溶栓相關(guān)試驗(yàn)及進(jìn)展課件

急性缺血性腦卒中血管再通

臨床證據(jù)與進(jìn)展首都醫(yī)科大學(xué)宣武醫(yī)院神經(jīng)外科王亞冰急性缺血性腦卒中血管再通

臨床證據(jù)與進(jìn)展首都醫(yī)科大學(xué)宣武醫(yī)院1溶栓相關(guān)試驗(yàn)及進(jìn)展課件2缺血性腦卒中溶栓治療循證靜脈溶栓（NINDS，ECASSIII）動(dòng)脈溶栓（PROACT）動(dòng)靜脈溶栓（IMS）機(jī)械取栓（MERCI，SEIS）指南其他證據(jù)缺血性腦卒中溶栓治療循證靜脈溶栓（NINDS，ECASS3靜脈溶栓治療美國(guó)FDA批準(zhǔn)臨床應(yīng)用----1995年NINDS研究證明3h內(nèi)靜脈注射重組組織纖溶酶原激活劑（rtPA）溶栓治療的有效性AHA:----2008年歐洲急性卒中協(xié)作ECASSIII研究表明靜脈rtPA溶栓治療的時(shí)間窗可延長(zhǎng)至4.5h靜脈溶栓治療美國(guó)FDA批準(zhǔn)臨床應(yīng)用4靜脈rtPA溶栓的不足受益患者少

-僅1-3%的患者能夠在發(fā)病3h內(nèi)接受治療血管再通率較低

-僅約6%的頸內(nèi)動(dòng)脈、30%大腦中動(dòng)脈和30%椎基底動(dòng)脈可獲得血管再通靜脈rtPA溶栓的不足受益患者少539歲女性，意識(shí)障礙2小時(shí)A：T2相正常B、C：DWI顯示右側(cè)MCA分布區(qū)細(xì)胞毒性水腫，以右側(cè)放射冠明顯動(dòng)脈內(nèi)溶栓治療3天后復(fù)查D：病變范圍無增大，僅皮層及放射冠有小梗塞灶。39歲女性，意識(shí)障礙2小時(shí)6Dismatch未行溶栓治療的病例Dismatch未行溶栓治療的病例7缺血性腦卒中的早期治療

血管再通臨床有效發(fā)現(xiàn)新策略!↑缺血區(qū)的血流灌注缺血性腦卒中的早期治療血管再通臨床有效發(fā)現(xiàn)新策略!↑缺血區(qū)8缺血性腦卒中血管再通：早期治療關(guān)鍵----NINDS：1995年，靜脈溶栓，3h----ECASS-Ⅲ：2008年，靜脈溶栓，4.5h----大血管閉塞（ICAT--6%，TCD）發(fā)展：----大血管閉塞（ICA，MCA，VA，BA）----Real-timewindow至病理生理時(shí)間窗----多模式的血管內(nèi)治療（單純/合并）有效快速容易復(fù)雜缺血性腦卒中血管再通：早期治療關(guān)鍵有效快速容易復(fù)雜9血管內(nèi)機(jī)械再通治療PROACTIIMERCIMultiMERCIPenumbraNINDSIVrtPAN121141164125182Age6467686468NIHSS1720191817Recanalization66%48%68%82%N/AsICH10%7.8%9.8%11.2%6.6%90daysmRS≤240%27.7%36%25%39%90daysmortality25%43.5%34%32.8%21%血管內(nèi)機(jī)械再通治療PROACTIIMERCIMulti10TheImpactofRecanalizationonIschemicStrokeOutcome

AMeta-Analysisspontaneous(24.1%),intravenousfibrinolytic(46.2%),intra-arterialfibrinolytic(63.2%),combinedintravenous–intra-arterial(67.5%),andmechanical(83.6%)recanalizedversusnonrecanalized:oddsratioof4.43(95%CI,3.32to5.91)mortalitywasreducedinrecanalizedpatients(oddsratio,0.24;95%CI,0.16to0.35)SICH:didnotdifferbetweenthe2groupsStroke.2007;38:967-973;TheImpactofRecanalizationo11Anteriorcirculation:randomizedthrombolysistrialsinhemisphericstrokeNINDS:NationalInstituteofNeurologicalDisordersandStroke;ECASS:EuropeanCooperativeAcuteStrokeStudyPROACT:ProlyseinAcuteCerebralThromboembolismAnteriorcirculation:randomiz12Posteriorcirculation:MajortreatmentstudiesinacutevertebrobasilarocclusionIVT:intravenousthrombolysis;LIT:localintraarterialthrombolysis;Posteriorcirculation:Majort13GuidelinesfortheEarlyManagementofPatientsWithAcuteIschemicStrokeIntravenousrtPA推薦對(duì)起病3小時(shí)內(nèi)符合標(biāo)準(zhǔn)的缺血性卒中患者靜脈輸注rtPA（0.9mg/kg，最大劑量90mg），I級(jí)推薦，A級(jí)證據(jù)。

