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IschemicStroke
Author:EdwardCJauch,MD,MS,FAHA,FACEPChiefEditor:HelmiLLutsep,MDmore...
Updated:Jan20,2015

PracticeEssentials
Ischemicstroke(seetheimagebelow)ischaracterizedbythesuddenlossofbloodcirculationtoanareaofthe
brain,resultinginacorrespondinglossofneurologicfunction.Acuteischemicstrokeiscausedbythromboticor
embolicocclusionofacerebralarteryandismorecommonthanhemorrhagicstroke.

Maximumintensityprojection(MIP)imagefromacomputedtomographyangiogram(CTA)demonstratesafillingdefectorhigh
gradestenosisatthebranchingpointoftherightmiddlecerebralartery(MCA)trunk(redcircle),suspiciousforthrombusor
embolus.CTAishighlyaccurateindetectinglargevesselstenosisandocclusions,whichaccountforapproximatelyonethirdof
ischemicstrokes.

SeeAcuteStroke,aCriticalImagesslideshow,formoreinformationonincidence,presentation,intervention,and
additionalresources.

Essentialupdate:Studyindicatesintraarterialtreatmentimprovesfunctionalrecoveryin
acuteischemicstroke
ArandomizedclinicaltrialfromtheNetherlandsindicatesthatendovascularinterventionbenefitsfunctional
outcomesinpatientswithacuteischemicstrokeresultingfromaproximalintracranialarterialocclusion.Inthestudy,
byBerkhemeretal,500patientswererandomizedtoreceiveintraarterialtreatment(within6hoursofsymptom
onset)orusualtreatmentalone.Although89%ofthepatientsweretreatedwithtissuetypeplasminogenactivator
(tPA)priortorandomization,onlythosewhowerefoundoncomputedtomography(CT)angiographytostillhavea
proximalarterialocclusionwereenteredintothestudy.Inmostofthepatientswhoreceivedintraarterialtreatment,
theprocedurewasperformedwithlatestgenerationstentretrievers. [1,2]
Theinvestigatorsfoundthatat90days,therateoffunctionalindependence(modifiedRankinscalescoreof02)in
theintraarterialtreatmentgroupwas32.6%,comparedwith19.1%intheusualtreatmentonlygroup,whileafter5
7days,theNationalInstitutesofHealthStrokeScale(NIHSS)scorewasanaverageof2.9pointslowerintheintra
arterialtreatmentpatientsthanitwasintheothergroup.Thetwogroupsdidnotdiffersignificantlywithregardto
therateofmoralityorsymptomaticintracerebralhemorrhage.

Signsandsymptoms
Considerstrokeinanypatientpresentingwithacuteneurologicdeficitoranyalterationinlevelofconsciousness.
Commonstrokesignsandsymptomsincludethefollowing:
Abruptonsetofhemiparesis,monoparesis,or(rarely)quadriparesis
Hemisensorydeficits
Monocularorbinocularvisualloss
Visualfielddeficits
Diplopia
Dysarthria
Facialdroop
Ataxia
Vertigo(rarelyinisolation)
Nystagmus
Aphasia
Suddendecreaseinlevelofconsciousness
Althoughsuchsymptomscanoccuralone,theyaremorelikelytooccurincombination.Nohistoricalfeature
distinguishesischemicfromhemorrhagicstroke,althoughnausea,vomiting,headache,andsuddenchangeinlevel
ofconsciousnessaremorecommoninhemorrhagicstrokes.Inyoungerpatients,ahistoryofrecenttrauma,
coagulopathies,illicitdruguse(especiallycocaine),migraines,oruseoforalcontraceptivesshouldbeelicited.
Withtheavailabilityoffibrinolytictherapyforacuteischemicstrokeinselectedpatients,thephysicianmustbeable
toperformabriefbutaccurateneurologicexaminationonpatientswithsuspectedstrokesyndromes.Thegoalsof
theneurologicexaminationincludethefollowing:
Confirmingthepresenceofastrokesyndrome
Distinguishingstrokefromstrokemimics
Establishinganeurologicbaseline,shouldthepatient'sconditionimproveordeteriorate

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Establishingstrokeseverity,usingastructuredneurologicexamandscore(NationalInstitutesofHealth
StrokeScale[NIHSS])toassistinprognosisandtherapeuticselection
Essentialcomponentsoftheneurologicexaminationincludethefollowingevaluations:
Cranialnerves
Motorfunction
Sensoryfunction
Cerebellarfunction
Gait
Deeptendonreflexes
Language(expressiveandreceptivecapabilities)
Mentalstatusandlevelofconsciousness
Theskullandspinealsoshouldbeexamined,andsignsofmeningismusshouldbesought.
SeeClinicalPresentationformoredetail.

Diagnosis
Emergentbrainimagingisessentialforconfirmingthediagnosisofischemicstroke.Noncontrastcomputed
tomography(CT)scanningisthemostcommonlyusedformofneuroimagingintheacuteevaluationofpatientswith
apparentacutestroke.Thefollowingneuroimagingtechniquesarealsoused:
CTangiographyandCTperfusionscanning
Magneticresonanceimaging(MRI)
Carotidduplexscanning
Digitalsubtractionangiography
Lumbarpuncture
AlumbarpunctureisrequiredtoruleoutmeningitisorsubarachnoidhemorrhagewhentheCTscanisnegativebut
theclinicalsuspicionremainshigh
Laboratorystudies
Laboratorytestsperformedinthediagnosisandevaluationofischemicstrokeincludethefollowing:
Completebloodcount(CBC):Abaselinestudythatmayrevealacauseforthestroke(eg,polycythemia,
thrombocytosis,thrombocytopenia,leukemia)orprovideevidenceofconcurrentillness(eg,anemia)
Basicchemistrypanel:Abaselinestudythatmayrevealastrokemimic(eg,hypoglycemia,hyponatremia)or
provideevidenceofconcurrentillness(eg,diabetes,renalinsufficiency)
Coagulationstudies:Mayrevealacoagulopathyandareusefulwhenfibrinolyticsoranticoagulantsaretobe
used
Cardiacbiomarkers:Importantbecauseoftheassociationofcerebralvasculardiseaseandcoronaryartery
disease
Toxicologyscreening:Mayassistinidentifyingintoxicatedpatientswithsymptoms/behaviormimickingstroke
syndromes
Pregnancytesting:Aurinepregnancytestshouldbeobtainedforallwomenofchildbearingagewithstroke
symptomsrecombinanttissuetypeplasminogenactivator(rtPA)isapregnancyclassCagent
Arterialbloodgasanalysis:Inselectedpatientswithsuspectedhypoxemia,arterialbloodgasdefinesthe
severityofhypoxemiaandmaybeusedtodetectacidbasedisturbances
SeeWorkupformoredetail.

