Collateral blood vessels in acute ischaemic stroke: a potential therapeutic target
TL;DR: Imaging of the brain and vessels has shown that collateral flow can sustain brain tissue for hours after the occlusion of major arteries to the brain, and the augmentation or maintenance of collateral flow is therefore a potential therapeutic target.
Abstract: Summary Ischaemic stroke results from acute arterial occlusion leading to focal hypoperfusion. Thrombolysis is the only proven treatment. Advanced neuroimaging techniques allow a detailed assessment of the cerebral circulation in patients with acute stroke, and provide information about the status of collateral vessels and collateral blood flow, which could attenuate the effects of arterial occlusion. Imaging of the brain and vessels has shown that collateral flow can sustain brain tissue for hours after the occlusion of major arteries to the brain, and the augmentation or maintenance of collateral flow is therefore a potential therapeutic target. Several interventions that might augment collateral blood flow are being investigated.
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TL;DR: A favorable penumbral pattern on neuroimaging did not identify patients who would differentially benefit from endovascular therapy for acute ischemic stroke, nor was embolectomy shown to be superior to standard care.
Abstract: BackgroundWhether brain imaging can identify patients who are most likely to benefit from therapies for acute ischemic stroke and whether endovascular thrombectomy improves clinical outcomes in such patients remains unclear. MethodsIn this study, we randomly assigned patients within 8 hours after the onset of large-vessel, anterior-circulation strokes to undergo mechanical embolectomy (Merci Retriever or Penumbra System) or receive standard care. All patients underwent pretreatment computed tomography or magnetic resonance imaging of the brain. Randomization was stratified according to whether the patient had a favorable penumbral pattern (substantial salvageable tissue and small infarct core) or a nonpenumbral pattern (large core or small or absent penumbra). We assessed outcomes using the 90-day modified Rankin scale, ranging from 0 (no symptoms) to 6 (dead). ResultsAmong 118 eligible patients, the mean age was 65.5 years, the mean time to enrollment was 5.5 hours, and 58% had a favorable penumbral patt...
1,298 citations
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TL;DR: The underlying pathophysiology of ischemic stroke is reviewed and the intertwined pathways that are promising therapeutic targets are revealed, leading to the development of numerous agents that target various injury pathways.
Abstract: Stroke is the second most common cause of death and the leading cause of disability worldwide. Brain injury following stroke results from a complex series of pathophysiological events including excitotoxicity, oxidative and nitrative stress, inflammation, and apoptosis. Moreover, there is a mechanistic link between brain ischemia, innate and adaptive immune cells, intracranial atherosclerosis, and also the gut microbiota in modifying the cerebral responses to ischemic insult. There are very few treatments for stroke injuries, partly owing to an incomplete understanding of the diverse cellular and molecular changes that occur following ischemic stroke and that are responsible for neuronal death. Experimental discoveries have begun to define the cellular and molecular mechanisms involved in stroke injury, leading to the development of numerous agents that target various injury pathways. In the present article, we review the underlying pathophysiology of ischemic stroke and reveal the intertwined pathways that are promising therapeutic targets.
408 citations
Cites methods from "Collateral blood vessels in acute i..."
...Important advances in the imaging of collateral blood vessels and collateral blood flow by multimodal CT and MRI techniques seem to be the most hopeful methods for the routine assessment and quantification of collateral blood flow in patients with acute ischemic stroke [316]....
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TL;DR: Though remarkable advances in understanding of HT have been made, additional efforts are needed to translate these discoveries to the clinic and reduce the impact of HT on patients with ischemic stroke.