推薦有適應(yīng)征、起病后3-4.5小時(shí)的卒中患者使用靜脈用rtPA（0.9mg/kg，最大劑量90mg），I級(jí)推薦，B級(jí)證據(jù)。AHA/ASAGuidelineGuidelinesfortheEarlyManag14GuidelinesfortheEarlyManagementofPatientsWithAcuteIschemicStrokeEndovascularInterventions時(shí)間窗內(nèi)：靜脈優(yōu)先于動(dòng)脈（I級(jí)推薦，A級(jí)證據(jù)）對(duì)于大腦中動(dòng)脈大面積缺血性卒中患者，病程小于6小時(shí)的，動(dòng)脈內(nèi)溶栓治療審慎選擇的患者（他們不適合使用rtPA治療）可以獲益。（I級(jí)推薦，B級(jí)證據(jù)）。機(jī)械取栓方面，支架取栓器（如SolitaireFR和Trevo）總體上優(yōu)于彈簧圈取栓器（如Merci）。Penumbra系統(tǒng)相較支架取栓器的相對(duì)效果尚不明確。I級(jí)推薦，A級(jí)證據(jù)。聯(lián)合溶栓：對(duì)于大動(dòng)脈梗死靜脈溶栓沒有出現(xiàn)應(yīng)答的患者進(jìn)行補(bǔ)救性動(dòng)脈內(nèi)溶栓或機(jī)械取栓術(shù)是合理的。需要更多的隨機(jī)試驗(yàn)結(jié)果（IIb級(jí)推薦，B級(jí)證據(jù)）。急診顱內(nèi)血管成形術(shù)和/或支架置入的效果尚不肯定。AHA/ASAGuidelineGuidelinesfortheEarlyManag15SWIFTTrial：Solitaire〉MerciSWIFTTrial：Solitaire〉Merci16MerciRetrievalDeviceX6、X5；L5；Kmini、VMerciRetrievalDeviceX6、X5；L517PenumbraSystemThrombusaspirationandproximalthrombectomy

FDA2007PenumbraSystemThrombusaspira18PenumbraSystemPenumbraSystem19支架回收機(jī)械取栓支架回收機(jī)械取栓20支架回收機(jī)械取栓Castanoetal.Stroke2010;41:1836-40支架回收機(jī)械取栓Castanoetal.Stroke21Endovasculartreatmentofacuteischemicstroke

theendorthebeginning??IMSIIII:interventionalManagementofStrokeMRRESCUE:MechanicalRetrievalandRecanalizationofStrokeClotsUsingEmbolectomySYNTHESISExpansion:ARandomizedControlledTrialonIntra-ArterialVersusIntravenousThrombolysisinAcuteIschemicStrokeNeurosurgFocus36(1):E5,2014Endovasculartreatmentofacut22BridgingTherapyBridgingTherapy23BridgingTherapyinAcuteIschemicStroke:ASystematicReviewandMeta-AnalysisSystematicreviewofallstudiesusingbridgingtherapypublishedbetweenJanuary1966andMarch2011Theliteraturesearchidentified15studies.Inthismeta-analysis,pooledestimatesassociatedwithbridgingtherapywere69.6%forrecanalizationrates,48.9%forfavorableoutcome,17.9%formortality,and8.6%forsICH.Stroke.2012;43:1302-1308BridgingTherapyinAcuteIsch24PooledRatesofRecanalizationandClinicalOutcomesConclusions—Bridgingtherapyisassociatedwithacceptablesafetyandefficacyinstrokepatients.Timetointravenoustreatmentiscriticaltoimproverecanalizationratesandfavorableoutcomes.PooledRatesofRecanalization25IMSIIItrialEndovascularTherapyafterIntravenoust-PAversust-PAAloneforStrokewithin3hoursStoppedearlybecauseoffutilityafter656participantshadundergonerandomization(434patientstoendovasculartherapyand222tointravenoust-PAalone)NEnglJMed.2013March7;368(10):893–903.IMSIIItrialEndovascularTher26溶栓相關(guān)試驗(yàn)及進(jìn)展課件27IMSIIItrialIMSIIItrial28IMSIIItrialCONCLUSIONS—Similar

safetyoutcomesandnosignificantdifferenceinfunctionalindependencewithendovasculartherapyafterintravenoust-PA,ascomparedwithintravenoust-PAaloneNEnglJMed.2013March7;368(10):893–903.IMSIIItrialCONCLUSIONS—Simil29Endovasculartreatmentofacuteischemicstroke

theendorthebeginning??IMSIIII:interventionalManagementofStrokeMRRESCUE:MechanicalRetrievalandRecanalizationofStrokeClotsUsingEmbolectomySYNTHESISExpansion:ARandomizedControlledTrialonIntra-ArterialVersusIntravenousThrombolysisinAcuteIschemicStrokeNeurosurgFocus36(1):E5,2014Endovasculartreatmentofacut30MRRESCUE

ATrialofImagingSelectionand

EndovascularTreatmentforIschemicStrokeAfavorablepenumbralpatternonneuroimagingdidnotidentifypatientswhowoulddifferentiallybenefitfromendovasculartherapyforacuteischemicstroke,norwasembolectomyshowntobesuperiortostandardcare.MRRESCUE

ATrialofImaging31SWIFTTrial美國(guó)多中心、隨機(jī)對(duì)照研究血管內(nèi)機(jī)械再通治療顱內(nèi)大血管閉塞SolitaireRetrievervsMerciRetriever主要療效終點(diǎn)：成功血管再通、無癥狀性出血次要療效終點(diǎn)：良好臨床結(jié)局、死亡率和嚴(yán)重并發(fā)癥Saveretal.ISC2012FebSWIFTTrial美國(guó)多中心、隨機(jī)對(duì)照研究Savere32SWIFTTrial:RandomizedEndpointSolitaireFR(n=58)Merci(n=55)Successfulrecanalizationstudydevice83.3%48.1%Endofproceduresuccessfulrecanalization88.9%67.3%SuccessfulrecanalizationwithoutsICH60.7%24.1%mRS≤2at90Days58.2%33.3%Mortalityat90Days17.2%33.3%AllP<0.001SWIFTTrial:RandomizedEndpoin33Endovasculartreatmentofacuteischemicstroke

theendorthebeginning??IMSIIII:interventionalManagementofStrokeMRRESCUE:MechanicalRetrievalandRecanalizationofStrokeClotsUsingEmbolectomySYNTHESISExpansion:ARandomizedControlledTrialonIntra-ArterialVersusIntravenousThrombolysisinAcuteIschemicStrokeNeurosurgFocus36(1):E5,2014Endovasculartreatmentofacut34SYNTHESISExpansion