Management
Thegoalfortheemergentmanagementofstrokeistocompletethefollowingwithin60minutesofpatientarrival[3]:
Assessairway,breathing,andcirculation(ABCs)andstabilizethepatientasnecessary
Completetheinitialevaluationandassessment,includingimagingandlaboratorystudies
Initiatereperfusiontherapy,ifappropriate
Criticaltreatmentdecisionsfocusonthefollowing:
Theneedforairwaymanagement
Optimalbloodpressurecontrol
Identifyingpotentialreperfusiontherapies(eg,intravenousfibrinolysiswithrtPAorintraarterialapproaches)
Involvementofaphysicianwithaspecialinterestinstrokeisideal.Strokecareunitswithspeciallytrainedpersonnel
existandimproveoutcomes.
Ischemicstroketherapiesincludethefollowing:
Fibrinolytictherapy
Antiplateletagents [4,5]
Mechanicalthrombectomy
Treatmentofcomorbidconditionsmayincludethefollowing:
Reducefever
Correcthypotension/significanthypertension
Correcthypoxia
Correcthypoglycemia
Managecardiacarrhythmias
Managemyocardialischemia
Strokeprevention

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Primarystrokepreventionreferstothetreatmentofindividualswithnoprevioushistoryofstroke.Measuresmay
includeuseofthefollowing:
Plateletantiaggregants
Statins
Exercise
Lifestyleinterventions(eg,smokingcessation,alcoholmoderation)
Secondarypreventionreferstothetreatmentofindividualswhohavealreadyhadastroke.Measuresmayinclude
useofthefollowing:
Plateletantiaggregants
Antihypertensives
Statins
Lifestyleinterventions
SeeTreatmentandMedicationformoredetail.

Background
Acuteischemicstroke(AIS)ischaracterizedbythesuddenlossofbloodcirculationtoanareaofthebrain,typically
inavascularterritory,resultinginacorrespondinglossofneurologicfunction.Alsopreviouslycalledcerebrovascular
accident(CVA)orstrokesyndrome,strokeisanonspecificstateofbraininjurywithneuronaldysfunctionthathas
severalpathophysiologiccauses.Strokescanbedividedinto2types:hemorrhagicorischemic.Acuteischemic
strokeiscausedbythromboticorembolicocclusionofacerebralartery.(Seetheimagebelow.)

Maximumintensityprojection(MIP)imagefromacomputedtomographyangiogram(CTA)demonstratesafillingdefectorhigh
gradestenosisatthebranchingpointoftherightmiddlecerebralartery(MCA)trunk(redcircle),suspiciousforthrombusor
embolus.CTAishighlyaccurateindetectinglargevesselstenosisandocclusions,whichaccountforapproximatelyonethirdof
ischemicstrokes.

Nearly800,000peoplesufferstrokeseachyearintheUnitedStates8292%ofthesestrokesareischemic.Stroke
isthefourthleadingcauseofadultdeathanddisability,resultinginover$72billioninannualcost. [6]
Ischemicandhemorrhagicstrokecannotbereliablydifferentiatedonthebasisofclinicalexaminationfindingsalone.
Furtherevaluation,especiallywithbrainimagingtests(ie,computedtomography[CT]scanningormagnetic
resonanceimaging[MRI]),isrequired.(SeeWorkup.)

Strokecategories
ThesystemofcategorizingstrokedevelopedinthemulticenterTrialofORG10172inAcuteStrokeTreatment
(TOAST)dividesischemicstrokesintothefollowing3majorsubtypes[4]:
Largeartery
Smallvessel,orlacunar
Cardioembolicinfarction
Largearteryinfarctionsofteninvolvethromboticinsituocclusionsonatheroscleroticlesionsinthecarotid,
vertebrobasilar,andcerebralarteries,typicallyproximaltomajorbrancheshowever,largearteryinfarctionsmay
alsobecardioembolic.
Cardiogenicemboliareacommonsourceofrecurrentstroke.Theymayaccountforupto20%ofacutestrokesand
havebeenreportedtohavethehighest1monthmortality. [7](SeePathophysiology.)

Treatment
Recanalizationstrategies,includingintravenousrecombinanttissuetypeplasminogenactivator(rtPA)andintra
arterialapproaches,attempttoestablishrevascularizationsothatcellsintheischemicpenumbra(ametabolically
activeregion,peripheraltotheischemicarea,wherebloodflowisreduced)canberescuedbeforeirreversibleinjury
occurs.Restoringbloodflowcanmitigatetheeffectsofischemiaonlyifperformedquickly.
TheUSFoodandDrugAdministration(FDA)hasapprovedtheuseofrtPAinpatientswhomeetcriteriasetforth
bytheNationalInstituteofNeurologicDisordersandStroke(NINDS).Inparticular,rtPAmustbegivenwithin3
hoursofstrokeonsetandonlyafterCTscanninghasruledouthemorrhagicstroke.
OnthebasisofrecentEuropeandata,theAmericanHeartAssociationandAmericanStrokeAssociation
recommendedexpandingthewindowoftreatmentfrom3hoursto4.5hours,withmorestringentexclusioncriteria
forthelaterperiod(seeTreatment).TheFDAhasnotyetapprovedrtPAforthisexpandedindication,butthishas
becomethecommunitystandardinmanyinstitutions.
Otheraspectsoftreatmentforacuteischemicstrokeincludethefollowing:
Treatmentofneurologiccomplications
Supplementaloxygenasrequired

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Antiplatelettherapy
Glycemiccontrol
Optimalbloodpressurecontrol
Preventionofhyperthermia
SeealsoHemorrhagicStroke.

Anatomy
Thebrainisthemostmetabolicallyactiveorganinthebody.Whilerepresentingonly2%ofthebody'smass,it
requires1520%ofthetotalrestingcardiacoutputtoprovidethenecessaryglucoseandoxygenforitsmetabolism.
Knowledgeofcerebrovasculararterialanatomyandtheterritoriessuppliedbythecerebralarteriesisusefulin
determiningwhichvesselsareinvolvedinacutestroke.Atypicalpatternsofbrainischemiathatdonotconformto
specificvasculardistributionsmayindicateadiagnosisotherthanischemicstroke,suchasvenousinfarction.

Arterialdistributions
Inasimplifiedmodel,thecerebralhemispheresaresuppliedby3pairedmajorarteries,specifically,theanterior,
middle,andposteriorcerebralarteries.
Theanteriorandmiddlecerebralarteriescarrytheanteriorcirculationandarisefromthesupraclinoidinternalcarotid
arteries.Theanteriorcerebralartery(ACA)suppliesthemedialportionofthefrontalandparietallobesandanterior
portionsofbasalgangliaandanteriorinternalcapsule.(Seetheimagebelow.)

