyofepilepsyandconcludedthatthecausewasexcessivephlegmleadingto
abnormalbrainconsistency.Hippocraticteachingswereforgotten,anddivineetiologiesagain
dominatedbeliefsaboutepilepticseizuresduringmedievaltimes.
Evenattheturnofthe19thcentury,excessivemasturbationwasconsideredacauseofepilepsy.This
hypothesisiscreditedasleadingtotheuseofthefirsteffectiveanticonvulsant(ie,bromides).
http://emedicine.medscape.com/article/1184846overview

4/25

11/17/2016

EpilepsyandSeizures:PracticeEssentials,Background,Pathophysiology

ModerninvestigationoftheetiologyofepilepsybeganwiththeworkofFritsch,Hitzig,Ferrier,and
Catoninthe1870s.Theseresearchersrecordedandevokedepilepticseizuresinthecerebralcortex
ofanimals.In1929,Bergerdiscoveredthatelectricalbrainsignalscouldberecordedfromthehuman
headbyusingscalpelectrodesthisdiscoveryledtotheuseofelectroencephalography(EEG)to
studyandclassifyepilepticseizures.
Gibbs,Lennox,Penfield,andJasperfurtheradvancedtheunderstandingofepilepsyanddeveloped
thesystemofthe2majorclassesofepilepticseizurescurrentlyused:localizationrelatedsyndromes
andgeneralizedonsetsyndromes.Anexcellenthistoricalreviewofseizuresandepilepsy,writtenby
E.Goldensohn,waspublishedinthejournalEpilepsiatocommemoratethe50thanniversaryofthe
creationoftheAmericanEpilepsySocietyin1997.Adecadelater,anotherreviewinEpilepsia
discussedthefoundationofthisprofessionalsociety.[4]

Pathophysiology
Seizuresareparoxysmalmanifestationsoftheelectricalpropertiesofthecerebralcortex.Aseizure
resultswhenasuddenimbalanceoccursbetweentheexcitatoryandinhibitoryforceswithinthe
networkofcorticalneuronsinfavorofasuddenonsetnetexcitation.
Thebrainisinvolvedinnearlyeverybodilyfunction,includingthehighercorticalfunctions.Ifthe
affectedcorticalnetworkisinthevisualcortex,theclinicalmanifestationsarevisualphenomena.
Otheraffectedareasofprimarycortexgiverisetosensory,gustatory,ormotormanifestations.The
psychicphenomenonofdjvuoccurswhenthetemporallobeisinvolved.
Thepathophysiologyoffocalonsetseizuresdiffersfromthemechanismsunderlyinggeneralized
onsetseizures.Overall,cellularexcitabilityisincreased,butthemechanismsofsynchronization
appeartosubstantiallydifferbetweenthese2typesofseizureandarethereforediscussedseparately.
Forareview,seetheepilepsybookofRho,Sankar,andCavazos.[5]Foramorerecentreview,see
KramerandCash.[6]

Pathophysiologyoffocalseizures
Theelectroencephalographic(EEG)hallmarkoffocalonsetseizuresisthefocalinterictalepileptiform
spikeorsharpwave.Thecellularneurophysiologiccorrelateofaninterictalfocalepileptiform
dischargeinsinglecorticalneuronsistheparoxysmaldepolarizationshift(PDS).
ThePDSischaracterizedbyaprolongedcalciumdependentdepolarizationthatresultsinmultiple
sodiummediatedactionpotentialsduringthedepolarizationphase,anditisfollowedbyaprominent
afterhyperpolarization,whichisahyperpolarizedmembranepotentialbeyondthebaselineresting
potential.Calciumdependentpotassiumchannelsmostlymediatetheafterhyperpolarizationphase.
WhenmultipleneuronsfirePDSsinasynchronousmanner,theextracellularfieldrecordingshowsan
interictalspike.
Ifthenumberofdischargingneuronsismorethanseveralmillion,theycanusuallyberecordedwith
scalpEEGelectrodes.Calculationsshowthattheinterictalspikesneedtospreadtoabout6cm2of
cerebralcortexbeforetheycanbedetectedwithscalpelectrodes.
Severalfactorsmaybeassociatedwiththetransitionfromaninterictalspiketoanepilepticseizure.
Thespikehastorecruitmoreneuraltissuetobecomeaseizure.Whenanyofthemechanismsthat
underlieanacuteseizurebecomesapermanentalteration,thepersonpresumablydevelopsa
propensityforrecurrentseizures(ie,epilepsy).

http://emedicine.medscape.com/article/1184846overview

5/25

11/17/2016

EpilepsyandSeizures:PracticeEssentials,Background,Pathophysiology

Thefollowingmechanisms(discussedbelow)maycoexistindifferentcombinationstocausefocal
onsetseizures:
Decreasedinhibition
Defectiveactivationofgammaaminobutyricacid(GABA)neurons
Increasedactivation
Ifthemechanismsleadingtoanetincreasedexcitabilitybecomepermanentalterations,patientsmay
developpharmacologicallyintractablefocalonsetepilepsy.
Currentlyavailablemedicationswerescreenedusingacutemodelsoffocalonsetorgeneralized
onsetconvulsions.Inclinicaluse,theseagentsaremosteffectiveatblockingthepropagationofa
seizure(ie,spreadfromtheepilepticfocustosecondarygeneralizedtonicclonicseizures).Further
understandingofthemechanismsthatpermanentlyincreasenetworkexcitabilitymayleadto
developmentoftrueantiepilepticdrugsthatalterthenaturalhistoryofepilepsy.

Decreasedinhibition
ThereleaseofGABAfromtheinterneuronterminalinhibitsthepostsynapticneuronbymeansof2
mechanisms:(1)directinductionofaninhibitorypostsynapticpotential(IPSP),whichaGABAA
chloridecurrenttypicallymediates,and(2)indirectinhibitionofthereleaseofexcitatory
neurotransmitterinthepresynapticafferentprojection,typicallywithaGABABpotassiumcurrent.
Alterationsormutationsinthedifferentchlorideorpotassiumchannelsubunitsorinthemolecules
thatregulatetheirfunctionmayaffecttheseizurethresholdorthepropensityforrecurrentseizures.
Mechanismsleadingtodecreasedinhibitionincludethefollowing:
DefectiveGABAAinhibition
DefectiveGABABinhibition
DefectiveactivationofGABAneurons
Defectiveintracellularbufferingofcalcium
NormalGABAAinhibitoryfunction
GABAisthemaininhibitoryneurotransmitterinthebrain,anditbindsprimarilyto2majorclassesof
receptors:GABAAandGABAB.GABAAreceptorsarecoupledtochloride(negativeanion)
channels,andtheyareoneofthemaintargetsmodulatedbytheanticonvulsantagentsthatare
currentlyinclinicaluse.
Thereversalpotentialofchlorideisaboutnegative70mV.Thecontributionofchloridechannels
duringrestingpotentialinneuronsisminimal,becausethetypicalrestingpotentialisnear70mV,and
thusthereisnosignificantelectromotiveforcefornetchlorideflux.However,chloridecurrents
becomemoreimportantatmoredepolarizedmembranepotentials.
Thesechannelsmakeitdifficulttoachievethethresholdmembranepotentialnecessaryforanaction
potential.Theinfluenceofchloridecurrentsontheneuronalmembranepotentialincreasesasthe
neuronbecomesmoredepolarizedbythesummationoftheexcitatorypostsynapticpotentials
(EPSPs).Inthismanner,thechloridecurrentsbecomeanotherforcethatmustbeovercometofirean
actionpotential,decreasingexcitability.
PropertiesofthechloridechannelsassociatedwiththeGABAAreceptorareoftenclinically
modulatedbyusingbenzodiazepines(eg,diazepam,lorazepam,clonazepam),barbiturates(eg,
phenobarbital,pentobarbital),ortopiramate.Benzodiazepinesincreasethefrequencyofopeningsof
chloridechannels,whereasbarbituratesincreasethedurationofopeningsofthesechannels.
http://emedicine.medscape.com/article/1184846overview