EndovascularTreatmentforAcuteIschemic

Strokewithin4.5hoursafteronsetendovasculartherapy(intraarterialthrombolysiswitht-PA,mechanicalclotdisruptionorretrieval,oracombinationoftheseapproaches)VSintravenoust-PAAt3months,55patientsintheendovascular-therapygroup(30.4%)and63intheintravenoust-PAgroup(34.8%)werealivewithoutdisabilityFatalornonfatalsymptomaticintracranialhemorrhagewithin7daysoccurredin6%ofthepatientsineachgroup,andtherewerenosignificantdifferencesbetweengroupsintheratesofotherseriousadverseeventsorthecasefatalityrateSYNTHESISExpansion

Endovascul35Conclusions:Theresultsofthistrialinpatientswithacuteischemicstrokeindicatethatendovasculartherapyisnotsuperiortostandardtreatmentwithintravenoust-PA.SYNTHESISExpansionConclusions:Theresultsofth36SYNTHESISExpansion

EndovascularTreatmentforAcuteIschemic

StrokeAt3months,55patientsintheendovascular-therapygroup(30.4%)and63intheintravenoust-PAgroup(34.8%)werealivewithoutdisabilityFatalornonfatalsymptomaticintracranialhemorrhagewithin7daysoccurredin6%ofthepatientsineachgroup,andtherewerenosignificantdifferencesbetweengroupsintheratesofotherseriousadverseeventsorthecasefatalityrateConclusions:Theresultsofthistrialinpatientswithacuteischemicstrokeindicatethatendovasculartherapyisnotsuperiortostandardtreatmentwithintravenoust-PA.SYNTHESISExpansion

Endovascul37Thrombolysis(differentdoses,routesofadministrationand

agents)foracuteischaemicstroke

(Review)20trialsfivetrials:oneagentversusanotherandfivetrials:differentroutesofadministration13trials:comparisonofhigherdosewithlowerdoseThrombolysis(differentdoses,38up-to-date:19March2013Therewasnoevidenceofanybenefitforintra-arterialoverintravenoustreatment.Atpresent,intravenousrt-PAat0.9mg/kgaslicensedinmanycountriesappearstorepresentbestpracticeandotherdrugs,dosesorroutesofadministrationshouldonlybeusedinrandomisedcontrolledtrials.up-to-date:19March2013There39EndovascularTherapyforAcuteIschemicStroke:

ASystematicReviewandMeta-analysisToFebruary12,20135randomizedtrialsenrolling1197patients;ET,711;IV,486;----Overall,nosignificantimprovementinanyoftheoutcomesinpatientsreceivingETcomparedwiththosereceivingIVthrombolysis.----Subgroupanalysis,ETwasfoundtohavebetteroutcomesinpatientswithseverestroke(NIHSS,＞20),showingadose-responsegradientandimprovingexcellent,good,andfairoutcomesbyanadditional4%,7%,and13%,respectively,comparedwithIVthrombolysis.2013MayoFoundationforMedicalEducationandResearchnMayoClinProc.EndovascularTherapyforAcute40EndovascularTherapyforAcuteIschemicStroke:

ASystematicReviewandMeta-analysisOverall,ETisnotsuperiortoIVthrombolysisforacuteischemicstrokes(levelBrecommendation).However,ETshowedpromiseandimprovedoutcomesinpatientswithseverestrokes,buttheevidenceislimitedduetosamplesize.ThereisaneedforfurthertrialsevaluatingtheroleofETinthishigh-riskgroup.2013MayoFoundationforMedicalEducationandResearchnMayoClinProc.EndovascularTherapyforAcute41問題局限性：一種方法，解決所有的閉塞----不同的閉塞部位（遠(yuǎn)近，前后循環(huán)）----閉塞的原因----栓子的性質(zhì)問題局限性：一種方法，解決所有的閉塞42Thrombusdensitypredictssuccessfulrecanalization

withSolitairestentretrieverthrombectomyinacute

ischemicstrokeInacutestroketreatedwithSolitairestentretrieverthrombectomy,higherthrombusHUvaluesarepredictiveofsuccessfulrecanalization.Suchinformationcanbeusedindecisionmakingwhenestimatingrecanalizationsuccessratewithdifferentendovasculartreatmentapproaches.Thrombusdensitypredictssucc43希望多模的血管內(nèi)再通方式，再通率高不同的方法----不同的閉塞部位（遠(yuǎn)近，前后循環(huán)）----閉塞的原因----栓子的性質(zhì)血管再通后的治療希望多模的血管內(nèi)再通方式，再通率高44溶栓相關(guān)試驗(yàn)及進(jìn)展課件45靜脈rtPA溶栓的不足受益患者少