Lateralviewofacerebralangiogramillustratesthebranchesoftheanteriorcerebralartery(ACA)andSylviantriangle.The
pericallosalarteryhasbeendescribedtoarisedistaltotheanteriorcommunicatingarteryordistaltotheoriginofthecallosomarginal
branchoftheACA.ThesegmentalanatomyoftheACAhasbeendescribedasfollows:theA1segmentextendsfromtheinternal
carotidartery(ICA)bifurcationtotheanteriorcommunicatingarteryA2extendstothejunctionoftherostrumandgenuofthecorpus
callosumA3extendsintothebendofthegenuofthecorpuscallosumA4andA5extendposteriorlyabovethecallosalbodyand
superiorportionofthesplenium.TheSylviantriangleoverliestheopercularbranchesofthemiddlecerebralartery(MCA),withthe
apexrepresentingtheSylvianpoint.

Themiddlecerebralartery(MCA)suppliesthelateralportionsofthefrontalandparietallobes,aswellasthe
anteriorandlateralportionsofthetemporallobes,andgivesrisetoperforatingbranchestotheglobuspallidus,
putamen,andinternalcapsule.TheMCAisthedominantsourceofvascularsupplytothehemispheres.(Seethe
imagesbelow.)

Thesupratentorialvascularterritoriesofthemajorcerebralarteriesaredemonstratedsuperimposedonaxial(left)andcoronal(right)
T2weightedimagesthroughthelevelofthebasalgangliaandthalami.Themiddlecerebralartery(MCAred)suppliesthelateral
aspectsofthehemispheres,includingthelateralfrontal,parietal,andanteriortemporallobesinsulaandbasalganglia.Theanterior
cerebralartery(ACAblue)suppliesthemedialfrontalandparietallobes.Theposteriorcerebralartery(PCAgreen)suppliesthe
thalamiandoccipitalandinferiortemporallobes.Theanteriorchoroidalartery(yellow)suppliestheposteriorlimboftheinternal
capsuleandpartofthehippocampusextendingtotheanteriorandsuperiorsurfaceoftheoccipitalhornofthelateralventricle.

Frontalviewofacerebralangiogramwithselectiveinjectionoftheleftinternalcarotidartery(ICA)illustratestheanteriorcirculation.
Theanteriorcerebralartery(ACA)consistsoftheA1segmentproximaltotheanteriorcommunicatingartery,withtheA2segment
distaltoit.Themiddlecerebralartery(MCA)canbedividedinto4segments:theM1(horizontalsegment)extendstotheanterior
basalportionoftheinsularcortex(thelimeninsulae)andgivesofflaterallenticulostriatebranches,theM2(insularsegment),M3
(opercularbranches),andM4(distalcorticalbranchesonthelateralhemisphericconvexities).

Theposteriorcerebralarteriesarisefromthebasilararteryandcarrytheposteriorcirculation.Theposteriorcerebral
artery(PCA)givesrisetoperforatingbranchesthatsupplythethalamiandbrainstemandthecorticalbranchesto
theposteriorandmedialtemporallobesandoccipitallobes.(SeeTable1,below.)
Thecerebellarhemispheresaresuppliedasfollows:
Inferiorlybytheposteriorinferiorcerebellarartery(PICA),arisingfromthevertebralartery(seetheimage
below)

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Frontalprojectionfromarightvertebralarteryangiogramillustratestheposteriorcirculation.Thevertebralarteriesjointo
formthebasilarartery.Theposteriorinferiorcerebellararteries(PICAs)arisefromthedistalvertebralarteries.Theanterior
inferiorcerebellararteries(AICAs)arisefromtheproximalbasilarartery.Thesuperiorcerebellararteries(SICAs)arise
distallyfromthebasilararterypriortoitsbifurcationintotheposteriorcerebralarteries(PCAs).

Superiorlybythesuperiorcerebellarartery
Anterolaterallybytheanteriorinferiorcerebellarartery(AICA),fromthebasilarartery
Table1.VascularSupplytotheBrain(OpenTableinanewwindow)
VASCULARTERRITORY

StructuresSupplied

AnteriorCirculation(Carotid)
AnteriorCerebralArtery

Corticalbranches:medialfrontalandparietallobe

Mediallenticulostriatebranches:caudatehead,globuspallidus,anteriorlimbof
internalcapsule

MiddleCerebralArtery

Corticalbranches:lateralfrontalandparietallobeslateralandanteriortemporal
lobe

Laterallenticulostriatebranches:globuspallidusandputamen,internalcapsule

AnteriorChoroidalArtery Optictracts,medialtemporallobe,ventrolateralthalamus,coronaradiata,posterior
limboftheinternalcapsule
PosteriorCirculation(Vertebrobasilar)
PosteriorCerebralArtery

Corticalbranches:occipitallobes,medialandposteriortemporalandparietallobes

Perforatingbranches:brainstem,posteriorthalamusandmidbrain

PosteriorInferior
CerebellarArtery

Inferiorvermisposteriorandinferiorcerebellarhemispheres

AnteriorInferior
CerebellarArtery

Anterolateralcerebellum

SuperiorCerebellarArtery Superiorvermissuperiorcerebellum

Pathophysiology
Acuteischemicstrokesresultfromvascularocclusionsecondarytothromboembolicdisease(seeEtiology).Ischemia
causescellhypoxiaanddepletionofcellularadenosinetriphosphate(ATP).WithoutATP,thereisnolongerthe
energytomaintainionicgradientsacrossthecellmembraneandcelldepolarization.Influxofsodiumandcalcium
ionsandpassiveinflowofwaterintothecellleadtocytotoxicedema. [8,9,10]

Ischemiccoreandpenumbra
Anacutevascularocclusionproducesheterogeneousregionsofischemiaintheaffectedvascularterritory.Local
bloodflowislimitedtoanyresidualflowinthemajorarterialsourceplusthecollateralsupply,ifany.
Affectedregionswithcerebralbloodflowoflowerthan10mL/100goftissue/minarereferredtocollectivelyasthe
core.Thesecellsarepresumedtodiewithinminutesofstrokeonset. [11]
Zonesofdecreasedormarginalperfusion(cerebralbloodflow<25mL/100goftissue/min)arecollectivelycalled
theischemicpenumbra.Tissueinthepenumbracanremainviableforseveralhoursbecauseofmarginaltissue
perfusion. [11]

Ischemiccascade
Onthecellularlevel,theischemicneuronbecomesdepolarizedasATPisdepletedandmembraneiontransport

