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1、Emergent Revascularization For Acute Ischemic Stroke,Rishi Gupta,MDStaff,Cerebrovascular CenterThe Cleveland Clinic Foundation,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 window1-Rates of d
2、elivery 3-19%at specialized centers vs.1-2%in the community-Other therapeutic options needed to benefit larger number of patients,1NINDS t-PA study group,NEJM 1995,2 Hacke et al.Lancet 2004,Intro(Contd),Potential ways to increase patients being treated:1)Utilization of perfusion mismatch to select p
3、atients for thrombolytic therapy2)Endovascular techniques to achieve recanalization:-Mechanical methods without thrombolysis for later strokes,Large Vessel Occlusion,-Toni et al.showed 25%of patients with acute stroke deteriorate within 96 hours=poor long term prognosis5-Further evaluation showed im
4、provement was linked to arterial patency or presence of collaterals-Interestingly,15-20%of patients have a delay in deterioration linked to vessel occlusion+poor collaterals6,5 Toni,et al Stroke 1997,6 Toni et al.Arch Neurol 1995,-Physiology based imaging studies:-MRI DWI/PWI-CT Perfusion-PET-Xenon
5、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,-The use of perfusion imaging has been studied to select patients beyond 3 hours for thromb
6、olysisTwo techniques utilized to assess mismatchMRI perfusion/diffusion imaging-difficult to obtain urgently in many centers CT perfusion imaging-can be done in the ER quickly,Semi Quantitative CBF Estimates,Thijs et al.1 looked at 12 patients with acute stroke 20%PWI/DWI mismatchMRI obtained at 4 t
7、o 7 days after stroke to compare final infarct volume to initial DWI lesion,1 Thijs VN et al.Neurology 2001,Example of PWI/DWI mismatch and final infarct,This study demonstrated that patients with an increased mean transit time the DWI lesion expanded into what was expected on PWIA second study by T
8、ong 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,Cerebral Blood Flow changes in Acute Ischemic Stroke,Tissue outcome following arterial occlusion is determined by
9、 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,ISCHEMIC PENUMBRA,Tissue that is functionally impaired but structurally intact CBF range 12-20 mL/100g/min Salvaging this
10、 tissue by restoring its flow to non-ischemic levels is the aim of reperfusion therapyPenumbra converts to ischemic core with hyperglycemia,acidosis,reduced local perfusion pressure1 Baron et.al,Cerebrovasc Dis 2001,2 Heiss et al.2001,Cerebral Blood Flow changes in Acute Ischemic Stroke,tissue irrev
11、ersibly 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 6,7,8,9,104 Baron et.al,Cerebr
12、ovasc 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,23 patient with MCA occlusion
13、 6 hour symptom onset and imaged with Xenon CT prior to IA lysis15 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 ICHPatients with a mean hemispheric CBF 13 cc/100 g/min were
14、at significantly higher risk of ICH,1 Gupta R,et al Stroke 2006,Xenon CT(Quantitative CBF),%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,CT Perfusion,Retrospective review of 57 patient
15、s treated with Intra-arterial t-PA for MCA occlusionMean NIHSS=16CT Perfusion performed prior to infusion of IA t-PAPatients 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,CBF,CBFmL/100
16、g/min,Scatterplot of patients comparing CBF to CBVIn patients treated with IA Thrombolysis,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 therapiesRecanalization has been consistently linked with improved
17、 outcome,but requires more testing,LIMITATIONS OF INTRAVENOUS TPA,Recanalization rate poor for larger arteries such as ICA or proximal MCAOutcomes for MCA occlusions poorNo information regarding site or presence of arterial occlusionEffectiveness beyond 3 hours not established,i.v t-PA recanalizatio
18、n at one hour(angiographic data),Del Zoppo et al.,Ann Neurol 1993,Intra-arterial Options,Chemical thrombolysisBalloon AngioplastyClot RetrievalClot MacerationStents-Multi-modal(combination chemical+mechanical),Intra-arterial(Contd),AdvantagesMaximum delivery of lytic agentEndpoint of clot lysisNot g
19、iven if spontaneous clot lysisDisadvantagesTime necessary to place catheterRequires interventionalistEmergent availability of angiography,PROACT II,Randomized multicenter controlled trial 9 mg IA r-proUK+IV heparin v.IV heparin aloneRandomized 2:1 to treatment v.control180 pts with M1 or M2 occlusio
20、n by angioTreatment started within 6 hours of stroke onsetIA r-proUK infused over 2 hours then repeat angioPrimary endpoint-mRS 2 at 90 days,PROACT II:90 DAY OUTCOMES Intent to Treat,PROACT II:MCA RECANALIZATION,4%,19%,2%,63%,66%,18%,TIMI 2+3,TIMI 3,(P=.001),(P=.003),ANGIOGRAM,IMS TRIAL Design,Eligi
21、ble 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.),Favorable Outcomeat 3 months(%)*,*Adjusted for baseline NIHSS and time-to-treatment,IMS Safety,Issues with
22、IA Chemical Lysis,Time consuming to dissolve clotMay be ineffective with long segments of clotPlatelet rich/Plasminogen poor clots resistant to IA thrombolysis,Mechanical thrombolysis,Merci Retrieval Device,MERCI trial,Study to determine the safety and potential efficacy of the MERCI clot retriever
23、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 population0-3 hours,contraindicated for IV tPA3-8 hoursNIHSSS 8 Angiogram shows a thrombotic occlusion in the internal carotid artery,M1 and/o
24、r M2 segment of the middle cerebral artery,basilar or vertebral artery,A total of 151 patients enrolled and 141 treated with MERCI deviceThe overall recanalization rate with the device was 48%this was significantly higher then control arm of PROACT IIClinically significant procedural complications w
25、ere 7.1%Symptomatic ICH occurred in 7.8%of patientsRecanalization rate was lower then PROACT II(66%vs.48%),authors argue because PROACT was MCA only lesions,while MERCI any arterial occlusionThe interventionalists graded rates of recanalization in MERCI trial,in PROACT a core lab graded recanalizati
26、on,Nakano et al.,Stroke 2003,MCA angioplasty,Multimodal Endovascular Therapy,Retrospective review of 168 patients over 6 years treated for acute cerebral arterial occlusions1Purpose was to determine which modality lead to the highest recanalization rates,1 Gupta R et al.Stroke 2005,*p0.045,*p0.012,I
27、ndependent predictors of TIMI 2 or 3 flow after endovascular intervention in Acute stroke.,Summary of Tx Modality and Recanalization Rate,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 de
28、ficit+CTA with RICA occlusion-MRI brain at 15 hours with infarct in the right insular cortex,CBF,MTT,RICA occlusion,At 24 hours,patient has hemiplegia(NIHSS 16)A repeat MRI performed showing extension of infarct into right posterior temporal and frontal areas,A Xenon CT performed at 28 hours to dete
29、rmine degree of tissue at riskCBF measurements in right hemisphere at 18 cc/100 g/min suggesting more tissue at risk,Patient taken to angiography,RICA occluded,R MCA patent viaACOMM,Collaterals via PCOMM,Microcatheter distalto occlusion,Post stent/plasty shows patentRICA,-Xenon CT post stent reveals
30、 normal and symmetric CBFs,-MRI post stent shows no further increase in infarct burden,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,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,
