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单击此处编辑母版标题样式,单击此处编辑母版文本样式,二级,三级,四级,五级,*,急性缺血性脑卒中血管成形术(英文),*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,二级,三级,四级,五级,急性缺血性脑卒中血管成形术(英文),*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,二级,三级,四级,五级,急性缺血性脑卒中血管成形术(英文),*,Emergent Revascularization For Acute Ischemic Stroke,Rishi Gupta, MD,Staff, Cerebrovascular Center,The Cleveland Clinic Foundation,急性缺血性脑卒中血管成形术(英文),Emergent Revascularization For,1,Introduction,-There are 700,000 ischemic strokes/year in the U.S.,-70% of patients with cerebral occlusions,-Since 1995, IV t-PA utilized within 0-3 hour time window,1,-Rates of delivery 3-19% at specialized centers vs. 1-2%,in the community,-Other therapeutic options needed to benefit larger number of,patients,1,NINDS t-PA study group, NEJM 1995,2,Hacke et al. Lancet 2004,急性缺血性脑卒中血管成形术(英文),Introduction-There are 700,000,2,Intro (Contd),Potential ways to increase patients being treated:,1) Utilization of perfusion mismatch to select patients,for thrombolytic therapy,2) Endovascular techniques to achieve recanalization:,- Mechanical methods without thrombolysis for later strokes,急性缺血性脑卒中血管成形术(英文),Intro (Contd) Potential ways,3,Large Vessel Occlusion,-Toni et al. showed 25% of patients with acute stroke deteriorate,within 96 hours = poor long term prognosis,5,-Further evaluation showed improvement was linked to arterial,patency or presence of collaterals,-Interestingly, 15-20% of patients have a delay in deterioration linked,to vessel occlusion + poor collaterals,6,5,Toni, et al Stroke 1997,6,Toni et al. Arch Neurol 1995,急性缺血性脑卒中血管成形术(英文),Large Vessel Occlusion-Toni et,4,-Physiology based imaging studies:,- MRI DWI/PWI,- CT Perfusion,- PET,- Xenon CT,-MRI not always available 24 hours, lengthy studies,-CT perfusion cannot delineate amount of tissue damaged,-PET impractical in acute stroke, but has led to quantification of,CBF values,Qualitative,Quantitative,急性缺血性脑卒中血管成形术(英文),-Physiology based imaging stud,5,- The use of perfusion imaging has been studied to select patients,beyond 3 hours for thrombolysis,Two techniques utilized to assess mismatch,MRI perfusion/diffusion imaging,- difficult to obtain urgently in many centers,CT perfusion imaging,- can be done in the ER quickly,Semi Quantitative CBF Estimates,急性缺血性脑卒中血管成形术(英文),Semi Quantitative CBF Estimate,6,Thijs et al.,1,looked at 12 patients with acute stroke 20% PWI/DWI mismatch,MRI obtained at 4 to 7 days after stroke to compare final infarct volume,to initial DWI lesion,1,Thijs VN et al. Neurology 2001,急性缺血性脑卒中血管成形术(英文),Thijs et al.1 looked at 12 pat,7,Example of PWI/DWI mismatch and final infarct,急性缺血性脑卒中血管成形术(英文),Example of PWI/DWI mismatch an,8,This study demonstrated that patients with an increased mean,transit time the DWI lesion expanded into what was expected on PWI,A second study by Tong et al.,1,showed that the initial NIHSS at admission,correlated more strongly with PWI and final infarct volume on day 7,as opposed to initial DWI lesion,1,Tong DC et al. Neurology 1998,急性缺血性脑卒中血管成形术(英文),This study demonstrated that p,9,Cerebral Blood Flow changes in Acute Ischemic Stroke,Tissue outcome following arterial occlusion is determined by cerebral blood flow thresholds below which neuronal integrity and function is differentially