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systemsfail.Disruptionofcellularmetabolismalsoimpairsnormalsodiumpotassiumplasmamembranepumps,
producinganintracellularincreaseinsodium,whichinturnsincreasesintracellularwatercontent.Thiscellular
swellingisreferredtoascytotoxicedemaandoccursveryearlyincerebralischemia.
Cerebralischemiaimpairsthenormalsodiumcalciumexchangeproteinalsofoundoncellplasmamembranes.The
resultinginfluxofcalciumleadstothereleaseofanumberofneurotransmitters,includinglargequantitiesof
glutamate,whichinturnactivatesNmethylDaspartate(NMDA)andotherexcitatoryreceptorsonotherneurons.
Theseneuronsthenbecomedepolarized,causingfurthercalciuminflux,furtherglutamaterelease,andlocal
amplificationoftheinitialischemicinsult.Thismassivecalciuminfluxalsoactivatesvariousdegradativeenzymes,
leadingtothedestructionofthecellmembraneandotheressentialneuronalstructures. [12]Freeradicals,
arachidonicacid,andnitricoxidearegeneratedbythisprocess,whichleadstofurtherneuronaldamage.
Ischemiaalsodirectlyresultsindysfunctionofthecerebralvasculature,withbreakdownofthebloodbrainbarrier
occurringwithin46hoursafterinfarction.Followingthebarriersbreakdown,proteinsandwaterfloodintothe
extracellularspace,leadingtovasogenicedema.Thisproducesgreaterlevelsofbrainswellingandmasseffectthat
peakat35daysandresolveoverthenextseveralweekswithresorptionofwaterandproteins. [13,14]
Withinhourstodaysafterastroke,specificgenesareactivated,leadingtotheformationofcytokinesandother
factorsthat,inturn,causefurtherinflammationandmicrocirculatorycompromise. [12]Ultimately,theischemic
penumbraisconsumedbytheseprogressiveinsults,coalescingwiththeinfarctedcore,oftenwithinhoursofthe
onsetofthestroke.
Infarctionresultsinthedeathofastrocytes,aswellasthesupportingoligodendroglialandmicroglialcells.The
infarctedtissueeventuallyundergoesliquefactionnecrosisandisremovedbymacrophages,withthedevelopment
ofparenchymalvolumeloss.Awellcircumscribedregionofcerebrospinalfluidlikelowdensity,resultingfrom
encephalomalaciaandcysticchange,iseventuallyseen.Theevolutionofthesechronicchangesmaybeseeninthe
weekstomonthsfollowingtheinfarction.(Seetheimagesbelow.)

Vasculardistributions:Middlecerebralartery(MCA)infarction.Noncontrastcomputedtomography(CT)scanningdemonstratesa
largeacuteinfarctionintheMCAterritoryinvolvingthelateralsurfacesoftheleftfrontal,parietal,andtemporallobes,aswellasthe
leftinsularandsubinsularregions,withmasseffectandrightwardmidlineshift.Thereissparingofthecaudateheadandatleastpart
ofthelentiformnucleusandinternalcapsule,whichreceivebloodsupplyfromthelaterallenticulostriatebranchesoftheM1segment
oftheMCA.Notethelackofinvolvementofthemedialfrontallobe(anteriorcerebralartery[ACA]territory),thalami,andparamedian
occipitallobe(posteriorcerebralartery[PCA]territory).

Vasculardistributions:Anteriorcerebralartery(ACA)infarction.Diffusionweightedimageontheleftdemonstrateshighsignalinthe
paramedianfrontalandhighparietalregions.Theoppositediffusionweightedimageinadifferentpatientdemonstratesrestricted
diffusioninalargerACAinfarctioninvolvingtheleftparamedianfrontalandposteriorparietalregions.Thereisalsoinfarctionofthe
lateraltemporoparietalregionsbilaterally(bothmiddlecerebralartery[MCA]distributions),greaterontheleftindicatingmultivessel
involvementandsuggestingemboli.

Vasculardistributions:Posteriorcerebralartery(PCA)infarction.Thenoncontrastcomputedtomography(CT)imagesdemonstrate
PCAdistributioninfarctioninvolvingtherightoccipitalandinferomedialtemporallobes.Theimageontherightdemonstrates
additionalinvolvementofthethalamus,alsopartofthePCAterritory.

Vasculardistributions:Anteriorchoroidalarteryinfarction.Thediffusionweightedimage(left)demonstrateshighsignalwith
associatedsignaldropoutontheapparentdiffusioncoefficient(ADC)mapinvolvingtheposteriorlimboftheinternalcapsule.Thisis
thetypicaldistributionoftheanteriorchoroidalartery,thelastbranchoftheinternalcarotidartery(ICA)beforebifurcatingintothe
anteriorandmiddlecerebralarteries.Theanteriorchoroidalarterymayalsoarisefromthemiddlecerebralartery(MCA).

Hemorrhagictransformationofischemicstroke
Hemorrhagictransformationrepresentstheconversionofanischemicinfarctionintoanareaofhemorrhage.Thisis
estimatedtooccurin5%ofuncomplicatedischemicstrokes,intheabsenceoffibrinolytictreatment.Hemorrhagic
transformationisnotalwaysassociatedwithneurologicdecline,withtheconversionrangingfromthedevelopment
ofsmallpetechialhemorrhagestotheformationofhematomasthatproduceneurologicdeclineandmay

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necessitatesurgicalevacuationordecompressivehemicraniectomy.
Proposedmechanismsforhemorrhagictransformationincludereperfusionofischemicallyinjuredtissue,eitherfrom
recanalizationofanoccludedvesselorfromcollateralbloodsupplytotheischemicterritoryordisruptionofthe
bloodbrainbarrier.Withdisruptionofthebloodbrainbarrier,redbloodcellsextravasatefromtheweakened
capillarybed,producingpetechialhemorrhageormorefrankintraparenchymalhematoma. [8,15,16]
Hemorrhagictransformationofanischemicinfarctoccurswithin214dayspostictus,usuallywithinthefirstweek.It
ismorecommonlyseenfollowingcardioembolicstrokesandismorelikelytooccurwithlargerinfarctvolumes. [5,8,
17]HemorrhagictransformationisalsomorelikelyfollowingadministrationofrtPAinpatientswhosenoncontrast
CT(NCCT)scansdemonstrateareasofhypodensity. [18,19,20]

Poststrokecerebraledemaandseizures
Althoughclinicallysignificantcerebraledemacanoccurafteranteriorcirculationischemicstroke,itisthoughttobe
somewhatrare(1020%). [3]Edemaandherniationarethemostcommoncausesofearlydeathinpatientswith
hemisphericstroke.
Seizuresoccurin223%ofpatientswithinthefirstdaysafterischemicstroke. [3]Afractionofpatientswhohave
experiencedstrokedevelopchronicseizuredisorders.

