Thrombolytic, stroke, extend window

BACKGROUND AND PURPOSE: Telestroke evaluation of patients with acute ischemic stroke is supported by American Heart and Stroke Association Guidelines. However, there is no data on outcomes or safety of administering IV thrombolytic stroke therapy using extended window criteria (>4.5 h since onset of symptoms with a hyperacute MRI diffusion T2/FLAIR mismatch) via telestroke. Here, we report adverse events and outcomes of extended-window thrombolysis by telestroke vs in-person care...

BACKGROUND AND PURPOSE: Tenecteplase (TNK) has demonstrated non-inferiority to alteplase in patients who had an acute ischaemic stroke presenting within 4.5 hours from symptom onset. The trial is aimed to explore the efficacy and safety of TNK in Chinese patients who had an acute ischaemic stroke with large/medium vessel occlusion in an extended time window. METHODS AND DESIGN: Chinese Acute Tissue-Based Imaging Selection for Lysis In Stroke Tenecteplase II (CHABLIS-T II) is a multicentre, prospective, block-randomised, open-label, blinded-endpoint, phase IIb study...

BACKGROUND: Mechanical thrombectomy (MT) has become increasingly common in recent years, as studies have shown that it can be an effective treatment for acute ischemic stroke (AIS) caused by large vessel occlusion (LVO). However, the efficacy of MT in the extended time window (6 to 24 h) is still uncertain. Our study aims to evaluate the outcomes of MT in the extended time window for AIS patients. METHODS: We reviewed data on AIS patients who received MT beyond six hours of stroke onset from 2015 to 2022...

This systematic review, meta-analysis, and novel time course analysis examines microvascular failure in the treatment of acute ischemic stroke (AIS) patients undergoing endovascular therapy (EVT) and/or thrombolytic administration for stroke management. A systematic review and meta-analysis following PRIMSA-2020 guidelines was conducted along with a novel curve-of-best fit analysis to elucidate the time-course of microvascular failure. Scopus and PubMed were searched using relevant keywords to identify studies that examine recanalization and reperfusion assessment of AIS patients following large vessel occlusion...

This article focuses on the emerging role of matrix metalloproteinase-12 (MMP-12) in ischaemic stroke (IS). MMP-12 expression in the brain increases dramatically in animal models of IS, and its suppression reduces brain damage and promotes neurological, sensorimotor and cognitive functional outcomes. Thus, MMP-12 could represent a potential target for the management of IS. This article provides an overview of MMP-12 upregulation in the brain following IS, its deleterious role in the post-stroke pathogenesis (blood-brain barrier disruption, inflammation, apoptosis and demyelination), possible molecular interactions and mechanistic insights, its involvement in post-ischaemic functional deficits and recovery as well as the limitations, perspectives, challenges and future directions for further research...

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Stroke is a leading cause of death, long-term disability, and socioeconomic costs, highlighting the urgent need for effective treatment. During acute phase, intravenous administration of recombinant tissue plasminogen activator (tPA), a thrombolytic agent, and endovascular thrombectomy (EVT), a mechanical intervention to retrieve clots, are the only FDA-approved treatments to re-establish cerebral blood flow. Due to a short therapeutic time window and high potential risk of cerebral hemorrhage, a limited number of acute stroke patients benefit from tPA treatment...

The current standard of care for moderate to severe ischemic stroke is thrombolytic therapy with tissue plasminogen activator (tPA). Treatment with tPA can significantly improve neurologic outcomes; however, thrombolytic therapy is associated with an increased risk of intracerebral hemorrhage (ICH). The risk of hemorrhage significantly limits the use of thrombolytic therapy, and identifying pathways induced by tPA that increase this risk could provide new therapeutic options to extend thrombolytic therapy to a wider patient population...

BACKGROUND: The number of mobile stroke programmes has increased with evidence, showing they expedite intravenous thrombolysis. Outstanding questions include whether time savings extend to patients eligible for endovascular therapy and impact clinical outcomes. OBJECTIVE: Our mobile stroke unit (MSU), based at an academic medical centre in upstate New York, launched in October 2018. We reviewed prospective observational data sets over 26 months to identify MSU and non-MSU emergency medical service (EMS) patients who underwent intravenous thrombolysis or endovascular thrombectomy for comparison of angiographic and clinical outcomes...

Upon acute ischemic stroke, rapid recanalization of the occluded cerebral vessel via intravenous thrombolytic therapy (IVT) is crucial to achieve good functional outcome. The time window of IVT with recombinant tissue plasminogen activator (rt-PA) has been extended from post-stroke 3 to 4.5 hours. In patients with cerebral penumbra identified using cerebral perfusion imaging, IVT is still beneficial within 4.5 to 9 hours after onset of stroke. For those without clear stroke onset time, DWI-FLAIR mismatch by brain MRI indicates hyperacute infarct and IVT is indicative...

