Abstract W P19: Large Single Center Experience of Safety of Parenteral Infusion and Maintenance of Antiplatelets in Patients with Acute Ischemic Stroke undergoing Mechanical Thrombectomy and Thrombolysis

A 42-year-old woman was referred to our institution with sudden onset of ataxia, facial paresis, horizontal gaze palsy, and progressive dysarthria. The patient worsened within a few minutes, with appearance of left hemiparesis. The National Institutes of Health Stroke Scale Score was 13. On computer tomography scan 2 hours after stroke onset, no brain stem lesion or intracranial bleeding was visible. Computed tomographic angiography revealed a mid basilar vessel occlusion, which suggested embolic basilar artery occlusion. A 4-vessel angiogram with a 5F diagnostic catheter confirmed the basilar artery occlusion and depicted more precisely the location of the thrombus (Figure 1A). Figure 1. A, Digital subtraction angiography after vertebral injection demonstrates a mid basilar vessel occlusion. B, The angiogram after placement of the stent from the left P1 segment (white arrow) into the basilar artery showed flow restoration of the basilar artery with a narrowing in the middle part of the vessel due to compression of the thrombus into the arterial wall (black arrows). C, …

Section Editors: Marc Fisher MD Antoni Davalos MD The Food and Drug Administration (FDA) evaluates applications for new human drugs, biologics, and complex medical devices. Companies must obtain FDA approval to legally market these products. In August, the FDA gave Concentric Medical clearance to market its Merci Retriever system to “remove blood clots from the brain in patients experiencing an ischemic stroke.” Given that the FDA is charged with “protecting the public health by assuring the safety, efficacy, and security of… biological products and medical devices…, ” “advancing public health by helping to speed innovations that make medicines … more effective, safer, and more affordable,” and “helping the public get the accurate, science-based information they need to use medicines … to improve their health,”1 the FDA’s decision to approve the Merci Retriever system is of concern. The pathways to approval are reviewed by Felten et al in the accompanying article and are outlined in Figure 1. Figure 1. Potential pathways for device approval. The decision to approve the Merci Retriever was based on data from the MERCI (Mechanical Embolus Removal in Cerebral Ischemia) Trial; the approval was granted through the 510(k) process. The Merci Retriever system includes a flexible nickel titanium (nitinol) wire that obtains a helical shape once it is passed through the tip of the guidance catheter. In practice, the catheter/wire is passed distal to the thrombus, the catheter is removed, and the helical configuration assumed by the wire; the clot is then trapped in the helix and withdrawn from the vasculature (Figure 2). The 510(k) clearance means that the Merci Retriever was felt to be substantially equivalent to a predicate device. In this case, the predicate device was the Concentric Retriever, which itself received 510(k) clearance by the FDA in May 2001 for “use in …

Direct to Thrombectomy.

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 …

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.

Large Vessel Occlusion Strokes After the DIRECT-MT and SKIP Trials: Is the Alteplase Syringe Half Empty or Half Full?

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 …

Role of Abciximab in the Management of Acute Ischemic Stroke

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 …

Intracranial bleeding is the most feared complication of thrombolytic therapy in acute stroke. The risk of brain hemorrhage is the main argument of the European authorities not to approve recombinant tissue plasminogen activator (rtPA), and the fear of hurting patients with rtPA explains its limited use in North America. The common argument is, “Treatment with rt-PA may have some beneficial effect, but that is traded off by a considerable risk of symptomatic hemorrhage.” This argument is false and based on misunderstanding and misconception. The misunderstanding: There is no such trade-off. The National Institute of Neurological Disorders and Stroke (NINDS) rtPA Stroke Study Group observed 2 patients (0.6%) with symptomatic and 1 patient (0.3%) with fatal hemorrhages in the placebo group (n=312) and 20 patients (6.4%) with symptomatic and 9 patients (2.9%) with fatal hemorrhages in the rtPA group (n=312).1 Despite this supposed excess in risks caused by rtPA treatment (odds ratios [OR], 10.6 and 9.2), rtPA treatment significantly reduced the risk for disability and death (modified Rankin Scale >1 at 12 months after stroke) from 73% to 59% (reduction for death alone: 28% to 24%).2 In both European Cooperative Acute Stroke Studies (ECASS) 1 and 2, rtPA increased the risk for parenchymal hematomas (OR, 3.0 and 4.2), but reduced the overall risk for disability and death by 6% and 8% (NS).3,4⇓ A similar observation—an overall risk reduction for disability and death despite an increased risk for intracranial hemorrhages—was made in the Multicenter Acute Stroke Trials (MAST) -Europe and -Italy. Why …

