Aspirin Resistance and Ischemic Stroke.

Objective: Acetylsalicylic acid (ASA) is the most widely used antiplatelet agent in treating ischemic strokes. ASA resistance varies between the populations, from 5% to 60%. We aimed to determine the prevalence of ASA resistance in our population, its association with demographic characteristics, risk factors, and the occurrence of recurrent ischemic stroke (IS). (IST). Methods: One hundred consecutive patients with primary or recurrent IS were prospectively included. Strokes were diagnosed with computed tomography (CT) or magnetic resonance imaging (MRI). In all patients a detailed history of cardiovascular risk factors and fasting blood analyzes (blood count, glycemia, HbA1c, degradation products, lipid profile) were taken, and the ASA resistance was examined with the Innovance PFA 200 system. The ASA resistance was examined after a minimum of 1 month of regular use of ASA 100 mg per day. Results: The prevalence of ASA resistance was 32%. ASA-resistant patients were statistically significantly older (69.9±7.5 vs, 61±1 y., p<0.05), and of male gender (75 vs, 45.6%, p<0.05). Previous cardiovascular diseases were statistically significantly more common in the ASA-resistant patients compared to the ASA-sensitive patients (46.8 vs 26.5%, p<0.05). The presence of recurrent stroke in the ASA-resistant versus ASA-sensitive patients was statistically significant (75% vs. 22.05%, p<0.0001). There was no statistically significant difference in the investigated laboratory parameters and the risk factors between the ASA-resistant and the ASA-sensitive patients. Conclusion. The prevalence of ASA resistance in our population is high. According to our results, ASA resistance testing should be done in the older male individuals with a previous burden of cardiovascular diseases.

Use of MLC901 in cerebral venous sinus thrombosis: Three case reports.

BACKGROUND: Cerebral venous sinus thrombosis (CVT) is rare cause of cerebrovascular disease. The incidence is 0.5% of all stroke. The majority of affected patients are young adults (mean age: 35-40 years) with mild to moderate disabilities. Poor outcome with severe disability is seen in 13% of cases. Early diagnosis and treatment are important for good outcomes and preventing complications. Treatment options are limited and mostly based on consensus. NeuroAiD II™ (MLC901; Moleac Pte, Ltd, Singapore) has a potential beneficial role in post-stroke recovery, by aiding the natural brain recovery process. CASE SUMMARY: MLC901 consists of nine natural herbal ingredients. Studies have shown its safety profile and aid in post stroke recovery. The aim of this case series was to demonstrate the potential role of MLC901 in stroke recovery of patients with cerebral venous sinus thrombosis (CVST) who received MLC901 in addition to standard of care. The prescribed dose of MLC901 is 400 mg/cap two capsules, three times a day. Data from these patients were prospectively collected at baseline and at monthly visits, for a duration of 3 mo. Outcome measures included adherence to therapy, side effects, National Institutes of Health Stroke Scale, Glasgow Coma Scale, modified Rankin Scale, and the Short Orientation-Memory-Concentration Test. MLC901 was well tolerated and no side effects were reported. All patients were stable with improved condition. CONCLUSION: This case series highlights the potential therapeutic effects of MLC901 on CVST and provides support for further studies.

Specialist Perspectives on the Imaging Selection of Large Vessel Occlusion in the Late Window.

BACKGROUND: The proper imaging modality for use in the selection of patients for endovascular thrombectomy (EVT) presenting in the late window remains controversial, despite current guidelines advocating the use of advanced imaging in this population. We sought to understand if clinicians with different specialty training differ in their approach to patient selection for EVT in the late time window. METHODS: We conducted an international survey of stroke and neurointerventional clinicians between January and May 2022 with questions focusing on imaging and treatment decisions of large vessel occlusion (LVO) patients presenting in the late window. Interventional neurologists, interventional neuroradiologists, and endovascular neurosurgeons were defined as interventionists whereas all other specialties were defined as non-interventionists. The non-interventionist group was defined by all other specialties of the respondents: stroke neurologist, neuroradiologist, emergency medicine physician, trainee (fellows and residents) and others. RESULTS: Of 3000 invited to participate, 1506 (1027 non-interventionists, 478 interventionists, 1 declined to specify) physicians completed the study. Interventionist respondents were more likely to proceed directly to EVT (39.5% vs. 19.5%; p < 0.0001) compared to non-interventionist respondents in patients with favorable ASPECTS (Alberta Stroke Program Early CT Score). Despite no difference in access to advanced imaging, interventionists were more likely to prefer CT/CTA alone (34.8% vs. 21.0%) and less likely to prefer CT/CTA/CTP (39.1% vs. 52.4%) for patient selection (p < 0.0001). When faced with uncertainty, non-interventionists were more likely to follow clinical guidelines (45.1% vs. 30.2%) while interventionists were more likely to follow their assessment of evidence (38.7% vs. 27.0%) (p < 0.0001). CONCLUSION: Interventionists were less likely to use advanced imaging techniques in selecting LVO patients presenting in the late window and more likely to base their decisions on their assessment of evidence rather than published guidelines. These results reflect gaps between interventionists and non-interventionists reliance on clinical guidelines, the limits of available evidence, and clinician belief in the utility of advanced imaging.