6/25

11/17/2016

EpilepsyandSeizures:PracticeEssentials,Background,Pathophysiology

Topiramatealsoincreasesthefrequencyofchannelopenings,butitbindstoasitedifferentfromthe
benzodiazepinereceptorsite.
Alterationsinthenormalstateofthechloridechannelsmayincreasethemembranepermeabilityand
conductanceofchlorideions.Intheend,thebehaviorofallindividualchloridechannelssumupto
formalargechloridemediatedhyperpolarizingcurrentthatcounterbalancesthedepolarizingcurrents
createdbythesummationofEPSPsinducedbyactivationoftheexcitatoryinput.
TheEPSPsarethemainformofcommunicationbetweenneurons,andthereleaseoftheexcitatory
aminoacidglutamatefromthepresynapticelementmediatesEPSPs.Threemainreceptorsmediate
theeffectofglutamateinthepostsynapticneuron:NmethylDasparticacid(NMDA),alphaamino3
hydroxy5methyl4isoxazolepropionicacid(AMPA)/kainate,andmetabotropic.Thesearecoupledby
meansofdifferentmechanismstoseveraldepolarizingchannels.
IPSPstempertheeffectsofEPSPs.IPSPsaremediatedmainlybythereleaseofGABAinthe
synapticcleftwithpostsynapticactivationofGABAAreceptors.
Allchannelsinthenervoussystemaresubjecttomodulationbyseveralmechanisms,suchas
phosphorylationand,possibly,achangeinthetridimensionalconformationofaproteininthechannel.
Thechloridechannelhasseveralphosphorylationsites,oneofwhichtopiramateappearsto
modulate.Phosphorylationofthischannelinducesachangeinnormalelectrophysiologicbehavior,
withanincreasedfrequencyofchannelopeningsbutforonlycertainchloridechannels.
Eachchannelhasamultimericstructurewithseveralsubunitsofdifferenttypes.Chloridechannels
arenoexceptiontheyhaveapentamericstructure.Thesubunitsaremadeupofmolecularlyrelated
butdifferentproteins.
TheheterogeneityofelectrophysiologicresponsesofdifferentGABAAreceptorsresultsfromdifferent
combinationsofthesubunits.Inmammals,atleast6alphasubunitsand3betaandgammasubunits
existfortheGABAAreceptorcomplex.AcompleteGABAAreceptorcomplex(which,inthiscase,is
thechloridechannelitself)isformedfrom1gamma,2alpha,and2betasubunits.Thenumberof
possiblecombinationsoftheknownsubunitsisalmost1000,butinpractice,onlyabout20ofthese
combinationshavebeenfoundinthenormalmammalianbrain.
DefectiveGABAAinhibition
SomeepilepsiesmayinvolvemutationsorlackofexpressionofthedifferentGABAAreceptor
complexsubunits,themoleculesthatgoverntheirassembly,orthemoleculesthatmodulatetheir
electricalproperties.Forexample,hippocampalpyramidalneuronsmaynotbeabletoassemble
alpha5beta3gamma3receptorsbecauseofdeletionofchromosome15(ie,Angelmansyndrome).
ChangesinthedistributionofsubunitsoftheGABAAreceptorcomplexhavebeendemonstratedin
severalanimalmodelsoffocalonsetepilepsy,suchastheelectricalkindling,chemicalkindling,and
pilocarpinemodels.Inthepilocarpinemodel,decreasedconcentrationsofmRNAforthealpha5
subunitofthesurvivinginterneuronswereobservedintheCA1regionoftherathippocampus.[7]
DefectiveGABABinhibition
TheGABABreceptoriscoupledtopotassiumchannels,formingacurrentthathasarelativelylong
durationofactioncomparedwiththechloridecurrentevokedbyactivationoftheGABAAreceptor.
Becauseofthelongdurationofaction,alterationsintheGABABreceptorarethoughttopossiblyplay
amajorroleinthetransitionbetweentheinterictalabnormalityandanictalevent(ie,focalonset
seizure).ThemolecularstructureoftheGABABreceptorcomplexconsistsof2subunitswith7
transmembranedomainseach.
http://emedicine.medscape.com/article/1184846overview

7/25

11/17/2016

EpilepsyandSeizures:PracticeEssentials,Background,Pathophysiology

Gproteins,asecondmessengersystem,mediatecouplingtothepotassiumchannel,explainingthe
latencyandlongdurationoftheresponse.Inmanycases,GABABreceptorsarelocatedinthe
presynapticelementofanexcitatoryprojection.

DefectiveactivationofGABAneurons
GABAneuronsareactivatedbymeansoffeedforwardandfeedbackprojectionsfromexcitatory
neurons.These2typesofinhibitioninaneuronalnetworkaredefinedonthebasisofthetimeof
activationoftheGABAergicneuronrelativetothatoftheprincipalneuronaloutputofthenetwork,as
seenwiththehippocampalpyramidalCA1cell.
Infeedforwardinhibition,GABAergiccellsreceiveacollateralprojectionfromthemainafferent
projectionthatactivatestheCA1neurons,namely,theSchaffercollateralaxonsfromtheCA3
pyramidalneurons.ThisfeedforwardprojectionactivatesthesomaofGABAergicneuronsbeforeor
simultaneouslywithactivationoftheapicaldendritesoftheCA1pyramidalneurons.
ActivationoftheGABAergicneuronsresultsinanIPSPthatinhibitsthesomaoraxonhillockofthe
CA1pyramidalneuronsalmostsimultaneouslywiththepassivepropagationoftheexcitatorypotential
(ie,EPSP)fromtheapicaldendritestotheaxonhillock.Thefeedforwardprojectionthusprimesthe
inhibitorysysteminamannerthatallowsittoinhibit,inatimelyfashion,thepyramidalcell's
depolarizationandfiringofanactionpotential.
FeedbackinhibitionisanothersystemthatallowsGABAergiccellstocontrolrepetitivefiringin
principalneurons,suchaspyramidalcells,andtoinhibitthesurroundingpyramidalcells.Recurrent
collateralsfromthepyramidalneuronsactivatetheGABAergicneuronsafterthepyramidalneurons
fireanactionpotential.
Experimentalevidencehasindicatedthatsomeotherkindofinterneuronmaybeagatebetweenthe
principalneuronsandtheGABAergicneurons.Inthedentategyrus,themossycellsofthehilar
polymorphicregionappeartogateinhibitorytoneandactivateGABAergicneurons.Themossycells
receivebothfeedbackandfeedforwardactivation,whichtheyconveytotheGABAergicneurons.
Incertaincircumstances,themossycellsappearhighlyvulnerabletoseizurerelatedneuronalloss.
Aftersomeofthemossycellsarelost,activationofGABAergicneuronsisimpaired.[8]
Synapticreorganizationisaformofbrainplasticityinducedbyneuronalloss,perhapstriggeredbythe
lossofthesynapticconnectionsofthedyingneuron,aprocesscalleddeafferentation.Formationof
newsproutedcircuitsincludesexcitatoryandinhibitorycells,andbothformsofsproutinghavebeen
demonstratedinmanyanimalmodelsoffocalonsetepilepsyandinhumanswithintractabletemporal
lobeepilepsy.
Mostoftheinitialattemptsofhippocampalsproutingarelikelytobeattemptstorestoreinhibition.As
theepilepsyprogresses,however,theoverwhelmingnumberofsproutedsynapticcontactsoccurs
withexcitatorytargets,creatingrecurrentexcitatorycircuitriesthatpermanentlyalterthebalance
betweenexcitatoryandinhibitorytoneinthehippocampalnetwork.
Defectiveintracellularbufferingofcalcium
Inrodents,recurrentseizuresinducedbyavarietyofmethodsresultinapatternofinterneuronlossin
thehilarpolymorphicregion,withstrikinglossoftheneuronsthatlackthecalciumbindingproteins
parvalbuminandcalbindin.Inrathippocampalsections,theseinterneuronsdemonstratea
progressiveinabilitytomaintainahyperpolarizedrestingmembranepotentialeventually,the
interneuronsdie.
http://emedicine.medscape.com/article/1184846overview

8/25

11/17/2016

EpilepsyandSeizures:PracticeEssentials,Background,Pathophysiology

Inanexperiment,researchersusedmicroelectrodescontainingthecalciumchelatorBAPTAand
demonstratedreversalofthedeteriorationinthemembranepotentialasthecalciumchelatorwas
allowedtodiffuseintheinterneuron.[9]Thesefindingsshowedthecriticalroleofadequate
concentrationsofcalciumbindingproteinsforneuronalsurvivalinsettingswithsustainedrisesof
intracellularcalcium,suchasinstatusepilepticusandotherbraininsults.Thismechanismmay
contributetomedicalintractabilityinsomeepilepsypatients.
Thevulnerabilityofinterneuronstohypoxiaandotherinsultsalsocorrelatestotherelativepresence
ofthesecalciumbindingproteins.Theprematurelossofinterneuronsaltersinhibitorycontroloverthe
localneuronalnetworkinfavorofnetexcitation.Thiseffectmayexplain,forexample,why2patients
whohaveasimilarevent(ie,simplefebrileconvulsion)mayhaveremarkablydissimilaroutcomes
thatis,onemayhavecompletelynormaldevelopment,andtheothermayhaveintractablefocalonset
epilepsyafterafewyears.

