Computational Modeling of Flow in an in Vitro Cerebrovascular Model Under Pulsatile Conditions with Experimental Validation

Role of Abciximab in the Management of Acute Ischemic Stroke

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.

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 …

Imaging

This article presents an investigation into the validation of velocity fields obtained from computational fluid dynamic (CFD) models of flow through the membrane oxygenators using x-ray digital subtraction angiography (DSA). Computational fluid dynamic is a useful tool in characterizing artificial lung devices, but numerical results must be experimentally validated. We used DSA to visualize flow through a membrane oxygenator at 2 L/min using 37% glycerin at 22°C. A Siemens Artis Zee system acquired biplane x-ray images at 7.5 frames per second, after infusion of an iodinated contrast agent at a rate of 33 ml/s. A maximum cross-correlation (MCC) method was used to track the contrast perfusion through the fiber bundle. For the CFD simulations, the fiber bundle was treated as a single momentum sink according to the Ergun equation. Blood was modeled as a Newtonian fluid, with constant viscosity (3.3 cP) and density (1050 kg/m3). Although CFD results and experimental pressure measurements were in general agreement, the simulated 2 L/min perfusion did not reproduce the flow behavior seen in vitro. Simulated velocities in the fiber bundle were on average 42% lower than experimental values. These results indicate that it is insufficient to use only pressure measurements for validation of the flow field because pressure-validated CFD results can still significantly miscalculate the physical velocity field. We have shown that a clinical x-ray modality, together with a MCC tracking algorithm, can provide a nondestructive technique for acquiring experimental data useful for validation of the velocity field inside membrane oxygenators.

Section Editors: Graeme J. Hankey MD, FRCP Acupuncture is widely used in the treatment of stroke in China and it is increasingly requested by patients in some Western countries. Experimental data indicate that acupuncture-like sensory stimulation activates multiple efferent (nerve) pathways leading to altered activity in numerous neural systems. The objectives of this study were to assess the effectiveness and safety of acupuncture in patients with acute stroke. We searched the Cochrane Stroke Group Trials Register (last searched August 2003), the Chinese Stroke Trials Register (August 2003), and the Chinese Acupuncture Trials Register (August 2003). Electronic searches were performed in the Cochrane Controlled Trials Register (The Cochrane Library, Issue 3, 2003), MEDLINE (1966 to 2003), EMBASE (1980 to 2003), …

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

Strokes attributable to basilar artery occlusion are fortunately uncommon but have a high risk of death or severe disability. Presentation is highly variable, and initial misdiagnosis by nonspecialists of patients with warning or progressive symptoms is common. Sometimes patients present at a late stage where intervention is unlikely to be successful. Hence, management of these patients is particularly challenging to vascular neurologists and stroke physicians. What do we know about basilar artery occlusion? As in anterior circulation ischemic strokes, “time is brain” and outcome depends on time to treatment, clinical state at presentation and whether and how quickly recanalization occurs. Without recanalization good recovery virtually never occurs. The rarity of basilar artery occlusion is reflected by the paucity of randomized controlled trials. One small randomized controlled trial of intra-arterial urokinase against anticoagulation in 16 patients with posterior circulation stroke suggested intra-arterial urokinase was associated with a better outcome.1 However, the main evidence base available to decide on the …

Introduction: Selective endovascular brain hypothermia has been proposed as a potential neuroprotective strategy; however, its effectiveness is still not well established. The primary objective of this trial is to investigate the efficacy and safety of selective endovascular brain hypothermia with edaravone dexborneol for endovascular treatment in acute ischemic stroke (AIS). Methods: The SHE study is a multicenter, single-blind, randomized controlled clinical trial. Patients with acute anterior circulation ischemic stroke who received endovascular treatment within 24 h after stroke onset and achieved successful recanalization will be enrolled and centrally randomized into combined selective endovascular brain hypothermia with edaravone dexborneol or edaravone dexborneol alone groups in a 1:1 ratio (n = 564). Patients allocated to the hypothermia group will receive 300 mL cool saline at 4°C through guiding catheter (30 mL/min) into target vessel within 3 min after recanalization and then receive edaravone dexborneol (edaravone dexborneol 15 mL + NS 100 mL ivgtt bid for 10–14 days) within 24 h after admission. The control group will receive 300 mL 37°C saline (30 mL/min) infused into target vessel through guiding catheter and then receive edaravone dexborneol. All patients enrolled will receive standard care according to current guidelines for stroke management. The primary outcome is the proportion of functional independence, defined as a mRS score of 0–2 at 90 days after randomization. Conclusion: This is a randomized clinical trial with a large sample size to compare combined selective endovascular brain hypothermia and edaravone dexborneol with edaravone dexborneol alone in patients with acute anterior ischemic stroke. The SHE trial aims to provide further evidence of the benefit of selective endovascular brain hypothermia in AIS patients who received endovascular treatment.

Computed Tomography Perfusion Imaging in Acute Ischemic Stroke: Accurate Interpretation Matters.

Objective To explore the clinical effects of simvastatin combined with aspirin in treatment of acute ischemic stroke (AIS).Methods From December 2010 to December 2011 98 patients with AIS treated in our hospital were randomly divided into simvastatin group and combination treatment group,simvastatin group only received simvastatin treatment,combination treatment group used simvastatin treatment based on given aspirin treatment,the clinical efficacy was compared in patients of two groups.Results After treatment by groups,29 cases,effective in 12 cases,8 cases were invalid,the total efficiency was 83.67％;the combination treatment group 33 cases,effective in 14 cases,2 cases were invalid,the total efficiency rate was 95.92％.The total effective rate in combination treatment group was significantly higher than that of simvastatin group,with statistical significant difference (x 2=25.14,P＜0.05).Conclusion Simvastatin treatment combined with aspirin therapy in treating patients with AIS can significantly improve the clinical treatment effect,which is worth popularizing. Key words: Simvastatin; Aspirin; Combination; Acute cerebral ischemic stroke (AIS)

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 …

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Should Tenecteplase be Given in Clinical Practice for Acute Ischemic Stroke Thrombolysis?