The World Stroke Academy: A World Stroke Organization global pathway to improve knowledge in stroke care.

BACKGROUND: The World Stroke Academy (WSA) (www.world-stroke-academy.org) is the educational platform of the World Stroke Organization (WSO). It facilitates educational activities (e.g. webinars and eLearning modules) and supports the WSO mission by providing high-quality stroke education to healthcare professionals. It provides evidence-based educational materials in a variety of formats to meet the needs of the WSO membership. AIM: This article introduces the WSA, its core activities, and outlines how to access the many educational resources it offers. RESULTS: The WSA offers high-quality peer reviewed stroke education material and uses outcome metrics to assess and improve the quality of medical training of healthcare professionals. This article also highlights the importance of identifying knowledge and knowledge-to-action gaps through the creation of special projects and initiatives. It describes three areas in which the WSA has carried out recent educational initiatives, namely: life after stroke, women in stroke, and stroke checklist/pre-printed stroke orders. CONCLUSION: WSA material is freely available, and we would encourage the global stroke community to use, and contribute to, its resources.

Colchicine for prevention of vascular inflammation in Non-CardioEmbolic stroke (CONVINCE) - study protocol for a randomised controlled trial.

BACKGROUND: Inflammation contributes to unstable atherosclerotic plaque and stroke. In randomised trials in patients with coronary disease, canukinumab (an interleukin-1B antagonist) and colchicine (a tubulin inhibitor with pleiotropic anti-inflammatory effects) reduced recurrent vascular events.Hypothesis: Anti-inflammatory therapy with low-dose colchicine plus usual care will reduce recurrent vascular events in patients with non-severe, non-cardioembolic stroke and TIA compared with usual care alone. DESIGN: CONVINCE is a multi-centre international (in 17 countries) Prospective, Randomised Open-label, Blinded-Endpoint assessment (PROBE) controlled Phase 3 clinical trial in 3154 participants. The intervention is colchicine 0.5 mg/day and usual care versus usual care alone (antiplatelet, lipid-lowering, antihypertensive treatment, lifestyle advice). Included patients are at least 40 years, with non-severe ischaemic stroke (modified Rankin score ≤3) or high-risk TIA (ABCD2 > 3, or positive DWI, or cranio-cervical artery stenosis) within 72 hours-28 days of randomisation, with qualifying stroke/TIA most likely caused by large artery stenosis, lacunar disease, or cryptogenic embolism. Exclusions are stroke/TIA caused by cardio-embolism or other defined cause (e.g. dissection), contra-indication to colchicine (including potential drug interactions), or incapacity for participation in a clinical trial. The anticipated median follow-up will be 36 months. The primary analysis will be by intention-to-treat. OUTCOME: The primary outcome is time to first recurrent ischaemic stroke, myocardial infarction, cardiac arrest, or hospitalisation with unstable angina (non-fatal or fatal). SUMMARY: CONVINCE will provide high-quality randomised data on the efficacy and safety of anti-inflammatory therapy with colchicine for secondary prevention after stroke. SCHEDULE: First-patient first-visit was December 2016. Recruitment to complete in 2021, follow-up to complete in 2023.

SiPP (Stroke in Pregnancy and Postpartum): A prospective, observational, international, multicentre study on pathophysiological mechanisms, clinical profile, management and outcome of cerebrovascular diseases in pregnant and postpartum women.