Increasedactivation
Mechanismsleadingtoincreasedexcitationincludethefollowing:
IncreasedactivationofNMDAreceptors
Increasedsynchronybetweenneuronsduetoephapticinteractions
Increasedsynchronyand/oractivationduetorecurrentexcitatorycollaterals
IncreasedactivationofNMDAreceptors
Glutamateisthemajorexcitatoryneurotransmitterinthebrain.Thereleaseofglutamatecausesan
EPSPinthepostsynapticneuronbyactivatingtheglutaminergicreceptorsAMPA/kainateandNMDA
andthemetabotropicreceptor.
Fastneurotransmissionisachievedwiththeactivationofthefirst2typesofreceptors.The
metabotropicreceptoralterscellularexcitabilitybymeansofasecondmessengersystemwithlater
onsetbutaprolongedduration.Themajorfunctionaldifferencebetweenthe2fastreceptorsisthat
theAMPA/kainatereceptoropenschannelsthatprimarilyallowthepassageofmonovalentcations(ie,
sodiumandpotassium),whereastheNMDAtypeiscoupledtochannelsthatalsoallowpassageof
divalentcations(ie,calcium).
Calciumisacatalystformanyintracellularreactionsthatleadtochangesinphosphorylationandgene
expression.Thus,itisinitselfasecondmessengersystem.NMDAreceptorsaregenerallyassumed
tobeassociatedwithlearningandmemory.TheactivationofNMDAreceptorsisincreasedinseveral
animalmodelsofepilepsy,suchaskindling,kainicacid,pilocarpine,andotherfocalonsetepilepsy
models.
Somepatientswithepilepsymayhaveaninheritedpredispositionforfastorlonglastingactivationof
NMDAchannelsthatalterstheirseizurethreshold.Otherpossiblealterationsincludetheabilityof
intracellularproteinstobuffercalcium,increasingthevulnerabilityofneuronstoanykindofinjurythat
otherwisewouldnotresultinneuronaldeath.
Increasedsynchronybetweenneuronscausedbyephapticinteractions
Electricalfieldscreatedbysynchronousactivationofpyramidalneuronsinlaminarstructures,suchas
thehippocampus,mayincreasefurthertheexcitabilityofneighboringneuronsbynonsynaptic(ie,
ephaptic)interactions.Changesinextracellularionicconcentrationsofpotassiumandcalciumare
anotherpossiblenonsynapticinteraction,asisincreasedcouplingofneuronsduetopermanent
increasesinthefunctionalavailabilityofgapjunctions.Thislastmaybeamechanismthat
predisposestoseizuresorstatusepilepticus.
http://emedicine.medscape.com/article/1184846overview

9/25

11/17/2016

EpilepsyandSeizures:PracticeEssentials,Background,Pathophysiology

Increasedsynchronyand/oractivationfromrecurrentexcitatorycollaterals
Neuropathologicstudiesofpatientswithintractablefocalonsetepilepsyhaverevealedfrequent
abnormalitiesinthelimbicsystem,particularlyinthehippocampalformation.Acommonlesionis
hippocampalsclerosis,whichconsistsofapatternofgliosisandneuronallossprimarilyaffectingthe
hilarpolymorphicregionandtheCA1pyramidalregion.Thesechangesareassociatedwithrelative
sparingoftheCA2pyramidalregionandanintermediateseverityofthelesionintheCA3pyramidal
regionanddentategranuleneurons.
Prominenthippocampalsclerosisisfoundinabouttwothirdsofpatientswithintractabletemporallobe
epilepsy.Animalmodelsofstatusepilepticushavereproducedthispatternofinjuryhowever,animals
withmorethan100briefconvulsionsinducedbykindlingseizureshadasimilarpattern,suggesting
thatrepeatedtemporallobeseizuresmaycontributetothedevelopmentofhippocampalsclerosis.[10]
Moresubtleandapparentlymorecommonthanoverthippocampalsclerosisismossyfibersprouting.
[11] Themossyfibersaretheaxonsofthedentategranuleneurons,andtheytypicallyprojectintothe
hilarpolymorphicregionandtowardtheCA3pyramidalneurons.Astheneuronsinthehilar
polymorphicregionareprogressivelylost,theirsynapticprojectionstothedentategranuleneurons
degenerate.
Denervationresultingfromlossofthehilarprojectioninducessproutingoftheneighboringmossyfiber
axons.Thenetconsequenceofthisphenomenonistheformationofrecurrentexcitatorycollaterals,
whichincreasethenetexcitatorydriveofdentategranuleneurons.
Recurrentexcitatorycollateralshavebeendemonstratedinhumantemporallobeepilepsyandinall
animalmodelsofintractablefocalonsetepilepsy.Theeffectofmossyfibersproutingonthe
hippocampalcircuitryhasbeenconfirmedincomputerizedmodelsoftheepileptichippocampus.
Otherneuralpathwaysinthehippocampus,suchastheprojectionfromCA1tothesubiculum,have
beenshowntoalsoremodelintheepilepticbrain.
Forfurtherreading,areviewbyMastrangeloandLeuzziaddresseshowgenesleadtoanepileptic
phenotypefortheearlyageencephalopathies.[12]

Pathophysiologyofgeneralizedseizures
Thebestunderstoodexampleofthepathophysiologicmechanismsofgeneralizedseizuresisthe
thalamocorticalinteractionthatmayunderlietypicalabsenceseizures.Thethalamocorticalcircuithas
normaloscillatoryrhythms,withperiodsofrelativelyincreasedexcitationandperiodsofrelatively
increasedinhibition.Itgeneratestheoscillationsobservedinsleepspindles.Thethalamocortical
circuitryincludesthepyramidalneuronsoftheneocortex,thethalamicrelayneurons,andtheneurons
inthenucleusreticularisofthethalamus(NRT).
Alteredthalamocorticalrhythmsmayresultinprimarygeneralizedonsetseizures.Thethalamicrelay
neuronsreceiveascendinginputsfromthespinalcordandprojecttotheneocorticalpyramidal
neurons.Cholinergicpathwaysfromtheforebrainandtheascendingserotonergic,noradrenergic,and
cholinergicbrainstempathwaysprominentlyregulatethiscircuitry.[13]
Thethalamicrelayneuronscanhaveoscillationsintherestingmembranepotential,whichincreases
theprobabilityofsynchronousactivationoftheneocorticalpyramidalneuronduringdepolarization
andwhichsignificantlylowerstheprobabilityofneocorticalactivationduringrelativehyperpolarization.
Thekeytotheseoscillationsisthetransientlowthresholdcalciumchannel,alsoknownasTcalcium
current.

http://emedicine.medscape.com/article/1184846overview

10/25

11/17/2016

EpilepsyandSeizures:PracticeEssentials,Background,Pathophysiology

Inanimalstudies,inhibitoryinputsfromtheNRTcontroltheactivityofthalamicrelayneurons.NRT
neuronsareinhibitoryandcontainGABAastheirmainneurotransmitter.Theyregulatetheactivation
oftheTcalciumchannelsinthalamicrelayneurons,becausethosechannelsmustbedeinactivated
toopentransitorily.
Tcalciumchannelshave3functionalstates:open,closed,andinactivated.Calciumentersthecells
whentheTcalciumchannelsareopen.Immediatelyafterclosing,thechannelcannotopenagainuntil
itreachesastateofinactivation.
ThethalamicrelayneuronshaveGABABreceptorsinthecellbodyandreceivetonicactivationby
GABAreleasedfromtheNRTprojectiontothethalamicrelayneuron.Theresultisahyperpolarization
thatswitchestheTcalciumchannelsawayfromtheinactivestateintotheclosedstate,whichisready
foractivationwhenneeded.Theswitchtoclosedstatepermitsthesynchronousopeningofalarge
populationoftheTcalciumchannelsevery100millisecondsorso,creatingtheoscillationsobserved
intheEEGrecordingsfromthecerebralcortex.
Findingsinseveralanimalmodelsofabsenceseizures,suchaslethargicmice,havedemonstrated
thatGABABreceptorantagonistssuppressabsenceseizures,whereasGABABagonistsworsen
theseseizures.[14]Anticonvulsantsthatpreventabsenceseizures,suchasvalproicacidand
ethosuximide,suppresstheTcalciumcurrent,blockingitschannels.
AclinicalproblemisthatsomeanticonvulsantsthatincreaseGABAlevels(eg,tiagabine,vigabatrin)
areassociatedwithanexacerbationofabsenceseizures.AnincreasedGABAlevelisthoughtto
increasethedegreeofsynchronizationofthethalamocorticalcircuitandtoenlargethepoolofT
calciumchannelsavailableforactivation.