Etiology
Ischemicstrokesresultfromeventsthatlimitorstopbloodflow,suchasextracranialorintracranialthrombotic
embolism,thrombosisinsitu,orrelativehypoperfusion.Asbloodflowdecreases,neuronsceasefunctioning.
Althougharangeofthresholdshasbeendescribed,irreversibleneuronalischemiaandinjuryisgenerallythoughtto
beginatbloodflowratesoflessthan18mL/100goftissue/min,withcelldeathoccurringrapidlyatratesbelow10
mL/100goftissue/min

Riskfactors
Riskfactorsforischemicstrokeincludemodifiableandnonmodifiableconditions.Identificationofriskfactorsineach
patientcanuncovercluestothecauseofthestrokeandthemostappropriatetreatmentandsecondaryprevention
plan.
Nonmodifiableriskfactorsincludethefollowing(althoughtherearelikelymanyothers):
Age
Race
Sex
Ethnicity
Historyofmigraineheadaches [21]
Fibromusculardysplasia
Heredity:Familyhistoryofstrokeortransientischemicattacks(TIAs)
Inaprospectivestudyof27,860womenaged45yearsorolderwhowereparticipatingintheWomen'sHealth
Study,Kurthetalfoundthatmigrainewithaurawasastrongriskfactorforanytypeofstroke.Theadjusted
incidenceofthisriskfactorper1000womenperyearwassimilartothoseofotherknownriskfactors,including
systolicbloodpressure180mmHgorhigher,bodymassindex35kg/m2orgreater,historyofdiabetes,family
historyofmyocardialinfarction,andsmoking. [22]
Formigrainewithaura,thetotalincidenceofstrokeinthestudywas4.3per1000womenperyear,theincidenceof
ischemicstrokewas3.4per1000peryear,andtheincidenceofhemorrhagicstrokewas0.8per1000peryear.
Modifiableriskfactorsincludethefollowing[23]:
Hypertension(themostimportant)
Diabetesmellitus
Cardiacdisease:Atrialfibrillation,valvulardisease,heartfailure,mitralstenosis,structuralanomalies
allowingrighttoleftshunting(eg,patentforamenovale),andatrialandventricularenlargement
Hypercholesterolemia
TIAs
Carotidstenosis
Hyperhomocystinemia
Lifestyleissues:Excessivealcoholintake,tobaccouse,illicitdruguse,physicalinactivity [24]
Obesity
Oralcontraceptiveuse/postmenopausalhormoneuse
Sicklecelldisease
In2014,theAmericanHeartAssociationandtheAmericanStrokeAssociationissuedguidelinesforthereductionof
strokeriskspecificallyinwomen.Thesegenderspecificrecommendationsincludethefollowing[25,26]:
Astrokeriskscoreshouldbedevelopedspecificallyforwomen
Womenwithahistoryofhighbloodpressurebeforepregnancyshouldbeconsideredforlowdoseaspirin
and/orcalciumsupplementtreatmenttoreducetheriskofpreeclampsia
Bloodpressuremedicationmaybeconsideredforpregnantwomenwithmoderatelyhighbloodpressure
(150159mmHg/100109mmHg),andpregnantwomenwithseverehighbloodpressure(160/110mmHgor
above)shouldbetreated
Womenshouldbescreenedforhighbloodpressurebeforetheystartusingbirthcontrolpillsbecauseofan
increasedriskofstroke
Womenwithmigraineheadacheswithaurashouldbeencouragedtoquitsmokingtoreducetheriskofstroke
Womenoverage75shouldbescreenedforatrialfibrillation

Geneticandinflammatorymechanisms

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Evidencecontinuestoaccumulatethatinflammationandgeneticfactorshaveimportantrolesinthedevelopmentof
atherosclerosisand,specifically,instroke.Accordingtothecurrentparadigm,atherosclerosisisnotabland
cholesterolstoragedisease,aspreviouslythought,butadynamic,chronic,inflammatoryconditioncausedbya
responsetoendothelialinjury.
Traditionalriskfactors,suchasoxidizedlowdensitylipoprotein(LDL)cholesterolandsmoking,contributetothis
injury.Ithasbeensuggested,however,thatinfectionsmayalsocontributetoendothelialinjuryandatherosclerosis.
Hostgeneticfactors,moreover,maymodifytheresponsetotheseenvironmentalchallenges,althoughinheritedrisk
forstrokeislikelymultigenic.Evenso,specificsinglegenedisorderswithstrokeasacomponentofthephenotype
demonstratethepotencyofgeneticsindeterminingstrokerisk.
Anumberofgenesareknowntoincreasesusceptibilitytoischemicstroke.MutationstotheF2andF5genesare
relativelycommoninthegeneralpopulationandincreasetheriskofthrombosis.Mutationsinthefollowinggenes
alsoareknowntoincreasetheriskofstroke:
NOS3:Anitricoxidesynthetasegeneinvolvedinvascularrelaxation[27]
ALOX5AP:Involvedinthemetabolismofarachidonicacid [28]
PRKCH:Involvedinmajorsignaltransductionsystems [29]
Hyperhomocysteinemiaandhomocystinuria
Hyperhomocysteinemiaisimplicatedinthepathogenesisofischemicstroke.Themostcommonconcernis
mutationsinthe5,10methylenetetrahydrofolatereductase(MTHFR)gene.Inmanypopulations,themutantallele
frequencyreachespolymorphicproportions,andtheriskfactorforcerebrovasculardiseaseisrelatedtotheserum
levelofhomocysteine.Furthermore,inpersonswhoarecompoundheterozygotesforMTHFRmutation,ifelevated
homocysteineisfounditcanbeloweredwithoralfolicacidtherapy.
Inaddition,hyperhomocysteinemiacanbeseenincystathionebetasynthetase(CBS)deficiency,whichisgenerally
referredtoashomocystinuria.Thisdisorderisinheritedinanautosomalrecessivemanner.Symptomsusually
manifestearlyinlife.Patientshaveamarfanoidhabitus,ectopialentis,andmyopiaandgenerallyhaveintellectual
disability. [30]
Thromboemboliceventsarethemostcommoncauseofdeathforpatientswithhomocystinuriaandmaybeofany
type,includingmyocardialinfarction.Theriskofhavingavasculareventinhomocystinuriais50%byage30. [31]It
waspreviouslysuggestedthatpersonswhoareheterozygousformutationsintheCBSgenemayhaveanincreased
riskofcerebrovasculardiseaseaswell,butseveralmorerecentstudiesonthissubjectfailedtoreplicatethisfinding.
Amyloidangiopathies
Amyloidangiopathiesarealsoknowntoincreaseriskforstrokeanddementia.MutationsintheCST3geneare
causativeandareinheritedinanautosomaldominantmanner.Suffererswillhavediffusedepositionofamyloid,
includinginthebrain.Theonsetofsymptomsistypicallyinthethirdorfourthdecadeoflife,withdeathoccurring
beforeage60years.TheseangiopathiesappeartobemostcommonintheIcelandicpopulation. [32]
CADASIL
Cerebralarteriopathy,autosomaldominant,withsubcorticalinfarctsandleukoencephalopathy(CADASIL),iscaused
bymutationsintheNOTCH3gene.Itaffectsthesmallarteriesofthebrain.Strokelikeepisodestypicallyoccurata
meanageof46years,withanagerangeof1967years.Whitematterchangesinthebrainaretypicallyevidentby
youngadulthoodandprogressovertime. [33]
Migraineheadachesoccurin3040%ofpeoplewithCADASIL.Approximately60%ofsymptomaticindividualshave
cognitivedeficits,whichcanstartasearlyasage35years,andmanydevelopmultiinfarctdementia. [34]
Othermutations
Genomewideassociationstudieshaverevealedadditionallocithatarecommonlyassociatedwithischemicstroke.
Earlyonsetischemicstrokehasbeenfoundtobeassociatedwith2singlenucleotidepolymorphismson2q23.3. [35]
LargevesselstrokehasbeenassociatedwithvariationsinHDAC9,PITX2,andZFHX3. [36]HDAC9islocated
on7p21.1,whilePITX2andZFHX3arelocatedon9p21.Itisofnotethatthe9p21locushasalsobeenassociated
withcardiovasculardisease.
Apolymorphismat2q36.3wasfoundinwhichadenosinesubstitutionconferredalowerriskofischemicstrokeinan
additivefashion. [37]Anadditionalstudysuggestedanassociationbetweenischemicstrokeandalocuson12p13.
[38]