The ischemic penumbra defined four decades ago has been the main battleground of ischemic stroke. The evolving ischemic penumbra concept has been providing insight for the development of vascular and cellular approaches as well as diagnostic tools for the treatment of ischemic stroke. rt-PA thrombolytic therapy to prevent the transition of ischemic penumbra to core has been approved for acute ischemic stroke within 3 h and was later recommended to extend to 4.5 h after symptom onset. Mechanical thrombectomy was introduced for the treatment of acute ischemic stroke with a therapeutic window of up to 24 h after stroke onset...

Ischemic stroke is a severe cerebrovascular disease with high mortality and morbidity. In recent years, reperfusion treatments based on thrombolytic and thrombectomy are major managements for ischemic stroke patients, and the recanalization time window has been extended to over 24 h. However, with the extension of the time window, the risk of ischemia/reperfusion (I/R) injury following reperfusion therapy becomes a big challenge for patient outcomes. I/R injury leads to neuronal death due to the imbalance in metabolic supply and demand, which is usually related to mitochondrial dysfunction...

BACKGROUND AND PURPOSE: Distal clot migration is a recognized event following intravenous thrombolysis (IVT) in the setting of acute ischemic stroke. Of note, clots that were initially retrievable by endovascular thrombectomy may migrate to a distal nonretrievable location and compromise clinical outcome. We investigated the incidence of clot migration leading to clot inaccessibility following IVT in the time window of 4.5 to 9 hours. METHODS: We performed a retrospective analysis of the EXTEND trial (Extending the Time for Thrombolysis in Emergency Neurological Deficits) data...

Ischemic stroke is one of the major causes of severe disability and death worldwide. It is mainly caused by a sudden reduction in cerebral blood flow due to obstruction of the supplying vessel by thrombi and subsequent initiation of a complex cascade of pathophysiological changes, which ultimately lead to brain ischemia and even irreversible infarction. Thus, timely and effective thrombolysis therapy remains a mainstay for acute ischemic stroke treatment. Tissue plasminogen activator (tPA), the only thrombolytic agent approved globally, provides substantial benefits by exerting a fibrinolysis effect, recovering the blood supply in occluded vessels and, thereby, salvaging the ischemic tissue...

OBJECTIVE: The objective of this study was to determine the proportion of stroke patients presenting in an extended time window who have a thrombolytic treatment target. BACKGROUND: Patients presenting up to 24 h after stroke onset have been found to have penumbral tissue on multimodal imaging. Stroke patients presenting in this extended time window without a large vessel occlusion (LVO) may benefit from reperfusion therapy using thrombolysis. METHODS: Patients seen at our institutions from 2011 through 2015 were reviewed to identify those who presented >4 h and <24 h from last seen normal (LSN) and did not receive acute treatment...

IMPORTANCE: Intravenous alteplase reduces disability after ischemic stroke in patients 4.5 to 9 hours after onset and with wake-up onset stroke selected using perfusion imaging mismatch. However, whether the benefit is consistent across the 4.5- to 6-hours, 6- to 9-hours, and wake-up stroke epochs is uncertain. OBJECTIVE: To examine the association of reperfusion with reduced disability, including by onset-to-randomization time strata in the Extending the Time for Thrombolysis in Emergency Neurological Deficits (EXTEND) and Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET) randomized clinical trials...

Wake-up stroke (WUS) is a subgroup of ischemic stroke in which patients show no abnormality before sleep while wake up with neurological deficits. In addition to the uncertain onset, WUS patients have difficulty to receive prompt and effective thrombolytic or reperfusion therapy, leading to relatively poor prognosis. A number of researches have indicated that CT or MRI based thrombolysis and endovascular therapy might have benefits for WUS patients. This review article narratively discusses the pathogenesis, risk factors, imaging-based diagnosis and recanalization treatments of WUS with the purpose of expanding current treatment options for this group of stroke patients and exploring better therapeutic methods...

Oxidative stress and inflammation are two critical pathological processes of cerebral ischemia-reperfusion injury. Myeloperoxidase (MPO) is a critical inflammatory enzyme and therapeutic target triggering both oxidative stress and neuroinflammation in the pathological process of cerebral ischemia-reperfusion injury. MPO is presented in infiltrated neutrophils, activated microglial cells, neurons, and astrocytes in the ischemic brain. Activation of MPO can catalyze the reaction of chloride and H2 O2 to produce HOCl...

Acute ischemic stroke is the leading cause of disability and among the leading causes of mortality worldwide. Intravenous tissue plasminogen activator has been a cornerstone for treatment of acute ischemic stroke for more than 20 years; however, its use is limited due to a narrow therapeutic window, several contraindications, and low efficacy to recanalize the artery in large vessel occlusion. Recently, the addition of endovascular mechanical thrombectomy of large artery occlusion has revolutionized the stroke treatment for most disabling strokes...

BACKGROUND: Current guidelines limit thrombolytic treatment of stroke to those patients who present within 4.5 h to minimize the risk of hemorrhagic complications. Risk of hemorrhage increases with increasing blood-brain barrier (BBB) disruption. This study aimed to determine, in a cohort of patients presenting outside of an IV-tPA treatment window, whether disruption of the BBB is time dependent, and what proportion of patients could be safely treated. METHODS: We analyzed untreated stroke patients, seen between 2011 and 2015, who had MRI studies in the time window of 4 to 24 h from symptoms onset...