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OfficialreprintfromUpToDate www.uptodate.com2015UpToDate
AuthorsJamaryOliveiraFilho,MD,MS,PhDWalterJKoroshetz,MD
SectionEditorScottEKasner,MD
DeputyEditorJohnFDashe,MD,PhD
Antithrombotictreatmentofacuteischemicstrokeandtransientischemicattack
Alltopicsareupdatedasnewevidencebecomesavailableandourpeerreviewprocessiscomplete.Literaturereviewcurrentthrough:Mar2015.|Thistopiclastupdated:Oct16,2013.
INTRODUCTIONThemanagementofpatientswithacuteischemicstrokeinvolvesseveralphases(see"Initialassessmentandmanagementofacutestroke").Thegoalsintheinitialphaseinclude:
Timelyrestorationofbloodflowusingthrombolytictherapyisthemosteffectivemaneuverforsalvagingischemicbraintissuethatisnotalreadyinfarcted.Thereisanarrowwindowduringwhichthiscanbeaccomplished,thatis,within4.5hoursofsymptomonset.Recommendationsforpatientsabletoreceivethrombolytictherapyarefoundelsewhere.(See"Intravenousfibrinolytic(thrombolytic)therapyinacuteischemicstroke:Therapeuticuse"and"Reperfusiontherapyforacuteischemicstroke".)
Inadditiontothrombolysis,therearetwomajorclassesofantithromboticdrugsthatcanbeusedtotreatacuteischemicstroke:
Thistopicwillreviewtheuseofacuteantithrombotictreatments(antiplateletagents,heparin,andlowmolecularweightheparin)forpatientswhoarenottreatedwiththrombolytictherapy.Themanagementofspecificsubtypesofischemicstrokebeyondtheacutephaseisdiscussedseparately.(See"Secondarypreventionforspecificcausesofischemicstrokeandtransientischemicattack".)
ANTIPLATELETAGENTSInlargerandomizedcontrolledtrials,early(within48hours)initiationofaspirinhasshownbenefitforthetreatmentofacuteischemicstroke.Inaddition,early(within24hours)initiationandshorttermuseofdualantiplatelettherapywithclopidogrelplusaspirinappearstobebeneficialforAsianpatientswithhighriskTIAorminorstroke.Theutilityofotherantiplateletagents,aloneorincombinationwithaspirin,remainstobeproveninthissetting.
Theuseofantiplateletagentsforthesecondarypreventionofischemicstrokeisdiscussedindetailseparately.(See"Antiplatelettherapyforsecondarypreventionofstroke".)
AspirinTwomajorclinicaltrialsstudiedthebenefitsandrisksofaspirininthesettingofacuteischemicstroke.
InsuringmedicalstabilityDeterminingeligibilityforthrombolytictherapy(table1)Movingtowarduncoveringthepathophysiologicbasisofthestroke
AntiplateletsAnticoagulants
TheInternationalStrokeTrial(IST)enrolled19,435patientswithsuspectedacuteischemicstroke[1].Patientsallocatedtoaspirin(300mg)within48hoursofsymptomonsetexperiencedsignificantreductionsinthe14dayrecurrenceofischemicstroke(2.8versus3.9percent)andinthecombinedoutcomeofnonfatalstrokeordeath(11.3versus12.4percent).
IntheChineseAcuteStrokeTrial(CAST),21,100patientswererandomizedto160mgofaspirindailyorplacebo,alsowithin48hoursoftheonsetofacuteischemicstroke[2].Aspirinallocatedpatientsexperienceda14percentreductionintotalmortalityatfourweeks(3.3versus3.9percent).
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Takentogether,theISTandCASTtrialsdemonstratedthataspirintherapyinacuteischemicstrokeledtoareductionof11nonfatalstrokesordeathsper1000patientsinthefirstfewweeksbutcausedapproximatelytwohemorrhagicstrokes[3].Thus,approximatelyninenonfatalstrokesordeathswereavoidedforevery1000earlytreatedpatients.Theseeffectsweresimilarinthepresenceorabsenceofatrialfibrillation.Usingtheendpointofdeathorresidualimpairmentleavingthepatientdependent,thecombineddatademonstratedareductionof13per1000patientsafterseveralweekstosixmonthsoffollowup.
Asystematicreviewofantiplatelettherapyforacutestrokeincluded12trialsinvolving43,041patients,buttheISTandCASTstudiescontributed94percentofthedata[4].Thereviewersconcludedthatstartingaspirin(160to300mgdaily)within48hoursofpresumedischemicstrokeonsetreducedtheriskofearlyrecurrentischemicstrokewithoutamajorriskofearlyhemorrhagiccomplicationsandimprovedlongtermoutcome.
CombinationantiplateletsEarlyinitiationandshorttermuseofcombinationantiplateletagentsforacuteischemicstrokeorTIAmaybebeneficial,buttheavailableevidenceisnotentirelyconsistent,andislimitedwithregardtothepopulationsstudied:
TheCHANCEtrialrandomlyassigned5170Chinesepatientswithin24hoursofonsetofhighriskTIAorminorischemicstroketoeitherdualantiplatelettherapywithclopidogrelandaspirin(clopidogrel300mgloadingdose,then75mgdailyfor90days,plusaspirin75mgdailyforthefirst21days)ortoplaceboandaspirin(75mgdailyfor90days)[5].Ondayone,allsubjectsinbothgroupsreceivedaspirinatadoseof75to300mgdeterminedbytheclinician.At90days,therewasasignificantreductioninallstrokefortheclopidogrelplusaspiringroupcomparedwiththeplaceboplusaspiringroup(8.2versus11.7percent,absoluteriskreduction3.5percent,hazardratio0.68,95%CI0.570.81).Therateofhemorrhagicstrokewaslowinbothtreatmentgroups(0.3percentineach).
NotethattheresultsoftheCHANCEtrialarenotgeneralizabletoallpatientswithacutestrokeorTIA,sincetheinclusioncriteriaselectedforpatientswithhighriskTIA,definedasanABCD
(forAge,Bloodpressure,Clinicalfeatures,Durationofsymptoms,andDiabetes)scoreof4(see"Initialevaluationandmanagementoftransientischemicattackandminorstroke",sectionon'ABCD2score'),andexcludedthosewithisolatedsensorysymptoms,isolatedvisualchanges,orisolateddizzinessorvertigo,andnoevidenceofacuteinfarctiononneuroimaging[5].Theinclusioncriteriaalsoselectedforpatientswithminorstroke,definedasanNIHSSscoreof3(see"Useandutilityofstrokescalesandgradingsystems",sectionon'NationalInstitutesofHealthStrokeScale').Furthermore,theChinesepopulationhasarelativelyhighrateoflargearteryintracranialatheroscleroticdiseasecomparedwithCaucasians(see"Intracraniallargearteryatherosclerosis",sectionon'Epidemiology').Thus,theCHANCEtrialresultsmaynotapplytononAsianpatientsortopatientswithlowriskTIA,andparticularlymaynotapplytopatientswithmoderateorsevereacuteischemicstroke,whoarelikelytobeathigherriskforhemorrhagictransformationwithdualantiplatelettherapy.