Formoreinformation,seeGeneticandInflammatoryMechanismsinStroke.Inaddition,completeinformationon
thefollowingmetabolicdiseasesandstrokecanbefoundinthefollowingmainarticles:
MethylmalonicAcidemia
Homocystinuria/Homocysteinemia
FabryDisease
MELASSyndrome
HyperglycemiaandHypoglycemiainStroke

Largearteryocclusion
Largearteryocclusiontypicallyresultsfromembolizationofatheroscleroticdebrisoriginatingfromthecommonor
internalcarotidarteriesorfromacardiacsource.Asmallernumberoflargearteryocclusionsmayarisefromplaque
ulcerationandinsituthrombosis.LargevesselischemicstrokesmorecommonlyaffecttheMCAterritory,withthe
ACAterritoryaffectedtoalesserdegree.(Seetheimagesbelow.)

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Noncontrastcomputedtomography(CT)scanina52yearoldmanwithahistoryofworseningrightsidedweaknessandaphasia
demonstratesdiffusehypodensityandsulcaleffacementwithmasseffectinvolvingtheleftanteriorandmiddlecerebralartery
territoriesconsistentwithacuteinfarction.Therearescatteredcurvilinearareasofhyperdensitynotedsuggestiveofdeveloping
petechialhemorrhageinthislargeareaofinfarction.

Magneticresonanceangiogram(MRA)ina52yearoldmandemonstratesocclusionoftheleftprecavernoussupraclinoidinternal
carotidartery(ICA,redcircle),occlusionorhighgradestenosisofthedistalmiddlecerebralartery(MCA)trunkandattenuationof
multipleM2branches.Thediffusionweightedimage(right)demonstrateshighsignalconfirmedtobetruerestricteddiffusiononthe
apparentdiffusioncoefficient(ADC)mapconsistentwithacuteinfarction.

Maximumintensityprojection(MIP)imagefromacomputedtomographyangiogram(CTA)demonstratesafillingdefectorhigh
gradestenosisatthebranchingpointoftherightmiddlecerebralartery(MCA)trunk(redcircle),suspiciousforthrombusor
embolus.CTAishighlyaccurateindetectinglargevesselstenosisandocclusions,whichaccountforapproximatelyonethirdof
ischemicstrokes.

Lacunarstrokes
Lacunarstrokesrepresent1320%ofallischemicstrokes.Theyresultfromocclusionofthepenetratingbranchesof
theMCA,thelenticulostriatearteries,orthepenetratingbranchesofthecircleofWillis,vertebralartery,orbasilar
artery.Thegreatmajorityoflacunarstrokesarerelatedtohypertension.(Seetheimagebelow.)

Axialnoncontrastcomputedtomography(CT)scandemonstratesafocalareaofhypodensityintheleftposteriorlimboftheinternal
capsuleina60yearoldmanwithacuteonsetofrightsidedweakness.Thelesiondemonstrateshighsignalonthefluidattenuated
inversionrecovery(FLAIR)sequence(middleimage)anddiffusionweightedmagneticresonanceimaging(MRI)scan(rightimage),
withlowsignalontheapparentdiffusioncoefficient(ADC)mapsindicatinganacutelacunarinfarction.Lacunarinfarctsaretypically
nomorethan1.5cminsizeandcanoccurinthedeepgraymatterstructures,coronaradiata,brainstem,andcerebellum.

Causesoflacunarinfarctsincludethefollowing:
Microatheroma
Lipohyalinosis
Fibrinoidnecrosissecondarytohypertensionorvasculitis
Hyalinearteriosclerosis
Amyloidangiopathy
Microemboli

Embolicstrokes
Cardiogenicembolimayaccountforupto20%ofacutestrokes.Embolimayarisefromtheheart,theextracranial
arteries,includingtheaorticarchor,rarely,therightsidedcirculation(paradoxicalemboli)withsubsequentpassage
throughapatentforamenovale. [39]Sourcesofcardiogenicemboliincludethefollowing:
Valvularthrombi(eg,inmitralstenosisorendocarditisorfromuseofaprostheticvalve)
Muralthrombi(eg,inmyocardialinfarction,atrialfibrillation,dilatedcardiomyopathy,orseverecongestive
heartfailure)
Atrialmyxoma
Acutemyocardialinfarctionisassociatedwitha23%incidenceofembolicstrokes,ofwhich85%occurinthefirst
monthaftertheinfarction. [40]Embolicstrokestendtohaveasuddenonset,andneuroimagingmaydemonstrate
previousinfarctsinseveralvascularterritoriesormayshowcalcificemboli.

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Cardioembolicstrokesmaybeisolated,multipleandinasinglehemisphere,orscatteredandbilateralthelatter2
typesindicatemultiplevasculardistributionsandaremorespecificforcardioembolism.Multipleandbilateralinfarcts
canbetheresultofembolicshowersorrecurrentemboli.Otherpossibilitiesforsingleandbilateralhemispheric
infarctionsincludeembolioriginatingfromtheaorticarchanddiffusethromboticorinflammatoryprocessesthatcan
leadtomultiplesmallvesselocclusions.(Seetheimagebelow.)[41,42]

Cardioembolicstroke:Axialdiffusionweightedimagesdemonstratescatteredfociofhighsignalinthesubcorticalanddeepwhite
matterbilaterallyinapatientwithaknowncardiacsourceforembolization.Anareaoflowsignalintheleftgangliocapsularregion
maybesecondarytopriorhemorrhageorsubacutetochroniclacunarinfarct.Recurrentstrokesaremostcommonlysecondaryto
cardioembolicphenomenon.