Etiology
Inasubstantialnumberofcases,thecauseofepilepsyremainsunknown.Identifiedcausestendto
varywithpatientage.Inheritedsyndromes,congenitalbrainmalformations,infection,andhead
traumaareleadingcausesinchildren.Headtraumaisthemostcommonknowncauseinyoung
adults.Strokes,tumors,andheadtraumabecomemorefrequentinmiddleage,withstrokebecoming
themostcommoncauseintheelderly,alongwithAlzheimerdiseaseandotherdegenerative
conditions.
Thegeneticcontributiontoseizuredisordersisnotcompletelyunderstood,butatthepresenttime,
hundredsofgeneshavebeenshowntocauseorpredisposeindividualstoseizuredisordersof
varioustypes.Seizuresarefrequentlyseeninpatientsthatarereferredtoageneticsclinic.Insome
cases,theseizuresareisolatedinanotherwisenormalchild.Inmanycases,seizuresarepartofa
syndromethatmayalsoincludeintellectualdisability,specificbrainmalformations,orahostof
multiplecongenitalanomalies.
Forthesakeofbrevityandclarity,geneticdisordersthatcancauseseizureswillbebrokenintothe
followingcategories:
Syndromesinwhichseizuresarecommon
Chromosomaldeletionorduplicationsyndromesthatcauseseizures
Metabolicdiseases
Mitochondrialdiseases
Seizuredisorderscausedbysinglegenemutations

Geneticsyndromeswithseizuredisorder
http://emedicine.medscape.com/article/1184846overview

11/25

11/17/2016

EpilepsyandSeizures:PracticeEssentials,Background,Pathophysiology

Anumberofgeneticsyndromesareknowntocausesseizurestherefore,thislistisnotmeanttobe
authoritative.However,anumberofmorecommonsyndromesshouldbeconsideredinthepatient
whopresentswithseizuresandotherfindings.
Angelmansyndrome
Angelmansyndromeisaninheriteddisorderthatismostfrequently(68%)causedbyadeletioninthe
maternallyinheritedregionofchromosome15q11.2q13.Approximately7%ofcasesarecausedby
paternaldisomyofthesameregion.Anadditional11%ofcasesofAngelmansyndromearedueto
sequencevariantsinthematernallyinheritedUBE3Agene.
PatientswithAngelmansyndromegenerallyhaveanormalprenatalandbirthhistory,withthefirst
evidenceofdevelopmentaldelayoccurringbetween6and12monthsofage.Seizuresoccurinover
80%ofpatientswithAngelmansyndrome,withonsetbeforeage3years.
Patientsgenerallyhavedecelerationofheadgrowth,resultinginmicrocephalybyearlychildhood.
Dysmorphicfaciesaretypicalandincludeaprotrudingtongue,prognathia,andawidemouthwith
widelyspacedteeth.Patientswithadeletionalsohavehypopigmentation.Intellectualimpairments
aretypicallysevereandspeechimpairmentisquitesevere,withmostpatientshavingfeworno
words.Patientsalsohaveataxiaandfrequentlaughterwithahappydemeanor.
Rettsyndrome
RettsyndromeinitsclassicalformiscausedbymutationsintheMECP2gene,althoughothersimilar
formscausedbydifferentgenesaredescribed.Additionally,althoughRettsyndromehasgenerally
beendescribedonlyinfemalepatients(withthesuppositionthatthiswouldbealethaldiseasein
males),rarecaseshavebeendescribedinmales.
PatientswithRettsyndromehaveanormalprenatalandbirthhistoryandnormalpsychomotor
developmentforthefirst6months,followedbydecelerationofheadgrowthinmostpatients,lossof
handskillsoverthefirst23yearsoflife,handstereotypies,socialwithdrawal,communication
dysfunction,lossofacquiredspeech,cognitiveimpairment,andimpairmentofmovement.[15]
Seizuresarereportedingreaterthan90%offemaleswithRettsyndrome.Seizuresmaybeofany
type,butgeneralizedtonicclonicandcomplexpartialseizuresarethemostcommon.[16]
PittHopkinssyndrome
PittHopkinssyndromeisclassicallycausedbymutationsintheTCF4gene,althoughseveralformsof
PittHopkinslikesyndromehavebeendescribed.PatientswithPittHopkinssyndromehavesevere
intellectualdisability,microcephaly,andlittleornospeech.Theyalsohaveanunusualbreathing
patterncharacterizedbyintermittenthyperventilationfollowedbyperiodsofapnea.
PatientswithPittHopkinsalsohavedistinctivefacies,whichmaynotbeapparentinearlychildhood.
Thesefeaturesincludemicrocephalywithacoarsefacialappearance,deeplyseteyes,upslanting
palpebralfissures,abroadandbeakednasalbridgewithadownturnednasaltip,awidemouthand
fleshylips,andwidelyspacedteeth.Thereisalsoatendencytowardprognathism.
Seizuresareseeninthissyndrome,withonestudyreportingafrequencyof20%.[17]Earlierstudies
suggestedthataround50%ofpatientswithPittHopkinshaveseizures.
Tuberoussclerosis
TuberoussclerosiscomplexiscausedbymutationsintheTSC1orTSC2genes.Majorfeaturesof
thisdiseaseincludethefollowing[18]:
http://emedicine.medscape.com/article/1184846overview

12/25

11/17/2016

EpilepsyandSeizures:PracticeEssentials,Background,Pathophysiology

Facialangiofibromata
Ungualorperiungualfibromas
Hypopigmentedmacules
Connectivetissuenevi
Retinalhamartomas
Corticaltubers
Subependymalnodulesorgiantcellastrocytomas
Cardiacrhabdomyomas
Lymphangiomyomatosis
Renalangiomyolipomas
Minorfeaturesincludethefollowing:
Dentalenamelpits
Rectalhamartomas
Bonecysts
Cerebralwhitemattermigrationlines
Gingivalfibromas
Nonrenalhamartomas
Retinalachromicpatches
Confettiskinlesions
Renalcysts
Adefinitediagnosisoftuberoussclerosisrequires2majorfeaturesor1majorand2minorfeatures.A
probablediagnosisoftuberoussclerosisrequires1majorand1minorfeature.
Morethan80%ofpatientswithtuberoussclerosisarereportedtohaveseizures,althoughthismaybe
anoverestimate.However,thisdiagnosisshouldalwaysbestronglyconsideredinthecaseofinfantile
spasms.
PraderWillisyndrome
PraderWillisyndromeismostfrequently(70%)causedbyadeletioninthepaternalinheritedportion
ofchromosome15q11.2q13.Theremainderofcasesarecausedbymaternaluniparentaldisomyof
chromosome15,complexchromosomalrearrangements,ordefectsinspecificimprintingcenters.
PatientswithPraderWillisyndromehaveneonatalhypotoniaandfailuretothriveduringinfancy.
Patientshavehyperphagia,andonsetofweightgainoccursbetweenage1and6years.Affected
individualsalsohavemildmoderateintellectualimpairment,hypogonadism,andcharacteristicfacies
consistingofanarrowbifrontaldiameter,almondshapedeyes,aroundface,anddownturnedcorners
ofthemouth.Handsandfeetwilltendtobesmallforsize.Seizuresoccurinapproximately1020%of
patients.
SturgeWebersyndrome
SturgeWebersyndromehasanunknowncauseandappearstooccurinasporadicfashion.This
disorderischaracterizedbyintracranialvascularanomaliescalledarteriovenousmalformationsand
portwinestainsontheface.PatientswithSturgeWebersyndromealsohaveseizuresandglaucoma.
Theseizurescanbeverydifficulttocontrolinsomeofthesepatients.

Chromosomaldeletionorduplicationsyndromeswithseizures
Chromosomal22qdeletionsyndromeisaspectrumoffindingscausedbyadeletiononchromosome
22q11.2.Thisdisorderhaspreviouslybeenknownbyavarietyofnames,includingDiGeorge
http://emedicine.medscape.com/article/1184846overview

13/25

11/17/2016

EpilepsyandSeizures:PracticeEssentials,Background,Pathophysiology

syndrome,velocardiofacialsyndrome,Shprintzensyndrome,OpitzG/BBBsyndrome,andCayler
asymmetricalcryingfacies,amongothers.Themostcommonfeaturesofthissyndromeare
congenitalheartdisease,palateanomalies,hypocalcemia,immunedeficiencies,andlearning
difficulties.Seizuresoccurin7%ofpatientswithchromosomal22qdeletionsyndrome.[19]
WolfHirschhornsyndromeiscausedbydeletionsofchromosome4p16.3.Typicalfaciesinthese
patientsincludeabroadnasalbridgecontinuingtotheforehead(theGreekwarriorhelmet
appearance),microcephaly,highforehead,hypertelorism,andhighlyarchedeyebrows.Themouth
tendstobeturneddownward.Growthretardationisseen,asisavariabledegreeofintellectual
disability.Althoughseizuresarepresentinbetween50100%ofpatientswithWolfHirschhorn
syndrome,theytendtoimprovewithage.[20]
Chromosomal1p36deletionsyndromeischaracterizedbydysmorphicfacies,includingstraight
eyebrows,deeplyseteyes,alongphiltrum,andmicrocephaly.Allpatientswiththissyndromehave
developmentaldelayandhypotonia,and4458%haveseizures.[21]