2
TheopenlabelEARLYtrialrandomlyassigned539patientswithin24hoursofsymptomonsettotreatmentwitheitherthecombinationofaspirinextendedreleasedipyridamole(aspirin25mgandextendedrelease200mgtwicedaily)oraspirin(100mgdaily)alone[6].Aftersevendays,allpatientsreceivedopenlabelaspirinextendedreleasedipyridamole.At90days,therewasnosignificantdifferencebetweenthetreatmentgroupsintheprimaryendpointofgoodneurologicoutcome,definedasamodifiedRankinscalescoreof0to1assessedbytelephone(56versus52percent).Inaddition,therewasnosignificantdifferenceinthecombinedendpointofvascularadverseeventsormortality(10versus15percent).
ThestrengthoftheEARLYstudyislimitedbymethodologicissues(theopenlabeldesign,telephoneassessment)andsmallpatientnumberscomparedwiththeISTandCASTtrialsdiscussedabove.
TheFASTERtrialrandomlyassigned392patientswithin24hoursofsymptomonsettoeitheraspirinplusclopidogrel(300mgloadingdose,then75mgdaily)oraspirinalone[7].Inaddition,patientswereseparatelyallocatedtoreceiveeithersimvastatinorplacebo.Thetrialendedprematurelyduetoslowrecruitment.At90days,therewasnosignificantdifferencebetweentreatmentgroups(aspirinplusclopidogrelversusaspirin
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Evidencefromongoingrandomizedcontrolledtrials(eg,POINTandTARDIS[10,11])isawaitedtoconfirmwhethercombinationantiplateletregimensaresafeandsuperiortoaspirinfortheearlytreatmentofacuteischemicstrokeandTIAinbroadpopulations.
ChoosingearlyantiplatelettherapyAlthoughaspirin,clopidogrel,andthecombinationofaspirinextendedreleasedipyridamoleareallacceptableoptionsforsecondarystrokeprevention,aspirinistheonlyantiplateletagentthathasbeenestablishedaseffectivefortheveryearlytreatmentofacuteischemicstroke(see'Aspirin'above).Clopidogrelorticlopidinearealternativesforpatientsintoleranttoaspirin,althoughtheeffectivenessoftheseantiplateletsinacutestrokeisnotestablished.Theuseofdualantiplatelettherapyremainslargelyunproven,withtheexceptionthatshorttermtreatmentwithclopidogrelplusaspirinappearstobebeneficialforhighriskTIAandminorstrokeinAsianpopulations(see'Combinationantiplatelets'above).
Asdiscussedbelow(see'Roleofearlyanticoagulation'below),wesuggestearlyparenteralanticoagulationratherthanaspirinonlyforselectpatientswithacutecardioembolicischemicstrokeorTIAwhohaveintracardiacthrombus.TheuseofantiplateletandanticoagulanttherapyforpatientswithacutestrokeorTIAcausedby
alone)fortheprimaryoutcomemeasureofcombinedischemicandhemorrhagicstroke(7.1versus10.8percent).
SinceFASTERenrolledmostlypatientswithmildstrokeorTIA[7],thesafetyresultsofFASTERwithrespecttohemorrhagictransformationmaynotapplytothegeneralischemicstrokepopulation.ThemuchlargerMATCHtrial,withover7500patients,foundthatthecombineduseofaspirinandclopidogreldidnotoffergreaterbenefitforstrokepreventionthaneitheragentalonebutdidsubstantiallyincreasetheriskofbleedingcomplications[8].(See"Antiplatelettherapyforsecondarypreventionofstroke",sectionon'Aspirinplusclopidogrel'.)
A2013metaanalysisofearlydualantiplatelettherapyversusmonotherapyforpatientswithnoncardioembolicacuteischemicstrokeorTIAidentified14trialswithover9000adults[9].ThemetaanalysisincludedpatientsfromtheCHANCE,EARLY,andFASTERtrials,whowereallenrolledwithin24hoursofonset,andthosepatientsfromsecondarypreventiontrialswhowereenrolledwithin72hoursofsymptomonset.Treatmentsinvolvedseveraldifferentcombinationsofdualantiplatelettherapy(aspirinplusclopidogrel,aspirinplusdipyridamole,aspirinpluscilostazol)andthreedifferentmonotherapyregimens(aspirin,clopidogrel,anddipyridamole).Comparedwithmonotherapy,dualantiplatelettherapywasassociatedwithastatisticallysignificantreductioninrecurrentstroke(relativerisk[RR]0.69,95%CI0.600.80)andcompositevasculareventsanddeath(RR0.71,95%CI0.630.81)andwithanonsignificantincreaseinmajorbleeding(RR1.35,95%CI0.702.59).Thestrengthofthesefindingsislimitedbymultipleissues,includingvariabilityamongtrialsregardingpatientpopulations,antiplateletmedications,andlengthoffollowup,theinclusionofpatientsubgroupsthatenrolledearlyinsecondarypreventiontrials,theopenlabeldesignofsevenoftheincludedtrials,thelackofintentiontotreatanalysisoffivetrials,andsmalleventnumbersforcertainoutcomessuchasintracerebralhemorrhageanddeath.
Werecommendearlyaspirintherapy(160to325mg/day)ratherthannoaspirintherapyorearlyanticoagulationformostpatientswithacuteischemicstroke.ThisrecommendationisinaccordwithcurrentguidelinesissuedbytheAmericanCollegeofChestPhysicians[12],theAmericanHeartAssociation/AmericanStrokeAssociation[13],andtheNationalInstituteforHealthandClinicalExcellence[14].
Werecommendearlydualantiplatelettreatmentwithclopidogrelplusaspirinfor21days,followedbyclopidogrelmonotherapythroughatleastday90,forAsianpatientswithhighriskTIA(ie,ABCD
scoreof4)orminorstroke(NIHSSscore3)(see'Combinationantiplatelets'above)[5].
2
BeyondtheacutephaseofischemicstrokeandTIA,longtermantiplatelettherapyforsecondarystrokepreventionshouldbecontinuedwithaspirin,clopidogrel,orthecombinationofaspirinextendedreleasedipyridamole.(See"Antiplatelettherapyforsecondarypreventionofstroke".)
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cervicocephalicarterydissectionisreviewedelsewhere.(See"Spontaneouscerebralandcervicalarterydissection:Treatmentandprognosis",sectionon'Antithrombotictherapy'.)
Antiplateletagentsshouldnotbeusedasanalternativetointravenousthrombolysisorotheracutetherapiesaimedatimprovingoutcomesafterstroke[13].Antiplateletagentsshouldbestartedasearlyaspossibleafterthediagnosisofischemicstrokeisconfirmed.However,aspirinandotherantithromboticagentsshouldnotbegivenaloneorincombinationforthefirst24hoursfollowingtreatmentwithintravenousalteplase.Aspirinandotherantiplateletagentsmaybeusedincombinationwithsubcutaneousheparinandlowmolecularweightheparinfordeepveinthrombosisprophylaxis.(See"Medicalcomplicationsofstroke",sectionon'VTEprophylaxis'.)
Thedevelopmentofsecondaryhemorrhagictransformationofanischemicinfarctdoesnotprecludetheearlyuseofaspirin,particularlywhenthehemorrhageispetechial(ie,scatteredandpunctate).Itisnotclearthatstoppingaspirinwillhavemuchimpactonhematomaprogressiongiventhelonglastingeffectofaspirinonplateletfunction,evenintheraresituationofseverehemorrhagictransformationassociatedwithclinicaldeteriorationanddevelopmentofparenchymalhematoma(ie,largerconfluentbleedingwithinaninfarct,oftenwithmasseffect).However,itmaybewisetodelayinitiationifaspirinhasnotyetbeenstartedinpatientswhodevelopparenchymalhematoma.Aspirincanthenbegivenoncethepatient'sneurologicconditionbecomesstable.
