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      Multivariate Dynamic Prediction of Ischemic Infarction and Tissue Salvage as a Function of Time and Degree of Recanalization

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          Abstract

          Benefit of endovascular recanalization beyond established treatment time windows likely exists in select stroke patients. However, there is currently no imaging model that predicts infarction adjusting for elapsed time between the pathologic snapshot of admission imaging until endovascular recanalization. We trained and cross validated a multivariate generalized linear model (GLM) that uses computer tomography perfusion and clinical data to quantify patient-specific dynamic change of tissue infarction depending on degree and time of recanalization. Multicenter data of 161 patients with proximal anterior circulation occlusion undergoing endovascular therapy were included. Multivariate voxelwise infarct probability was calculated within the GLM. The effect of increasing time to treatment and degree of recanalization on voxelwise infarction was calculated in each patient. Tissue benefit of successful relative to unsuccessful recanalization was shown up to 15 hours after onset in individual patients and decreased nonlinearly with time. On average, the relative reduction of infarct volume at the treatment interval of 5 hours was 53% and this salvage effect decreased by 5% units per hour to <5% after 10 additional hours to treatment. Treatment time-adjusted multivariate prediction of infarction by perfusion and clinical status may identify patients who benefit from extended time to recanalization therapy.

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          Perfusion-CT assessment of infarct core and penumbra: receiver operating characteristic curve analysis in 130 patients suspected of acute hemispheric stroke.

          Max Wintermark, Adam Flanders, Birgitta K. Velthuis … (2006)
          Different definitions have been proposed to define the ischemic penumbra from perfusion-CT (PCT) data, based on parameters and thresholds tested only in small pilot studies. The purpose of this study was to perform a systematic evaluation of all PCT parameters (cerebral blood flow, volume [CBV], mean transit time [MTT], time-to-peak) in a large series of acute stroke patients, to determine which (combination of) parameters most accurately predicts infarct and penumbra. One hundred and thirty patients with symptoms suggesting hemispheric stroke < or =12 hours from onset were enrolled in a prospective multicenter trial. They all underwent admission PCT and follow-up diffusion-weighted imaging/fluid-attenuated inversion recovery (DWI/FLAIR); 25 patients also underwent admission DWI/FLAIR. PCT maps were assessed for absolute and relative reduced CBV, reduced cerebral blood flow, increased MTT, and increased time-to-peak. Receiver-operating characteristic curve analysis was performed to determine the most accurate PCT parameter, and the optimal threshold for each parameter, using DWI/FLAIR as the gold standard. The PCT parameter that most accurately describes the tissue at risk of infarction in case of persistent arterial occlusion is the relative MTT (area under the curve=0.962), with an optimal threshold of 145%. The PCT parameter that most accurately describes the infarct core on admission is the absolute CBV (area under the curve=0.927), with an optimal threshold at 2.0 ml x 100 g(-1). In a large series of 130 patients, the optimal approach to define the infarct and the penumbra is a combined approach using 2 PCT parameters: relative MTT and absolute CBV, with dedicated thresholds.
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            Early stroke treatment associated with better outcome: the NINDS rt-PA stroke study.