Abstract: Hemorrhagic transformation (HT) is a common complication of ischemic stroke that is exacerbated by thrombolytic therapy Methods to better prevent, predict, and treat HT are needed In this review, we summarize studies of HT in both animals and humans We propose that early HT ( 18 to 24 hours after stroke) that relates to ischemia activation of brain proteases (MMP-2, MMP-3, MMP-9, and endogenous tissue plasminogen activator), neuroinflammation, and factors that promote vascular remodeling (vascular endothelial growth factor and high-moblity-group-box-1) Processes that mediate BBB repair and reduce HT risk are discussed, including transforming growth factor beta signaling in monocytes, Src kinase signaling, MMP inhibitors, and inhibitors of reactive oxygen species Finally, clinical features associated with HT in patients with stroke are reviewed, including approaches to predict HT by clinical factors, brain imaging, and blood biomarkers Though remarkable advances in our understanding of HT have been made, additional efforts are needed to translate these discoveries to the clinic and reduce the impact of HT on patients with ischemic stroke
387 citations
TL;DR: In this paper, the early phase of cerebral blood volume (CBV) increase is likely due to the improvement in collateral flow, also known as arteriogenesis, whereas the late phase of CBV increase is attributed to the surge of angiogenesis.
271 citations
TL;DR: A new method is described to outline the flow profile of the cerebral vascular tree, including reference values, and should be used for grading the collateral flow system.
Abstract: High-resolution phase-contrast magnetic resonance imaging can now assess flow in proximal and distal cerebral arteries. The aim of this study was to describe how total cerebral blood flow (tCBF) is ...
231 citations
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TL;DR: The TOAST stroke subtype classification system is easy to use and has good interobserver agreement and should allow investigators to report responses to treatment among important subgroups of patients with ischemic stroke.
Abstract: The etiology of ischemic stroke affects prognosis, outcome, and management. Trials of therapies for patients with acute stroke should include measurements of responses as influenced by subtype of ischemic stroke. A system for categorization of subtypes of ischemic stroke mainly based on etiology has been developed for the Trial of Org 10172 in Acute Stroke Treatment (TOAST). A classification of subtypes was prepared using clinical features and the results of ancillary diagnostic studies. "Possible" and "probable" diagnoses can be made based on the physician9s certainty of diagnosis. The usefulness and interrater agreement of the classification were tested by two neurologists who had not participated in the writing of the criteria. The neurologists independently used the TOAST classification system in their bedside evaluation of 20 patients, first based only on clinical features and then after reviewing the results of diagnostic tests. The TOAST classification denotes five subtypes of ischemic stroke: 1) large-artery atherosclerosis, 2) cardioembolism, 3) small-vessel occlusion, 4) stroke of other determined etiology, and 5) stroke of undetermined etiology. Using this rating system, interphysician agreement was very high. The two physicians disagreed in only one patient. They were both able to reach a specific etiologic diagnosis in 11 patients, whereas the cause of stroke was not determined in nine. The TOAST stroke subtype classification system is easy to use and has good interobserver agreement. This system should allow investigators to report responses to treatment among important subgroups of patients with ischemic stroke. Clinical trials testing treatments for acute ischemic stroke should include similar methods to diagnose subtypes of stroke.
9,913 citations
TL;DR: The Statistical Update brings together the most up-to-date statistics on heart disease, stroke, other vascular diseases, and their risk factors and presents them in its Heart Disease and Stroke Statistical Update each year.
Abstract: Appendix I: List of Statistical Fact Sheets. URL: http://www.americanheart.org/presenter.jhtml?identifier=2007
We wish to thank Drs Brian Eigel and Michael Wolz for their valuable comments and contributions. We would like to acknowledge Tim Anderson and Tom Schneider for their editorial contributions and Karen Modesitt for her administrative assistance.
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# Summary {#article-title-2}
Each year, the American Heart Association, in conjunction with the Centers for Disease Control and Prevention, the National Institutes of Health, and other government agencies, brings together the most up-to-date statistics on heart disease, stroke, other vascular diseases, and their risk factors and presents them in its Heart Disease and Stroke Statistical Update. The Statistical Update is a valuable resource for researchers, clinicians, healthcare policy makers, media professionals, the lay public, and many others who seek the best national data available on disease …
6,176 citations
TL;DR: Recent evidence indicates that immediate failure of basic functions such as synaptic transmission, ion pumping and energy metabolism in the ischemic brain, is critically dependent on residual blood flow, and that these functions fail at certain critical flow thresholds.
