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Continuum (Minneapolis, Minn.) Apr 2020The article "Update on Treatment of Acute Ischemic Stroke" by Dr Rabinstein was first published in the February 2017 Cerebrovascular Disease issue of Continuum: Lifelong... (Review)
Review
EDITOR'S NOTE
The article "Update on Treatment of Acute Ischemic Stroke" by Dr Rabinstein was first published in the February 2017 Cerebrovascular Disease issue of Continuum: Lifelong Learning in Neurology as "Treatment of Acute Ischemic Stroke" and has been updated by Dr Rabinstein for this issue at the request of the Editor-in-Chief.
ABSTRACT
PURPOSE OF REVIEWThis article provides an update on the state of the art of the treatment of acute ischemic stroke with particular emphasis on the indications for reperfusion therapy.RECENT FINDINGSIn addition to the previously established indications for intravenous (IV) thrombolysis with recombinant tissue plasminogen activator (rtPA) within 4.5 hours of stroke symptom onset and endovascular therapy with mechanical thrombectomy for patients with large artery occlusion who can be treated within 6 hours of symptom onset, recent randomized controlled trials have now established new indications for emergency reperfusion in patients with wake-up stroke or delayed presentation (up to 24 hours from last known well in the case of mechanical thrombectomy). Identification of patients who may benefit from acute reperfusion therapy within this extended time window requires screening with perfusion brain imaging or, in the case of IV thrombolysis for wake-up strokes, emergency brain MRI. Collateral status and time to reperfusion remain the primary determinants of outcome.SUMMARYTimely successful reperfusion is the most effective treatment for patients with acute ischemic stroke. Recent evidence supports the expansion of the time window for reperfusion treatment in carefully selected patients.
Topics: Fibrinolytic Agents; Humans; Ischemic Stroke; Mechanical Thrombolysis; Outcome and Process Assessment, Health Care; Reperfusion; Thrombolytic Therapy
PubMed: 32224752
DOI: 10.1212/CON.0000000000000840 -
JAMA Apr 2015Acute ischemic stroke is a major cause of mortality and morbidity in the United States. We review the latest data and evidence supporting catheter-directed treatment for... (Review)
Review
IMPORTANCE
Acute ischemic stroke is a major cause of mortality and morbidity in the United States. We review the latest data and evidence supporting catheter-directed treatment for proximal artery occlusion as an adjunct to intravenous thrombolysis in patients with acute stroke.
OBJECTIVE
To review the pathophysiology of acute brain ischemia and infarction and the evidence supporting various stroke reperfusion treatments.
EVIDENCE REVIEW
Systematic literature search of MEDLINE databases published between January 1, 1990, and February 11, 2015, was performed to identify studies addressing the role of thrombolysis and mechanical thrombectomy in acute stroke management. Studies included randomized clinical trials, observational studies, guideline statements, and review articles. Sixty-eight articles (N = 108,082 patients) were selected for review.
FINDINGS
Intravenous thrombolysis is the mainstay of acute ischemic stroke management for any patient with disabling deficits presenting within 4.5 hours from symptom onset. Randomized trials have demonstrated that more patients return to having good function (defined by being independent and having slight disability or less) when treated within 4.5 hours after symptom onset with intravenous recombinant tissue plasminogen activator (IV rtPA) therapy. Mechanical thrombectomy in select patients with acute ischemic stroke and proximal artery occlusions has demonstrated substantial rates of partial or complete arterial recanalization and improved outcomes compared with IV rtPA or best medical treatment alone in multiple randomized clinical trials. Regardless of mode of reperfusion, earlier reperfusion is associated with better clinical outcomes.
CONCLUSIONS AND RELEVANCE
Intravenous rtPA remains the standard of care for patients with moderate to severe neurological deficits who present within 4.5 hours of symptom onset. Outcomes for some patients with acute ischemic stroke and moderate to severe neurological deficits due to proximal artery occlusion are improved with endovascular reperfusion therapy. Efforts to hasten reperfusion therapy, regardless of the mode, should be undertaken within organized stroke systems of care.
