Heads Down for Acute Stroke: Supine Position for Acute Large Vessel Occlusion in Ischemic Stroke

Validation of the National Institutes of Health Stroke Scale-8 to Detect Large Vessel Occlusion in Ischemic Stroke

See related article, pages 1751–1758. Since the ischemic penumbra was discovered and since a therapeutic window for acute ischemic stroke has been postulated, stroke experts are looking for safe and effective drugs to treat as many acute ischemic stroke patients as possible. Maturation of ischemic damage is a complex process, triggered by hypoperfusion at critical levels and spontaneously evolving toward cell death. It is a self-perpetuating process in which some critical steps (such as ion pumps failure and iNOS production) maintain and enhance the process.1 Reperfusion may reverse the ischemic cascade but, at the same time, induces a further damage. The risk/benefit ratio of reperfusion depends on the amount of penumbral salvageable tissue, that is “individual” and only partially predictable.2,3 Spontaneous reperfusion may occur, and symptoms may reverse, partially or totally, but the percentages of spontaneous reperfusion so far reported account for approximately the 24% of all stroke cases.4 A review of published articles about cerebral angiography in stroke reported that the percentage of spontaneous reperfusion …

A multicenter randomized clinical trial of endovascular treatment for acute ischemic stroke caused by proximal arterial occlusion in the anterior circulation.

The development of additional effective therapies for acute ischemic stroke remains a challenging but critical endeavor. Intravenous recombinant tissue plasminogen activator (rtPA) initiated within 3 hours of stroke onset remains the only approved and validated therapy for acute ischemic stroke, and regulatory approval has expanded recently. Many other therapies have been evaluated, and these trials have either been inconclusive or negative.1 These acute stroke trials do provide valuable information concerning how to implement future trials and some glimmers of hope about existing data. Some of the lessons learned from prior acute stroke trials that will help to guide future trials are outlined below. The two fundamental approaches to the development of acute stroke therapy remain reperfusion and neuroprotection. This short review will focus on the current status of both approaches and how they might be combined, hopefully in the near future. Negative acute stroke treatment trials may be explained by the following: 1. The agents evaluated in clinical trials may not have been adequately tested in preclinical studies to provide robust confirmation of efficacy in appropriate animal models. 2. Side effects precluded adequate drug assessment or did not allow use of adequate drug concentrations. 3. Because of macro-occlusions and, perhaps, micro-occlusions, the drug did not penetrate into or beyond the penumbral tissue in adequate concentrations. 4. Trials included patients not appropriate for the purported mechanism of action of the drug being tested. 5. Patients were included too late after stoke onset to allow for adequate assessment of the drug’s efficacy, and imaging studies were not done to identify patients with appropriate tissue for treatment. 6. Trials have been inadequately powered to detect modest treatment effects. 7. Trials included too many patients with mild or very severe deficits in whom treatment effects are likely difficult to assess with currently used outcome measures. 8. The single primary outcome measure …

Marc Fisher MD Kennedy Lees MD Section Editors: On September 26, 2008, the New England Journal of Medicine published the results of the European Cooperative Stroke Study (ECASS) III,1 the first randomized, placebo-controlled trial to demonstrate safe and effective use of intravenous recombinant tissue plasminogen activator (rtPA) to treat patients with acute ischemic stroke (AIS) beyond 3 hours from stroke onset. The ECASS investigators studied the safety and efficacy of administering intravenous rtPA to patients with AIS 3 to 4.5 hours after AIS onset. Using the modified Rankin Scale score at 90 days after stroke occurrence as the primary end point of the study, the investigators demonstrated a modest, statistically significant increase in the likelihood of having normal or near normal recovery (modified Rankin Scale=0 or 1) in favor of rtPA treatment compared with placebo (unadjusted OR, 1.34; 95% CI, 1.02 to 1.76; P =0.04). So, what impact will the results of the study have on acute stroke management and stroke research in the United States and elsewhere? With regard to the first part of the question, the answer is complex. First, the ECASS III results will hopefully help to increase the number of thrombolysis eligible patients with AIS who receive rtPA. Twelve years after the US Food and Drug Administration approved the management of AIS within 3 hours of symptom onset as an indication for the use of intravenous rtPA, less than 5% of patients with AIS are being treated worldwide with rtPA within 3 hours of stroke onset. One of the major factors contributing to this parlous state of affairs has been disagreement among healthcare professionals about the validity of the results of the National Institutes of Neurological Disorders and Stroke (NINDS) trial of rtPA for acute stroke.2 In the late 1990s, the stroke community unexpectedly …

Evaluating Age, Sex, Racial, and Ethnic Representation in Acute Ischemic Stroke Trials, 2010 to 2020: A Systematic Review and Meta-Analysis.

Correction to: 2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association.

August 2020 Highlights.