PARENTERALANTICOAGULATIONTheavailableevidencesuggeststhatearlyanticoagulationwithheparinorlowmolecularweightheparinisassociatedwithahighermortalityandworseoutcomescomparedwithaspirintreatmentinitiatedwithin48hoursofischemicstrokeonset[15].However,asdescribedinthefollowingsections,clinicaltrialshavenotadequatelyevaluatedadjusteddoseintravenousanticoagulationinpatientswithselectedstrokesubtypes,andonlyonetrialhasevaluatedtheroleofveryearlyanticoagulationafterstrokeonset[16].
Whileparenteralanticoagulationisnotrecommendedduringthefirst48hoursafteracuteischemicstroke,oralanticoagulationisrecommendedforsecondarystrokepreventioninpatientswithatrialfibrillationandotherhighrisksourcesofcardiogenicembolism.Thetimingofitsinitiationforsuchpatientsismainlydependentonthesizeoftheinfarct,whichispresumedtocorrelatewiththeriskofhemorrhagictransformation.Thus,formedicallystablepatientswithasmallormoderatesizedinfarct,warfarincanbeinitiatedsoon(after24hours)afteradmissionwithminimalriskoftransformationtohemorrhagicstroke,whilewithholdinganticoagulationfortwoweeksisgenerallyrecommendedforthosewithlargeinfarctions,symptomatichemorrhagictransformation,orpoorlycontrolledhypertension.(See"Strokeinpatientswithatrialfibrillation",sectionon'Timingafteracutestroke'.)
TrialsThelargestrandomizedcontrolledtrial(IST)studiedtwodosesofsubcutaneousheparininover19,000patientswithundefinedischemicstrokeandfoundnosignificantbenefitwithheparin[1].
Asystematicreviewpublishedin2008examinedtheeffectofanticoagulanttherapyversuscontrolintheearlytreatmentofpatientswithacuteischemicstroke[17].Thisreviewincluded24trialsinvolving23,748subjectsover80percentofthesubjectswerefromtheISTtrial.Thequalityofthetrialsvariedconsiderably.Theanticoagulantstestedwerestandardunfractionatedheparin,lowmolecularweightheparins,heparinoids,oralanticoagulants,andthrombininhibitors.Thefollowingwerethemajorfindings:
Basedupon11trials(22,776patients),anticoagulanttherapydidnotreducetheoddsofdeathfromallcauses(oddsratio1.05,95%CI0.981.12).
Baseduponeighttrials(22,125patients),anticoagulantsdidnotreducetheoddsofbeingdeadordependentattheendoffollowup(oddsratio0.99,95%CI0.931.04).
Althoughfullanticoagulanttherapywasassociatedwithaboutninefewerrecurrentischemicstrokesper1000patientstreated,itwasalsoassociatedwithanineper1000increaseinsymptomaticintracranialhemorrhages.Similarly,anticoagulantsavoidedaboutfourpulmonaryemboliper1000,butthisbenefitwasoffsetbyanextraninemajorextracranialhemorrhagesper1000.
Sensitivityanalysesdidnotidentifyaparticulartypeofanticoagulantregimenorpatientcharacteristicassociatedwithnetbenefit.
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Similarly,a2013individualpatientlevelmetaanalysisoffivetrialsthatcomparedheparins(ie,unfractionatedheparin,heparinoids,orlowmolecularweightheparin)withaspirinorplaceboforacuteischemicstrokefoundnobenefitofheparinsforsubgroupsofpatientsconsideredtohaveanincreasedriskofthromboticeventsoradecreasedriskofhemorrhagicevents[18].Again,theISTtrialprovidedover80percentoftheoutcomes.
A2002systematicreviewassessedtheeffectivenessofanticoagulantscomparedwithantiplateletagentsinacuteischemicstroke[15].Thereviewersconcludedthatanticoagulantsoffernonetadvantagesoverantiplateletagentsandrecommendthatantiplateletagentsshouldbetheantithromboticagentsoffirstchoice.However,thisconclusionwasdriveninpartbythelackofrandomizedtrialscomparinganticoagulationwithantiplatelettherapyinthehighrisksettingswherewebelieveanticoagulationshouldbeconsidered.
StrokesubtypesClinicaltrialshavenotadequatelyevaluatedadjustedintravenousanticoagulationinpatientswithselectedstrokesubtypes.Withthiscaveatinmind,thereareconflictingdataregardingthebenefitofintravenousunfractionatedheparinorlowmolecularweightheparininthesubgroupofpatientswithlargevesselatheroscleroticdisease.
Otherstudiesofheparintherapyinacutestrokedidnotconsidertheetiologyofstrokeandyieldedmixedresults[1,2224].
AtrialfibrillationandcardioembolicstrokeAsubjectofintensedebateistheroleofimmediateanticoagulationwithheparininstrokepatientswithatrialfibrillation(AF).ItappearsthatearlytreatmentwithheparininpatientswithAFwhohaveanacutestrokecausesmoreharmthangood.(See"Strokeinpatientswithatrialfibrillation".)
A2007metaanalysisexaminedseventrialsinvolving4624patientsandcomparedheparinorlowmolecularweightheparinsstartedwithin48hoursforacutecardioembolicstrokewithothertreatments(aspirinorplacebo)[25].Thefollowingobservationswerereported:
TheTOASTtrialevaluatedtheefficacyofthelowmolecularweightheparinoiddanaparoidadministeredasanintravenousboluswithin24hoursofsymptomonsetandcontinuedforsevendaysin1281patientswithacuteischemicstroke[19].Comparedtoplacebo,danaparoidwasassociatedwithnoimprovementinoveralloutcomeatthreemonths(75and74percent).However,subgroupanalysissuggestedahigherrateoffavorableoutcomesinpatientstreatedwithdanaparoidwhohadalargearteryatheroscleroticstroke(68versus55percentwithplacebo).Asubsequentanalysisofthisstudysuggestedthatacuteperformanceofcarotiddupleximagingtoidentifypatientswithcarotidocclusionorseverestenosismayimproveselectionofpatientswhocouldbenefitfromuseofthisagent[20].
TheFISStristrialevaluatedthelowmolecularweightheparinnadroparin(3800antifactorXainternationalunits,0.4mLsubcutaneouslytwicedaily)versusaspirin(160mgoncedaily)startedwithin48hoursofacuteischemicstrokeonsetandcontinuedfor10days[21].Themainstudypopulationwas353patientswithconfirmedlargearteryocclusivedisease,consistingof300withintracranial,11withextracranial,and42withbothintracranialandextracranialdisease.Themeantimetotreatmentwasnearly30hours.Therewasnosignificantdifferencebetweentreatmentwithnadroparinoraspirinfortheproportionofpatientswithgoodoutcomeatsixmonths(73versus69percent).
