Adequate Knowledge of Stroke Symptoms, Risk Factors, and Necessary Actions in the General Population of Southern Poland

The cut of the clot(h): snake venom fibrinogenases as therapeutic agents.

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the catheter is removed, and the helical configuration assumed by the wire; the clot is then trapped in the helix and withdrawn from the vasculature (Figure 2).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 …

Results of two randomized trials did not show benefit of revascularization with extracranial-intracranial (EC-IC) flow augmentation bypass in patients with symptomatic occlusion of internal carotid artery (ICA). However, patients with acute stroke were not included in these studies. Herein, we systematically analyze and discuss the literature about flow augmentation bypass for treatment of acute ischemic stroke. This systematic review followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. MEDLINE, Web of Science and EMBASE were independently searched by two reviewers for published series to identify literature relating to EC-IC bypass in the surgical management of acute ischemic stroke up to June 2020. Studies were categorized according to their level of evidence. Nineteen studies met the inclusion criteria for the systematic literature review, including 16 level IV studies (ten case series and six6 case reports) and three level III studies (retrospective cohort case-control studies). Occurrence of fatal or non-fatal ischemic or hemorrhagic postoperative stroke, as well as clinical functional outcome at follow-up were considered as primary and secondary endpoints, respectively. The literature about flow augmentation bypass for treatment of acute ischemic stroke is scarce and heterogenous, with only 19 studies. The results of the present systematic review encourage further study to explore and validate the use of EC-IC bypass in the treatment of anterior circulation acute ischemic stroke in highly selected patients (symptomatic and with persistent penumbra despite best medical/endovascular treatment).

BackgroundStroke is the most common acquired neurological disease in the adult population worldwide with an incidence of 16 million new cases every year responsible for about 6.1 million deaths and 130.6 million disability-adjusted life-years (DALYs). The objectives of this work were to study the level of stroke awareness and the proper response for suspected stroke patients in urban and rural areas of Tanta City, Egypt. The study was conducted on 1869 Egyptian Citizens; 908 and 961 reside in urban and rural areas, respectively, who were submitted to a face-to-face interview using the stroke awareness questionnaire (Arabic version).ResultsRural participants showed a significant reduction in acute cerebrovascular stroke (CVS) awareness and knowledge including the most affected organ by CVS, what are the risk factors, what are the early stroke symptoms, is there specific treatment for acute ischemic stroke, and what is the proper reaction when confronted with a case of acute CVS?ConclusionUrban populations have better recognition of stroke risk factors, early stroke symptoms, and the proper response when confronted with a case of acute CVS when compared with rural people possibly due to better socioeconomic status and higher educational levels.

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 …

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

Stroke is the third leading cause of death and a leading cause of adult disability in the United States.1 From a global perspective, stroke is also a leading cause of death and disability. The past 20 years have seen significant improvements in stroke prevention, yet each year, >700 000 people have a new or recurrent stroke.2,3 The medical and societal costs of stroke exceed $62 billion in the United States alone.4 Any intervention that could reverse or limit the effects of a stroke would have dramatic medical, societal, and public health benefits. This section will focus on treatment of acute ischemic stroke, which accounts for 80% to 85% of all strokes. Other recent publications have focused on therapies for intracerebral hemorrhage. Acute interventions to reduce the effects of an ischemic stroke can be organized into several main approaches: (1) reperfusion strategies (lytics, endovascular/mechanical); (2) neuroprotection; and (3) restoration, regeneration, and rehabilitation. ### Medical Therapies Thrombolytic therapies for acute ischemic stroke have been used or under study for 30 to 40 years, yet only recently has an agent been approved by the US Food and Drug Administration (FDA) and included in the treatment guidelines. Intravenous recombinant tissue plasminogen activator (rtPA) is the only FDA-approved medical therapy proven to reduce the effects of an ischemic stroke.5,6 Its main mechanism of action is to lyse a clot that is occluding a cerebral vessel, thereby reperfusing distal ischemic brain tissue and preventing or limiting the area of cell death and tissue necrosis. The efficacy of intravenous rtPA was proven in the pivotal National Institute of Neurological Disorders and Stroke (NINDS) rtPA study, which showed improved outcomes for patients treated within 3 hours of stroke onset.7 The NINDS tissue plasminogen activator (tPA) trial had an efficacy end point that was equivalent to the …