Metabolicdisordersthatcancauseseizures
Manydifferentmetabolicdisorderscancauseseizures,someasaresultofametabolicdisturbance
suchashypoglycemiaoracidosisandsomeasaprimarymanifestationoftheseizuredisorder.Some
seizuresareresponsivetoadministrationofcertainvitamins(eg,pyridoxineresponsiveorfolinicacid
responsiveseizures).
Peroxisomalbiogenesisdisorders,whichcancauseseizures,resultfromhomozygosityformutationin
oneofthemanyPEXgenes.Oneofthesedisorders,Zellwegersyndrome,presentsintheneonatal
periodashypotonia,seizures,andhepaticdysfunction.Deathtypicallyoccursfromrespiratoryfailure
withinthefirstyearoflife.
Congenitaldisordersofglycosylationareagroupofdisordersthat(astheirnamesuggests)involve
malfunctioninoneofthemanyenzymesinvolvedinthepathwaythatattachescertain
oligosaccharidestoproteins.Thesedisordersvarysignificantlyintheirseverityandcharacteristic
manifestations.Hypotonia,intellectualdisability,failuretothrive/feedingdifficulties,andunusualfat
distributionarecommon.Seizuresoccurinsomecases.
Otherrarediseasesalsocommonlycauseseizures,includingthefollowing:
Neuronalceroidlipofuscinosis
Disordersofmetalandmetalcofactordeficiency
Disordersofneurotransmittermetabolism
Lysosomalstoragediseases

Mitochondrialdiseases
Mitochondrialdisordersareunderdiagnosedbutofteninvolveseizuresandotherneurologic
manifestations.Mitochondrialencephalomyopathy,lacticacidosis,andstrokelikeepisodes(MELAS)
syndromeisamitochondrialdisorderthatisassociatedwithseizuresoften,seizuresarethe
presentingmanifestation.Patientscanalsohaverecurrentheadacheandvomiting.
Myoclonicepilepsywithraggedredfibers(MERRF)ischaracterizedbymyoclonus,seizures,and
ataxiamyopathy,hearingloss,andvisionlosscanalsooccur.Genetictestsareavailableforthese
disorders.

Seizuredisorderscausedbysinglegenemutations
http://emedicine.medscape.com/article/1184846overview

14/25

11/17/2016

EpilepsyandSeizures:PracticeEssentials,Background,Pathophysiology

AutosomaldominantnocturnalfrontallobeepilepsyiscausedbymutationsintheCHRNA4,
CHRNB2,orCHRNA2genes.Itischaracterizedbynocturnalmotorseizures.Theseverityof
autosomaldominantnocturnalfrontallobeepilepsycanbevariable,canincludeawakeningepisodes,
andcanresultinimpressivedystoniceffects.Affectedindividualsaregenerallyotherwisenormal,and
theattackstendtobecomelessseverewithage.
Autosomaldominantjuvenilemyoclonicepilepsyiscausedbyamutationinoneofanumberof
genes.Patientsreportmyoclonicjerks,mostcommonlyinthemorning,buttheycanalsohaveboth
generalizedtonicclonicseizuresandabsenceseizures.Theonsetofthisdisorderistypicallyinlate
childhoodorearlyadolescence.
BenignfamilialneonatalseizuresarecausedbymutationsintheKCNQ2orKCNQ3genesandare
inheritedinanautosomaldominantmanner.Neonateswiththisdisorderwillexperiencetonicclonic
seizuresafewdaysafterbirth,andtheseseizureswillremitwithin1month.Mostinfantswillhave
normaldevelopment,butthereisa1015%riskofseizuredisorderlaterinlife.
Mutationsinothergenes,suchasSCN1A,cancausearangeofseizuresyndromes.Atthemildend
ofthisspectrum,patientsmayhavefamilialfebrileseizuresandmayotherwisebenormal.Atthe
severeend,patientsmayhaveseveremyoclonicepilepsyofinfancy(alsoknownasDravet
syndrome).
MutationsinSCN2AandSCN1Bareknowntocausegeneralizedepilepsywithfebrileseizures.
MutationsinSCN9A,GPA6,andGPR98areknowntocausefamilialfebrileseizures.
MutationinGABRG2isknowntocausegeneralizedepilepsywithfebrileseizures,andfamilialfebrile
seizures.

Epidemiology
Hauserandcollaboratorsdemonstratedthattheannualincidenceofrecurrentnonfebrileseizuresin
OlmstedCounty,Minnesota,wasabout100casesper100,000personsaged01year,40per
100,000personsaged3940years,and140per100,000personsaged7980years.Bytheageof75
years,thecumulativeincidenceofepilepsyis3400per100,000men(3.4%)and2800per100,000
women(2.8%).[22]
Studiesinseveraldevelopedcountrieshaveshownincidencesandprevalencesofseizuressimilarto
thoseintheUnitedStates.Insomecountries,parasiticinfectionsaccountforanincreasedincidence
ofepilepsyandseizures.

Prognosis
Thepatient'sprognosisfordisabilityandforarecurrenceofepilepticseizuresdependsonthetypeof
epilepticseizureandtheepilepticsyndromeinquestion.Impairmentofconsciousnessduringa
seizuremayunpredictablyresultinmorbidityorevenmortality.
Regardingmorbidity,traumaisnotuncommonamongpeoplewithgeneralizedtonicclonicseizures.
Injuriessuchasecchymosishematomasabrasionstongue,facial,andlimblacerationsandeven
shoulderdislocationcandevelopasaresultoftherepeatedtonicclonicmovements.Atonicseizures
arealsofrequentlyassociatedwithfacialinjuries,aswellasinjuriestotheneck.Worldwide,burnsare
themostcommonseriousinjuryassociatedwithepilepticseizures.

SUDEP
http://emedicine.medscape.com/article/1184846overview

15/25

11/17/2016

EpilepsyandSeizures:PracticeEssentials,Background,Pathophysiology

Regardingmortality,seizurescausedeathinasmallproportionofindividuals.Mostdeathsare
accidentalandresultfromimpairedconsciousness.However,sudden,unexpecteddeathinepilepsy
(SUDEP)isariskinpersonswithepilepsy,anditmayoccurevenwhenpatientsarerestingina
protectedenvironment(ie,inabedwithrailguardsorinthehospital).
TheincidenceofSUDEPislow,about2.3timeshigherthantheincidenceofsuddendeathinthe
generalpopulation.Theincreasedriskofdeathisseenmostlyinpeoplewithlongstandingfocal
onsetepilepsy,butitisalsopresentinindividualswithprimarygeneralizedepilepsy.Theriskof
SUDEPincreasesinthesettingofuncontrolledseizuresandinpeoplewithpoormedication
compliance.Theriskincreasesfurtherinpeoplewithuncontrolledsecondarygeneralizedtonicclonic
seizures.
ThemechanismofdeathinSUDEPiscontroversial,butsuggestionsincludecardiacarrhythmias,
neurogenicpulmonaryedema,andsuffocationduringanepilepticseizurewithimpairmentof
consciousness.Treatmentwithanticonvulsantsdecreasesthelikelihoodofanaccidentalseizure
relateddeath,andsuccessfulepilepsysurgerydecreasestheriskofSUDEPtothatofthegeneral
population.
In2011,theNationalInstitutesofHealth(NIH)convenedaworkshoponSUDEPtofocusresearch
effortsandtodeterminebenchmarksforfurtherstudy.[23]Asummaryoftheirreportcanbefoundat:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3115809/.

