TheMostCommonQuestionsAboutStrokeandTIA

SharonPoisson,MDMASUniversityofColorado,DenverAssociateProfessorofNeurology

Disclosures

• NIHU54granttostudyischemicstrokeinchildrenandyoungadults

• Nootherdisclosures

LearningObjectives• Uponcompletionofthisprogram,theparticipantshouldbe

ableto:– Identifyhighrisktransientischemicattacks,understandwhatstudiesareneedtobedoneurgently,andunderstandearlymanagementdecisionsneededforsecondarystrokeprevention.

– Outlinerecentadvancesintheacutetreatmentofischemicstrokewithinterventionaltreatments,andunderstandthesignsoflargevesselocclusionswhichhelptoidentifycandidatesforinterventionaltreatment.

– Applytheguidelinesaswellasexpertopinionindeterminingwhatantithrombotictreatmentisappropriatefordifferenttypesofpatientswithstroke,andtounderstandtheappropriatetimingofstartingantithrombotictreatments.

Consult#1• 68 year old man with DM, HTN, h/o CAD • Admitted for hypertensive urgency, spent a day in the

MICU, and is now on the floor. – BP on admission was in the 190s/110s, and has now improved

to the160s/90s. • He reports a couple of episodes in the 2 days prior to

admission:– RUE numbness and clumsiness, dizziness – All of the episodes lasted <5 min.

• He now has no neurologic symptoms and normal exam.• Getting ready for discharge when he gave this history

Consult#1

• “Myquestionsforyou”:– CouldtheseepisodeshavebeenTIAs?– WhatdoIneedtodonow?– Canhegohome?

TransientIschemicAttack

• What is a TIA?– Episode of temporary, focal cerebral dysfunction due

to vascular disease– Classic definition <24 hours– Reality, most <10 minutes

• Why should I care?– High risk of stroke following TIA

• 7 days: ~ 8%• 30 days: ~ 10%• 90 days: 10-20% (average 11%)

– Risk within 90 days after stroke: 2-7% (avg 4%)

Stroke 2014; 45(7): 2160-236

HowdoIknowifitisaTIA?

• Manymimics– Migraine– Changesinelectrolytes– Peripheralnerveproblems– Hypotensive/Hypertensiveepisodes– Functionaldisorders– Nonspecificsymptoms– difficulttodefine

RiskStratificationbyClinicalFeatures

• ClinicalfeaturesarethemostextensivelyvalidatedpredictorsofoutcomeafterTIA

• ABCD2 Score– Finalscore=0-7Clinical Feature Values Points

Age ≥ 60 1Blood Pressure ≥140/90 1Clinical Symptoms Unilateral Weakness 2

Speech disturbance without Weakness

1

Duration ≥60 minutes 210-59 minutes 1

Diabetes Yes - historical 1

ABCD2 Score

SCJohnstonetal.,Lancet2007369:283

ABCD2andRiskCategories

RiskGroup ABCD2

ScoreRiskofStroke

2days 7days 90daysLow 0-3 1% 1.2% 9.8%

Moderate 4-5 4.1% 5.9% 9.8%High 6-7 8.1% 11.7% 17.8%

SomefindingsthatABCD2 isaccurateatpredictingseverestroke,butlessaccurateinpredictingANYsubsequentstroke

WhatdoIdonow?

• ABCD2 =5(age,BP,weakness,DM)• WhatamImostworriedabout?• Whatwillchangemanagementorpredicthigherrisk?

• Whatistheetiology?

RiskStratificationbyEtiology

• Meta-analysis:riskofrecurrentstrokebysubtypeusingTOAST

• N=1709patientswithstroke

• Largearteryatherosclerosishadthehighestearlyriskofrecurrence

Lovettetal.,Neurology200462:569

LAA

ManagementofTIA

• Evaluatefortheetiology• Treattheunderlyingetiology• Secondarystrokeprophylaxis

– Antiplateletoranticoagulant– BPcontrol– DMcontrol– Statinforatheroscleroticrisk

Consult#2• 68 year old man with DM, HTN, h/o CAD • Admitted for hypertensive urgency, spent a day in the

MICU, and is now on the floor. – BP on admission was in the 190s/110s, and has now improved

to the160s/90s. • He reports a couple of episodes in the 2 days prior to

admission:– RUE numbness and clumsiness, dizziness – All of the episodes lasted <5 min.

