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1、Emergent Revascularization For Acute Ischemic Stroke,Rishi Gupta, MD Staff, Cerebrovascular Center The 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-Rate
2、s of delivery 3-19% at specialized centers vs. 1-2% in the community-Other therapeutic options needed to benefit larger number ofpatients,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 mismatc
3、h to select patientsfor 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 deterioratewithin 96 hours = poor long term prognosis5-Further eva
4、luation showed improvement was linked to arterialpatency or presence of collaterals-Interestingly, 15-20% of patients have a delay in deterioration linkedto vessel occlusion + poor collaterals6,5 Toni, et al Stroke 1997, 6 Toni et al. Arch Neurol 1995,-Physiology based imaging studies:- MRI DWI/PWI
5、- 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 ofCBF values,Qualitative,Quantitative,- The use of perfusion imaging has been studied to select pati
6、entsbeyond 3 hours for thrombolysisTwo 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
7、/DWI mismatchMRI obtained at 4 to 7 days after stroke to compare final infarct volumeto 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 meantransit time the DWI lesion expanded into what was exp
8、ected on PWIA second study by Tong et al.1 showed that the initial NIHSS at admissioncorrelated 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 arte
9、rial 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,ISCHEMIC PENUMBRA,Tissue that is functionally impaired but structurally intact CBF range
10、12-20 mL/100g/minSalvaging this 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 i
11、n Acute Ischemic Stroke,tissue irreversibly damaged beyond a certain time limit it corresponds to CBF values of less than 12 ml/100g/min 4, 5thrombolytic therapy administered to patients with large amounts of core is associated with an increased risk of symptomatic hemorrhage and malignant cerebral
12、edema 6, 7, 8, 9, 104 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 Change
13、s in Acute Ischemic Stroke,23 patient with MCA occlusion 6 hour symptom onset and imaged with Xenon CT prior to IA lysis15 patients developed parenchymal hematoma post IA-lysis with t-PAUnivariate modeling found patients with hyperglycemia, higher % core infarct (33%) and low CBF at higher risk of I
14、CHPatients with a mean hemispheric CBF 13 cc/100 g/min were atsignificantly 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 ipsi
15、lateral MCA CBF,CT Perfusion,Retrospective review of 57 patients 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
16、 19 patient with hemorrhage initial CBV 2.0 mL/100 g,CBF,CBF mL/100g/min,Scatterplot of patients comparing CBF to CBV In patients treated with IA Thrombolysis,These studies did not look at outcomes, but may givethresholds for future studies? If CBF parameters can replace time of onset for acutestrok
17、e therapiesRecanalization has been consistently linked with improvedoutcome, but requires more testing,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,