PatientEducation
Topreventinjury,provideeducationaboutseizureprecautionstopatientswhohavelapsesof
consciousnessduringwakefulnessandinwhomseizuresaresuspected.Mostaccidentsoccurwhen
patientshaveimpairedconsciousness.Thisisoneofthereasonsforrestrictionsondriving,
swimming,takingunsupervisedbaths,workingatsignificantheights,andtheuseoffireandpower
toolsforpeoplewhohaveepilepticseizuresandotherspellsofsuddenonsetseizures.
Therestrictionsdifferforeachpatientbecauseoftheindividualfeaturesoftheseizures,thedegreeof
seizurecontrol,and,intheUnitedStates,statelaws.Othercountrieshavemorepermissiveormore
restrictivelawsregardingdriving.Checkstatedrivinglawsbeforemakingrecommendations.
EpilepsyFoundationofAmericahasalargelibraryofeducationalmaterialsthatareavailableto
healthcareprofessionalsandthegeneralpublic.TheAmericanEpilepsySocietyisaprofessional
organizationforpeoplewhotakecareofpatientswithepilepsy.TheirWebsiteprovidesalarge
amountofcredibleinformation.
Forpatienteducationinformation,seetheBrainandNervousSystemCenter,aswellasEpilepsyand
SeizuresEmergencies.
ClinicalPresentation
References

1.FisherRS,vanEmdeBoasW,BlumeW,etal.Epilepticseizuresandepilepsy:definitions
proposedbytheInternationalLeagueAgainstEpilepsy(ILAE)andtheInternationalBureaufor
Epilepsy(IBE).Epilepsia.2005Apr.46(4):4702.[Medline].
2.Epilepsysurgeryinchildhoodcanprotectmemory.MedicalNewsToday.November14,2014.
[FullText].
http://emedicine.medscape.com/article/1184846overview

16/25

11/17/2016

EpilepsyandSeizures:PracticeEssentials,Background,Pathophysiology

3.SkirrowC,CrossJH,HarrisonS,CormackF,HarknessW,ColemanR,etal.Temporallobe
surgeryinchildhoodandneuroanatomicalpredictorsoflongtermdeclarativememoryoutcome.
Brain.2014Nov12.[Medline].
4.GoodkinHP.ThefoundingoftheAmericanEpilepsySociety:19361971.Epilepsia.2007Jan.
48(1):1522.[Medline].
5.RhoJM,SankarR,CavazosJE.Epilepsy:ScientificFoundationsofClinicalPractice.NewYork,
NY:MarcelDekker2004.
6.KramerMA,CashSS.Epilepsyasadisorderofcorticalnetworkorganization.Neuroscientist.
2012Aug.18(4):36072.[Medline].
7.HouserCR,EsclapezM.VulnerabilityandplasticityoftheGABAsysteminthepilocarpine
modelofspontaneousrecurrentseizures.EpilepsyRes.1996Dec.26(1):20718.[Medline].
8.SloviterRS.Statusepilepticusinducedneuronalinjuryandnetworkreorganization.Epilepsia.
1999.40(suppl1):S349discussionS401.[Medline].
9.ScharfmanHE,SchwartzkroinPA.Protectionofdentatehilarcellsfromprolongedstimulationby
intracellularcalciumchelation.Science.1989Oct13.246(4927):25760.[Medline].
10.CavazosJE,DasI,SutulaTP.Neuronallossinducedinlimbicpathwaysbykindling:evidence
forinductionofhippocampalsclerosisbyrepeatedbriefseizures.JNeurosci.1994May.14(5pt
2):310621.[Medline].
11.SutulaT,CascinoG,CavazosJ,etal.Mossyfibersynapticreorganizationintheepileptic
humantemporallobe.AnnNeurol.1989Sep.26(3):32130.[Medline].
12.MastrangeloM,LeuzziV.Genesofearlyonsetepilepticencephalopathies:fromgenotypeto
phenotype.PediatrNeurol.2012Jan.46(1):2431.[Medline].
13.McCormickDA.Cellularmechanismsunderlyingcholinergicandnoradrenergicmodulationof
neuronalfiringmodeinthecatandguineapigdorsallateralgeniculatenucleus.JNeurosci.
1992Jan.12(1):27889.[Medline].
14.HosfordDA,ClarkS,CaoZ,etal.TheroleofGABABreceptoractivationinabsenceseizuresof
lethargic(lh/lh)mice.Science.1992Jul17.257(5068):398401.[Medline].
15.HagbergB,HanefeldF,PercyA,SkjeldalO.Anupdateonclinicallyapplicablediagnosticcriteria
inRettsyndrome.CommentstoRettSyndromeClinicalCriteriaConsensusPanelSatelliteto
EuropeanPaediatricNeurologySocietyMeeting,BadenBaden,Germany,11September2001.
EurJPaediatrNeurol.2002.6(5):2937.[Medline].
16.SteffenburgU,HagbergG,HagbergB.EpilepsyinarepresentativeseriesofRettsyndrome.
ActaPaediatr.2001Jan.90(1):349.[Medline].
17.WhalenS,HronD,GaillonT,MoldovanO,RossiM,DevillardF,etal.Novelcomprehensive
diagnosticstrategyinPittHopkinssyndrome:clinicalscoreandfurtherdelineationoftheTCF4
mutationalspectrum.HumMutat.2012Jan.33(1):6472.[Medline].
18.RoachES,SparaganaSP.Diagnosisoftuberoussclerosiscomplex.JChildNeurol.2004Sep.
19(9):6439.[Medline].
19.KaoA,MarianiJ,McDonaldMcGinnDM,MaisenbacherMK,BrooksKayalAR,ZackaiEH,etal.
Increasedprevalenceofunprovokedseizuresinpatientswitha22q11.2deletion.AmJMed
http://emedicine.medscape.com/article/1184846overview

17/25

11/17/2016

EpilepsyandSeizures:PracticeEssentials,Background,Pathophysiology

GenetA.2004Aug15.129A(1):2934.[Medline].
20.BattagliaA,FilippiT,SouthST,CareyJC.Spectrumofepilepsyandelectroencephalogram
patternsinWolfHirschhornsyndrome:experiencewith87patients.DevMedChildNeurol.2009
May.51(5):37380.[Medline].
21.BattagliaA,HoymeHE,DallapiccolaB,ZackaiE,HudginsL,McDonaldMcGinnD,etal.Further
delineationofdeletion1p36syndromein60patients:arecognizablephenotypeandcommon
causeofdevelopmentaldelayandmentalretardation.Pediatrics.2008Feb.121(2):40410.
[Medline].
22.HauserWA,AnnegersJF,RoccaWA.Descriptiveepidemiologyofepilepsy:contributionsof
populationbasedstudiesfromRochester,Minnesota.MayoClinProc.1996Jun.71(6):57686.
[Medline].
23.HirschLJ,DonnerEJ,SoEL,JacobsM,NashefL,NoebelsJL,etal.Abbreviatedreportofthe
NIH/NINDSworkshoponsuddenunexpecteddeathinepilepsy.Neurology.2011May31.
76(22):19328.[Medline].[FullText].
24.LudersH,AcharyaJ,BaumgartnerC,etal.Semiologicalseizureclassification.Epilepsia.1998
Sep.39(9):100613.[Medline].
25.LoddenkemperT,KellinghausC,WyllieE,NajmIM,GuptaA,RosenowF.Aproposalforafive
dimensionalpatientorientedepilepsyclassification.EpilepticDisord.2005Dec.7(4):30816.
[Medline].
26.EngelJJr.ReportoftheILAEclassificationcoregroup.Epilepsia.2006Sep.47(9):155868.
[Medline].
27.WolfP.BasicprinciplesoftheILAEsyndromeclassification.EpilepsyRes.2006Aug.70suppl
1:S206.[Medline].
28.BergAT,BerkovicSF,BrodieMJ,etal.Revisedterminologyandconceptsfororganizationof
seizuresandepilepsies:reportoftheILAECommissiononClassificationandTerminology,
20052009.Epilepsia.2010Apr.51(4):67685.[Medline].
29.EngelJJr.Aproposeddiagnosticschemeforpeoplewithepilepticseizuresandwithepilepsy:
reportoftheILAETaskForceonClassificationandTerminology.Epilepsia.2001Jun.42(6):796
803.[Medline].
30.WolfP.Ofcabbagesandkings:someconsiderationsonclassifications,diagnosticschemes,
semiology,andconcepts.Epilepsia.2003Jan.44(1):14discussion413.[Medline].
31.BeghiE.Theconceptoftheepilepsysyndrome:howusefulisitinclinicalpractice?.Epilepsia.
2009May.50suppl5:410.[Medline].
32.[Guideline]ChenDK,SoYT,FisherRS.Useofserumprolactinindiagnosingepilepticseizures:
reportoftheTherapeuticsandTechnologyAssessmentSubcommitteeoftheAmerican
AcademyofNeurology.Neurology.2005Sep13.65(5):66875.[Medline].
33.FirstSeizureTrialGroup(FIR.S.TGroup).Randomizedclinicaltrialontheefficacyof
antiepilepticdrugsinreducingtheriskofrelapseafterafirstunprovokedtonicclonicseizure.
Neurology.1993Mar.43(3pt1):47883.[Medline].
34.GlauserTA,CnaanA,ShinnarS,etal,fortheChildhoodAbsenceEpilepsyStudyGroup.
Ethosuximide,valproicacid,andlamotrigineinchildhoodabsenceepilepsy.NEnglJMed.2010
http://emedicine.medscape.com/article/1184846overview