Several studies regarding the treatment of both acute ischemic and hemorrhagic stroke, and the secondary prevention have been completed and presented in the first few months of this year. The main results of these controversial studies are discussed in this article. Neurothrombectomy is the new standard in the treatment of acute ischemic stroke. During the 9th World Stroke Congress in Istanbul, the treatment of acute stroke entirely changed with presentation of the positive results of the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MrClean) study on October 28th, 2014, regarding the effectiveness of thrombectomy. Following the announcement of these positive results, data collection in other thrombectomy studies with similar designs was aborted and the results were subjected to analysis; all neurologists became enthusiastic about the positive results for which they had been waiting for (1). However, this enthusiasm has waned after a more careful evaluation of the situation, because many countries, including Turkey, do not have the economic capacity to broadly and ethically implement this treatment. Therefore, it is believed that it is time to reorganize and implement the national acute stroke treatment system (2). The use of previous methods is no longer possible. The results were striking and they cannot be ignored. The highly effective reperfusion evaluated in Multiple Endovascular Stroke collaboration pooled data from five trials and found that the number needed to treat with endovascular thrombectomy to reduce disability by at least one level on the modified Rankin scale for one patient was 2.6 (3). Of course, this rate is a very rare; a fairly low rate in medicine. However, thrombectomy should be performed within 6-12 hours after stroke, so patients must be referred to eligible treatment centers within this short period of time known as the “therapeutic window.” In this case, regional regulations and national dissemination seems to be obligatory. Stroke can be observed everywhere, not only in metropoles, and every patient with severe stroke can only be treated in this way. Turkey was one of the last countries in Europe to initiate intravenous thrombolytic treatment. To avoid a similar situation in thrombectomy, and for the benefit of our patients and people, this scientific data must be implemented in Turkey with a collaborative and multidisciplinary approach. It is clear that Turkish Neurological Society should undertake the most critical role in this context. Low-dose intravenous thrombolytic treatment is not more effective in acute ischemic stroke. In the Enhanced Control of Hypertension and Thrombolysis Stroke Study, low-dose (0.6 mg/kg) and standard dose (0.9 mg/ kg) intravenous tissue plasminogen activator (tPA) were compared in 3.310 patients within 4.5 hours of the onset of stroke (4). The primary outcome was death or disability at 90 days, and was found similar in both groups (53.2% with low-dose tPA and 51.1% with standard dose). However, although mortality rates were less with low-dose, disability rates tended to be higher. This study suggests that 19 patients would not die if 1.000 patients were given low-dose tPA instead of a standard dose, but an extra 40 patients would be disabled. Also, major symptomatic intracerebral hemorrhage was less with low-dose tPA (1% vs. 2.1%). Although