Intheonlytrialofunfractionatedheparininhyperacutestroke,asinglecenterrandomlyassigned418patientswithnonlacunarhemisphericinfarction(ofcardioembolic,atherothrombotic,orunknown/undeterminedorigin)toreceiveeitherintravenousheparinorsalinewithinthreehoursofstrokeonset[16].Treatmentcontinuedforfivedays.Afavorableoutcomeat90days,theprimaryendpoint,wassignificantlymorefrequentinpatientsassignedtoheparincomparedwiththoseassignedtosaline(38.9versus28.6percent).Heparinusewasassociatedwithanincreasedriskofintracranialandextracranialbleeding,butnoincreaseinmortality.
Anticoagulantswereassociatedwithastatisticallynonsignificantreductioninrecurrentischemicstrokewithin7to14days(3.0versus4.9percent,oddsratio[OR]0.68,95%CI0.441.06)
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Thus,theresultsdonotsupportearlyanticoagulanttreatmentofacutecardioembolicstroke[25].
ProgressingstrokeHeparinwasoncewidelyusedtotreatpatientswhocontinuedtohaveneurologicdeteriorationinthefirsthoursordaysafterischemicstroke(ie,progressingstroke,alsoreferredtoasstrokeinevolution).TheTOASTtrialdidnotfindanimprovementinoutcomeswithdanaparoidtreatmentinsuchpatients[19],nordidanonrandomizedstudyofheparintherapy[26].Thesefindingsdonotsupportaroleforheparininhaltingneurologicworseningafterstroke.
RoleofearlyanticoagulationGuidelinesissuedin2013bytheAmericanHeartAssociation/AmericanStrokeAssociationstatethaturgentanticoagulationisnotrecommendedforthetreatmentofpatientswithacuteischemicstroke[13].Similarly,2012guidelinesfromtheAmericanCollegeofChestPhysicians(ACCP)recommendearlyaspirintherapyovertherapeuticparenteralanticoagulationforpatientswithacuteischemicstrokeorTIA[12].
Whilemanyspecialistsbelieveithasnoroleatallintheearlyacutephaseofischemicstroke,someexpertshaveusedearlyanticoagulationforvariousischemicstrokesubtypes,includingcardioembolicstrokeduetoatrialfibrillationandstrokeduetolargearterystenosesorarterialdissection.However,the2012ACCPguidelinesnotethatareviewoftheliteraturedoesnotsupporttheuseofanticoagulationinthesesubgroups[12].Othersubgroupsatparticularlyhighriskforrecurrentembolism,suchaspatientswithmechanicalheartvalvesorintracardiacthrombus,wereeithernotincludedorwereunderrepresentedintrialsofacuteantithrombotictherapyforstroke.TheACCPnotesthattheoptimalchoiceofacuteantithrombotictherapyinthesepatientsisuncertain[12].
Inagreementwiththenationalguidelines,werecommendnotusingfulldoseparenteralanticoagulationfortreatmentofunselectedpatientswithacuteischemicstrokebecauseoflimitedefficacyandanincreasedriskofbleedingcomplications.Instead,werecommendearlyaspirintherapy(160to325mg/day)formostpatientswithacuteischemicstrokeorTIA.(See'Aspirin'aboveand'Choosingearlyantiplatelettherapy'above.)
Althoughbenefitisunproven,wesuggestearlyparenteralanticoagulationratherthanaspirinforselectpatientswithacutecardioembolicischemicstrokeorTIAwhohaveintracardiacthrombusassociatedwithmechanicalornativeheartvalves.Werecognizethatthisapproachiscontroversialsomeexpertsfavortreatmentwithaspirinratherthananticoagulationinthissettingforpatientswithanacutebraininfarction.OursuggestiontouseearlyparenteralanticoagulationfortheseselectedpatientsappliesonlytothosewithasmallbraininfarctorTIAandnoevidenceofhemorrhageonbrainimaging.Anticoagulationshouldnotbegivenforthefirst24hoursfollowingtreatmentwithintravenousalteplase.
TheuseofantithrombotictherapyforischemicstrokeandTIAcausedbycervicalarterydissectionisdiscussedelsewhere.(See"Spontaneouscerebralandcervicalarterydissection:Treatmentandprognosis",sectionon'Antithrombotictherapy'.)
Fulldoseanticoagulationshouldnotbeusedforpatientswithalargeinfarction(baseduponclinicalsyndromeorbrainimagingfindings),uncontrolledhypertension,orotherbleedingconditions.(See'Contraindications'below.)
AdministrationIntheselectedpatientswhoreceiveheparinintheacutestrokesetting,abolusisnotadministered.Onegrouphasproposedaweightbasednomogramforheparininfusionsthat,comparedwithusualheparintherapy,isassociatedwithfewercomplications,fewermistakesindoseadjustment,improvedanticoagulation,anddecreasednursingandhousestafflabor(table2)[27].
Enoxaparin1mg/kgdoseevery12hours(orotherlowmolecularweightheparins)maybeusedasanalternativetointravenousheparininpatientswithacutestrokewhenearlyanticoagulationisdesiredtopreventrecurrentcerebralembolismthelimitedavailableevidencesuggeststhatlowmolecularweightheparinshavesimilarefficacy,
Anticoagulantswereassociatedwithastatisticallysignificantincreaseinsymptomaticintracranialhemorrhage(2.5versus0.7percent,OR2.89,95%CI1.197.01)
Anticoagulantsandothertreatmentshadasimilarrateofdeathordisabilityatfinalfollowup(approximately74percent)
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advantagesinadministrationandmonitoring,andreducedratesofthrombocytopeniacomparedwithheparin.
Theuseofintravenousanticoagulationforprophylaxisofdeepveinthrombosisisdiscussedseparately.(See"Medicalcomplicationsofstroke",sectionon'VTEprophylaxis'.)
ContraindicationsAnticoagulationinthesettingofacutestrokemayonlybeconsideredafterabrainimagingstudyhasexcludedhemorrhageandestimatedthesizeoftheinfarct.Earlyanticoagulationshouldbeavoidedwhenpotentialcontraindicationstoanticoagulationarepresent,suchasalargeinfarction(baseduponclinicalsyndromeorbrainimagingfindings),uncontrolledhypertension,orotherbleedingconditions.
Althoughthereisnostandarddefinition,manystrokeexpertsconsider"large"infarctstobethosethatinvolvemorethanonethirdofthemiddlecerebralarteryterritoryormorethanonehalfoftheposteriorcerebralarteryterritorybaseduponneuroimagingwithCTorMRI.Infarctsizecanalsobeclinicallydefined,butthisprocesscanresultinunderestimationofthetrueinfarctvolumewhensocalled"silent"areasofassociationcortexareinvolved.
Clinicalestimationofinfarctsizemaybeimprovedbyusingvalidatedscalesthathavebeencorrelatedwithinfarctvolumeandclinicaloutcome,suchastheNationalInstitutesofHealthStrokeScale(NIHSS)(table3).Asanexample,onestudyfoundthatanNIHSSscore>15wasassociatedwithamedianinfarctvolumeof55.8cm
andworseoutcomethanNIHSSscoresof1to7(medianvolumeof7.9cm
)or8to15(medianvolumeof31.4cm )[28].
Thus,patientswithanNIHSSscore>15generallyhavealargeinfarct.However,itshouldberecognizedthatpartoftheclinicaldeficitintheearlyhoursofanacutestrokemaybeattributedtothepenumbra,wherethebrainisischemicbutnotinfarcted.