18/25

11/17/2016

EpilepsyandSeizures:PracticeEssentials,Background,Pathophysiology

Mar4.362(9):7909.[Medline].
35.NgYT,ConryJA,DrummondR,StolleJ,WeinbergMA.Randomized,phaseIIIstudyresultsof
clobazaminLennoxGastautsyndrome.Neurology.2011Oct11.77(15):14731481.[Medline].
36.BastingsE.Newdrugapplication(NDA)approvalletter:QudexyXR(topiramate)extended
releasecapsules.NDAno.205122.Availableat
http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2014/205122Orig1s000ltr.pdf.
Accessed:March14,2014.
37.QudexyXR:FDAapprovallabelingtextdatedMarch11,2014.Availableat
http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205122s000lbl.pdf.Accessed:
March14,2014.
38.JeffreyS.FDAokaysanotherextendedreleasetopiramateforepilepsy.MedscapeMedical
News.March13,2014.[FullText].
39.UpsherSmithLaboratories,Inc.UpsherSmithreceivesFDAapprovalforQudexyXR
(topiramate)extendedreleasecapsules[pressrelease].March12,2014.Availableat
http://www.upshersmith.com/wpcontent/uploads/108885.01QXRPRFDAApproval
FINAL.pdf.Accessed:March14,2014.
40.MarsonAG,AlKharusiAM,AlwaidhM,etal,fortheSANADStudygroup.TheSANADstudyof
effectivenessofvalproate,lamotrigine,ortopiramateforgeneralisedandunclassifiableepilepsy:
anunblindedrandomisedcontrolledtrial.Lancet.2007Mar24.369(9566):101626.[Medline].
41.BrooksM.LevetiracetamTakeninPregnancyFoundSafeforChildNeurodevelopment.
MedscapeMedicalNews.Availableathttp://www.medscape.com/viewarticle/818902.Accessed:
January16,214.
42.ShallcrossR,BromleyRL,CheyneCP,GarcaFianaM,IrwinB,MorrowJ,etal.Inutero
exposuretolevetiracetamvsvalproate:Developmentandlanguageat3yearsofage.
Neurology.2014Jan8.[Medline].
43.USFoodandDrugAdministration.FDAapprovesFycompatotreatseizures.October22,2012.
Availableathttp://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm325038.htm.
Accessed:Sept19,2013.
44.MattsonRH,CramerJA,CollinsJF,etal.Comparisonofcarbamazepine,phenobarbital,
phenytoin,andprimidoneinpartialandsecondarilygeneralizedtonicclonicseizures.NEnglJ
Med.1985Jul18.313(3):14551.[Medline].
45.MattsonRH,CramerJA,CollinsJF.Acomparisonofvalproatewithcarbamazepineforthe
treatmentofcomplexpartialseizuresandsecondarilygeneralizedtonicclonicseizuresinadults.
TheDepartmentofVeteransAffairsEpilepsyCooperativeStudyNo.264Group.NEnglJMed.
1992Sep10.327(11):76571.[Medline].
46.RowanAJ,RamsayRE,CollinsJF,etal,fortheVACooperativeStudy428Group.Newonset
geriatricepilepsy:arandomizedstudyofgabapentin,lamotrigine,andcarbamazepine.
Neurology.2005Jun14.64(11):186873.[Medline].
47.MarsonAG,AlKharusiAM,AlwaidhM,etal,fortheSANADStudyGroup.TheSANADstudyof
effectivenessofcarbamazepine,gabapentin,lamotrigine,oxcarbazepine,ortopiramatefor
treatmentofpartialepilepsy:anunblindedrandomisedcontrolledtrial.Lancet.2007Mar24.
369(9566):100015.[Medline].
http://emedicine.medscape.com/article/1184846overview

19/25

11/17/2016

EpilepsyandSeizures:PracticeEssentials,Background,Pathophysiology

48.FrenchJA,KannerAM,BautistaJ,etal,fortheTherapeuticsandTechnologyAssessment
SubcommitteeoftheAANQualityStandardsSubcommitteeoftheAANandAES.Efficacyand
tolerabilityofthenewantiepilepticdrugsI:treatmentofnewonsetepilepsy:reportofthe
TherapeuticsandTechnologyAssessmentSubcommitteeandQualityStandardsSubcommittee
oftheAmericanAcademyofNeurologyandtheAmericanEpilepsySociety.Neurology.2004
Apr27.62(8):125260.[Medline].
49.FrenchJA,KannerAM,BautistaJ,etalfortheTherapeuticsandTechnologyAssessment
SubcommitteeoftheAANQualityStandardsSubcommitteeoftheAANandAES.Efficacyand
tolerabilityofthenewantiepilepticdrugs,II:treatmentofrefractoryepilepsy.Reportofthe
TherapeuticsandTechnologyAssessmentSubcommitteeandQualityStandardsSubcommittee
oftheAmericanAcademyofNeurologyandtheAmericanEpilepsySociety.Neurology.2004
Apr27.62(8):126173.[Medline].
50.HermanAO.Antiseizuredruglinkedtoretinalabnormalities,skindiscoloration.Physician'sFirst
Watch.April29,2013.[FullText].
51.JeffreyS.FDALabelChangesUnderlineRisksWithEzogabine.MedscapeMedicalNews.Oct
312013.[FullText].
52.FDA.FDADrugSafetyCommunication:FDAapproveslabelchangesforantiseizuredrug
Potiga(ezogabine)describingriskofretinalabnormalities,potentialvisionloss,andskin
discoloration.USFoodandDrugAdministration.Oct312013.Availableat
http://www.fda.gov/Drugs/DrugSafety/ucm372774.htm.
53.KwanP,ArzimanoglouA,BergAT,BrodieMJ,AllenHauserW,MathernG,etal.Definitionof
drugresistantepilepsy:consensusproposalbytheadhocTaskForceoftheILAECommission
onTherapeuticStrategies.Epilepsia.2010Jun.51(6):106977.[Medline].
54.RamosLizanaJ,RodriguezLucenillaMI,AguileraLpezP,AguirreRodrguezJ,Cassinello
GarcaE.AstudyofdrugresistantchildhoodepilepsytestingthenewILAEcriteria.Seizure.
2012May.21(4):26672.[Medline].
55.IorioR,AssenzaG,DellaMarcaG,etal.Neuralautoantibodiesandimmunotherapyresponsive
epilepsy:aprospectivestudy[abstract1956].Presentedat:XXIWorldCongressofNeurology
(WNC),2013September22,2013Vienna,Austria.[FullText].
56.KellerDM.Immunotherapyhelpsepilepticpatientswithneuralantibodies.MedscapeMedical
News.September27,2013.[FullText].
57.[Guideline]HardenCL,PennellPB,KoppelBS,etal,fortheAANandAES.Managementissues
forwomenwithepilepsyfocusonpregnancy(anevidencebasedreview):III.VitaminK,folic
acid,bloodlevels,andbreastfeeding:ReportoftheQualityStandardsSubcommitteeand
TherapeuticsandTechnologyAssessmentSubcommitteeoftheAmericanAcademyof
NeurologyandtheAmericanEpilepsySociety.Epilepsia.2009May.50(5):124755.[Medline].
58.[Guideline]BirbeckGL,FrenchJA,PeruccaE,SimpsonDM,FraimowH,GeorgeJM,etal.
AntiepilepticdrugselectionforpeoplewithHIV/AIDS:evidencebasedguidelinesfromtheILAE
andAAN.Epilepsia.2012Jan.53(1):20714.[Medline].
59.[Guideline]HardenCL,HoppJ,TingTY,etal,fortheAANandAES.Managementissuesfor
womenwithepilepsyFocusonpregnancy(anevidencebasedreview):I.Obstetrical
complicationsandchangeinseizurefrequency:ReportoftheQualityStandardsSubcommittee
andTherapeuticsandTechnologyAssessmentSubcommitteeoftheAmericanAcademyof
NeurologyandtheAmericanEpilepsySociety.Epilepsia.2009May.50(5):122936.[Medline].
http://emedicine.medscape.com/article/1184846overview

