1、急性缺血性腦卒中血管成形術(shù)英文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 delivery 3-19% at specialized centers vs. 1-2% in the community-Other therapeutic options needed to benefit larg

2、er number of patients1NINDS t-PA study group, NEJM 1995, 2 Hacke et al. Lancet 2004Intro (Contd) Potential ways to increase patients being treated:1) Utilization of perfusion mismatch to select patients for thrombolytic therapy2) Endovascular techniques to achieve recanalization: - Mechanical method

3、s 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 improvement was linked to arterial patency or presence of collaterals-Interestingly, 15-20% of patien

4、ts have a delay in deterioration linked to vessel occlusion + poor collaterals65 Toni, et al Stroke 1997, 6 Toni et al. Arch Neurol 1995-Physiology based imaging studies:- MRI DWI/PWI - CT Perfusion - PET- Xenon CT-MRI not always available 24 hours, lengthy studies-CT perfusion cannot delineate amou

5、nt of tissue damaged-PET impractical in acute stroke, but has led to quantification of CBF valuesQualitativeQuantitative- The use of perfusion imaging has been studied to select patients beyond 3 hours for thrombolysisTwo techniques utilized to assess mismatchMRI perfusion/diffusion imaging - diffic

6、ult to obtain urgently in many centers CT perfusion imaging - can be done in the ER quicklySemi Quantitative CBF EstimatesThijs et al.1 looked at 12 patients with acute stroke 20% PWI/DWI mismatchMRI obtained at 4 to 7 days after stroke to compare final infarct volume to initial DWI lesion1 Thijs VN

7、 et al. Neurology 2001Example of PWI/DWI mismatch and final infarctThis study demonstrated that patients with an increased mean transit time the DWI lesion expanded into what was expected on PWIA second study by Tong et al.1 showed that the initial NIHSS at admission correlated more strongly with PW

8、I and final infarct volume on day 7 as opposed to initial DWI lesion1 Tong DC et al. Neurology 1998Cerebral Blood Flow changes in Acute Ischemic StrokeTissue outcome following arterial occlusion is determined by cerebral blood flow thresholds below which neuronal integrity and function is differenti

9、ally affected 11 Baron JC, Cerebrovasc Dis 2001CBF thresholds in human cerebral ischemiaISCHEMIC 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 therapyPenum

10、bra 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 irreversibly damaged beyond a certain time limit it corresponds to CBF values of less than

11、 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, Cerebrovasc Dis 2001 , 5 Heiss et al, Stroke 2000, 6 Goldstein et al., Stroke 2000,

12、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 CORECerebral Blood Flow Changes in Acute Ischemic Stroke23 patient with MCA occlusion 6 hour symptom onset and imaged with Xenon CT prior to IA lysis15

13、 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 at significantly higher risk of ICH1 Gupta R, et al Stroke 20

14、06Xenon CT (Quantitative CBF)% Ipsilateral MCA Territory CoreMean Ipsilateral MCA CBF (cc/100g/min)Scatterplot of patients in relation to percent of core infarct and mean ipsilateral MCA CBFCT PerfusionRetrospective review of 57 patients treated with Intra-arterial t-PA for MCA occlusionMean NIHSS =

15、 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 gCBFIpsilateral Cerebral Blood Volume (mL/100 g)5.0004.5004.0003.5003.0002.5

16、002.0001.5001.0000.5000.00050.0045.0040.0035.0030.0025.0020.0015.0010.005.000.00CBFmL/100g/minScatterplot of patients comparing CBF to CBVIn patients treated with IA ThrombolysisThese studies did not look at outcomes, but may give thresholds for future studies? If CBF parameters can replace time of

17、onset for acute stroke therapiesRecanalization has been consistently linked with improved outcome, but requires more testingLIMITATIONS OF INTRAVENOUS TPARecanalization rate poor for larger arteries such as ICA or proximal MCAOutcomes for MCA occlusions poorNo information regarding site or presence