affected,1,1,Baron JC, Cerebrovasc Dis 2001,CBF thresholds in human cerebral ischemia,急性缺血性脑卒中血管成形术(英文),Cerebral Blood Flow changes in,10,ISCHEMIC PENUMBRA,Tissue that is functionally impaired but structurally intact,CBF range 12-20 mL/100g/min,Salvaging this tissue by restoring its flow to non-ischemic levels is the aim of reperfusion therapy,Penumbra converts to ischemic core with hyperglycemia,acidosis, reduced local perfusion pressure,1,Baron et. al, Cerebrovasc Dis 2001,2,Heiss et al. 2001,Cerebral Blood Flow changes in Acute Ischemic Stroke,急性缺血性脑卒中血管成形术(英文),ISCHEMIC PENUMBRA Tissue that,11,tissue irreversibly damaged,beyond a certain time limit it corresponds to CBF values of less than 12 ml/100g/min,4, 5,thrombolytic therapy administered to patients with large amounts of core is associated with an increased risk of symptomatic hemorrhage and malignant cerebral edema,6, 7, 8, 9, 10,4,Baron et. al, Cerebrovasc Dis 2001 ,5,Heiss et al, Stroke 2000,6,Goldstein et al., Stroke 2000,7,Ueda et al., J Cereb Blood Flow Metab 1999 ,8,Larue et al., Stroke 2001,9,Firlik et al., J Neurosurg 1998, Jovin et al., Neurology 2002,ISCHEMIC CORE,Cerebral Blood Flow Changes in Acute Ischemic Stroke,急性缺血性脑卒中血管成形术(英文),tissue irreversibly damaged,12,23 patient with MCA occlusion 6 hour symptom onset and imaged,with Xenon CT prior to IA lysis,1,5 patients developed parenchymal hematoma post IA-lysis with t-PA,Univariate modeling found patients with hyperglycemia,higher % core infarct (33%) and low CBF at higher risk of ICH,Patients with a mean hemispheric CBF 13 cc/100 g/min were at,significantly higher risk of ICH,1,Gupta R, et al Stroke 2006,Xenon CT (Quantitative CBF),急性缺血性脑卒中血管成形术(英文),23 patient with MCA occlusion,13,% Ipsilateral MCA Territory Core,Mean Ipsilateral MCA CBF,(cc/100g/min),Scatterplot of patients in relation to percent of,core infarct and mean ipsilateral MCA CBF,急性缺血性脑卒中血管成形术(英文),% Ipsilateral MCA Territory Co,14,CT Perfusion,Retrospective review of 57 patients treated with Intra-arterial,t-PA for MCA occlusion,Mean NIHSS = 16,CT Perfusion performed prior to infusion of IA t-PA,Patients with lower pre-treatment Cerebral blood volume found to be at increased risk of intracranial hemorrhage,- 16 of 19 patient with hemorrhage initial CBV 2.0 mL/100 g,急性缺血性脑卒中血管成形术(英文),CT PerfusionRetrospective revi,15,CBF,Ipsilateral Cerebral Blood Volume (mL/100 g),5.000,4.500,4.000,3.500,3.000,2.500,2.000,1.500,1.000,0.500,0.000,50.00,45.00,40.00,35.00,30.00,25.00,20.00,15.00,10.00,5.00,0.00,CBF,mL/100g/min,Scatterplot of patients comparing CBF to CBV,In patients treated with IA Thrombolysis,急性缺血性脑卒中血管成形术(英文),CBFIpsilateral Cerebral Blood,16,These studies did not look at outcomes, but may give,thresholds for future studies,? If CBF parameters can replace time of onset for acute,stroke therapies,Recanalization has been consistently linked with improved,outcome, but requires more testing,急性缺血性脑卒中血管成形术(英文),These studies did not look at,17,LIMITATIONS OF INTRAVENOUS TPA,Recanalization rate poor for larger arteries such as ICA or proximal MCA,Outcomes for MCA occlusions poor,No information regarding site or presence of arterial occlusion,Effectiveness beyond 3 hours not established,急性缺血性脑卒中血管成形术(英文),LIMITATIONS OF INTRAVENOUS TPA,18,i.v t-PA recanalization at one hour (angiographic data),Del Zoppo et al., Ann Neurol 1993,急性缺血性脑卒中血管成形术(英文),i.v t-PA recanalization at one,19,Intra-arterial Options,Chemical thrombolysis,Balloon Angioplasty,Clot Retrieval,Clot Maceration,Stents,- Multi-modal (combination chemical +mechanical),急性缺血性脑卒中血管成形术(英文),Intra-arterial OptionsChemical,20,Intra-arterial (Contd),Advantages,Maximum delivery of lytic agent,Endpoint of clot lysis,Not given if spontaneous clot lysis,Disadvantages,Time necessary to place catheter,Requires interventionalist,Emergent availability of angiography,急性缺血性脑卒中血管成形术(英文),Intra-arterial (Contd)Advanta,21,PROACT II,Randomized multicenter controlled trial,9 mg IA r-proUK + IV heparin v. IV heparin alone,Randomized 2:1 to treatment v. control,180 pts with M1 or M2 occlusion by angio,Treatment started within 6 hours of stroke onset,IA r-proUK infused over 2 hours then repeat angio,Primary endpoint - mRS 2 at 90 days,急性缺血性脑卒中血管成形术(英文),PROACT IIRandomized multicente,22,PROACT II: 90 DAY OUTCOMES,Intent to Treat,急性缺血性脑卒中血管成形术(英文),PROACT II: 90 DAY OUTCOMES In,23,PROACT II: MCA RECANALIZATION,4%,19%,2%,63%,66%,18%,TIMI 2+3,TIMI 3,( P= .001 ),( P=.003),ANGIOGRAM,急性缺血性脑卒中血管成形术(英文),PROACT II: MCA RECANALIZATION4,24,IMS TRIAL Design,Eligible,patients,Start IV,t-PA entry into study,(0.6 mg/kg, 15% bolus, 30 min inf., 60 mg max.),Angiography,Thrombus,No clot stop,Clot IA Therapy:,2 mg-distal, 2 mg-intraclot, 9 mg/hr x 2 hrs, 22 mg max.),急性缺血性脑卒中血管成形术(英文),IMS TRIAL DesignEligible patie,25,Favorable Outcome,at 3 months (%)*,IMS,Study,(n = 80),NINDS,Placebo,(n = 211),Odds Ratio (95% CI),Rankin 0-1,30%,18%,2.29,(1.2, 4.4),Rankin 0-2,43%,28%,2.04,(1.2, 3.6),NIHSS 1,25%,15%,2.24,(1.1, 4.5),*,Adjusted for baseline NIHSS and time-to-treatment,急性缺血性脑卒中血管成形术(英文),Favorable Outcomeat 3 months,26,IMS Safety,IMS,Study,(n = 80),NINDS,Placebo,(n = 211),NINDS,t-PA,(n = 182),Mortality (%),At 3 months,16%,24%,21%,Symptomatic,ICH,36 hrs (%),6%,1%,7%,Serious Bleeding Event (%),3%, %,1%,急性缺血性脑卒中血管成形术(英文),IMS Safety IMSNINDSNINDSMortal,27,Issues with IA Chemical Lysis,Time consuming to dissolve clot,May be ineffective with long segments of clot,Platelet rich/Plasminogen poor clots resistant to IA thrombolysis,急性缺血性脑卒中血管成形术(英文),Issues with IA Chemical LysisT,28,Mechanical thrombolysis,急性缺血性脑卒中血管成形术(英文),Mechanical thrombolysis急性缺血性脑卒,29,Merci Retrieval Device,急性缺血性脑卒中血管成形术(英文),Merci Retrieval Device急性缺血性脑卒中,30,MERCI trial,Study to determine the safety and potential efficacy of the MERCI,clot retriever device in patients with cerebral artery occlusion 8 hours (MCA, ICA or basilar),Clinical signs consistent with the diagnosis of ischemic stroke,Must meet either population,0-3 hours, contraindicated for IV tPA,3-8 hours,NIHSSS 8,Angiogram shows a thrombotic occlusion in the internal carotid artery, M1 and/or M2 segment of the middle cerebral artery, basilar or vertebral artery,急性缺血性脑卒中血管成形术(英文),MERCI trialStudy to determine,31,A total of 151 patients enrolled and 141 treated with MERCI device,The overall recanalization rate with the device was 48% this was significantly higher then control arm of PROACT II,Clinically significant procedural complications were 7.1%,Symptomatic ICH occurred in 7.8% of patients,Recanalization rate was lower then PROACT II (66% vs. 48%), authors argue because PROACT was MCA