-僅1-3%的患者能夠在發(fā)病3h內(nèi)接受治療血管再通率較低

-僅約6%的頸內(nèi)動(dòng)脈、30%大腦中動(dòng)脈和30%椎基底動(dòng)脈可獲得血管再通靜脈rtPA溶栓的不足受益患者少46動(dòng)脈溶栓治療發(fā)病6h內(nèi)，超選擇性腦動(dòng)脈內(nèi)溶栓治療藥物經(jīng)動(dòng)脈途徑可以迅速到達(dá)靶點(diǎn)發(fā)揮作用，直接接觸血栓，降低全身應(yīng)用溶栓藥物引起的出血并發(fā)癥采用rtPA或尿激酶動(dòng)脈內(nèi)溶栓是一種有效的治療方法，但至今未獲美國(guó)FDA批準(zhǔn)卒中介入治療的IMSI/II研究證實(shí)了靜脈和動(dòng)脈內(nèi)rtPA聯(lián)合溶栓治療的有效性動(dòng)脈溶栓治療發(fā)病6h內(nèi)，超選擇性腦動(dòng)脈內(nèi)溶栓治療47TIMIFlowTIMI0NoperfusionTIMI1Penetrationwithoutperfusion.perfusionpasttheinitialocclusion,butnodistalbranchfillingTIMI2PartialperfusionofthearterywithincompleteorslowdistalbranchfillingTIMI3CompleteperfusionofthearterywithfillingofalldistalbranchesTIMI2/TIMI3：成功血管再通TIMIFlowTIMI0NoperfusionT48出血性轉(zhuǎn)化ECASS標(biāo)準(zhǔn)，分為出血性梗塞和腦實(shí)質(zhì)血腫兩類出血性梗塞1型（HI-1）：沿梗塞灶邊緣有小瘀點(diǎn)、瘀斑出血性梗塞2型（HI-2）：在梗塞區(qū)內(nèi)有融合的瘀點(diǎn)、瘀斑，但未形成占位效應(yīng)出血性轉(zhuǎn)化ECASS標(biāo)準(zhǔn)，分為出血性梗塞和腦實(shí)質(zhì)血腫兩類49出血性轉(zhuǎn)化實(shí)質(zhì)性血腫1型（PH-1）：腦實(shí)質(zhì)血腫占小于30%的梗塞面積，伴一些輕微的占位效應(yīng)實(shí)質(zhì)性血腫2型（PH-2）：腦實(shí)質(zhì)血腫占大于30%的梗塞面積，有大量占位效應(yīng)出血性轉(zhuǎn)化實(shí)質(zhì)性血腫1型（PH-1）：腦實(shí)質(zhì)血腫占小于30%50出血性轉(zhuǎn)化無癥狀性出血轉(zhuǎn)化癥狀性出血性轉(zhuǎn)化-術(shù)后24小時(shí)-NIHSS≥4出血性轉(zhuǎn)化無癥狀性出血轉(zhuǎn)化51改良Rankin評(píng)分0

完全無癥狀1盡管有癥狀，但無明顯功能障礙，能完成所有日常職責(zé)和活動(dòng)2輕度殘疾，不能完成病前所有活動(dòng)，但不需幫助能照顧自己的事務(wù)3中度殘疾，要求一些幫助，但行走不需幫助4重度殘疾，不能獨(dú)立行走，無他人幫助不能滿足自身需求5嚴(yán)重殘疾，臥床、失禁，要求持續(xù)護(hù)理和關(guān)注6死亡mRS≤2：良好臨床結(jié)局改良Rankin評(píng)分0完全無癥狀1盡管有癥狀，但無明顯功52動(dòng)脈溶栓治療53歲，男性，突發(fā)左側(cè)肢體偏癱右側(cè)頂葉區(qū)域低灌注，右側(cè)MCA閉塞IArtPA治療完全再通動(dòng)脈溶栓治療53歲，男性，突發(fā)左側(cè)肢體偏癱IArtPA治療53PROACTII研究尿激酶組121例對(duì)照組59例P值血管再通66%18%<0.001癥狀性出血10%2%0.063個(gè)月良好臨床結(jié)局40%25%0.043個(gè)月死亡率25%27%0.80PROACTII研究尿激酶組對(duì)照組P值血管再通66%18%54溶栓治療NIHSSVesselsRecanalizationsICHGoodoutcomeMortalityNINDSIVrtPA(n=182)17N/AN/A6.6%39%21%ECASSIIIIVrtPA(n=418)9N/AN/A2.4%52.4%7.7%PROACTIIIAr-proUK(n=121)17MCA66%10%40%25%IMSIIV+IArtPA(n=80)18MCA、ICA、VA、BA56%6.3%43%16%IMSIIIV+IArtPA(n=81)19MCA、ICA、VA、BA60%9.9%46%16%溶栓治療NIHSSVesselsRecanalization55溶栓治療的局限性治療時(shí)間窗

-＞3h，＞4.5h

-＞6h靜脈溶栓無效患者溶栓治療（靜脈或動(dòng)脈）禁忌患者新治療策略溶栓治療的局限性治療時(shí)間窗56血管內(nèi)機(jī)械再通治療迅速恢復(fù)顱內(nèi)閉塞血管的血流延長(zhǎng)卒中治療的時(shí)間窗至8h適用于靜脈溶栓治療無效或靜脈溶栓禁忌的卒中患者治療方法-FDA批準(zhǔn)：Merci取栓、Penumbra吸栓

-支架植入、支架輔助性回收機(jī)械取栓

血管內(nèi)機(jī)械再通治療迅速恢復(fù)顱內(nèi)閉塞血管的血流57MechanicalThrombectomyThrombusaspirationandproximalthrombectomy