Background For patients with acute ischemic stroke undergoing endovascular mechanical thrombectomy with x-ray angiography, the use of adjuncts to maintain vessel patency, such as stents or antiplatelet medications, can increase risk of periprocedural complications. Criteria for using these adjuncts are not well defined. Purpose To evaluate use of MRI to guide critical decision making by using a combined biplane x-ray neuroangiography 3.0-T MRI suite during acute ischemic stroke intervention. Materials and Methods This retrospective observational study evaluated consecutive patients undergoing endovascular intervention for acute ischemic stroke between July 2019 and May 2020 who underwent either angiography with MRI or angiography alone. Cerebral tissue viability was assessed by using MRI as the reference standard. For statistical analysis, Fisher exact test and Student t test were used to compare groups. Results Of 47 patients undergoing acute stroke intervention, 12 patients (median age, 69 years; interquartile range, 60-77 years; nine men) underwent x-ray angiography with MRI whereas the remaining 35 patients (median age, 80 years; interquartile range, 68-86 years; 22 men) underwent angiography alone. MRI results influenced clinical decision making in one of three ways: whether or not to perform initial or additional mechanical thrombectomy, whether or not to place an intracranial stent, and administration of antithrombotic or blood pressure medications. In this initial experience, decision making during endovascular acute stroke intervention in the combined angiography-MRI suite was better informed at MRI, such that therapy was guided in real time by the viability of the at-risk cerebral tissue. Conclusion Integrating intraprocedural 3.0-T MRI into acute ischemic stroke treatment was feasible and guided decisions of whether or not to continue thrombectomy, to place stents, or to administer antithrombotic medication or provide blood pressure medications. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Lev and Leslie-Mazwi in this issue.

Treatment of blood pressure in acute stroke is controversial, whether attempts are made to reduce or to increase blood pressure. Few clinical studies are available to guide clinicians. A Cochrane review1 on deliberately altering blood pressure within 2 weeks of stroke onset found 5 small trials, involving 218 patients randomized to nimodipine, nicardipine, captopril, clonidine, glyceryl trinitrate, or perindopril versus placebo or control treatment. The limited number of data made it impossible to assess the relationship between blood pressure and clinical outcome. Ahmed et al2 made a post hoc analysis on the effect of intravenous nimodipine in acute ischemic stroke within 24 hours. They found that a reduction of diastolic blood pressure of about 15 mm Hg was associated with poor outcome, whereas a spontaneous fall in the placebo group of about 8 …

Objective: Most acute stroke treatment trials exclude patients above the age of 80. Given the clear benefit of revascularization with intravenous tissue plasminogen activator (IV tPA) and mechanical thrombectomy (MT), we sought to assess functional outcomes in patients treated above the age of 80. Methods: We conducted a review of all patients admitted to Houston Methodist Hospital between January 2019 and August 2020 with an acute ischemic stroke (AIS) presentation[MOU1] for whom premorbid, discharge, and 90 day modified Rankin Scale scores were available. Patients were categorized by acute stroke treatment (IV tPA, MT, both or none[MOU2] ). mRS values were assessed during admission prior to discharge and at 90 days post stroke event. A delta mRS (Discharge vs. 90-day [MOU3] ) was defined and grouped as no change, improved, or worsened to assess overall functional disability in regards to the index stroke presentation. Results: A total of 865 patients with AIS presentation were included, of whom 651 (75.3%) were <80 years and 214 (24.7%) were > 80 years of age at presentation. A total of 208 patients received IV tPA, 176 underwent revascularization with MT only, 71 had both treatments, and 552 had no acute intervention. In patients >80 yrs who had no acute stroke intervention. mRS improvement was noted in 71.4% compared to 54.1% observed in those patients <80 years. Among patients who received IV tPA, 81.5% of > 80 years improved vs. 61.6% in the younger cohort. A similar trend was noted in the MT and combined treatment groups (76.2% vs. 71.2% and 78.6% vs. 79.3%, respectively). Conclusion: Based on our cohort of acute stroke patients, there was no significant difference in outcomes (as measured by delta mRS) for octogenarians and nonagenarians when compared to younger patients. There was a trend towards improvement in the elderly patients. Chronological age by itself may be an insufficient predictor of functional outcome among stroke patients and age cutoffs for enrollment of patients in acute stroke trials may need additional considerations.

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 …