Topics: Brain; Brain Infarction; Brain Ischemia; Endovascular Procedures; Fibrinolytic Agents; Humans; Infusions, Intravenous; Reperfusion; Stroke; Thrombectomy; Thrombolytic Therapy; Tissue Plasminogen Activator
PubMed: 25871671
DOI: 10.1001/jama.2015.3058 -
Oxidative Medicine and Cellular... 2021Myocardial ischemia is a disease with high morbidity and mortality, for which reperfusion is currently the standard intervention. However, the reperfusion may lead to... (Review)
Review
Myocardial ischemia is a disease with high morbidity and mortality, for which reperfusion is currently the standard intervention. However, the reperfusion may lead to further myocardial damage, known as myocardial ischemia/reperfusion injury (MI/RI). Oxidative stress is one of the most important pathological mechanisms in reperfusion injury, which causes apoptosis, autophagy, inflammation, and some other damage in cardiomyocytes through multiple pathways, thus causing irreversible cardiomyocyte damage and cardiac dysfunction. This article reviews the pathological mechanisms of oxidative stress involved in reperfusion injury and the interventions for different pathways and targets, so as to form systematic treatments for oxidative stress-induced myocardial reperfusion injury and make up for the lack of monotherapy.
Topics: Humans; Myocardial Ischemia; Oxidative Stress; Reperfusion
PubMed: 34055195
DOI: 10.1155/2021/6614009 -
European Heart Journal Mar 2017The incidence of ST segment elevation myocardial infarction (STEMI) has decreased over the last two decades in developed countries, but mortality from STEMI despite... (Review)
Review
The incidence of ST segment elevation myocardial infarction (STEMI) has decreased over the last two decades in developed countries, but mortality from STEMI despite widespread access to reperfusion therapy is still substantial as is the development of heart failure, particularly among an expanding older population. In developing countries, the incidence of STEMI is increasing and interventional reperfusion is often not available. We here review the pathophysiology of acute myocardial infarction and reperfusion, notably the temporal and spatial evolution of ischaemic and reperfusion injury, the different modes of cell death, and the resulting coronary microvascular dysfunction. We then go on to briefly characterize the cardioprotective phenomena of ischaemic preconditioning, ischaemic postconditioning, and remote ischaemic conditioning and their underlying signal transduction pathways. We discuss in detail the attempts to translate conditioning strategies and drug therapy into the clinical setting. Most attempts have failed so far to reduce infarct size and improve clinical outcomes in STEMI patients, and we discuss potential reasons for such failure. Currently, it appears that remote ischaemic conditioning and a few drugs (atrial natriuretic peptide, exenatide, metoprolol, and esmolol) reduce infarct size, but studies with clinical outcome as primary endpoint are still underway.
Topics: Animals; Cardiotonic Agents; Coronary Circulation; Disease Models, Animal; Humans; Ischemic Postconditioning; Ischemic Preconditioning, Myocardial; Microvascular Angina; Myocardial Reperfusion; Myocardial Reperfusion Injury; Percutaneous Coronary Intervention; ST Elevation Myocardial Infarction; Single Photon Emission Computed Tomography Computed Tomography; Treatment Outcome
PubMed: 27354052
DOI: 10.1093/eurheartj/ehw224 -
Nature Reviews. Neurology Apr 2022For over 40 years, attempts to develop treatments that protect neurons and other brain cells against the cellular and biochemical consequences of cerebral ischaemia in... (Review)
Review
For over 40 years, attempts to develop treatments that protect neurons and other brain cells against the cellular and biochemical consequences of cerebral ischaemia in acute ischaemic stroke (AIS) have been unsuccessful. However, the advent of intravenous thrombolysis and endovascular thrombectomy has taken us into a new era of treatment for AIS in which highly effective reperfusion therapy is widely available. In this context, cytoprotective treatments should be revisited as adjunctive treatment to reperfusion therapy. Renewed efforts should focus on developing new drugs that target multiple aspects of the ischaemic cascade, and previously developed drugs should be reconsidered if they produced robust cytoprotective effects in preclinical models and their safety profiles were reasonable in previous clinical trials. Several development pathways for cytoprotection as an adjunct to reperfusion can be envisioned. In this Review, we outline the targets for cytoprotective therapy and discuss considerations for future drug development, highlighting the recent ESCAPE-NA1 trial of nerinetide, which produced the most promising results to date. We review new types of clinical trial to evaluate whether cytoprotective drugs can slow infarct growth prior to reperfusion and/or ameliorate the consequences of reperfusion, such as haemorrhagic transformation. We also highlight how advanced brain imaging can help to identify patients with salvageable ischaemic tissue who are likely to benefit from cytoprotective therapy.