Objective To analyse the risk factors for tirofiban efficacy in the early treatment of acute ischemic stroke. Methods The clinical data of 204 patients with acute ischemic stroke treated with tirofiban were retrospectively analysed. The early efficacy of tirofiban was assessed by a ≥ 4-point decline in the National Institutes of Health Stroke Scale (NIHSS) score or via the complete disappearance of neurological deficits at the end of ischemic stroke treatment, and patients were divided into an effective groupand an ineffective group. Univariate and multivariate logistic regression analyses were used to compare the differences in clinical data between the two groups. Results Multivariate logistic regression analysis showed that heavy drinking (OR 0.477, 95% CI 0.249–0.899, P = 0.023), elevated total cholesterol (OR 0.331, 95% CI 0.141–0.734, P = 0.008), NIHSS score at initiation of treatment (OR 1.130, 95% CI 1.026–1.253, P = 0.016) and time from onset to treatment (OR 0.839, 95% CI 0.700–0.979, P = 0.038) were independent risk factors affecting the early efficacy of tirofiban. Conclusion The early curative effect of tirofiban in acute ischemic stroke patients with a heavy drinking history and elevated total cholesterol was poor. In patients with acute ischemic stroke, the higher the NIHSS score was within a certain range (8 < NIHSS ≤15 and the Org 10,172 Trial in the Treatment of Acute Stroke (TOAST) belongs to small-artery occlusion lacunar) at the initiation of treatment and the shorter the time from onset to treatment, the better the early curative effect was.

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.

Background and Purpose- To assess the effect of inter-hospital transfer on time to treatment and functional outcome after endovascular treatment (EVT) for acute ischemic stroke, we compared patients transferred from a primary stroke center to patients directly admitted to an intervention center in a large nationwide registry. Methods- MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) Registry is an ongoing, prospective, observational study in all centers that perform EVT in the Netherlands. We included adult patients with an acute anterior circulation stroke who received EVT between March 2014 to June 2016. Primary outcome was time from arrival at the first hospital to arterial groin puncture. Secondary outcomes included the 90-day modified Rankin Scale score and functional independence (modified Rankin Scale score of 0-2). Results- In total 821/1526 patients, (54%) were transferred from a primary stroke center. Transferred patients less often had prestroke disability (227/800 [28%] versus 255/699 [36%]; P=0.02) and more often received intravenous thrombolytics (659/819 [81%] versus 511/704 [73%]; P<0.01). Time from first presentation to groin puncture was longer for transferred patients (164 versus 104 minutes; P<0.01, adjusted delay 57 minutes [95% CI, 51-62]). Transferred patients had worse functional outcome (adjusted common OR, 0.75 [95% CI, 0.62-0.90]) and less often achieved functional independence (244/720 [34%] versus 289/681 [42%], absolute risk difference -8.5% [95% CI, -8.7 to -8.3]). Conclusions- Interhospital transfer of patients with acute ischemic stroke is associated with delay of EVT and worse outcomes in routine clinical practice, even in a country where between-center distances are short. Direct transportation of patients potentially eligible for EVT to an intervention center may improve functional outcome.