            J. Marler, B C Tilley, M. Lu … (2000)
            The National Institute of Neurological Disorders and Stroke (NINDS) rt-PA Stroke Study showed a similar percentage of intracranial hemorrhage and good outcome in patients 3 months after stroke treatment given 0 to 90 minutes and 91 to 180 minutes after stroke onset. At 24 hours after stroke onset more patients treated 0 to 90 compared to 91 to 180 minutes after stroke onset had improved by four or more points on the NIH Stroke Scale (NIHSS). The authors performed further analyses to characterize the relationship of onset-to-treatment time (OTT) to outcome at 3 months, early improvement at 24 hours, and intracranial hemorrhage within 36 hours. Univariate analyses identified potentially confounding variables associated with OTT that could mask an OTT-treatment interaction. Tests for OTT-treatment interactions adjusting for potential masking confounders were performed. An OTT-treatment interaction was considered significant if p < or = 0.10, implying that treatment effectiveness was related to OTT. For 24-hour improvement, there were no masking confounders identified and there was an OTT-treatment interaction (p = 0.08). For 3-month favorable outcome, the NIHSS met criteria for a masking confounder. After adjusting for NIHSS as a covariate, an OTT-treatment interaction was detected (p = 0.09): the adjusted OR (95% CI) for a favorable 3-month outcome associated with recombinant tissue-type plasminogen activator (rt-PA) was 2.11 (1.33 to 3.35) in the 0 to 90 minute stratum and 1.69 (1.09 to 2.62) in the 91 to 180 minute stratum. In the group treated with rt-PA, after adjusting for baseline NIHSS, an effect of OTT on the occurrence of intracranial hemorrhage was not detected. If the NINDS rt-PA Stroke Trial treatment protocol is followed, this analysis suggests that patients treated 0 to 90 minutes from stroke onset with rt-PA have an increased odds of improvement at 24 hours and favorable 3-month outcome compared to patients treated later than 90 minutes. No effect of OTT on intracranial hemorrhage was detected within the group treated with rt-PA, possibly due to low power.
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              Good clinical outcome after ischemic stroke with successful revascularization is time-dependent.

              Harsh Khatri, Barry J. Broderick, S Yeatts … (2009)
              Trials of IV recombinant tissue plasminogen activator (rt-PA) have demonstrated that longer times from ischemic stroke symptom onset to initiation of treatment are associated with progressively lower likelihoods of clinical benefit, and likely no benefit beyond 4.5 hours. How the timing of IV rt-PA initiation relates to timing of restoration of blood flow has been unclear. An understanding of the relationship between timing of angiographic reperfusion and clinical outcome is needed to establish time parameters for intraarterial (IA) therapies. The Interventional Management of Stroke pilot trials tested combined IV/IA therapy for moderate-to-severe ischemic strokes within 3 hours from symptom onset. To isolate the effect of time to angiographic reperfusion on clinical outcome, we analyzed only middle cerebral artery and distal internal carotid artery occlusions with successful reperfusion (Thrombolysis in Cerebral Infarction 2-3) during the interventional procedure (<7 hours). Time to angiographic reperfusion was defined as time from stroke onset to procedure termination. Good clinical outcome was defined as modified Rankin Score 0-2 at 3 months. Among the 54 cases, only time to angiographic reperfusion and age independently predicted good clinical outcome after angiographic reperfusion. The probability of good clinical outcome decreased as time to angiographic reperfusion increased (unadjusted p = 0.02, adjusted p = 0.01) and approached that of cases without angiographic reperfusion within 7 hours. We provide evidence that good clinical outcome following angiographically successful reperfusion is significantly time-dependent. At later times, angiographic reperfusion may be associated with a poor risk-benefit ratio in unselected patients.
              Article 0 comments Cited 101 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Title: Journal of Cerebral Blood Flow & Metabolism
                Abbreviated Title: J Cereb Blood Flow Metab
                Publisher: Springer Nature
                ISSN (Print): 0271-678X
                ISSN (Electronic): 1559-7016
                Publication date Created: June 17 2015
                Publication date Created: September 2015
                Publication date (Electronic): July 08 2015
                Publication date (Print): September 2015
                Volume: 35
                Issue: 9
                Pages: 1397-1405
                Affiliations
                [1 ] Department of Diagnostic and Interventional Neuroradiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
                [2 ] Department of Clinical Radiology, University of Muenster, Muenster, Germany
                [3 ] Institute of Neuroradiology, University Medical Center Schleswig Holstein, Lübeck, Germany
                [4 ] Department of Radiology and Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada
                [5 ] Department of Neurology, University of Muenster, Muenster, Germany
                [6 ] Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
                [7 ] Department of Neuroradiology, Asklepios Hospital Altona, Hamburg, Germany
                [8 ] Department of Neuroradiology, University of Medicine Goettingen, Goettingen, Germany
                [9 ] Institute of Diagnostic Radiology and Neuroradiology, University of Medicine Greifswald, Greifswald, Germany.
                Article
                DOI: 10.1038/jcbfm.2015.144
                PMC ID: 4640330
                PubMed ID: 26154867
                SO-VID: 01b13956-3c35-45c2-bf19-af6c5881e86c
                Copyright © © 2015
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