INFORMATIONFORPATIENTSUpToDateofferstwotypesofpatienteducationmaterials,TheBasicsandBeyondtheBasics.TheBasicspatienteducationpiecesarewritteninplainlanguage,atthe5
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gradereadinglevel,andtheyanswerthefourorfivekeyquestionsapatientmighthaveaboutagivencondition.Thesearticlesarebestforpatientswhowantageneraloverviewandwhoprefershort,easytoreadmaterials.BeyondtheBasicspatienteducationpiecesarelonger,moresophisticated,andmoredetailed.Thesearticlesarewrittenatthe10
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gradereadinglevelandarebestforpatientswhowantindepthinformationandarecomfortablewithsomemedicaljargon.
Herearethepatienteducationarticlesthatarerelevanttothistopic.Weencourageyoutoprintoremailthesetopicstoyourpatients.(Youcanalsolocatepatienteducationarticlesonavarietyofsubjectsbysearchingonpatientinfoandthekeyword(s)ofinterest.)
SUMMARYANDRECOMMENDATIONS
33 3
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Basicstopics(see"Patientinformation:Stroke(TheBasics)")
BeyondtheBasicstopics(see"Patientinformation:Strokesymptomsanddiagnosis(BeyondtheBasics)"and"Patientinformation:Ischemicstroketreatment(BeyondtheBasics)")
Althoughaspirin,clopidogrel,andthecombinationofaspirinextendedreleasedipyridamoleareallacceptableoptionsforsecondarystrokeprevention,aspirinistheonlyantiplateletagentthathasbeenestablishedaseffectivefortheearlytreatmentofacuteischemicstroke.(See'Antiplateletagents'above.)
Clinicaltrialshavenotadequatelyevaluatedtheroleofveryearly(ie,withinhoursofstrokeonset)anticoagulationforacuteischemicstrokeorforselectedstrokesubtypes.However,theavailableevidencesuggeststhatearlyanticoagulationisassociatedwithahighermortalityandworseoutcomescomparedwithaspirintreatmentinitiatedwithin48hoursofischemicstrokeonset.(See'Parenteralanticoagulation'above.)
FormostpatientswithacuteischemicstrokeorTIAwhoarenotreceivingoralanticoagulants,werecommendearlyaspirintherapy(160to325mg/day)ratherthannoaspirintherapy(Grade1A)orparenteralanticoagulationtherapy(Grade1B).Aspirinshouldbestartedasearlyaspossibleafterthediagnosisof
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REFERENCES
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TheInternationalStrokeTrial(IST):arandomisedtrialofaspirin,subcutaneousheparin,both,orneitheramong19435patientswithacuteischaemicstroke.InternationalStrokeTrialCollaborativeGroup.Lancet1997349:1569.
2.
CAST:randomisedplacebocontrolledtrialofearlyaspirinusein20,000patientswithacuteischaemicstroke.CAST(ChineseAcuteStrokeTrial)CollaborativeGroup.Lancet1997349:1641.
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ChenZM,SandercockP,PanHC,etal.Indicationsforearlyaspirinuseinacuteischemicstroke:Acombinedanalysisof40000randomizedpatientsfromthechineseacutestroketrialandtheinternationalstroketrial.OnbehalfoftheCASTandISTcollaborativegroups.Stroke200031:1240.
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SandercockPA,CounsellC,GubitzGJ,TsengMC.Antiplatelettherapyforacuteischaemicstroke.CochraneDatabaseSystRev2008:CD000029.
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WangY,WangY,ZhaoX,etal.Clopidogrelwithaspirininacuteminorstrokeortransientischemicattack.NEnglJMed2013369:11.
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DenglerR,DienerHC,SchwartzA,etal.Earlytreatmentwithaspirinplusextendedreleasedipyridamolefortransientischaemicattackorischaemicstrokewithin24hofsymptomonset(EARLYtrial):arandomised,openlabel,blindedendpointtrial.LancetNeurol20109:159.
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KennedyJ,HillMD,RyckborstKJ,etal.Fastassessmentofstrokeandtransientischaemicattacktopreventearlyrecurrence(FASTER):arandomisedcontrolledpilottrial.LancetNeurol20076:961.
8.
DienerHC,BogousslavskyJ,BrassLM,etal.Aspirinandclopidogrelcomparedwithclopidogrelaloneafterrecentischaemicstrokeortransientischaemicattackinhighriskpatients(MATCH):randomised,doubleblind,placebocontrolledtrial.Lancet2004364:331.
9.
WongKS,WangY,LengX,etal.Earlydualversusmonoantiplatelettherapyforacutenoncardioembolic
ischemicstrokeisconfirmedandideallywithin48hoursofstrokeonset.However,aspirinshouldnotbegivenforthefirst24hoursfollowingtreatmentwithintravenousorintraarterialthrombolytictherapy.(See'Aspirin'aboveand'Choosingearlyantiplatelettherapy'above.)
ForAsianpatientswithhighriskTIA(ie,ABCD
scoreof4)orminorstroke(ie,NIHSSscore3),werecommendearlydualantiplatelettreatment,ratherthanaspirinmonotherapy,withclopidogrel(300mgloadingdose,then75mgdaily)plusaspirin(75to300mgloadingdose,then75to81mgdaily)for21days,followedbyclopidogrelmonotherapy(75mgdaily)throughatleastday90(Grade1B).Treatmentshouldbestartedwithin24hoursofsymptomonset.(See'Combinationantiplatelets'aboveand'Choosingearlyantiplatelettherapy'above.)
2
BeyondtheacutephaseofischemicstrokeandTIA,longtermantiplatelettherapyforsecondarystrokepreventionshouldbecontinuedwithaspirin,clopidogrel,orthecombinationofaspirinextendedreleasedipyridamole.(See"Antiplatelettherapyforsecondarypreventionofstroke".)
Theuseofantithrombotictherapyforpatientswhohaveischemicneurologicsymptomscausedbycervicalorintracranialarterydissectionisdiscussedseparately.(See"Spontaneouscerebralandcervicalarterydissection:Treatmentandprognosis",sectionon'Antithrombotictherapy'.)
ForpatientswithacutecardioembolicischemicstrokeorTIAwhohaveintracardiacthrombusassociatedwithmechanicalornativeheartvalves,wesuggestearlyparenteralanticoagulationratherthanaspirin(Grade2C).Thisapproachiscontroversial.Otherexpertsfavorearlytreatmentwithaspirinratherthananticoagulationinthissettingforpatientswithaninfarct.OursuggestiontouseearlyparenteralanticoagulationfortheseselectedpatientsappliesonlytothosewithasmallbraininfarctorTIAandnoevidenceofhemorrhageonbrainimaging.(See'Roleofearlyanticoagulation'above.)
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ischemicstrokeortransientischemicattack:anupdatedsystematicreviewandmetaanalysis.Circulation2013128:1656.
10.
PlateletOrientedInhibitioninNewTIAandMinorIschemicStroke(POINT)Trialhttp://clinicaltrials.gov/ct2/show/NCT00991029(AccessedonJuly02,2013).
11.
TripleAntiplateletsforReducingDependencyafterIschaemicStroke(TARDIS)http://clinicaltrials.gov/show/NCT01661322(AccessedonJuly02,2013).
12.
LansbergMG,O'DonnellMJ,KhatriP,etal.Antithromboticandthrombolytictherapyforischemicstroke:AntithromboticTherapyandPreventionofThrombosis,9thed:AmericanCollegeofChestPhysiciansEvidenceBasedClinicalPracticeGuidelines.Chest2012141:e601S.