Topics: Brain; Brain Ischemia; Cytoprotection; Endovascular Procedures; Humans; Ischemic Stroke; Reperfusion; Stroke; Thrombectomy; Treatment Outcome
PubMed: 35079135
DOI: 10.1038/s41582-021-00605-6 -
FP Essentials Jan 2022Urgent evaluation of patients with acute ischemic stroke allows for a comprehensive assessment of management options. These include thrombolysis and thrombectomy,...
Urgent evaluation of patients with acute ischemic stroke allows for a comprehensive assessment of management options. These include thrombolysis and thrombectomy, depending on symptom onset and severity, the presumed location of the occlusion, and patient comorbidities and potential for improvement. For patients who present within 4.5 hours of onset of disabling symptoms consistent with acute ischemic stroke and with no contraindications, intravenous thrombolysis is indicated. Acute mechanical thrombectomy may be indicated for patients who present within 24 hours of symptom onset and have symptoms consistent with a large vessel occlusion. After reperfusion therapy, patients require close neurologic monitoring. Patients who receive reperfusion therapy tend to have better functional outcomes than patients who do not. Secondary prevention includes use of antithrombotics and glycemic control. Common issues in the acute setting include cerebral edema, hemorrhagic transformation, and symptomatic carotid disease.
Topics: Brain Ischemia; Hospitals; Humans; Reperfusion; Stroke; Thrombectomy
PubMed: 35006662
DOI: No ID Found -
JAMA Sep 2021Mechanical thrombectomy using a stent retriever or contact aspiration is widely used for treatment of patients with acute ischemic stroke due to anterior circulation... (Comparative Study)
Comparative Study Randomized Controlled Trial
Effect of Thrombectomy With Combined Contact Aspiration and Stent Retriever vs Stent Retriever Alone on Revascularization in Patients With Acute Ischemic Stroke and Large Vessel Occlusion: The ASTER2 Randomized Clinical Trial.
IMPORTANCE
Mechanical thrombectomy using a stent retriever or contact aspiration is widely used for treatment of patients with acute ischemic stroke due to anterior circulation large vessel occlusion, but the additional benefit of combining contact aspiration with stent retriever is uncertain.
OBJECTIVE
To determine whether mechanical thrombectomy for treatment of anterior circulation large vessel occlusion stroke with initial contact aspiration and stent retriever combined results in better final angiographic outcome than with standard stent retriever alone.
DESIGN, SETTING, AND PARTICIPANTS
This trial was a multicenter randomized, open-label, blinded end point evaluation that enrolled 408 patients from October 16, 2017, to May 29, 2018, in 11 French comprehensive stroke centers, with a 12-month outcome follow-up. Patients with a large vessel occlusion in the anterior circulation were included up to 8 hours after symptom onset. The final date of follow-up was June, 19, 2019.
INTERVENTIONS
Patients were randomly assigned (1:1 allocation) to receive initial thrombectomy with contact aspiration and stent retriever combined (205) or stent retriever alone (203).
