Prospective Cohort Study

National Institute of Neurological Disorders and Stroke

The treatment of acute ischemic stroke has undergone dramatic changes recently subsequent to the demonstrated efficacy of intra-arterial (IA) device-based therapy in multiple trials. The selection of patients for both intravenous and IA therapy is based on timely imaging with either computed tomography or magnetic resonance imaging, and if IA therapy is considered noninvasive, angiography with one of these modalities is necessary to document a large-vessel occlusion amenable for intervention. More advanced computed tomography and magnetic resonance imaging studies are available that can be used to identify a small ischemic core and ischemic penumbra, and this information will contribute increasingly in treatment decisions as the therapeutic time window is lengthened. Intravenous thrombolysis with tissue-type plasminogen activator remains the mainstay of acute stroke therapy within the initial 4.5 hours after stroke onset, despite the lack of Food and Drug Administration approval in the 3- to 4.5-hour time window. In patients with proximal, large-vessel occlusions, IA device-based treatment should be initiated in patients with small/moderate-sized ischemic cores who can be treated within 6 hours of stroke onset. The organization and implementation of regional stroke care systems will be needed to treat as many eligible patients as expeditiously as possible. Novel treatment paradigms can be envisioned combining neuroprotection with IA device treatment to potentially increase the number of patients who can be treated despite long transport times and to ameliorate the consequences of reperfusion injury. Acute stroke treatment has entered a golden age, and many additional advances can be anticipated.

Acute Ischemic Stroke Therapy Overview

Revascularization encompasses all treatment-related improvements in blood flow, including recanalization of the proximal arterial occlusion and reperfusion of the downstream territory. Recanalization is required for antegrade tissue reperfusion, but recanalization may not necessarily lead to reperfusion in regions where distal emboli or established infarctions are present.1,2 On the contrary, acute reperfusion without recanalization may occur in patients who received or did not received endovascular therapies, and reperfusion ≤6 hours was consistently superior to recanalization in predicting tissue and clinical outcome.3 The cerebral collateral circulation refers to the subsidiary network of vascular channels that stabilize cerebral blood flow when principal conduits fail. Collateral status differs among patients with acute ischemic stroke. Relatively sparse attention has been devoted to the role of baseline collateral circulation in patients with acute ischemic stroke who are candidates for revascularization.

The Interventional Management of Stroke (IMS) III,4 Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy (MR RESCUE),5 and Intra-Arterial Versus Systemic Thrombolysis for Acute Ischemic Stroke (SYNTHESIS EXP) trials6 were 3 multicenter, prospective, randomized controlled trials, which failed to show a benefit from endovascular intervention for acute ischemic stroke. In addition, successful recanalization failed to improve the functional outcome in a significant proportion of patients, ranging from 26% to 49% (futile and dangerous recanalization), stimulating the need to improve the selection of patients based on individual pathophysiology.7,8

Among neuroimaging parameters, a large core and poor collaterals are demonstrated to be strong predictors of both response to endovascular therapy and functional outcome,9–13 and excluding patients with large core and poor collateral circulation may improve the therapeutic benefit from endovascular therapy. In the subgroup analysis of the IMS III trial, more robust collateral grade was associated with better clinical outcomes.14 Adequate collateral circulation …

Collateral Circulation in Ischemic Stroke: Assessment Tools and Therapeutic Strategies

Thank you for downloading applied methods of cost effectiveness analysis in healthcare. As you may know, people have search hundreds times for their favorite books like this applied methods of cost effectiveness analysis in healthcare, but end up in malicious downloads. Rather than enjoying a good book with a cup of tea in the afternoon, instead they are facing with some infectious virus inside their laptop.

Applied Methods Of Cost Effectiveness Analysis In Healthcare

Purpose To validate the use of perfusion computed tomography (CT) with whole-brain coverage to measure the ischemic penumbra and core and to compare its performance to that of limited-coverage perfusion CT. Materials and Methods Institutional ethics committee approval and informed consent were obtained. Patients (n = 296) who underwent 320-detector CT perfusion within 6 hours of the onset of ischemic stroke were studied. First, the ischemic volume at CT perfusion was compared with the penumbra and core reference values at magnetic resonance (MR) imaging to derive CT perfusion penumbra and core thresholds. Second, the thresholds were tested in a different group of patients to predict the final infarction at diffusion-weighted imaging 24 hours after CT perfusion. Third, the change in ischemic volume delineated by the optimal penumbra and core threshold was determined as the brain coverage was gradually reduced from 160 mm to 20 mm. The Wilcoxon signed-rank test, concordance correlation coefficient (CCC), and analysis of variance were used for the first, second, and third steps, respectively. Results CT perfusion at penumbra and core thresholds resulted in the least volumetric difference from MR imaging reference values with delay times greater than 3 seconds and delay-corrected cerebral blood flow of less than 30% (P = .34 and .33, respectively). When the thresholds were applied to the new group of patients, prediction of the final infarction was allowed with delay times greater than 3 seconds in patients with no recanalization of the occluded artery (CCC, 0.96 [95% confidence interval: 0.92, 0.98]) and with delay-corrected cerebral blood flow less than 30% in patients with complete recanalization (CCC, 0.91 [95% confidence interval: 0.83, 0.95]). However, the ischemic volume with a delay time greater than 3 seconds was underestimated when the brain coverage was reduced to 80 mm (P = .04) and the core volume measured as cerebral blood flow less than 30% was underestimated when brain coverage was 40 mm or less (P < .0001). Conclusion Correct threshold setting and whole-brain coverage CT perfusion allowed differentiation of the penumbra from the ischemic core in patients with acute ischemic stroke. (©) RSNA, 2016 Online supplemental material is available for this article.