Imaging

In the recent Humana Lecture,1 Harold Adams quoted what might be the prevailing sentiment guiding the search for a treatment for acute ischemic stroke: “When we have a treatment for stroke, we will know it.” The implicit assumption is that there is a treatment that will dramatically improve acute stroke outcome. The current approach to finding a treatment for ischemic stroke is based on single-agent trials, sponsored mainly by pharmaceutical companies, that may produce a “winner,” to be followed by a “therapeutic cocktail” to combat the complex events set in motion by cerebral ischemia. Progress in ischemic stroke treatment trials over the last two decades has included improved statistical design, radically shortened entry windows, standardized rating instruments, and shared sponsorship between industry and government. We wish to raise concerns about the current approach to testing new stroke treatments and the impact that changes in healthcare delivery in the United States may have on the conduct of acute stroke trials. The success of clinical research in the treatment of acute stroke depends not only on trial design but on local, regional, and national factors that determine the environment in which acute stroke care is provided and that affect the feasibility of trial execution. In this editorial, we present some of the important issues facing those who design and implement acute stroke treatment studies. Our opinions pertain primarily to the medical environment in the United States. Our goal is to stimulate discussion and suggest a forum for the critical evaluation of trial design issues and also the development of a national strategy for stroke. We are concerned about the optimal use of critical resources needed to conduct stroke treatment trials. By “resources” we mean the investigators and stroke research teams; acute stroke patients available for enrollment; cooperative referring doctors and emergency-services …

Vasculocentricity Versus Cerebrocentricity: What Stroke-Related Baroreceptor Reflex Sensitivity Changes Might Be Telling Us

Emerging Therapies for Cerebrovascular Disorders

Introduction: Intravenous recombinant tissue plasminogen activator (rtPA) treatment for acute ischemic stroke works by achieving recanalization of intracranial occlusion resulting in restoration of flow and prevention of infarct expansion. Data on recanalization after intravenous thrombolysis are performed by angiographic methods and transcranial Doppler monitoring studies. We aimed to report one case of complete recanalization of large vessel occlusion in ischemic stroke with intravenous thrombolysis with rtPA. Case report: Pacient, 27 years old, male, brown, with coronary artery disease and ischemic cardiomyopathy, with clinical presentation of weakness in the left side and speech alteration 75 minutes ago, with National Institutes of Health Stroke Scale (NIHSS) of 9 points. At admission, magnética ressonante imaging of the head showed restriction in the diffusion-wighted imaging sequence in basal ganglia and internal capsule topography, with magnetic resoance angiography (MRA) showing a stop in the M1 segment of the right middle cerebral artery (MCA). The patient underwent IV thrombolysis with rtPA 160 minutes after the ictus, uneventfully (NIHSS 0 points at the end of treatment). Control MRA (four hours after thrombolysis) showed complete recanalization of the M1 segment of the right MCA. Discussion: Despite the known limitation of intravenous rtPA in recanalization of large vessel occlusion and the increasing use of mechanical thrombectomy, it is necessary to value the role of intravenous thrombolysis in this setting, considering the difficulties in accessing endovascular treatment still present in our country. More studies are needed on recanalization rates ntravenous thrombolysis in large vessel occlusion cases.

Background: Stent retriever technology has evolved, and significantly longer devices have become available for mechanical thrombectomy (MT) of large cerebral vessel occlusions in ischemic stroke. We hypothesized that increased stent retriever length may improve the rate of complete angiographic reperfusion and decrease the respective number of attempts, resulting in a better clinical outcome. Methods: Retrospective analysis of patients with large vessel occlusion in the anterior and posterior circulation treated with stent retriever MT. The study group was dichotomized into short (20 mm) and long (>20 mm) retrievers using propensity matching. In the anterior circulation, the clot burden score was evaluated. Primary end points were first-pass modified thrombolysis in cerebral infarction (mTICI) 3 reperfusion and first-pass mTICI ≥ 2b reperfusion, and the secondary end point was functional independence (defined as modified Rankin Scale score 0–2) at discharge and 90 days. Results: Overall, 394 patients were included in the analysis. In the anterior circulation, short stent retrievers had a significantly higher rate of first-pass reperfusion in cases with low clot burden (mTICI 3: 27% vs. 17%; p = 0.009; mTICI ≥ 2b: 42 vs. 30%; p = 0.005) and in middle cerebral artery occlusions (mTICI ≥ 2b: 51 vs. 41%; p = 0.024). Higher rates of favorable outcome at discharge and 90 days were observed for the short stent retriever group (p < 0.001). Conclusion: Stent retriever length should be adjusted to clot burden score and vessel occlusion site.

Dramatic changes have occurred in the area of critical care and emergency stroke treatments of intracerebral hemorrhage (ICH). New data from three sponsored clinical trials: STICH (British National Health System-Medical Research Council), NOVO Seven (Novonordisk), and intraventricular hemorrhage (IVH) clot lysis (FDA Orphan Drug Program)1 were presented at the 29th International Stroke Meeting2 and the World Stroke Congress. Several avenues of approach to the problem of ICH are opening. Although the data from these trials are now under peer review, the initial presentations have demonstrated several principles that seem clear. First, craniotomy (though not better than initial medical management) is safe and not worse than initial medical management. Second, deterioration occurs frequently (≈25% of the time) in the initial days after ICH. Deterioration was treated with surgery. Third, a strategy of emergent clot stabilization is safe and shows trends toward efficacy in the NOVO Seven dose finding study.2 Finally, catheter-assisted removal of blood clot from the obstructed ventricular system in IVH can be accomplished safely with low dose recombinant tissue plasminogen activator (rtPA).3 These trial results suggest that the basic elements of aneurysm care are now being applied to ICH care: emergent stabilization of the bleeding site, followed by removal of blood and management of cranial vault mechanics. Data are now beginning to support that applying these principles leads to improvement in mortality and morbidity. We hope that the robustness of the peer-reviewed data continues to point to the value of emergent intervention for the ICH patient. New sponsored trials have already started: CLEAR IVH, a phase IIb dose optimization trial directed at finding the best dose of rtPA to rapidly remove blood from the ventricles (FDA Orphan drug program)4; MISTIE, an NIH sponsored phase II safety study of minimally invasive surgery plus …