Abstract: COMPLETE ARREST of the cerebral circulation leads within seconds to cessation of neuronal electrical activity and within a few minutes to deterioration of the energy state and ion homeostasis. Depletion of high energy phosphates, membrane ion pump failure, efflux of cellular potassium, influx of sodium, chloride and water, and membrane depolarization occur swiftly. If such chaos persists for longer than 5-10 minutes, irreversible cell damage is likely. Such is the inevitable sequence of events if blood flow to the brain is arrested. If, however, the ischemia is incomplete the outcome is more difficult to predict and is largely dependent on residual perfusion and oxygen availability. It is in large measure the outcome of incomplete cerebral ischemia, which is of particular interest in cerebrovascular disease. With occlusion of a cere-bral vessel and signs of acute stroke, ischemia is hardly ever total. Some residual perfusion persists in the ischemic area dependent on collateral vessels and local perfusion pressures. Recent evidence indicates that immediate failure of basic functions such as synaptic transmission, ion pumping and energy metabolism in the ischemic brain, is critically dependent on residual blood flow, and that these functions fail at certain critical flow thresholds. It appears, further, that the development of infarction is critically correlated to residual per-fusion, and there is a lethal threshold of residual blood flow below which tissue infarction develops after a certain time. Such knowledge provides the theoretical background for application of the instrumentation now being developed for repeated non-invasive 3-dimensional imaging of residual flow in the ischemic brain. By these means one hopes it will become possible to conduct treatment and to evaluate prognosis in the acute stroke patient by reproducible repeatable measurement in man. In man, flattening of the EEG occurs immediately if hemispheric flow falls below 0.16-0.17 ml-g^min 1 as evidenced by measurements of cerebral blood flow and EEG during clamping of one carotid artery in end-arterectomy. 1-* The critical relationship between cere-bral electrical activity and blood flow which such clinical observation suggested has been amply proven in exDerimental studies. Svmon and Branston and co-workers' demonstrated that the evoked somato-sensory potential recorded in baboon cortex was abolished at local flows below about 0.15 ml'gr^mirr 1. This flow level could be regarded as critical in the sense that electrical function in the cortex was abolished below but sustained above this level. It has, therefore, been referred to as the flow threshold of electrical …
2,727 citations
Journal Article•
TL;DR: The goal is to provide an overview of the current evidence about components of the evaluation and treatment of adults with acute ischemic stroke.
Abstract: Chelsea Kidwell, Patrick D. Lyden, Lewis B. Morgenstern, Adnan I. Qureshi, Robert Brass, Anthony Furlan, Robert L. Grubb, Randall T. Higashida, Edward C. Jauch, Harold P. Adams, Jr, Gregory del Zoppo, Mark J. Alberts, Deepak L. Bhatt, Lawrence Guidelines for the Early Management of Adults With Ischemic Stroke : ISSN: 1524-4628 Copyright © 2007 American Heart Association. All rights reserved. Print ISSN: 0039-2499. Online Stroke is published by the American Heart Association. 7272 Greenville Avenue, Dallas, TX 72514 doi: 10.1161/STROKEAHA.107.181486 2007, 38:1655-1711: originally published online April 12, 2007 Stroke http://stroke.ahajournals.org/content/38/5/1655 located on the World Wide Web at: The online version of this article, along with updated information and services, is http://stroke.ahajournals.org/ http://stroke.ahajournals.org/ An erratum has been published regarding this article. Please see the attached page for:
2,687 citations
TL;DR: In this paper, the authors provide an overview of the current evidence about components of the evaluation and treatment of adults with acute ischemic stroke and provide information for healthcare policy makers.
Abstract: Purpose— Our goal is to provide an overview of the current evidence about components of the evaluation and treatment of adults with acute ischemic stroke. The intended audience is physicians and other emergency healthcare providers who treat patients within the first 48 hours after stroke. In addition, information for healthcare policy makers is included. Methods— Members of the panel were appointed by the American Heart Association Stroke Council’s Scientific Statement Oversight Committee and represented different areas of expertise. The panel reviewed the relevant literature with an emphasis on reports published since 2003 and used the American Heart Association Stroke Council’s Levels of Evidence grading algorithm to rate the evidence and to make recommendations. After approval of the statement by the panel, it underwent peer review and approval by the American Heart Association Science Advisory and Coordinating Committee. It is intended that this guideline be fully updated in 3 years. Results— Managem...
2,263 citations