Whole-Brain CT Perfusion to Quantify Acute Ischemic Penumbra and Core

The cornerstone of acute ischemic stroke treatment relies on rapid clearance of an offending thrombus in the cerebrovascular system. There are various drugs and different methods of assessment to select patients more likely to respond to treatment. Current clinical guidelines recommend the administration of intravenous alteplase (following a brain noncontract CT to exclude hemorrhage) within 4.5 hours of stroke onset. Because of the short therapeutic time window, the risk of hemorrhage, and relatively limited efficacy of alteplase for large clot burden, research is ongoing to find more effective and safer reperfusion therapy, as well as focussing on refinement of patient selection for acute reperfusion treatment. Studies using advanced imaging (incorporating perfusion CT or diffusion/perfusion MRI) may allow us to use thrombolytics, or possibly endovascular therapy, in an extended time window. Recent clinical trials have suggested that Tenecteplase, used in conjunction with advanced imaging selection, resulted in more effective reperfusion than alteplase, which translated into increased clinical benefit. Studies using Desmoteplase have suggested its potential benefit in a sub-group of patients with large artery occlusion and salveageable tissue, in an extended time window. Other ways to improve acute reperfusion approaches are being actively explored, including endovascular therapy, and the enhancement of thrombolysis by ultrasound insonation of the clot (sono-thrombolysis).

/pdf/review-of-stroke-thrombolytics-r6e63528ek.pdf

Review of stroke thrombolytics

INTRODUCTION: We aimed to identify whether acute ischemic stroke patients with known complete reperfusion after thrombectomy had the same baseline computed tomography perfusion (CTP) ischemic core threshold to predict infarction as thrombolysis patients with complete reperfusion. METHODS: Patients who underwent thrombectomy were matched by age, clinical severity, occlusion location, and baseline perfusion lesion volume to patients who were treated with intravenous alteplase alone from the International Stroke Perfusion Imaging Registry. A pixel-based analysis of coregistered pretreatment CTP and 24-hour diffusion-weighted imaging (DWI) was then undertaken to define the optimum CTP thresholds for the ischemic core. RESULTS: There were 132 eligible thrombectomy patients and 132 matched controls treated with alteplase alone. Baseline National Institutes of Health Stroke Scale (median, 15; interquartile range [IQR], 11-19), age (median, 65; IQR, 59-80), and time to intravenous treatment (median, 153 minutes; IQR, 82-315) were well matched (all p > 0.05). Despite similar baseline CTP ischemic core volumes using the previously validated measure (relative cerebral blood flow [rCBF], <30%), thrombectomy patients had a smaller median 24-hour infarct core of 17.3ml (IQR, 11.3-32.8) versus 24.3ml (IQR, 16.7-42.2; p = 0.011) in alteplase-treated controls. As a result, the optimal threshold to define the ischemic core in thrombectomy patients was rCBF <20% (area under the curve [AUC], 0.89; 95% CI, 0.84, 0.94), whereas in alteplase controls the optimal ischemic core threshold remained rCBF <30% (AUC, 0.83; 95% CI, 0.77, 0.85). INTERPRETATION: Thrombectomy salvaged tissue with lower CBF, likely attributed to earlier reperfusion. For patients who achieve rapid reperfusion, a stricter rCBF threshold to estimate the ischemic core should be considered. Ann Neurol 2017;82:995-1003.

/pdf/ischemic-core-thresholds-change-with-time-to-reperfusion-a-473drr7yfw.pdf

Ischemic core thresholds change with time to reperfusion: A case control study.

Background and Purpose—Magnetic resonance perfusion (MRP) and computed tomographic perfusion (CTP) are being increasingly applied in acute stroke trials and clinical practice, yet the comparability of their perfusion values is not well validated. The aim of this study was to validate the comparability of CTP and MRP measures. Methods—A 3-step approach was used. Step 1 was a derivation step, where we analyzed 45 patients with acute ischemic stroke who had both CTP and MRP performed within 2 hours of each other and within 9 hours of stroke onset. In this step, we derived the optimal perfusion map with the least difference between MRP and CTP. In step 2, the optimal map was validated on whole-brain perfusion data of 15 patients. Step 3 was to apply the optimal perfusion map to define cross-modality reperfusion from acute CTP to 24-hour MRP in 45 patients and, in turn, to assess how accurately this predicted 3-month clinical outcome. Results—Among 8 different perfusion maps included in this study, time to pea...

Comparison of Computed Tomographic and Magnetic Resonance Perfusion Measurements in Acute Ischemic Stroke Back-to-Back Quantitative Analysis

We aimed to investigate optimal perfusion thresholds defining ischemic core and penumbra for hemispheric-cortical gray matter (GM) and subcortical white matter (WM). A total of 65 sub-6 h ischemic ...

/pdf/thresholds-for-infarction-vary-between-gray-matter-and-white-48jrc79pug.pdf

Longting Lin

Papers

Whole-Brain CT Perfusion to Quantify Acute Ischemic Penumbra and Core

Review of stroke thrombolytics

Ischemic core thresholds change with time to reperfusion: A case control study.

Comparison of Computed Tomographic and Magnetic Resonance Perfusion Measurements in Acute Ischemic Stroke Back-to-Back Quantitative Analysis

Thresholds for infarction vary between gray matter and white matter in acute ischemic stroke: A CT perfusion study.