13.
JauchEC,SaverJL,AdamsHPJr,etal.Guidelinesfortheearlymanagementofpatientswithacuteischemicstroke:aguidelineforhealthcareprofessionalsfromtheAmericanHeartAssociation/AmericanStrokeAssociation.Stroke201344:870.
14.
NationalInstituteforHealthandClinicalExcellence.Stroke:Thediagnosisandacutemanagementofstrokeandtransientischaemicattacks.RoyalCollegeofPhysicians,London2008.http://www.nice.org.uk/CG068(AccessedonFebruary01,2011).
15.
BergeE,SandercockP.Anticoagulantsversusantiplateletagentsforacuteischaemicstroke.CochraneDatabaseSystRev2002:CD003242.
16.
CamerlingoM,SalviP,BelloniG,etal.Intravenousheparinstartedwithinthefirst3hoursafteronsetofsymptomsasatreatmentforacutenonlacunarhemisphericcerebralinfarctions.Stroke200536:2415.
17.
SandercockPA,CounsellC,KamalAK.Anticoagulantsforacuteischaemicstroke.CochraneDatabaseSystRev2008:CD000024.
18.
WhiteleyWN,AdamsHPJr,BathPM,etal.Targeteduseofheparin,heparinoids,orlowmolecularweightheparintoimproveoutcomeafteracuteischaemicstroke:anindividualpatientdatametaanalysisofrandomisedcontrolledtrials.LancetNeurol201312:539.
19.
Lowmolecularweightheparinoid,ORG10172(danaparoid),andoutcomeafteracuteischemicstroke:arandomizedcontrolledtrial.ThePublicationsCommitteefortheTrialofORG10172inAcuteStrokeTreatment(TOAST)Investigators.JAMA1998279:1265.
20.
AdamsHPJr,BendixenBH,LeiraE,etal.Antithrombotictreatmentofischemicstrokeamongpatientswithocclusionorseverestenosisoftheinternalcarotidartery:AreportoftheTrialofOrg10172inAcuteStrokeTreatment(TOAST).Neurology199953:122.
21.
WongKS,ChenC,NgPW,etal.LowmolecularweightheparincomparedwithaspirinforthetreatmentofacuteischaemicstrokeinAsianpatientswithlargearteryocclusivedisease:arandomisedstudy.LancetNeurol20076:407.
22.
KayR,WongKS,YuYL,etal.Lowmolecularweightheparinforthetreatmentofacuteischemicstroke.NEnglJMed1995333:1588.
23.
DienerHC,RingelsteinEB,vonKummerR,etal.Treatmentofacuteischemicstrokewiththelowmolecularweightheparincertoparin:resultsoftheTOPAStrial.TherapyofPatientsWithAcuteStroke(TOPAS)Investigators.Stroke200132:22.
24.
BathPM,LindenstromE,BoysenG,etal.Tinzaparininacuteischaemicstroke(TAIST):arandomisedaspirincontrolledtrial.Lancet2001358:702.
25.
PaciaroniM,AgnelliG,MicheliS,CasoV.Efficacyandsafetyofanticoagulanttreatmentinacutecardioembolicstroke:ametaanalysisofrandomizedcontrolledtrials.Stroke200738:423.
26.
RdnJlligA,BrittonM.Effectivenessofheparintreatmentforprogressingischaemicstroke:beforeandafterstudy.JInternMed2000248:287.
27.
TothC,VollC.Validationofaweightbasednomogramfortheuseofintravenousheparinintransientischemicattackorstroke.Stroke200233:670.
28.
ThijsVN,LansbergMG,BeaulieuC,etal.Isearlyischemiclesionvolumeondiffusionweightedimaginganindependentpredictorofstrokeoutcome?Amultivariableanalysis.Stroke200031:2597.
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GRAPHICS
Eligibilitycriteriaforthetreatmentofacuteischemicstrokewithrecombinanttissueplasminogenactivator(alteplase)
Inclusioncriteria
Clinicaldiagnosisofischemicstrokecausingmeasurableneurologicdeficit
Onsetofsymptoms
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Gastrointestinalorurinarytractbleedingintheprevious21days
Myocardialinfarctioninthepreviousthreemonths
Seizureattheonsetofstrokewithpostictalneurologicimpairments
Pregnancy
Additionalrelativeexclusioncriteriafortreatmentfrom3to4.5hoursfromsymptomonset
Age>80years
OralanticoagulantuseregardlessofINR
Severestroke(NIHSSscore>25)
Combinationofbothpreviousischemicstrokeanddiabetesmellitus
aPTT:activatedpartialthromboplastintimeECT:ecarinclottingtimeINR:internationalnormalizedratioPT:prothrombintimeNIHSS:NationalInstitutesofHealthStrokeScaleTT:thrombintime.*Althoughitisdesirabletoknowtheresultsofthesetests,thrombolytictherapyshouldnotbedelayedwhileresultsarependingunless(1)thereisclinicalsuspicionofableedingabnormalityorthrombocytopenia,(2)thepatientiscurrentlyonorhasrecentlyreceivedanticoagulants(eg,heparin,warfarin,adirectthrombininhibitor,oradirectfactorXainhibitor),(3)useofanticoagulantsisnotknown.Forpatientswithoutrecentuseoforalanticoagulantsorheparin,treatmentwithintravenoustPAcanbestartedbeforeavailabilityofcoagulationtestresultsbutshouldbediscontinuediftheINR,PT,oraPTTexceedthelimitsstatedinthetable.Theavailabledatasuggestthatundersomecircumstanceswithcarefulconsiderationandweightingofrisktobenefitpatientsmayreceivefibrinolytictherapydespiteoneormorerelativecontraindications.Inparticular,thereisnowconsensusthatpatientswhohaveapersistentneurologicdeficitthatispotentiallydisabling,despiteimprovementofanydegree,shouldbetreatedwithtPAintheabsenceofothercontraindications.Anyofthefollowingshouldbeconsidereddisablingdeficits:
Completehemianopsia:2onNIHSSquestion3,orSevereaphasia:2onNIHSSquestion9,orVisualorsensoryextinction:1onNIHSSquestion11,orAnyweaknesslimitingsustainedeffortagainstgravity:2onNIHSSquestion5or6,orAnydeficitsthatleadtoatotalNIHSS>5,orAnyremainingdeficitconsideredpotentiallydisablingintheviewofthepatientandthetreatingpractitionerusingclinicaljudgement
Adaptedfrom:1.
HackeW,KasteM,BluhmkiE,etal.Thrombolysiswithalteplase3to4.5hoursafteracute
ischemicstroke.NEnglJMed2008359:1317.2.
DelZoppoGJ,SaverJL,JauchEC,etal.Expansionofthetimewindowfortreatmentofacute
ischemicstrokewithintravenoustissueplasminogenactivator.AscienceadvisoryfromtheAmericanHeartAssociation/AmericanStrokeAssociation.Stroke200940:2945.
3.
JauchEC,SaverJL,AdamsHPJr,etal.Guidelinesfortheearlymanagementofpatientswithacuteischemicstroke:aguidelineforhealthcareprofessionalsfromtheAmericanHeartAssociation/AmericanStrokeAssociation.Stroke201344:870.
4.