• He now has no neurologic symptoms and normal exam.• Getting ready for discharge when he gave this history• We did a TIA workup…

Consult#2- workup

• Patienthasbeenontelemetryfor24hours– Noarrhythmias

• Lipidpanelchecked:LDL120• HemoglobinA1c5.9• MRIdonewithnoacuteinfarctseen• MRAheadandneck…

RiskStratificationbyEtiology

• Meta-analysis:riskofrecurrentstrokebysubtypeusingTOAST

• N=1709patientswithstroke

• Largearteryatherosclerosishadthehighestearlyriskofrecurrence

Lovettetal.,Neurology200462:569

LAA

TIA&CarotidDisease• SubgroupanalysisofNASCET• SubjectswithhemisphericTIAandseverecarotidstenosistreatedmedically– 1-monthstrokeriskof22%(2xthatofallcauseTIA)

• CombinedsubgroupanalysisofNASCETandECSTinpatientswithhemisphericTIAandseverecarotidstenosis:– 15.4%ARRofipsilateralstrokewithin5years– Bestoutcomeswinterventionwithin2weeks

Rothwell et al, Lancet 2004; 363

Consult#3

• 37yearoldman,previouslyhealthy– Wasatworkat08:15andtalkingonthephonewhenhesuddenlyhadnonsensicalandslurredspeech

– Co-workerfoundthepatientontheground30minuteslaterandcalledEMS

– BroughttotheED,wherehewasawake,alertbutconfused,perseverating,aggitated

– Noweaknessorotherfocalneurologicsymptomsnoted

– Headlacerationthatrequired3stitchesinED

Consult#3

• Noncontrast HeadCTdoneandwasnormal• Patientwasadmittedtomedicineforconcernfortoxicityversuspost-concussivesyndrome

• Nosignificantfindingsontox screen,basiclabs

• At5pm,hiswifenoticedsomedroopingofhisleftface

• MRIbraindone

DWI ADC

NowWhat??

• ShouldIcallastrokealert?

• Isthereanyacutestroketreatmentthatheisacandidatefor?

• Whatisthewindowforacutetreatment??

tPA for Ischemic Stroke

• Only FDA approved medication for treatment of arterial ischemic stroke– Up to 3 hours from last known normal

• Not approved, but standard practice to use up to 4.5 hours

• As time progresses, chance of benefit decreases, and risk of hemorrhage increases

NEJM (333):597-602.NEJM. (359):1317-1329

Benefits of Thrombolysis

tPA forCerebralIschemiawithin3hoursofonset–changesinoutcomeduetotreatment

Stroke 2010: 41; 300-306

Normal or Nearly NormalBetterNo Major ChangeWorseSeverely Disabled or Dead

Final Outcome:

EarlyCourse:NoearlyworseningEarlyworseningwhemorrhage

WhatistheEvidenceforInterventionalTreatment??

Five New Trials in 2015:

Allmulticenterrandomizedtrialsinadults,assessingthrombectomy and/orintra-arterialthrombolytics intheanteriorcirculation(ICA,M1,M2)comparedwithstandardtreatment

Study NOnsettoGroin

Puncturewindow

NIHSSlimits

MedianNIHSS

%treatedwithIVtPA

Medianonsettogroin

puncturetime

mRS0-2at90-days

(endovascularvscontrol)

Mortalityat90days

(endovascularvscontrol)

Mr.CLEAN 500 6h ≥2 18 89% 260m(4h20m)

33%vs19%(RR1.7)