-Penumbrasystem,FDA2007Distalthrombectomy

-MerciRetriever,FDA2004-StentRetrieverFDA？SolitaireFR;TREVO;PULSE;ReviveMechanicalThrombectomyThrombu58Merci機(jī)械取栓UCLA發(fā)明研制，2001年5月首例2004年8月獲美國(guó)FDA批準(zhǔn)臨床應(yīng)用Merci機(jī)械取栓UCLA發(fā)明研制，2001年5月首例59MerciRetrievalDeviceX6、X5；L5；Kmini、VMerciRetrievalDeviceX6、X5；L560適應(yīng)證患者年齡18～85歲具有急性顱內(nèi)前或后循環(huán)卒中的癥狀體征NIHSS評(píng)分≥8分頭部CT掃描排除顱內(nèi)出血適應(yīng)證患者年齡18～85歲61適應(yīng)證卒中發(fā)病3-8h的患者或者發(fā)病3h內(nèi)靜脈溶栓治療禁忌或標(biāo)準(zhǔn)靜脈溶栓治療后無效的患者預(yù)計(jì)在卒中癥狀出現(xiàn)后8h內(nèi)能夠進(jìn)行介入治療全腦血管造影檢查后，證實(shí)可治療的血管閉塞部位，包括頸內(nèi)動(dòng)脈、大腦中動(dòng)脈和椎基底動(dòng)脈適應(yīng)證卒中發(fā)病3-8h的患者或者發(fā)病3h內(nèi)靜脈溶栓治療禁忌或62禁忌證NIHSS評(píng)分≥30分妊娠患者血糖<50mg/dL頸部血管嚴(yán)重異常情況導(dǎo)致介入治療所需的導(dǎo)管和器械無法進(jìn)入顱內(nèi)病變部位已知全身出血性疾病和凝血功能障礙疾病禁忌證NIHSS評(píng)分≥30分63禁忌證正在進(jìn)行口服抗凝藥物治療并且INR>1.048h內(nèi)應(yīng)用肝素治療且PTT大于2倍正常值血小板<30000/μL造影劑嚴(yán)重過敏的病史治療后血壓持續(xù)性升高，收縮壓>185mmHg或舒張壓>110mmHg禁忌證正在進(jìn)行口服抗凝藥物治療并且INR>1.064禁忌證CT檢查發(fā)現(xiàn)顯著的占位效應(yīng)伴有中線結(jié)構(gòu)移位或者>1/3的MCA供血區(qū)域呈低密度影責(zé)任病灶的近端血管狹窄程度大于50%預(yù)計(jì)生存時(shí)間小于3個(gè)月禁忌證CT檢查發(fā)現(xiàn)顯著的占位效應(yīng)伴有中線結(jié)構(gòu)移位或者>1/365Merci治療ICA卒中Merci治療ICA卒中66血管造影左側(cè)ICA閉塞血管造影左側(cè)ICA閉塞67Merci機(jī)械取栓Merci機(jī)械取栓68Merci機(jī)械取栓Merci機(jī)械取栓69完全血管再通完全血管再通70DWIPWINIHSS治療前

24治療后

6DWIPWI71Merci治療MCA卒中DWIPWIMerci治療MCA卒中DWIPWI72血管造影右側(cè)MCAM1閉塞血管造影右側(cè)MCAM1閉塞73Merci機(jī)械取栓Merci機(jī)械取栓74機(jī)械再通治療后復(fù)查CT和MRI機(jī)械再通治療后復(fù)查CT和MRI75Merci機(jī)械再通治療效果北美多中心前瞻性研究：MERCI和MultiMERCI卒中8h內(nèi)Merci機(jī)械取栓治療ICA、MCA和椎基底動(dòng)脈閉塞均有效305例患者，血管再通率64.6%

3個(gè)月良好結(jié)局32.4%Merci機(jī)械再通治療效果北美多中心前瞻性研究：MERCI和76血管再通：Mercivs靜脈溶栓血管再通：Mercivs靜脈溶栓77Merci治療ICA卒中血管再通率63%癥狀性出血率10%3個(gè)月良好臨床結(jié)局25%3個(gè)月死亡率46%Merci治療ICA卒中血管再通率63%78Merci治療MCA卒中：M1vsM2MCAM1(n=150)MCAM2(n=28)PAttemptstoremoveclot3.12±1.552.11±1.310.001FinalTIMIII/IIIflow60.0%82.1%0.03Clinicallysignificantprocedureadverseevents5.3%3.6%＞0.99mRS≤2at90days33.3%40.7%0.51Mortalityat90days32.9%25.9%0.65Symptomatichemorrhage6.7%3.6%＞0.99Merci治療MCA卒中：M1vsM2MCAM1MC79靜脈溶栓+MercivsMerciFailedIVt-PA(n=48)NonIVt-PA(n=257)FinalTIMIII/IIIflow72.9%63.0%Clinicallysignificantprocedureadverseevents4.2%6.6%mRS≤2at90days38.3%31.3%Mortalityat90days27.7%40.1%Symptomatichemorrhage10.4%8.6%靜脈溶栓+MercivsMerciFailedIVt80P=0.09P<0.001P=0.09P<0.00181OutcomesbyrevascularizationandIVtPAoverallandbyocclusionsiteOutcomesbyrevascularization82MortalitybyrevascularizationandIVtPAoverallandbyocclusionsiteMortalitybyrevascularization83MERCI：癥狀性出血性轉(zhuǎn)化141例，7.8%MERCI：癥狀性出血性轉(zhuǎn)化141例，7.8%84MultiMERCI：癥狀性出血性轉(zhuǎn)化164例，9.8%MultiMERCI：癥狀性出血性轉(zhuǎn)化164例，9.8%85血管內(nèi)再通治療：SAHMerciThrombectomy(n=128)IAT(n=31)PBaselineNIHSSscore18.2±6.812.8±6.7<0.001SAH14.1%(18/128)6.5%(2/31)0.37血管內(nèi)再通治療：SAHMerciThrombectomyI86血管內(nèi)再通治療：SAH臨床預(yù)后差SAHFisherIII級(jí)SAH合并PH血管內(nèi)再通治療：SAH臨床預(yù)后差87Merci治療：出血轉(zhuǎn)化的預(yù)測(cè)因素溶栓和血管內(nèi)機(jī)械再通治療缺血性卒中后均可發(fā)生出血性轉(zhuǎn)化嚴(yán)重的顱內(nèi)出血并發(fā)癥可導(dǎo)致患者嚴(yán)重的預(yù)后不良研究表明腦白質(zhì)疏松是IV和IArtPA溶栓治療后出血轉(zhuǎn)化的一個(gè)危險(xiǎn)因素腦白質(zhì)疏松是否可以預(yù)測(cè)血管內(nèi)機(jī)械取栓治療后的出血并發(fā)癥Merci治療：出血轉(zhuǎn)化的預(yù)測(cè)因素溶栓和血管內(nèi)機(jī)械再通治療缺88FazekasandSchmidtscoresof0to3Score0Score1Score2Score30，無1，輕度2，中度3，重度FazekasandSchmidtscoresof89腦白質(zhì)疏松預(yù)測(cè)Merci術(shù)后出血分析Merci治療大腦前循環(huán)卒中患者資料治療前MRFLAIR序列，判斷患者腦白質(zhì)疏松的部位（深部和腦室周圍）和嚴(yán)重程度有無中重度深部腦白質(zhì)疏松（2-3級(jí)）分為兩組分析兩組患者的臨床特征、治療后出血性轉(zhuǎn)化和臨床結(jié)局腦白質(zhì)疏松預(yù)測(cè)Merci術(shù)后出血分析Merci治療大腦前循環(huán)90BaselineCharacteristicsModeratetoseveredeepLANonmoderatetoseveredeepLAP#ofpatients26(24.8%)79(75.2%)Age79.0±10.161.6±19.1<0.001Age≥80years57.7%20.3%0.001Cardioembolicstrokesource88.5%60.8%0.008Hypertension92.3%57.0%0.001Hyperlipidemia53.8%29.1%0.03Atrialfibrillation69.2%32.9%0.002BaselineNIHSSscore19.8±6.417.5±6.00.05BaselineCharacteristicsModera91RevascularizationandClinicalOutcomebyLeukoaraiosis

