International journal of stroke : official journal of the International Stroke Society
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The discovery that brain tissue could potentially be salvaged from ischaemia due to stroke, has led to major advances in the development of therapies for ischemic stroke. In this review, we detail the advances in the understanding of this area termed the ischaemic penumbra, from its discovery to the evolution of imaging techniques, and finally some of the treatments developed. ⋯ Importantly, 40 years of critical imaging research on the ischaemic penumbra have allowed for considerable extension of the treatment time window and better patient selection for reperfusion therapy. The translation of the penumbra concept into routine clinical practice has shown that "tissue is at least as important as time."
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The coronavirus disease 2019 is associated with neurological manifestations including stroke. ⋯ Despite timely intervention and favorable reperfusion, the mortality rate in coronavirus disease 2019 patients with large vessel occlusion was high in our series and in the pooled analysis. Notable features were younger age group, involvement of both the arterial and venous vasculature, multivessel involvement, and complicated procedures due to the clot consistency and burden.
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Low-density lipoprotein (LDL) cholesterol has been long associated with the risk for ischemic stroke, myocardial infarction, and cardiovascular death. For more than a decade, the main pharmacological option to prevent stroke and myocardial infarction through LDL-cholesterol lowering was the use of statins. During the recent years, two novel classes of drugs have proven their efficacy and safety to reduce LDL-cholesterol and prevent cardiovascular events in large, well-conducted randomized controlled trials: ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. ⋯ Stroke physicians should aim for low LDL-cholesterol levels by intensive statin treatment in all ischemic stroke patients. For those patients who are at the highest risk for recurrent stroke or another cardiovascular event and have unacceptable LDL-cholesterol levels despite intensive statin treatment, PCSK9 inhibitors should be considered.
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The concept of the ischemic penumbra was formulated on the basis of animal experiments showing functional impairment and electrophysiologic disturbances with decreasing flow to the brain below defined values (the threshold for function) and irreversible tissue damage with blood supply further decreased (the threshold for infarction). The perfusion range between these thresholds was termed the "penumbra," and restitution of flow above the functional threshold was able to reverse the deficits without permanent damage. In further experiments, the dependency of the development of irreversible lesions on the interaction of the severity and the duration of critically reduced blood flow was established, proving that the lower the flow, the shorter the time for efficient reperfusion. ⋯ However, this analysis did not confirm an improvement in clinical outcome with delayed thrombolysis. Randomized controlled trials that did enroll patients based on the presence of a target mismatch on multimodal imaging demonstrated a higher benefit of revascularization treatment by comparison with those who did not and demonstrated for the first time that revascularization treatment for occlusion of an internal carotid artery (ICA) or a proximal middle cerebral artery (MCA) was still beneficial from 6 to 24 h after onset among patients in whom the clinical examination and the multimodal brain imaging indicate a persistent penumbra. On this background, the yield of imaging for the selection of patients for a revascularization therapy will be discussed.
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Alteplase has been the mainstay of thrombolytic treatment since the National Institutes of Neurological Disorders and Stroke trial was published in 1995. Over recent years, several trials have investigated alternative thrombolytic agents. ⋯ We review the literature on tenecteplase for the treatment of acute ischemic stroke, with a focus on the major completed and ongoing trials. Overall, tenecteplase shows promise for treatment of acute ischemic stroke, both in populations currently eligible for alteplase and also in groups not currently treated with thrombolysis.