ReexaminingAcuteEligibilityforThrombolysis(TREAT)TaskForce:,LevineSR,KhatriP,etal.Review,historicalcontext,andclarificationsoftheNINDSrtPAstroketrialsexclusioncriteria:Part1:rapidlyimprovingstrokesymptoms.Stroke201344:2500.
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Heparinadjustednomogramforstroke
Initialdosingforcontinuousintravenousheparininfusion
Weight(kg) Initialinfusion(U/hour)
119 1400
HeparinadjustmentbaseduponaPTTdrawnsixhoursafterinitiationoftherapy
aPTT(seconds) Stopinfusion Ratechange RepeataPTT
120 No Decreaseby250U/hour 6hours
Nobolusisadministeredinpatientswithacutestroke.
Datafrom:TothC,VollC.Validationofaweightbasednomogramfortheuseofintravenousheparinintransientischemicattackorstroke.Stroke200233:670.
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NationalInstitutesofHealthStrokeScale(NIHSS)
Administerstrokescaleitemsintheorderlisted.Recordperformanceineachcategoryaftereachsubscaleexam.Donotgobackandchangescores.Followdirectionsprovidedforeachexamtechnique.Scoresshouldreflectwhatthepatientdoes,notwhattheclinicianthinksthepatientcando.Theclinicianshouldrecordanswerswhileadministeringtheexamandworkquickly.Exceptwhereindicated,thepatientshouldnotbecoached(ie,repeatedrequeststopatienttomakeaspecialeffort).
Instructions Scaledefinition Score
1a.Levelofconsciousness:Theinvestigatormustchoosearesponseifafullevaluationispreventedbysuchobstaclesasanendotrachealtube,languagebarrier,orotrachealtrauma/bandages.A3isscoredonlyifthepatientmakesnomovement(otherthanreflexiveposturing)inresponsetonoxiousstimulation.
0=Alertkeenlyresponsive.
1=Notalertbutarousablebyminorstimulationtoobey,answer,orrespond.
2=Notalertrequiresrepeatedstimulationtoattend,orisobtundedandrequiresstrongorpainfulstimulationtomakemovements(notstereotyped).
3=Respondsonlywithreflexmotororautonomiceffectsortotallyunresponsive,flaccid,andareflexic.
_____
1b.LOCquestions:Thepatientisaskedthemonthandhis/herage.Theanswermustbecorrectthereisnopartialcreditforbeingclose.Aphasicandstuporouspatientswhodonotcomprehendthequestionswillscore2.Patientsunabletospeakbecauseofendotrachealintubation,orotrachealtrauma,severedysarthriafromanycause,languagebarrier,oranyotherproblemnotsecondarytoaphasiaaregivena1.Itisimportantthatonlytheinitialanswerbegradedandthattheexaminernot"help"thepatientwithverbalornonverbalcues.
0=Answersbothquestionscorrectly.
1=Answersonequestioncorrectly.
2=Answersneitherquestioncorrectly.
_____
1c.LOCcommands:Thepatientisaskedtoopenandclosetheeyesandthentogripandreleasethenonparetichand.Substituteanotheronestepcommandifthehandscannotbeused.Creditisgivenifanunequivocalattemptismadebutnotcompletedduetoweakness.Ifthepatientdoesnotrespondtocommand,thetaskshouldbedemonstratedtohimorher(pantomime),andtheresultscored(ie,followsnone,oneortwocommands).
0=Performsbothtaskscorrectly.
1=Performsonetaskcorrectly.
2=Performsneithertaskcorrectly.
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Patientswithtrauma,amputation,orotherphysicalimpedimentsshouldbegivensuitableonestepcommands.Onlythefirstattemptisscored.
2.Bestgaze:Onlyhorizontaleyemovementswillbetested.Voluntaryorreflexive(oculocephalic)eyemovementswillbescored,butcalorictestingisnotdone.Ifthepatienthasaconjugatedeviationoftheeyesthatcanbeovercomebyvoluntaryorreflexiveactivity,thescorewillbe1.Ifapatienthasanisolatedperipheralnerveparesis(CNIII,IVorVI),scorea1.Gazeistestableinallaphasicpatients.Patientswithoculartrauma,bandages,preexistingblindness,orotherdisorderofvisualacuityorfieldsshouldbetestedwithreflexivemovements,andachoicemadebytheinvestigator.Establishingeyecontactandthenmovingaboutthepatientfromsidetosidewilloccasionallyclarifythepresenceofapartialgazepalsy.
0=Normal.
1=Partialgazepalsygazeisabnormalinoneorbotheyes,butforceddeviationortotalgazeparesisisnotpresent.
2=Forceddeviation,ortotalgazeparesisnotovercomebytheoculocephalicmaneuver.
_____
3.Visual:Visualfields(upperandlowerquadrants)aretestedbyconfrontation,usingfingercountingorvisualthreat,asappropriate.Patientsmaybeencouraged,butiftheylookatthesideofthemovingfingersappropriately,thiscanbescoredasnormal.Ifthereisunilateralblindnessorenucleation,visualfieldsintheremainingeyearescored.Score1onlyifaclearcutasymmetry,includingquadrantanopia,isfound.Ifpatientisblindfromanycause,score3.Doublesimultaneousstimulationisperformedatthispoint.Ifthereisextinction,patientreceivesa1,andtheresultsareusedtorespondtoitem11.
0=Novisualloss.
1=Partialhemianopia.
2=Completehemianopia.
3=Bilateralhemianopia(blindincludingcorticalblindness).
_____
4.Facialpalsy:Askorusepantomimetoencouragethepatienttoshowteethorraiseeyebrowsandcloseeyes.Scoresymmetryofgrimaceinresponsetonoxiousstimuliinthepoorlyresponsiveornoncomprehendingpatient.Iffacialtrauma/bandages,orotrachealtube,tapeorotherphysical
0=Normalsymmetricalmovements.
1=Minorparalysis(flattenednasolabialfold,asymmetryonsmiling).
2=Partialparalysis(totalorneartotalparalysisoflowerface).
3=Completeparalysisofoneorbothsides(absenceoffacialmovementinthe
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barriersobscuretheface,theseshouldberemovedtotheextentpossible.
upperandlowerface).
5.Motorarm:Thelimbisplacedintheappropriateposition:extendthearms(palmsdown)90degrees(ifsitting)or45degrees(ifsupine).Driftisscoredifthearmfallsbefore10seconds.Theaphasicpatientisencouragedusingurgencyinthevoiceandpantomime,butnotnoxiousstimulation.Eachlimbistestedinturn,beginningwiththenonpareticarm.Onlyinthecaseofamputationorjointfusionattheshoulder,theexaminershouldrecordthescoreasuntestable(UN),andclearlywritetheexplanationforthischoice.
0=Nodriftlimbholds90(or45)degreesforfull10seconds.
1=Driftlimbholds90(or45)degrees,butdriftsdownbeforefull10secondsdoesnothitbedorothersupport.
2=Someeffortagainstgravitylimbcannotgettoormaintain(ifcued)90(or45)degrees,driftsdowntobed,buthassomeeffortagainstgravity.
3=Noeffortagainstgravitylimbfalls.
4=Nomovement.