ModeratetosevereLANonmoderatetosevereLAPPurethrombectomy50.0%58.2%0.50IVorIAlyticuse38.5%27.8%0.33FinalTIMIII/IIIflow80.8%72.2%0.45AllHT65.4%41.8%0.04PH42.3%19.0%0.03PH-223.1%5.1%0.02HI23.1%22.8%>0.99mRSatdischarge5.0(1-6)4.0(0-6)0.02mRS≤2atdischarge24.0%25.6%>0.99In-hospitalmortality48.0%11.5%<0.001RevascularizationandClinical92SeveredeepLAvsParenchymalHematoma

SeveredeepLAvsParenchymal93UnivariateAnalysisof

PredictorsforHemorrhageafterThrombectomyNoHT(n=55)AnyHT(n=50)PCardioembolicstrokesource58.2%78.0%0.03Atrialfibrillation32.7%52.0%0.05BaselineNIHSSscore16.8±6.119.5±5.80.06ModerateorsevereLA16.4%34.0%0.04In-hospitalmortality9.3%32.7%0.003mRSatdischarge3.0(0-6)4.0(1-6)0.003UnivariateAnalysisofPredict94UnivariateAnalysisofPredictorsforParenchymalHematomaNoPH(n=79)AnyPH(n=26)PPremorbidwarfarinuse6.3%23.1%0.04BaselineNIHSSscore17.3±6.120.5±5.80.05ModerateorsevereLAinDWM19.0%42.3%0.03IVorIAlyticuse25.3%46.2%0.05IArtPAuse2.5%23.1%0.003Procedure-relatedvesselperforation3.8%19.2%0.03mRS≤2atdischarge32.5%3.8%0.003In-hospitalmortality10.4%50.0%<0.001mRSatdischarge3.0(0-6)5.5(1-6)<0.001UnivariateAnalysisofPredict95MultivariateAnalysisof

PredictorsforParenchymalHematomaVariableOddsratios(95%CI)PPremorbidwarfarinuse7.701(1.334-44.455)0.022Moderateorsevereleukoaraiosisindeepwhitematter4.180(1.245-14.036)0.021Intra-arteriallyticuse8.064(1.235-52.660)0.029MultivariateAnalysisofPredi96腦白質(zhì)疏松預(yù)測(cè)Merci術(shù)后出血中重度深部腦白質(zhì)疏松組的患者治療后出血轉(zhuǎn)化和腦實(shí)質(zhì)血腫發(fā)生較高，但是出血性梗塞和SAH的發(fā)生率無差別中重度深部腦白質(zhì)疏松分別是Merci術(shù)后出血轉(zhuǎn)化和腦實(shí)質(zhì)血腫的危險(xiǎn)因素治療后出現(xiàn)腦實(shí)質(zhì)血腫的患者出院時(shí)臨床結(jié)局較差，住院期間死亡率較高深部白質(zhì)區(qū)域的中重度腦白質(zhì)疏松可預(yù)測(cè)Merci取栓治療后的腦實(shí)質(zhì)血腫并發(fā)癥腦白質(zhì)疏松預(yù)測(cè)Merci術(shù)后出血中重度深部腦白質(zhì)疏松組的患者97PenumbraSystemThrombusaspirationandproximalthrombectomy

FDA2007PenumbraSystemThrombusaspira98PenumbraSystemPenumbraSystem99PenumbraPivotalStrokeTrial125例卒中8h內(nèi)治療ICA、MCA和椎基底動(dòng)脈閉塞血管再通率82%癥狀性出血率11%3個(gè)月良好臨床預(yù)后25%3個(gè)月死亡率33%PenumbraPivotalStrokeTrial1100PenumbraPivotalvsPenumbraPOSTtrialEndpointPivotal(n=125)POST(n=157)Revascularization82%87%ProceduralSAE’s3%5.8%SymptomaticICH11%6.4%Mortalityat90Days33%20%*mRS≤2at90Days25%41%**P<0.05PenumbraPivotalvsPenumbraP101PenumbraTrial100%(21/21)82%(102/125)87%(137/157)200720082009PenumbraTrial100%82%87%20072010210%(2/20)11%(14/125)6.4%(10/157)200720082009PenumbraTrial10%11%6.4%200720082009Penumbra10345%(9/20)33%(41/125)20%*(31/157)200720082009PenumbraTrial45%33%20%*200720082009Penumbra10435%(7/20)25%(31/125)41%*(50/122)200720082009(30dayoutcomes)PenumbraTrial35%25%41%*200720082009(30day105血管內(nèi)機(jī)械再通治療PROACTIIMERCIMultiMERCIPenumbraNINDSIVrtPAN121141164125182Age6467686468NIHSS1720191817Recanalization66%48%68%82%N/AsICH10%7.8%9.8%11.2%6.6%90daysmRS≤240%27.7%36%25%39%90daysmortality25%43.5%34%32.8%21%血管內(nèi)機(jī)械再通治療PROACTIIMERCIMulti106支架回收機(jī)械取栓支架回收機(jī)械取栓107支架回收機(jī)械取栓Castanoetal.Stroke2010;41:1836-40支架回收機(jī)械取栓Castanoetal.Stroke108StentRetriever