Role of Abciximab in the Management of Acute Ischemic Stroke

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, …

HomeStrokeVol. 50, No. 9Letter by Seners and Baron Regarding Article, “Effect of Interhospital Transfer on Endovascular Treatment for Acute Ischemic Stroke” Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBLetter by Seners and Baron Regarding Article, “Effect of Interhospital Transfer on Endovascular Treatment for Acute Ischemic Stroke” Pierre Seners, MD, PhD and Jean-Claude Baron, MD, ScD Pierre SenersPierre Seners Neurology Department, Sainte-Anne Hospital, INSERM U1266, Université de Paris, France Search for more papers by this author and Jean-Claude BaronJean-Claude Baron Neurology Department, Sainte-Anne Hospital, INSERM U1266, Université de Paris, France Search for more papers by this author Originally published5 Jul 2019https://doi.org/10.1161/STROKEAHA.119.026088Stroke. 2019;50:e259Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: July 5, 2019: Ahead of Print To the Editor:In their article, Venema et al1 assessed the effects of inter-hospital transfer on (1) time to treatment and (2) functional outcome, in acute stroke patients with large vessel occlusion (LVO) undergoing endovascular treatment (EVT). They compared these 2 outcomes between patients directly admitted to an EVT-capable center (mothership) and those transferred to such center from a non-EVT-capable center (drip-and-ship), using the MR-CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) Registry, a nationwide prospective observational study of all patients treated with EVT across the Netherlands since EVT became standard-of-care. This registry includes all patients who receive groin puncture, regardless of whether the procedure was pursued or stopped at this stage.They found that (1) time from arrival at the first hospital to groin puncture was significantly longer in the drip-and-ship patients and (2) drip-and-ship patients less often achieved functional independence (modified Rankin Scale score 0–2, 34% versus 42%, respectively; adjusted odds ratio: 0.69 [95% CI, 0.54–0.89]). They conclude “Direct transportation of patients potentially eligible for EVT to an intervention center may improve functional outcome.”1An important feature of Venema et al’s1 study—intrinsic to the MR-CLEAN registry—is that only LVO patients who received groin puncture were considered, that is, the fraction of drip-and-ship patients transferred for potential EVT but who did not undergo groin puncture were excluded a priori. Indeed, as the authors indicate, patients who deteriorated or substantially improved during transfer underwent repeat computed tomography/computed tomography angiography on arrival at the EVT center,1 and those with early recanalization did not proceed to groin puncture and were, therefore, excluded. Given that 77% of their cohort received intravenous thrombolysis (IVT), this design likely impacted their results because post-IVT recanalization within 3hours of IVT start occurs in ≈20% of drip-and-ship patients,2,3 and early post-IVT recanalizers have lower baseline National Institutes of Health Stroke Scale, shorter thrombus and more distal occlusions,2,4 implying better functional outcomes. Consequently, excluding from the MR-CLEAN registry those drip-and-ship patients who have recanalized on repeat pre-EVT imaging inevitably leads to underestimating the functional outcome of real-life drip-and-ship patients. In their discussion, Venema et al1 briefly mention this limitation but do not discuss its potential impact, and go on to generalize their conclusion to the overall LVO stroke care pathway, whereas their findings apply only to those LVO patients who effectively undergo groin puncture.A similar design was also used in another study5 based on the STRATIS (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke) Registry of EVT-treated patients, which excludes all early recanalizers even if they underwent groin puncture. Unsurprisingly, it also found better 3-month functional outcome in the mothership subgroup.5 In contrary, another study on IVT-treated patients referred for EVT—including those who eventually did not receive EVT—, reported similar 3-month functional outcome in mothership and drip-and-ship patients.3Considering the time-dependence of the functional benefit from EVT and the longer treatment delays inherent to the drip-and-ship paradigm,1,3,5 better functional outcome may indeed exist in patients treated according to the mothership, as compared with the drip-and-ship, paradigm. However, Venema et al’s1 study only concerned the subset of LVO stroke population eligible for EVT who received groin puncture, and for the reasons explained above likely overestimated this difference. Ongoing trials are expected to provide the real effect of paradigm on functional outcome.Pierre Seners, MD, PhDJean-Claude Baron, MD, ScDNeurology DepartmentSainte-Anne HospitalINSERM U1266, Université de ParisFranceDisclosuresNone.FootnotesStroke welcomes Letters to the Editor and will publish them, if suitable, as space permits. Letters must reference a Stroke published-ahead-of-print article or an article printed within the past 4 weeks. The maximum length is 750 words including no more than 5 references and 3 authors. Please submit letters typed double-spaced. Letters may be shortened or edited.

Intravenous thrombolysis with tissue plasminogen activator is currently the most effective treatment of acute ischemic stroke if administerd within 3 hours after symptom onset. Intraarterial thrombolysis by prourokinase is the another choise if the middle cerebral artery is occluded and within less than 6 hours after onset. Although heparin especially a moderate dose is not proved to be effective, a randomized, placebo-controlled trial to determine the safety and efficacy of argatroban (a selective thrombin inhibitor) in patients with acute ischemic stroke was started in USA. Aspirin provides some benefit to patients with acute stroke. However, its effect is not fully satisfactory. Although reports of numerous trials for neuroprotective drugs have been disappointing, edaravone (free radical scavenger) was approved for the treatment of acute ischemic stroke in Japan. In the future, thrombolytic and neuroprotective drugs will be used in combination.