UN=Amputationorjointfusion,explain:________________
5a.Leftarm
5b.Rightarm
_____
6.Motorleg:Thelimbisplacedintheappropriateposition:holdthelegat30degrees(alwaystestedsupine).Driftisscoredifthelegfallsbefore5seconds.Theaphasicpatientisencouragedusingurgencyinthevoiceandpantomime,butnotnoxiousstimulation.Eachlimbistestedinturn,beginningwiththenonpareticleg.Onlyinthecaseofamputationorjointfusionatthehip,theexaminershouldrecordthescoreasuntestable(UN),andclearlywritetheexplanationforthischoice.
0=Nodriftlegholds30degreepositionforfull5seconds.
1=Driftlegfallsbytheendofthe5secondperiodbutdoesnothitbed.
2=Someeffortagainstgravitylegfallstobedby5seconds,buthassomeeffortagainstgravity.
3=Noeffortagainstgravitylegfallstobedimmediately.
4=Nomovement.
UN=Amputationorjointfusion,explain:________________
6a.Leftleg
6b.Rightleg
_____
7.Limbataxia:Thisitemisaimedatfindingevidenceofaunilateralcerebellarlesion.Testwitheyesopen.Incaseofvisualdefect,ensuretestingisdoneinintactvisualfield.Thefingernosefingerandheelshintestsareperformedonbothsides,andataxiaisscoredonlyifpresentoutofproportiontoweakness.Ataxiaisabsentinthepatientwhocannotunderstandorisparalyzed.Onlyinthecaseofamputationorjointfusion,theexaminershouldrecordthescoreasuntestable(UN),andclearlywritetheexplanation
0=Absent.
1=Presentinonelimb.
2=Presentintwolimbs.
UN=Amputationorjointfusion,explain:________________
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forthischoice.Incaseofblindness,testbyhavingthepatienttouchnosefromextendedarmposition.
8.Sensory:Sensationorgrimacetopinprickwhentested,orwithdrawalfromnoxiousstimulusintheobtundedoraphasicpatient.Onlysensorylossattributedtostrokeisscoredasabnormalandtheexaminershouldtestasmanybodyareas(arms[nothands],legs,trunk,face)asneededtoaccuratelycheckforhemisensoryloss.Ascoreof2,"severeortotalsensoryloss,"shouldonlybegivenwhenasevereortotallossofsensationcanbeclearlydemonstrated.Stuporousandaphasicpatientswill,therefore,probablyscore1or0.Thepatientwithbrainstemstrokewhohasbilaterallossofsensationisscored2.Ifthepatientdoesnotrespondandisquadriplegic,score2.Patientsinacoma(item1a=3)areautomaticallygivena2onthisitem.
0=Normalnosensoryloss.
1=Mildtomoderatesensorylosspatientfeelspinprickislesssharporisdullontheaffectedsideorthereisalossofsuperficialpainwithpinprick,butpatientisawareofbeingtouched.
2=Severetototalsensorylosspatientisnotawareofbeingtouchedintheface,arm,andleg.
_____
9.Bestlanguage:Agreatdealofinformationaboutcomprehensionwillbeobtainedduringtheprecedingsectionsoftheexamination.Forthisscaleitem,thepatientisaskedtodescribewhatishappeningintheattachedpicture,tonametheitemsontheattachednamingsheetandtoreadfromtheattachedlistofsentences.Comprehensionisjudgedfromresponseshere,aswellastoallofthecommandsintheprecedinggeneralneurologicalexam.Ifvisuallossinterfereswiththetests,askthepatienttoidentifyobjectsplacedinthehand,repeat,andproducespeech.Theintubatedpatientshouldbeaskedtowrite.Thepatientinacoma(item1a=3)willautomaticallyscore3onthisitem.Theexaminermustchooseascoreforthepatientwithstupororlimitedcooperation,butascoreof3shouldbeusedonlyifthepatientismuteandfollowsnoonestepcommands.
0=Noaphasianormal.
1=Mildtomoderateaphasiasomeobviouslossoffluencyorfacilityofcomprehension,withoutsignificantlimitationonideasexpressedorformofexpression.Reductionofspeechand/orcomprehension,however,makesconversationaboutprovidedmaterialsdifficultorimpossible.Forexample,inconversationaboutprovidedmaterials,examinercanidentifypictureornamingcardcontentfrompatient'sresponse.
2=Severeaphasiaallcommunicationisthroughfragmentaryexpressiongreatneedforinference,questioning,andguessingbythelistener.Rangeofinformationthatcanbeexchangedislimitedlistenercarriesburdenofcommunication.Examinercannotidentifymaterialsprovidedfrompatientresponse.
3=Mute,globalaphasianousablespeechorauditorycomprehension.
_____
10.Dysarthria:Ifpatientisthoughttobenormal,anadequatesampleof
0=Normal.
1=Mildtomoderatedysarthria
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speechmustbeobtainedbyaskingpatienttoreadorrepeatwordsfromtheattachedlist.Ifthepatienthassevereaphasia,theclarityofarticulationofspontaneousspeechcanberated.Onlyifthepatientisintubatedorhasotherphysicalbarrierstoproducingspeech,theexaminershouldrecordthescoreasuntestable(UN),andclearlywriteanexplanationforthischoice.Donottellthepatientwhyheorsheisbeingtested.
patientslursatleastsomewordsand,atworst,canbeunderstoodwithsomedifficulty.
2=Severedysarthriapatient'sspeechissoslurredastobeunintelligibleintheabsenceoforoutofproportiontoanydysphasia,orismute/anarthric.
UN=Intubatedorotherphysicalbarrier,explain:________________
_____
11.Extinctionandinattention(formerlyneglect):Sufficientinformationtoidentifyneglectmaybeobtainedduringthepriortesting.Ifthepatienthasaseverevisuallosspreventingvisualdoublesimultaneousstimulation,andthecutaneousstimuliarenormal,thescoreisnormal.Ifthepatienthasaphasiabutdoesappeartoattendtobothsides,thescoreisnormal.Thepresenceofvisualspatialneglectoranosognosiamayalsobetakenasevidenceofabnormality.Sincetheabnormalityisscoredonlyifpresent,theitemisneveruntestable.
0=Noabnormality.
1=Visual,tactile,auditory,spatial,orpersonalinattentionorextinctiontobilateralsimultaneousstimulationinoneofthesensorymodalities.
2=Profoundhemiinattentionorextinctiontomorethanonemodalitydoesnotrecognizeownhandororientstoonlyonesideofspace.
_____
_____
Adaptedfrom:GoldsteinLB,SamsaGP,Stroke199728:307.
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Disclosures:JamaryOliveiraFilho,MD,MS,PhDNothingtodisclose.WalterJKoroshetz,MDNothingtodisclose.ScottEKasner,MD(Ticagrelor)].Consultant/AdvisoryBoards:Medtronic[Stroke,atrialf
ibrillation(CoreValve,REVEAL)]Merck[Stroke]Pfizer[Stroke]Novartis[Stroke]GSK[Stroke]AbbVie[Stroke]DaiichiSankyo[Stroke]BoehringerIngelheim[Stroke].disclose.Contributordisclosuresarereview
edforconflictsofinterestbytheeditorialgroup.Whenfound,theseareaddressedbyvettingthroughamultilevelreview
process,andthroughrequirementsforreferencestobeprovidedtosupportthecontent.AppropriatelyreferencedcontentisrequiredofallauthorsandmustconformtoUpToDatestandardsofevidence.Conflictofinterestpolicy
Disclosures