Formoreinformation,seeCardioembolicStroke.

Thromboticstrokes
Thrombogenicfactorsmayincludeinjurytoandlossofendothelialcellsthislossexposesthesubendotheliumand
resultsinplateletactivationbythesubendothelium,activationoftheclottingcascade,inhibitionoffibrinolysis,and
bloodstasis.Thromboticstrokesaregenerallythoughttooriginateonrupturedatheroscleroticplaques.Arterial
stenosiscancauseturbulentbloodflow,whichcanpromotethrombusformationatherosclerosis(ie,ulcerated
plaques)andplateletadherence.Allcausetheformationofbloodclotsthateitherembolizeoroccludetheartery.
Intracranialatherosclerosismaybethecauseofthromboticstrokeinpatientswithwidespreadatherosclerosis.In
otherpatients,especiallyyoungerpatients,othercausesshouldbeconsidered,includingthefollowing[8,43]:
Hypercoagulablestates(eg,antiphospholipidantibodies,proteinCdeficiency,proteinSdeficiency,
pregnancy)
Sicklecelldisease
Fibromusculardysplasia
Arterialdissections
Vasoconstrictionassociatedwithsubstanceabuse(eg,cocaine,amphetamines)

Watershedinfarcts
Vascularwatershed,orborderzone,infarctionsoccuratthemostdistalareasbetweenarterialterritories.Theyare
believedtobesecondarytoembolicphenomenonortoseverehypoperfusion,asoccurs,forexample,incarotid
occlusionorprolongedhypotension.(Seetheimagebelow.)[44,45,46]

Magneticresonanceimaging(MRI)scanwasobtainedina62yearoldmanwithhypertensionanddiabetesandahistoryoftransient
episodesofrightsidedweaknessandaphasia.Thefluidattenuatedinversionrecovery(FLAIR)image(left)demonstratespatchy
areasofhighsignalarrangedinalinearfashioninthedeepwhitematter,bilaterally.Thisconfigurationistypicalfordeepborder
zone,orwatershed,infarction,inthiscasetheanteriorandposteriormiddlecerebralartery(MCA)watershedareas.Theleftsided
infarctshavecorrespondinglowsignalontheapparentdiffusioncoefficient(ADC)map(right),signifyingacuity.Anoldleftposterior
parietalinfarctisnotedaswell.

Flowdisturbances
Strokesymptomscanresultfrominadequatecerebralbloodflowbecauseofdecreasedbloodpressure(and
specifically,decreasedcerebralperfusionpressure)orasaresultofhematologichyperviscosityfromsicklecell
diseaseorotherhematologicillnesses,suchasmultiplemyelomaandpolycythemiavera.Intheseinstances,
cerebralinjurymayoccurinthepresenceofdamagetootherorgansystems.Formoreinformation,seeBlood
DyscrasiasandStroke.

Epidemiology
StrokeistheleadingcauseofdisabilityandthefourthleadingcauseofdeathintheUnitedStates. [47,48]Each
year,approximately795,000peopleintheUnitedStatesexperiencenew(610,000people)orrecurrent(185,000
people)stroke. [6]Epidemiologicstudiesindicatethat8292%ofstrokesintheUnitedStatesareischemic.
AccordingtotheWorldHealthOrganization(WHO),15millionpeoplesufferstrokeworldwideeachyear.Ofthese,5
milliondie,andanother5millionareleftpermanentlydisabled. [49]

Race,sex,andagerelateddemographics
IntheUnitedStates,blackshaveanageadjustedriskofdeathfromstrokethatis1.49timesthatofwhites. [50]
Hispanicshavealoweroverallincidenceofstrokethanwhitesandblacksbutmorefrequentlacunarstrokesand
strokeatanearlierage.
Menareathigherriskforstrokethanwomenwhitemenhaveastrokeincidenceof62.8per100,000,withdeath
beingthefinaloutcomein26.3%ofcases,whilewomenhaveastrokeincidenceof59per100,000andadeath
rateof39.2%.
Althoughstrokeoftenisconsideredadiseaseofelderlypersons,onethirdofstrokesoccurinpersonsyoungerthan

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65years. [48]Riskofstrokeincreaseswithage,especiallyinpatientsolderthan64years,inwhom75%ofallstrokes
occur.

Prognosis
IntheFraminghamandRochesterstrokestudies,theoverallmortalityrateat30daysafterstrokewas28%,the
mortalityrateat30daysafterischemicstrokewas19%,andthe1yearsurvivalrateforpatientswithischemic
strokewas77%.However,theprognosisafteracuteischemicstrokevariesgreatlyinindividualpatients,depending
onthestrokeseverityandonthepatientspremorbidcondition,age,andpoststrokecomplications. [4]
AstudyutilizingthelargenationalGetWithTheGuidelinesStrokeregistryfoundthatthebaselineNational
InstitutesofHealthStrokeScale(NIHSS)scorewasthestrongestpredictorofearlymortalityrisk,evenmoreso
thancurrentlyusedmortalitypredictionmodelsincorporatingmultipleclinicaldata. [51]Cardiogenicemboliare
associatedwiththehighest1monthmortalityinpatientswithacutestroke.
Thepresenceofcomputedtomography(CT)scanevidenceofinfarctionearlyinpresentationhasbeenassociated
withpooroutcomeandwithanincreasedpropensityforhemorrhagictransformationafterfibrinolytictherapy(see
Pathophysiology). [5,52,53]Hemorrhagictransformationisestimatedtooccurin5%ofuncomplicatedischemic
strokesintheabsenceoffibrinolytictherapy,althoughitisnotalwaysassociatedwithneurologicdecline.Indeed,
hemorrhagictransformationrangesfromthedevelopmentofsmallpetechialhemorrhagestotheformationof
hematomasrequiringevacuation.
Acuteischemicstrokehasbeenassociatedwithacutecardiacdysfunctionandarrhythmia,whichthencorrelatewith
worsefunctionaloutcomeandmorbidityat3months.Datasuggestthatseverehyperglycemiaisindependently
associatedwithpooroutcomeandreducedreperfusioninfibrinolysis,aswellasextensionoftheinfarctedterritory.
[54,55,56]

InstrokesurvivorsfromtheFraminghamHeartStudy,31%neededhelpcaringforthemselves,20%neededhelp
whenwalking,and71%hadimpairedvocationalcapacityinlongtermfollowup.Formoreinformation,seethe
MedscapeReferencearticleMotorRecoveryinStroke.