MAIN OUTCOMES AND MEASURES
The primary outcome was the rate of expanded Thrombolysis In Cerebral Infarction score of 2c or 3 (eTICI 2c/3; ie, scores indicate near-total and total reperfusion grades) at the end of the procedure.
RESULTS
Among the 408 patients who were randomized, 3 were excluded, and 405 (99.3%) patients (mean age, 73 years; 220 [54%] women and 185 [46%] men) were included in the primary analysis. The rate of eTICI 2c/3 at the end of the endovascular procedure was not significantly different between the 2 thrombectomy groups (64.5% [131 of 203 patients] for contact aspiration and stent retriever combined vs 57.9% [117 of 202 patients] for stent retriever alone; risk difference, 6.6% [95% CI, -3.0% to 16.2%]; adjusted odds ratio [OR], 1.33 [95% CI, 0.88 to 1.99]; P = .17). Of 14 prespecified secondary efficacy end points, 12 showed no significant difference. A higher rate of successful reperfusion was achieved in the contact aspiration combined with stent retriever group vs the stent retriever alone group (eTICI 2b50/2c/3, 86.2% vs 72.3%; adjusted OR, 2.54 [95% CI, 1.51 to 4.28]; P < .001) and of near-total or total reperfusion (eTICI 2c/3, 59.6% vs 49.5%; adjusted OR, 1.52 [95% CI, 1.02 to 2.27]; P = .04) after the assigned initial intervention alone.
CONCLUSIONS AND RELEVANCE
Among patients with acute ischemic stroke due to large vessel occlusion, an initial thrombectomy technique consisting of contact aspiration and stent retriever combined, compared with stent retriever alone, did not significantly improve the rate of near-total or total reperfusion (eTICI 2c/3) at the end of the endovascular procedure, although the trial may have been underpowered to detect smaller differences between groups.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT03290885.
Topics: Aged; Arterial Occlusive Diseases; Combined Modality Therapy; Device Removal; Female; Humans; Ischemic Stroke; Male; Reperfusion; Stents; Thrombectomy; Treatment Outcome
PubMed: 34581737
DOI: 10.1001/jama.2021.13827 -
Stroke and Vascular Neurology Feb 2024Recombinant human TNK tissue-type plasminogen activator (rhTNK-tPA) was not inferior to alteplase for ischaemic stroke within 4.5 hours. Our study aimed to investigate... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND AND PURPOSE
Recombinant human TNK tissue-type plasminogen activator (rhTNK-tPA) was not inferior to alteplase for ischaemic stroke within 4.5 hours. Our study aimed to investigate the efficacy and safety of rhTNK-tPA in patients who had an ischaemic stroke due to large vessel occlusion (LVO) of anterior circulation beyond 4.5 hours.
METHODS AND DESIGN
Tenecteplase Reperfusion Therapy in Acute Ischaemic Cerebrovascular Events-III (TRACE III) is a multicentre, prospective, randomised, open-label, blind endpoint, controlled clinical trial. Patients who had an ischaemic stroke due to anterior circulation LVO (internal carotid artery, middle cerebral artery M1 and M2 segments) within 4.5-24 hours from last known well (including wake-up stroke and no witness stroke) and with salvageable tissue (ischaemic core volume <70 mL, mismatch ratio ≥1.8 and mismatch volume ≥15 mL) based on CT perfusion or MRI perfusion-weighted imaging (PWI) were included and randomised to rhTNK-tPA 0.25 mg/kg (single bolus) to a maximum of 25 mg or standard medical therapy. Specially, we will exclude patients who are intended for direct thrombectomy. All will be followed up for 90 days.