18、of arterial occlusionEffectiveness beyond 3 hours not establishedi.v t-PA recanalization at one hour (angiographic data)Del Zoppo et al., Ann Neurol 1993Intra-arterial OptionsChemical thrombolysisBalloon AngioplastyClot RetrievalClot MacerationStents- Multi-modal (combination chemical +mechanical)In

19、tra-arterial (Contd)AdvantagesMaximum delivery of lytic agentEndpoint of clot lysisNot given if spontaneous clot lysisDisadvantagesTime necessary to place catheterRequires interventionalistEmergent availability of angiographyPROACT IIRandomized multicenter controlled trial 9 mg IA r-proUK + IV hepar

20、in v. IV heparin aloneRandomized 2:1 to treatment v. control180 pts with M1 or M2 occlusion by angioTreatment started within 6 hours of stroke onsetIA r-proUK infused over 2 hours then repeat angioPrimary endpoint - mRS 2 at 90 daysPROACT II: 90 DAY OUTCOMES Intent to TreatPROACT II: MCA RECANALIZAT

21、ION4%19%2%63%66%18%TIMI 2+3TIMI 3( P= .001 )( P=.003) ANGIOGRAMIMS TRIAL DesignEligible patientsStart IV t-PA entry into study(0.6 mg/kg, 15% bolus, 30 min inf., 60 mg max.)AngiographyThrombusNo clot stopClot IA Therapy: 2 mg-distal, 2 mg-intraclot, 9 mg/hr x 2 hrs, 22 mg max.)Favorable Outcomeat 3

22、months (%)* IMSStudy(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 125%15%2.24 (1.1, 4.5)*Adjusted for baseline NIHSS and time-to-treatmentIMS Safety IMSStudy(n = 80)NINDSPlacebo(n = 211)NINDSt-PA(n = 182)Mortality (%)At 3 mont

23、hs 16%24%21%SymptomaticICH 36 hrs (%)6%1%7%Serious Bleeding Event (%)3% %1%Issues with IA Chemical LysisTime consuming to dissolve clotMay be ineffective with long segments of clotPlatelet rich/Plasminogen poor clots resistant to IA thrombolysisMechanical thrombolysisMerci Retrieval DeviceMERCI tria

24、lStudy 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 population0-3 hours, contraindicated for IV tPA3-8 hoursNI

25、HSSS 8 Angiogram shows a thrombotic occlusion in the internal carotid artery, M1 and/or M2 segment of the middle cerebral artery, basilar or vertebral arteryA total of 151 patients enrolled and 141 treated with MERCI deviceThe overall recanalization rate with the device was 48% this was significantl

26、y higher then control arm of PROACT IIClinically significant procedural complications were 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 intervention

27、alists graded rates of recanalization in MERCI trial, in PROACT a core lab graded recanalizationNakano et al., Stroke 2003MCA angioplastyMultimodal Endovascular TherapyRetrospective review of 168 patients over 6 years treated for acute cerebral arterial occlusions1Purpose was to determine which moda

28、lity lead to the highest recanalization rates1 Gupta R et al. Stroke 2005TIMI 2-3 N(%)TIMI 3 N(%)Sx HemorrhageAsx HemorrhageOne 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, * p0.012Independe

29、nt predictors of TIMI 2 or 3 flow after endovascular intervention in Acute stroke.VariableOdds Ratio95% CIp-valueICA Terminus0.30.16-0.730.006GP IIb/IIIa + IA thrombolytics2.91.04-6.70.048Extra-cranial Stenting4.21.4-9.80.01Intra-cranial Stenting4.81.8-10.00.01Tx ModalityTIMI 2-3 Flow(ICA / M1 MCA)Symptomatic Hemorrhage RateIV t-PA125%5-7%IV t-PA + TCD246%6%IA pro-UK366%10%MERCI clot retrieval455%7%GP IIb/IIIa + IA Lytics85%5%Multimodal Therapy70%11%Angioplasty760-90%7%Primary Stenting890%5