only lesions, while MERCI any arterial occlusion,The interventionalists graded rates of recanalization in MERCI trial, in PROACT a core lab graded recanalization,急性缺血性脑卒中血管成形术(英文),A total of 151 patients enroll,32,Nakano et al., Stroke 2003,MCA angioplasty,急性缺血性脑卒中血管成形术(英文),Nakano et al., Stroke 2003MCA,33,Multimodal Endovascular Therapy,Retrospective review of 168 patients over,6 years treated for acute cerebral,arterial occlusions,1,Purpose was to determine which modality,lead to the highest recanalization rates,1,Gupta R et al. Stroke 2005,急性缺血性脑卒中血管成形术(英文),Multimodal Endovascular Therap,34,TIMI 2-3,N(%),TIMI 3,N(%),Sx Hemorrhage,Asx Hemorrhage,One Modality (N=40),20(50%),10(25%),5 (13%),8(20%),Two Modalities (N=65),39(60%),18(28%),9(14%),14(22%),Three + modalities (N=63),45(71%),*,25(40%),*,10(15%),14(22%),*,p0.045, * p0.012,急性缺血性脑卒中血管成形术(英文),TIMI 2-3 TIMI 3 Sx Hemorrhag,35,Independent predictors of TIMI 2 or 3 flow after,endovascular intervention in Acute stroke.,Variable,Odds Ratio,95% CI,p-value,ICA Terminus,0.3,0.16-0.73,0.006,GP IIb/IIIa + IA thrombolytics,2.9,1.04-6.7,0.048,Extra-cranial Stenting,4.2,1.4-9.8,0.01,Intra-cranial Stenting,4.8,1.8-10.0,0.01,急性缺血性脑卒中血管成形术(英文),Independent predictors of TIMI,36,Tx Modality,TIMI 2-3 Flow,(ICA / M1 MCA),Symptomatic Hemorrhage Rate,IV t-PA,1,25%,5-7%,IV t-PA + TCD,2,46%,6%,IA pro-UK,3,66%,10%,MERCI clot retrieval,4,55%,7%,GP IIb/IIIa + IA Lytics,85%,5%,Multimodal Therapy,70%,11%,Angioplasty,7,60-90%,7%,Primary Stenting,8,90%,5%,Summary of Tx Modality and Recanalization Rate,急性缺血性脑卒中血管成形术(英文),Tx ModalityTIMI 2-3 FlowSympto,37,Case Example,- 45 year old man arrived at our ER 12 hours from symptom,onset with left hemiparesis + right gaze preference,(NIHSS 11),A CT head with large perfusion deficit +,CTA with RICA occlusion,- MRI brain at 15 hours with infarct in the right insular cortex,急性缺血性脑卒中血管成形术(英文),Case Example- 45 year old man,38,CBF,MTT,RICA occlusion,急性缺血性脑卒中血管成形术(英文), CBF MTTRICA occlusion急性缺血,39,At 24 hours, patient has hemiplegia (NIHSS 16),A repeat MRI performed showing extension of infarct,into right posterior temporal and frontal areas,急性缺血性脑卒中血管成形术(英文),At 24 hours, patient has hemip,40,A Xenon CT performed at 28 hours to determine degree,of tissue at risk,CBF measurements in right hemisphere at,18 cc/100 g/min, suggesting more tissue at risk,急性缺血性脑卒中血管成形术(英文),A Xenon CT performed at 28 hou,41,Patient taken to angiography,RICA occluded,R MCA patent via,ACOMM,Collaterals via PCOMM,急性缺血性脑卒中血管成形术(英文),Patient taken to angiography R,42,Microcatheter distal,to occlusion,Post stent/plasty shows patent,RICA,急性缺血性脑卒中血管成形术(英文),Microcatheter distalPost stent,43,- Xenon CT post stent reveals normal and symmetric CBFs,- MRI post stent shows no further increase in infarct burden,急性缺血性脑卒中血管成形术(英文),- Xenon CT post stent reveals,44,Patient improved to a NIHSS of 10 the next day,At 30 day f/u has a NIHSS of 6 with a mRS of 2,急性缺血性脑卒中血管成形术(英文),Patient improved to a NIHSS of,45,Conclusions,Endovascular therapies may have benefit in select patients,-Utilization of perfusion studies may improve patient selection,-A better understanding of the treatment modality utilized may,reduce complication rates,急性缺血性脑卒中血管成形术(英文),ConclusionsEndovascular therap,46,
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