ThrombectomyRothetal2010Castanoetal2010Costalatetal2011TREVOstudy2012ISCDeviceSolitaireAB/FRSolitaireABSolitaireAB/FRTrevoN22205060NIHSS19.41914.718Recanalization91%90%88%91%Meanpasses1.771.42—sICH9.1%10%2%5%90daysmRS≤250%45%54%57%90daysmortality18.1%20%12%22%StentRetrieverThrombectomyRo109SWIFTTrial美國(guó)多中心、隨機(jī)對(duì)照研究血管內(nèi)機(jī)械再通治療顱內(nèi)大血管閉塞SolitaireRetrievervsMerciRetriever主要療效終點(diǎn)：成功血管再通、無癥狀性出血次要療效終點(diǎn)：良好臨床結(jié)局、死亡率和嚴(yán)重并發(fā)癥Saveretal.ISC2012FebSWIFTTrial美國(guó)多中心、隨機(jī)對(duì)照研究Savere110SWIFTTrial:RandomizedEndpointSolitaireFR(n=58)Merci(n=55)Successfulrecanalizationstudydevice83.3%48.1%Endofproceduresuccessfulrecanalization88.9%67.3%SuccessfulrecanalizationwithoutsICH60.7%24.1%mRS≤2at90Days58.2%33.3%Mortalityat90Days17.2%33.3%AllP<0.001SWIFTTrial:RandomizedEndpoin111問題和展望術(shù)前MR選擇最佳適應(yīng)證何種介入技術(shù)更好降低再通治療后出血性轉(zhuǎn)化機(jī)械再通聯(lián)合血管內(nèi)注入神經(jīng)保護(hù)藥物術(shù)中MR評(píng)估問題和展望術(shù)前MR選擇最佳適應(yīng)證112急性缺血性腦卒中血管再通

臨床證據(jù)與進(jìn)展首都醫(yī)科大學(xué)宣武醫(yī)院神經(jīng)外科王亞冰急性缺血性腦卒中血管再通

臨床證據(jù)與進(jìn)展首都醫(yī)科大學(xué)宣武醫(yī)院113溶栓相關(guān)試驗(yàn)及進(jìn)展課件114缺血性腦卒中溶栓治療循證靜脈溶栓（NINDS，ECASSIII）動(dòng)脈溶栓（PROACT）動(dòng)靜脈溶栓（IMS）機(jī)械取栓（MERCI，SEIS）指南其他證據(jù)缺血性腦卒中溶栓治療循證靜脈溶栓（NINDS，ECASS115靜脈溶栓治療美國(guó)FDA批準(zhǔn)臨床應(yīng)用----1995年NINDS研究證明3h內(nèi)靜脈注射重組組織纖溶酶原激活劑（rtPA）溶栓治療的有效性AHA:----2008年歐洲急性卒中協(xié)作ECASSIII研究表明靜脈rtPA溶栓治療的時(shí)間窗可延長(zhǎng)至4.5h靜脈溶栓治療美國(guó)FDA批準(zhǔn)臨床應(yīng)用116靜脈rtPA溶栓的不足受益患者少

-僅1-3%的患者能夠在發(fā)病3h內(nèi)接受治療血管再通率較低

-僅約6%的頸內(nèi)動(dòng)脈、30%大腦中動(dòng)脈和30%椎基底動(dòng)脈可獲得血管再通靜脈rtPA溶栓的不足受益患者少11739歲女性，意識(shí)障礙2小時(shí)A：T2相正常B、C：DWI顯示右側(cè)MCA分布區(qū)細(xì)胞毒性水腫，以右側(cè)放射冠明顯動(dòng)脈內(nèi)溶栓治療3天后復(fù)查D：病變范圍無增大，僅皮層及放射冠有小梗塞灶。39歲女性，意識(shí)障礙2小時(shí)118Dismatch未行溶栓治療的病例Dismatch未行溶栓治療的病例119缺血性腦卒中的早期治療

血管再通臨床有效發(fā)現(xiàn)新策略!↑缺血區(qū)的血流灌注缺血性腦卒中的早期治療血管再通臨床有效發(fā)現(xiàn)新策略!↑缺血區(qū)120缺血性腦卒中血管再通：早期治療關(guān)鍵----NINDS：1995年，靜脈溶栓，3h----ECASS-Ⅲ：2008年，靜脈溶栓，4.5h----大血管閉塞（ICAT--6%，TCD）發(fā)展：----大血管閉塞（ICA，MCA，VA，BA）----Real-timewindow至病理生理時(shí)間窗----多模式的血管內(nèi)治療（單純/合并）有效快速容易復(fù)雜缺血性腦卒中血管再通：早期治療關(guān)鍵有效快速容易復(fù)雜121血管內(nèi)機(jī)械再通治療PROACTIIMERCIMultiMERCIPenumbraNINDSIVrtPAN121141164125182Age6467686468NIHSS1720191817Recanalization66%48%68%82%N/AsICH10%7.8%9.8%11.2%6.6%90daysmRS≤240%27.7%36%25%39%90daysmortality25%43.5%34%32.8%21%血管內(nèi)機(jī)械再通治療PROACTIIMERCIMulti122TheImpactofRecanalizationonIschemicStrokeOutcome