PatientEducation
Publiceducationmustinvolveallagegroups.Incorporatingstrokeintobasiclifesupport(BLS)andcardiopulmonary
resuscitation(CPR)curriculaisjustonewaytoreachayoungeraudience.Avenuestoreachanaudiencewitha
higherstrokeriskcouldincludelocalchurches,employers,andseniororganizationstopromotestrokeawareness.
TheAmericanStrokeAssociation(ASA)advisesthepublictobeawareofthesymptomsofstrokethatareeasily
recognized,includingthesuddenonsetofanyofthefollowing,andtocall911immediately:
Numbnessorweaknessofface,arm,orleg,especiallyon1sideofthebody
Confusion
Difficultyinspeakingorunderstanding
Deteriorationofvisionin1orbotheyes
Difficultyinwalking,dizziness,andlossofbalanceorcoordination
Severeheadachewithnoknowncause
Inthespringof2013,theASAlaunchedastrokepubliceducationcampaignthatusestheacronymFASTtoteach
thewarningsignsofstrokeandtheimportanceofcalling911,asfollows:
F:Facedrooping
A:Armweakness
S:Speechdifficulty
T:Timetocall911
Forpatienteducationinformation,seetheStrokeHealthCenterandtheBrainandNervousSystemHealthCenter,
aswellasStroke,TransientIschemicAttack(TIA,Ministroke),andStrokeRelatedDementia.

ContributorInformationandDisclosures
Author
EdwardCJauch,MD,MS,FAHA,FACEPProfessor,Director,DivisionofEmergencyMedicine,Professor,
DepartmentofNeurosciences,AssociateViceChairofResearch,DepartmentofMedicine,MedicalUniversityof
SouthCarolinaCollegeofMedicine
EdwardCJauch,MD,MS,FAHA,FACEPisamemberofthefollowingmedicalsocieties:AmericanCollegeof
EmergencyPhysicians,AmericanHeartAssociation,AmericanMedicalAssociation,NationalStrokeAssociation,
SocietyforAcademicEmergencyMedicine,andSouthCarolinaMedicalAssociation
Disclosure:GenentechGrant/researchfundsSitePI
Coauthor(s)
BrianStettler,MDAssistantProfessor,ProgramDirector,EmergencyMedicineResidencyProgram,
DepartmentofEmergencyMedicine,andFacultyGreaterCincinnati/NorthernKentuckyStrokeTeam,University
ofCincinnati
Disclosure:Nothingtodisclose.
ChiefEditor
HelmiLLutsep,MDProfessorandViceChair,DepartmentofNeurology,OregonHealthandScience
UniversitySchoolofMedicineAssociateDirector,OregonStrokeCenter
HelmiLLutsep,MDisamemberofthefollowingmedicalsocieties:AmericanAcademyofNeurologyand
AmericanStrokeAssociation
Disclosure:StrykerNeurovascularConsultingfeeReviewpanelmembership

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AdditionalContributors
JeffreyLArnold,MD,FACEPChairman,DepartmentofEmergencyMedicine,SantaClaraValleyMedical
Center
JeffreyLArnold,MD,FACEPisamemberofthefollowingmedicalsocieties:AmericanAcademyofEmergency
MedicineandAmericanCollegeofPhysicians
Disclosure:Nothingtodisclose.
JosephUBecker,MDFellow,GlobalHealthandInternationalEmergencyMedicine,StanfordUniversitySchool
ofMedicine
JosephUBecker,MDisamemberofthefollowingmedicalsocieties:AmericanCollegeofEmergency
Physicians,EmergencyMedicineResidentsAssociation,PhiBetaKappa,andSocietyforAcademicEmergency
Medicine
Disclosure:Nothingtodisclose.
SalvadorCruzFlores,MD,MPH,FAHA,FCCMProfessorofNeurologyandEpidemiology,SidneyWSouers
EndowedChair,DirectorofSouersStrokeInstitute,CerebrovascularandNeurointensiveCareSection,Director,
VascularNeurologyFellowshipTrainingProgram,InterimChairman,DepartmentofNeurologyandPsychiatry,St
LouisUniversitySchoolofMedicineDirector,NeuroscienceIntensiveCareUnit(5ICU),StLouisUniversity
Hospital
SalvadorCruzFlores,MD,MPH,FAHA,FCCMisamemberofthefollowingmedicalsocieties:American
AcademyofHospiceandPalliativeMedicine,AmericanAcademyofNeurology,AmericanCollegeofPhysicians,
AmericanHeartAssociation,AmericanSocietyofNeuroimaging,AmericanStrokeAssociation,NationalStroke
Association,NeurocriticalCareSociety,andSocietyofCriticalCareMedicine
Disclosure:AxioincHonorariaReviewpanelmembershipRocheHonorariaReviewpanelmembershipLilly
HonorariaReviewpanelmembershipBiotronikHonorariaReviewpanelmembership
JStephenHuff,MDAssociateProfessorofEmergencyMedicineandNeurology,DepartmentofEmergency
Medicine,UniversityofVirginiaSchoolofMedicine
JStephenHuff,MDisamemberofthefollowingmedicalsocieties:AmericanAcademyofEmergencyMedicine,
AmericanAcademyofNeurology,AmericanCollegeofEmergencyPhysicians,andSocietyforAcademic
EmergencyMedicine
Disclosure:Nothingtodisclose.
RichardSKrause,MDSeniorClinicalFaculty/ClinicalAssistantProfessor,DepartmentofEmergencyMedicine,
UniversityofBuffaloStateUniversityofNewYorkSchoolofMedicineandBiomedicalSciences
RichardSKrause,MDisamemberofthefollowingmedicalsocieties:AlphaOmegaAlpha,AmericanAcademy
ofEmergencyMedicine,AmericanCollegeofEmergencyPhysicians,andSocietyforAcademicEmergency
Medicine
Disclosure:Nothingtodisclose.
FranciscoTalavera,PharmD,PhDAdjunctAssistantProfessor,UniversityofNebraskaMedicalCenterCollege
ofPharmacyEditorinChief,MedscapeDrugReference
Disclosure:MedscapeSalaryEmployment
CharlesRWiraIII,MDAssistantProfessor,SectionofEmergencyMedicine,YaleUniversitySchoolof
MedicineDEMLiaisonandAttendingPhysician,YaleAcuteStrokeService,DepartmentofNeurology,Yale
NewHavenHospital
CharlesRWiraIII,MDisamemberofthefollowingmedicalsocieties:AmericanCollegeofEmergency
Physicians,AmericanHeartAssociation,AmericanStrokeAssociation,NeurocriticalCareSociety,Societyfor
AcademicEmergencyMedicine,andSocietyofCriticalCareMedicine
Disclosure:Nothingtodisclose.

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