STUDY OUTCOMES
Primary efficacy outcome is modified Rankin Scale (mRS) score ≤1 at 90 days. Secondary efficacy outcomes include ordinal distribution of mRS at 90 days, major neurological improvement defined by a decrease ≥8 points compared with the initial deficit or a score ≤1 on the National Institutes of Health Stroke Scale (NIHSS) at 72 hours, mRS score ≤2 at 90 days, the rate of improvement on Tmax >6 s at 24 hours and NIHSS score change from baseline at 7 days. Safety outcomes are symptomatic intracerebral haemorrhage within 36 hours and mortality at 90 days.
DISCUSSION
TRACE III will provide evidence for the efficacy and safety of rhTNK-tPA in patients who had an ischaemic strokes due to anterior circulation LVO beyond 4.5 hours.
TRIAL REGISTRATION NUMBER
NCT05141305.
Topics: United States; Humans; Tenecteplase; Fibrinolytic Agents; Stroke; Brain Ischemia; Prospective Studies; Treatment Outcome; Ischemic Stroke; Reperfusion
PubMed: 37247876
DOI: 10.1136/svn-2023-002310 -
Emergency Medicine Clinics of North... Aug 2015Cardiogenic shock is the leading cause of morbidity and mortality in patients presenting with acute coronary syndrome. Although early reperfusion strategies are... (Review)
Review
Cardiogenic shock is the leading cause of morbidity and mortality in patients presenting with acute coronary syndrome. Although early reperfusion strategies are essential to the management of these critically ill patients, additional treatment plans are often needed to stabilize and treat the patient before reperfusion may be possible. This article discusses pharmacologic and surgical interventions, their indications and contraindications, management strategies, and treatment algorithms.
Topics: Adrenergic alpha-Agonists; Assisted Circulation; Cardiotonic Agents; Disease Management; Extracorporeal Circulation; Heart Failure; Humans; Reperfusion; Shock, Cardiogenic; Time Factors
PubMed: 26226871
DOI: 10.1016/j.emc.2015.04.013 -
Epilepsy & Behavior : E&B Mar 2020Seizures are not only a frequent complication of stroke but have been associated with an unfavorable functional and vital outcome of patients who have had stroke. Facing... (Review)
Review
Seizures are not only a frequent complication of stroke but have been associated with an unfavorable functional and vital outcome of patients who have had stroke. Facing a new paradigm of acute standard stroke care, acute symptomatic seizures in this clinical setting deserve to be rethought. Reperfusion therapies, the gold standard treatment for acute ischemic stroke, improve long-term survival and outcome of patients who have had stroke and have been associated both with clinical seizures and the occurrence of epileptiform activity in the electroencephalogram (EEG). This narrative review describes the different physiopathological mechanisms underlying the possible association between reperfusion therapies and seizures, both acute symptomatic seizures and unprovoked seizures, and the current evidence regarding the risk of poststroke seizures in treated patients. It also identifies the gaps in our knowledge to foster future studies in this field. By different mechanisms, reperfusions therapies may have opposing effects on the risk of poststroke seizures. There is a need for a better definition of the specific physiopathology of seizures in clinical practice, as many factors can be recognized. Additionally, most of the current clinical evidence refers to acute symptomatic seizures and not to unprovoked seizures or poststroke epilepsy, and our analysis does not support the existence of a strong association between thrombolysis and poststroke seizures. So far, the impact of reperfusion therapies on the frequency of poststroke seizures is unclear. To study this effect, many clinical challenges must be overcome, including a better and clear operational definition of seizures and stroke characteristics, the standard of stroke and epilepsy care and EEG monitoring, and the degree of reperfusion success. Prospective, high quality, larger, and longer follow-up multicentric studies are urgently needed. Additionally, stroke registries can also prove useful in better elucidate whether there is an association between reperfusion therapies and seizures. This article is part of the Special Issue "Seizures & Stroke".
Topics: Animals; Brain Ischemia; Case-Control Studies; Electroencephalography; Follow-Up Studies; Humans; Prospective Studies; Registries; Reperfusion; Retrospective Studies; Seizures; Stroke
PubMed: 31727547
DOI: 10.1016/j.yebeh.2019.106524