AMeta-Analysisspontaneous(24.1%),intravenousfibrinolytic(46.2%),intra-arterialfibrinolytic(63.2%),combinedintravenous–intra-arterial(67.5%),andmechanical(83.6%)recanalizedversusnonrecanalized:oddsratioof4.43(95%CI,3.32to5.91)mortalitywasreducedinrecanalizedpatients(oddsratio,0.24;95%CI,0.16to0.35)SICH:didnotdifferbetweenthe2groupsStroke.2007;38:967-973;TheImpactofRecanalizationo123Anteriorcirculation:randomizedthrombolysistrialsinhemisphericstrokeNINDS:NationalInstituteofNeurologicalDisordersandStroke;ECASS:EuropeanCooperativeAcuteStrokeStudyPROACT:ProlyseinAcuteCerebralThromboembolismAnteriorcirculation:randomiz124Posteriorcirculation:MajortreatmentstudiesinacutevertebrobasilarocclusionIVT:intravenousthrombolysis;LIT:localintraarterialthrombolysis;Posteriorcirculation:Majort125GuidelinesfortheEarlyManagementofPatientsWithAcuteIschemicStrokeIntravenousrtPA推薦對(duì)起病3小時(shí)內(nèi)符合標(biāo)準(zhǔn)的缺血性卒中患者靜脈輸注rtPA（0.9mg/kg，最大劑量90mg），I級(jí)推薦，A級(jí)證據(jù)。

推薦有適應(yīng)征、起病后3-4.5小時(shí)的卒中患者使用靜脈用rtPA（0.9mg/kg，最大劑量90mg），I級(jí)推薦，B級(jí)證據(jù)。AHA/ASAGuidelineGuidelinesfortheEarlyManag126GuidelinesfortheEarlyManagementofPatientsWithAcuteIschemicStrokeEndovascularInterventions時(shí)間窗內(nèi)：靜脈優(yōu)先于動(dòng)脈（I級(jí)推薦，A級(jí)證據(jù)）對(duì)于大腦中動(dòng)脈大面積缺血性卒中患者，病程小于6小時(shí)的，動(dòng)脈內(nèi)溶栓治療審慎選擇的患者（他們不適合使用rtPA治療）可以獲益。（I級(jí)推薦，B級(jí)證據(jù)）。機(jī)械取栓方面，支架取栓器（如SolitaireFR和Trevo）總體上優(yōu)于彈簧圈取栓器（如Merci）。Penumbra系統(tǒng)相較支架取栓器的相對(duì)效果尚不明確。I級(jí)推薦，A級(jí)證據(jù)。聯(lián)合溶栓：對(duì)于大動(dòng)脈梗死靜脈溶栓沒有出現(xiàn)應(yīng)答的患者進(jìn)行補(bǔ)救性動(dòng)脈內(nèi)溶栓或機(jī)械取栓術(shù)是合理的。需要更多的隨機(jī)試驗(yàn)結(jié)果（IIb級(jí)推薦，B級(jí)證據(jù)）。急診顱內(nèi)血管成形術(shù)和/或支架置入的效果尚不肯定。AHA/ASAGuidelineGuidelinesfortheEarlyManag127SWIFTTrial：Solitaire〉MerciSWIFTTrial：Solitaire〉Merci128MerciRetrievalDeviceX6、X5；L5；Kmini、VMerciRetrievalDeviceX6、X5；L5129PenumbraSystemThrombusaspirationandproximalthrombectomy

FDA2007PenumbraSystemThrombusaspira130PenumbraSystemPenumbraSystem131支架回收機(jī)械取栓支架回收機(jī)械取栓132支架回收機(jī)械取栓Castanoetal.Stroke2010;41:1836-40支架回收機(jī)械取栓Castanoetal.Stroke133Endovasculartreatmentofacuteischemicstroke

theendorthebeginning??IMSIIII:interventionalManagementofStrokeMRRESCUE:MechanicalRetrievalandRecanalizationofStrokeClotsUsingEmbolectomySYNTHESISExpansion:ARandomizedControlledTrialonIntra-ArterialVersusIntravenousThrombolysisinAcuteIschemicStrokeNeurosurgFocus36(1):E5,2014Endovasculartreatmentofacut134BridgingTherapyBridgingTherapy135BridgingTherapyinAcuteIschemicStroke:ASystematicReviewandMeta-AnalysisSystematicreviewofallstudiesusingbridgingtherapypublishedbetweenJanuary1966andMarch2011Theliteraturesearchidentified15studies.Inthismeta-analysis,pooledestimatesassociatedwithbridgingtherapywere69.6%forrecanalizationrates,48.9%forfavorableoutcome,17.9%formortality,and8.6%forsICH.Stroke.2012;43:1302-1308BridgingTherapyinAcuteIsch136PooledRatesofRecanalizationandClinicalOutcomesConclusions—Bridgingtherapyisassociatedwithacceptablesafetyandefficacyinstrokepatients.Timetointravenoustreatmentiscriticaltoimproverecanalizationratesandfavorableoutcomes.PooledRatesofRecanalization137IMSIIItrialEndovascularTherapyafterIntravenoust-PAversust-PAAloneforStrokewithin3hoursStoppedearlybecauseoffutilityafter656participantshadundergonerandomization(434patientstoendovasculartherapyand222tointravenoust-PAalone)NEnglJMed.2013March7;368(10):893–903.IMSIIItrialEndovascularTher138溶栓相關(guān)試驗(yàn)及進(jìn)展課件139IMSIIItrialIMSIIItrial140IMSIIItrialCONCLUSIONS—Similar

safetyoutcomesandnosignificantdifferenceinfunctionalindependencewithendovasculartherapyafterintravenoust-PA,ascomparedwithintravenoust-PAaloneNEnglJMed.2013March7;368(10):893–903.IMSIIItrialCONCLUSIONS—Simil141Endovasculartreatmentofacuteischemicstroke

theendorthebeginning??IMSIIII:interventionalManagementofStrokeMRRESCUE:MechanicalRetrievalandRecanalizationofStrokeClotsUsingEmbolectomySYNTHESISExpansion:ARandomizedControlledTrialonIntra-ArterialVersusIntravenousThrombolysisinAcuteIschemicStrokeNeurosurgFocus36(1):E5,2014Endo