20/25

11/17/2016

EpilepsyandSeizures:PracticeEssentials,Background,Pathophysiology

60.[Guideline]HardenCL,MeadorKJ,PennellPB,etal,fortheAANandAES.Management
issuesforwomenwithepilepsyFocusonpregnancy(anevidencebasedreview):II.
Teratogenesisandperinataloutcomes:ReportoftheQualityStandardsSubcommitteeand
TherapeuticsandTechnologySubcommitteeoftheAmericanAcademyofNeurologyandthe
AmericanEpilepsySociety.Epilepsia.2009May.50(5):123746.[Medline].
61.LevyRG,CooperPN,GiriP.Ketogenicdietandotherdietarytreatmentsforepilepsy.Cochrane
DatabaseSystRev.2012Mar14.3:CD001903.[Medline].
62.KossoffEH,TurnerZ,BlumlRM,PyzikPL,ViningEP.Arandomized,crossovercomparisonof
dailycarbohydratelimitsusingthemodifiedAtkinsdiet.EpilepsyBehav.2007May.10(3):4326.
[Medline].
63.WeberS,MlgaardC,Karentaudorf,UldallP.ModifiedAtkinsdiettochildrenandadolescents
withmedicalintractableepilepsy.Seizure.2009May.18(4):23740.[Medline].
64.SmithM,PolitzerN,MacgarvieD,McAndrewsMP,DelCampoM.Efficacyandtolerabilityofthe
modifiedAtkinsdietinadultswithpharmacoresistantepilepsy:aprospectiveobservational
study.Epilepsia.2011Apr.52(4):77580.[Medline].
65.AndersonP.FDAapprovesextendedreleaseoncedailyepilepsydrug.MedscapeMedical
News.August21,2013.[FullText].
66.SupernusPharmaceuticals,Inc.SupernusannouncesfinalFDAapprovalandupcominglaunch
ofTrokendiXR(TM)[pressrelease].August19,2013.Availableat
http://ir.supernus.com/releasedetail.cfm?ReleaseID=785927.Accessed:August27,2013.
67.EnglotDJ,ChangEF,AugusteKI.Vagusnervestimulationforepilepsy:ametaanalysisof
efficacyandpredictorsofresponse.JNeurosurg.2011Dec.115(6):124855.[Medline].
68.AndersonP.FDAPanelEndorsesEpilepsyNeurostimulator.MedscapeMedicalNews.Available
athttp://www.medscape.com/viewarticle/779901.Accessed:March4,2013.
69.LowesR.FDAApprovesImplantableNeurostimulatorforEpilepsy.MedscapeMedicalNews.
Nov142013.[FullText].
70.FDA.FDAapprovesmedicaldevicetotreatepilepsy.Nov142013.[FullText].
71.WiebeS,BlumeWT,GirvinJP,EliasziwM,fortheEffectivenessandEfficiencyofSurgeryfor
TemporalLobeEpilepsyStudyGroup.Arandomized,controlledtrialofsurgeryfortemporallobe
epilepsy.NEnglJMed.2001Aug2.345(5):3118.[Medline].
72.HyslopA,MillerI,BhatiaS,JayakarP.Functionallesionectomy:aminimallyresectivestrategy
effectiveinchildrenwithMRInegative,intractableepilepsy[abstract1.280].Presentedat:66th
AnnualMeetingoftheAmericanEpilepsySocietyDecember1,2012SanDiego,Calif.
73.MelvilleNA.Minimalresectioneffectiveforsomepatientswithepilepsy.MedscapeMedical
News.January3,2013.[FullText].
74.EngelJJr,McDermottMP,WiebeS,LangfittJT,SternJM,DewarS,etal.Earlysurgicaltherapy
fordrugresistanttemporallobeepilepsy:arandomizedtrial.JAMA.2012Mar7.307(9):92230.
[Medline].
75.AndersonP.Laserablationpromisinginpatientswithepilepsy.MedscapeMedicalNews.
December9,2013.[FullText].
http://emedicine.medscape.com/article/1184846overview

21/25

11/17/2016

EpilepsyandSeizures:PracticeEssentials,Background,Pathophysiology

76.NovakB.MidazolamMoreEffectiveforSeizuresThanDiazepamWhenGivenIM.Medscape.
Jan242014.[FullText].
MediaGallery
of0
Tables

BacktoList
ContributorInformationandDisclosures

Author
DavidYKo,MDAssociateProfessorofClinicalNeurology,AssociateDirector,USCAdultEpilepsy
Program,KeckSchoolofMedicineoftheUniversityofSouthernCalifornia
DavidYKo,MDisamemberofthefollowingmedicalsocieties:AmericanAcademyofNeurology,
AmericanEpilepsySociety,AmericanHeadacheSociety,AmericanClinicalNeurophysiologySociety
Disclosure:ReceivedhonorariafromUCBforspeakingandteachingReceivedconsultingfeefrom
LundbeckforconsultingReceivedconsultingfeefromWestwardforconsultingReceivedconsulting
feefromEsaiforconsultingReceivedconsultingfeefromSupernusforconsultingReceived
consultingfeefromSunovionforspeakingandteaching.
ChiefEditor
SelimRBenbadis,MDProfessor,DirectorofComprehensiveEpilepsyProgram,Departmentsof
NeurologyandNeurosurgery,TampaGeneralHospital,UniversityofSouthFloridaMorsaniCollegeof
Medicine
SelimRBenbadis,MDisamemberofthefollowingmedicalsocieties:AmericanAcademyof
Neurology,AmericanAcademyofSleepMedicine,AmericanClinicalNeurophysiologySociety,
AmericanEpilepsySociety,AmericanMedicalAssociation
Disclosure:Serve(d)asadirector,officer,partner,employee,advisor,consultantortrusteefor:
CyberonicsEisaiLundbeckSunovionUCBUpsherSmith<br/>Serve(d)asaspeakeroramember
ofaspeakersbureaufor:Cyberonics(Livanova)EisaiLundbeckSunovionUCB<br/>Received
researchgrantfrom:Cyberonics(Livanova)GW,LundbeckSunovionUCBUpsherSmith.
Acknowledgements
JoseECavazos,MD,PhD,FAAN,FANA,FACNSProfessorwithTenure,DepartmentsofNeurology,
Pharmacology,andPhysiology,AssistantDeanfortheMD/PhDProgram,ProgramDirectorofthe
ClinicalNeurophysiologyFellowship,UniversityofTexasSchoolofMedicineatSanAntonioCo
Director,SouthTexasComprehensiveEpilepsyCenter,UniversityHospitalSystemDirector,San
AntonioVeteransAffairsEpilepsyCenterofExcellenceandNeurodiagnosticCenters,AudieLMurphy
VeteransAffairsMedicalCenter

http://emedicine.medscape.com/article/1184846overview

22/25

11/17/2016

EpilepsyandSeizures:PracticeEssentials,Background,Pathophysiology

JoseECavazos,MD,PhD,FAAN,FANA,FACNSisamemberofthefollowingmedicalsocieties:
AmericanAcademyofNeurology,AmericanClinicalNeurophysiologySociety,AmericanEpilepsy
Society,AmericanNeurologicalAssociation,andSocietyforNeuroscience
Disclosure:LGCH,IncOwnershipinterestConsulting
RamonDiazArrastia,MD,PhDProfessor,DepartmentofNeurology,UniversityofTexas
SouthwesternMedicalCenteratDallas,SouthwesternMedicalSchoolDirector,NorthTexasTBI
ResearchCenter,ComprehensiveEpilepsyCenter,ParklandMemorialHospital
RamonDiazArrastia,MD,PhDisamemberofthefollowingmedicalsocieties:AlphaOmegaAlpha,
AmericanAcademyofNeurology,NewYorkAcademyofSciences,andPhiBetaKappa
Disclosure:Nothingtodisclose.
MarkSpitz,MDProfessor,DepartmentofNeurology,UniversityofColoradoHealthSciencesCenter
MarkSpitz,MDisamemberofthefollowingmedicalsocieties:AmericanAcademyofNeurology,
AmericanClinicalNeurophysiologySociety,andAmericanEpilepsySociety
Disclosure:pfizerHonorariaSpeakingandteachingucbHonorariaSpeakingandteachinglumdbeck
HonorariaConsulting
FranciscoTalavera,PharmD,PhDAdjunctAssistantProfessor,UniversityofNebraskaMedical
CenterCollegeofPharmacyEditorinChief,MedscapeDrugReference
Disclosure:MedscapeSalaryEmployment
WhattoReadNextonMedscape
RelatedConditionsandDiseases

SeizureDisordersinPregnancy
Women'sHealthandEpilepsy
BenignChildhoodEpilepsy
EEGinCommonEpilepsySyndromes
LocalizationRelatedEpilepsiesonEEG
OutcomeofEpilepsySurgery
News&Perspective

ComparingNeurostimulationTechnologiesinRefractoryFocalonsetEpilepsy
SanofiWillAcceptEpilepsyDrugBlameIfCourtRulesThatWay

http://emedicine.medscape.com/article/1184846overview

23/25

11/17/2016

EpilepsyandSeizures:PracticeEssentials,Background,Pathophysiology

LaserAblation'sRoleinDrugResistantEpilepsy
Tools

DrugInteractionChecker
PillIdentifier
Calculators
Formulary
Slideshow

HospitalistGuidelines:2016MidyearReview
MostPopularArticles

AccordingtoNeurologists
1.'MedicalFood'MaySlowBrainAtrophyinPatientsWithAlzheimer'sandRelatedDisorders
2.NewTypeofMigraineMayBeDuetoLowIron
3.NewAHA/ASAStatementonTelemedicineinStroke
4.DietaryFactorsLinkedtoBetterorWorseFunctioninALS
5.QualityofLifeProblemsLingerLongTermEvenAfterSuccessfulStrokeTreatment
ViewMore

http://emedicine.medscape.com/article/1184846overview

24/25

11/17/2016

EpilepsyandSeizures:PracticeEssentials,Background,Pathophysiology

http://emedicine.medscape.com/article/1184846overview

25/25