21%vs22%(RR1.0)

ESCAPE 316 12h(84%in<6h) ≥6 17 76% 200m

(3h20m)53%vs29%(RR1.8)

10%vs19%(RR0.5)

EXTEND-IA 70 6h Nolimits 15 100% 210m(3h30m)

71%vs40%(RR1.8)

9%vs20%(RR0.4)

SWIFT-PRIME 196 6h ≥6 17 100% 224m

(3h44m)60%vs35%(RR1.7)

9%vs12%(RR0.7)

REVASCAT 206 8h(90%in<6h)

≥6 17 73% 269m(4h29m)

44%vs28%(RR1.6)

18%vs16%(RR1.2)

NumberNeededtoTreat

RevisionofAHAGuidelines

• StillgiveIVtpa• IAthrombectomy recommendedwithin6hourwindowforICAandMCAclots• Stronglyrecommendnoninvasivevascularimagingtoscreenpatients• Usestentretrievers

– Aspirationthrombectomy alsohashighrecanalizationrates– THERAPYtrialstoppedearly

• Goodtrendsandconfidenceintervals• Notagooddirectcomparison

• Useaballoonguidecatheter(ordistalaspirationcatheter)alongwithastentretriever

NewTrialAnnounced…• May2017– EuropeanStrokeOrganizationConference,Prague– DAWNtrialresultspresented(notyetpublished)

• Patientswithstrokeandlargevesselocclusionbetween6-24hourspostonsetofsymptoms

• Smallcoreinfarctvolumeonimaging,largepenumbra• 73%relativeriskreductionindependencyofADLs

HowDoWeKnowWhoisaCandidate?

• Thekeyisrecognitionofpossiblelargevesselocclusion

StrokePatternsCOMMON STROKEPATTERNS

AnteriorCirculation

ACAOcclusion

• Contralateralhemiparesis:Legweakness>Arm• Contralateral sensoryloss:Leg>arm• Confusion,personalitychanges

MCAocclusion: • Contralateralhemiparesis:Armandfaceweakness>Leg• Contralateralsensoryloss: Arm/face>leg• Aphasia (usuallyleftbrain)• Spatialneglect (usuallyrightbrain)• Homonymoushemianopiaonoppositesideoftheinfarct• Gazedeviationtowardssideofstroke

PosteriorCirculation

PCA occlusion: • Homonymoushemianopiaonoppositesideoftheinfarct• Contralateralsensoryloss• Possibleaphasia• Disconjugate gaze(uncommon)

Vertebro-basilarocclusion:

• ataxia,vertigo,diplopia,dysarthria,hiccups,nausea,vomiting• disconjugate gaze• crossedsigns• decreasedLOC

WhoShouldWeConsiderforIntervention?

• Inpatients,atleastoutto12hoursfromlasttimeknownnormal,evaluateforcorticalsigns– Aphasia– Neglect– HomonymousHemianopsia– GazeDeviation

• Rapidimagingevaluationwithvesselimaging(CTAorMRA)andevaluationofsizeofstroke(CTperfusionorMRI)

Consult#3• Oncompleteneurologicalexam,pt intubated,agitated,mildLfacialdroop,gazepreferencetoR,Lsidedneglect,nolimbweakness

Consult#3

• Post-thrombectomy,patientdidwell,withimprovementinspeech,neglect

• Returnedhomewithoutpatienttherapies

Consult#4

Consult#4:65yearoldmanwithrightface/arm/legweakness

• Admittedforpneumonia• Post-surgically,hada45minuteepisodeofRface/arm/legweakness

• Nowneurologicallynormal• Previouslyonnomedications

• 7599patientswithstroke/TIAwithin3months,andanothervascularriskfactor

• RandomizedtoPlavixvs Plavix/ASA75mg

ASAplusClopidogrel?MATCHtrial

• 15,603patientswithcardiovasculardiseaseormultiplevascularriskfactors

• RandomizedtoASAalonevs ASA/Plavix• After2years,nobenefitinpreventionofMI/stroke/ordeathduetoCVcauses

