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4/4/2015 Antithrombotictreatmentofacuteischemicstrokeandtransientischemicattack

http://www.uptodate.com/contents/antithrombotictreatmentofacuteischemicstrokeandtransientischemicattack?topicKey=NEURO%2F1082&elapsedTime 1/19

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).



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



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".)



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.



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)



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)



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 to6 gradereadinglevel,andtheyanswerthefourorfivekeyquestionsapatientmighthaveaboutagivencondition.Thesearticlesarebestforpatientswhowantageneraloverviewandwhoprefershort,easytoreadmaterials.BeyondtheBasicspatienteducationpiecesarelonger,moresophisticated,andmoredetailed.Thesearticlesarewrittenatthe10 to12 gradereadinglevelandarebestforpatientswhowantindepthinformationandarecomfortablewithsomemedicaljargon.

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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

1. TheInternationalStrokeTrial(IST):arandomisedtrialofaspirin,subcutaneousheparin,both,orneitheramong19435patientswithacuteischaemicstroke.InternationalStrokeTrialCollaborativeGroup.Lancet1997349:1569.

2. CAST:randomisedplacebocontrolledtrialofearlyaspirinusein20,000patientswithacuteischaemicstroke.CAST(ChineseAcuteStrokeTrial)CollaborativeGroup.Lancet1997349:1641.

3. ChenZM,SandercockP,PanHC,etal.Indicationsforearlyaspirinuseinacuteischemicstroke:Acombinedanalysisof40000randomizedpatientsfromthechineseacutestroketrialandtheinternationalstroketrial.OnbehalfoftheCASTandISTcollaborativegroups.Stroke200031:1240.

4. SandercockPA,CounsellC,GubitzGJ,TsengMC.Antiplatelettherapyforacuteischaemicstroke.CochraneDatabaseSystRev2008:CD000029.

5. WangY,WangY,ZhaoX,etal.Clopidogrelwithaspirininacuteminorstrokeortransientischemicattack.NEnglJMed2013369:11.

6. DenglerR,DienerHC,SchwartzA,etal.Earlytreatmentwithaspirinplusextendedreleasedipyridamolefortransientischaemicattackorischaemicstrokewithin24hofsymptomonset(EARLYtrial):arandomised,openlabel,blindedendpointtrial.LancetNeurol20109:159.

7. 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.)



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.

Topic1082Version16.0



GRAPHICS

Eligibilitycriteriaforthetreatmentofacuteischemicstrokewithrecombinanttissueplasminogenactivator(alteplase)

Inclusioncriteria

Clinicaldiagnosisofischemicstrokecausingmeasurableneurologicdeficit

Onsetofsymptoms



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.

Graphic71462Version11.0



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.




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.

_____



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

_____



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.


6a.Leftleg

6b.Rightleg

_____

7.Limbataxia:Thisitemisaimedatfindingevidenceofaunilateralcerebellarlesion.Testwitheyesopen.Incaseofvisualdefect,ensuretestingisdoneinintactvisualfield.Thefingernosefingerandheelshintestsareperformedonbothsides,andataxiaisscoredonlyifpresentoutofproportiontoweakness.Ataxiaisabsentinthepatientwhocannotunderstandorisparalyzed.Onlyinthecaseofamputationorjointfusion,theexaminershouldrecordthescoreasuntestable(UN),andclearlywritetheexplanation

0=Absent.

1=Presentinonelimb.

2=Presentintwolimbs.


_____



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



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.




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