• IncreasedbleedingriskinsubgroupwithhistoryofstrokeonASA/Plavix

ASA/Plavix- CHARISMA

• EffectivenessofASA/Plavixvs ASAinpatientswithTIAorminorstrokewithin24hours

• Trialclosedearlyduetopoorrecruitment– Alsostudyingstatins,andpt’s withprioruseofstatinwereexcluded,SPARCLpublished

• 392patientsenrolled– ARRof4.4%in90-dayriskofstrokeinASA/Plavixgroup(9.5%vs 5.1%)

– ARRof5.5%in90-dayriskofstroke/MI/vasc deathinASA/plavix group11.6%vs 6.1%)

– Underpoweredduetopoorenrollmentandfactorialdesign

ASA/Plavix- FASTER

• US/internationalandChineseversionsofsimilartrials

• ASAversusPlavix+ASA inpatientswithhighriskTIAandminorstrokeacutelyandfor90days

• POINTcurrentlyenrolling

POINT…CHANCE

• ResultspresentedatISC2013– notyetpublished

• 5170ChinesepatientswithminorstrokeorTIA

• ASAgroupwith11.7%outcomestroke,8.2%inASA/Plavixgroup(HR0.68,CI0.57-0.81)

• Changein“standardofcare”?

CHANCE

Whendoweusedualantiplatelettherapy?

• Intracranialstenosis:SAMMPRIStrial– 70-99%stenosis– TIAorstroke

• Randomizedtostentingvsaggressivemedicalmanagement– ASA+plavix for2months– Rosuvastatin– Oneanti-HTNmedwasgivenforfree

Chimowitz MI. Stenting versus Aggressive Medical Therapy for Intracranial Stenosis. NEJM 2011;365:993-1003.

Thetrialstops…Early.

• Becausemedicalmanagementwins!– 30-daystrokeordeath

• Stenting:14.7%• MedicalManagement:5.8%

Questions

• Whatistheguidelinerecommendedtimelineforinterventionaltreatmentofacutestroke?a.0-4.5hoursafteranyacuteischemicstrokeb.0-6hoursafteranteriorcirculationlargevesselocclusionc.0-6hoursafteranylargevesselocclusiond.0-24hoursafteranteriorcirculationlargevesselocclusion

Questions

• Whatistheguidelinerecommendedtimelineforinterventionaltreatmentofacutestroke?a.0-4.5hoursafteranyacuteischemicstrokeb.0-6hoursafteranteriorcirculationlargevesselocclusionc.0-6hoursafteranylargevesselocclusiond.0-24hoursafteranteriorcirculationlargevesselocclusion

Question#2

• WhatisthemostcriticalstudynecessaryafterTIAtodeterminetheetiologyandsecondarystrokeprevention?a. ABCD2scoreb. Telemetryc. Lipidpaneld. Vesselimagingofthebraine. Vesselimagingoftheneck

Question#2

• WhatisthemostcriticalstudynecessaryafterTIAtodeterminetheetiologyandsecondarystrokeprevention?a. ABCD2scoreb. Telemetryc. Lipidpaneld. Vesselimagingofthebraine. Vesselimagingoftheneck

Question#3

• Inwhichscenarioshoulddualantiplatelettherapybeconsideredforsecondarystrokeprevention?a. First3monthsafterTIAwithABCD2score=2b. First3monthsafterstrokewithNIHSS=10c. Symptomaticseverecervicalcarotidstenosisd. Alloftheabovee. Noneoftheabove

Question#3

• Inwhichscenarioshoulddualantiplatelettherapybeconsideredforsecondarystrokeprevention?a. First3monthsafterTIAwithABCD2score=2b. First3monthsafterstrokewithNIHSS=10c. Symptomaticseverecervicalcarotidstenosisd. Alloftheabovee. Noneoftheabove

Questions??