RATIONALE: Cerebrovascular diseases associated with pregnancy and postpartum period are uncommon; however, they can have an important impact on health of both women and foetus or newborn. AIMS: To evaluate the frequency, characteristics and management of cerebrovascular events in pregnant/postpartum women, to clarify pathophysiological mechanisms underlying the occurrence of these events including biomolecular aspects, and to assess the short- and long-term cerebrovascular and global cardiovascular outcome of these patients, their predictors and infant outcome. METHODS AND DESIGN: This is an observational, prospective, multicentre, international case-control study. The study will include patients with cerebrovascular events during pregnancy and/or within six months after delivery. For each included case, two controls will be prospectively recruited: one pregnant or puerperal subject without any history of cerebrovascular event and one non-pregnant or non-puerperal subject with a recent cerebrovascular event. All controls will be matched by age, ethnicity and type of cerebrovascular event with their assigned cases. The pregnant controls will be matched also by pregnancy weeks/trimester. Follow-up will last 24 months for the mother and 12 months for the infant. SUMMARY: To better understand causes and outcomes of uncommon conditions like pregnancy/postpartum-related cerebrovascular events, the development of multisite, multidisciplinary registry-based studies, such as the Stroke in Pregnancy and Postpartum study, is needed in order to collect an adequate number of patients, draw reliable conclusions and give definite recommendations on their management.

Enhancing and accelerating stroke treatment in Eastern European region: Methods and achievement of the ESO EAST program.

INTRODUCTION: Despite the availability of prevention and therapies of stroke, their implementation in clinical practice, even of low-cost ones, remains poor. In 2015, the European Stroke Organisation (ESO) initiated the ESO Enhancing and Accelerating Stroke Treatment (EAST) program, which aims to improve stroke care quality, primarily in Eastern Europe. Here, we describe its methods and milestones. PATIENTS AND METHODS: The ESO EAST program is using an implementation strategy based on a 'detecting-understanding-reducing disparities' conceptual framework: stroke care quality is first measured (after developing a platform for data collection), gaps are identified in the current service delivery, and ultimately feedback is provided to participating hospitals, followed by the application of interventions to reduce disparities. The ESO EAST program is carried out by establishing a stroke quality registry, stroke management infrastructure, and creating education and training opportunities for healthcare professionals. RESULTS: Program management and leadership infrastructure has been established in 19 countries (Country Representatives in 22 countries, National Steering Committee in 19 countries). A software platform for data collection and analysis: Registry of Stroke Care Quality was developed, and launched in 2016, and has been used to collect data from over 90,000 patients from >750 hospitals and 56 countries between September 2016 and May 2019. Training in thrombolysis, nursing and research skills has been initiated. DISCUSSION: ESO EAST is the first pan-Eastern European (and beyond) multifaceted quality improvement intervention putting evidence-informed policies into practice. Continuous monitoring of stroke care quality allows hospital-to-hospital and country-to-country benchmarking and identification of the gaps and needs in health care.

Building a European 'network of networks' for stroke clinical research - The European Stroke Organisation Trials Alliance (ESOTA).

Promoting research to improve stroke prevention, acute care, and recovery is a key mission of the European Stroke Organisation (ESO). Stroke research networks may increase efficiencies and reduce waste in randomised clinical trials of stroke treatments. Several European countries have established national or regional stroke research networks, or have informal groups or stroke registers which may serve as a foundation for establishing a research network. To increase international collaboration on randomised trials for stroke in Europe, the ESO Trials Network Committee is leading the development of an alliance of national networks, the ESO Trials Alliance (ESOTA). Following initial consultation work in 2017, this paper describes an overview of progress to date in the first year of ESOTA activity. Beginning with five founding networks in England, Ireland, Netherlands, Spain, and Switzerland, ESOTA aims to gradually grow, ultimately including several hundred stroke centres and affiliated investigators working collectively on randomised trials of new stroke treatments.

Symptomatic intracranial atherosclerotic disease: an ultrasound 2-year follow-up pilot study.

INTRODUCTION: The objective of this single-center pilot study was to assess if symptomatic intracranial atherosclerotic disease (ICAD) ultrasound features change through the 2 years after acute ischemic stroke or TIA, being ICAD a relevant cause of acute ischemic stroke or TIA, linked to high rates of recurrent stroke. METHODS: We consecutively enrolled 48 patients with acute ischemic stroke or TIA with symptomatic ICAD detected by transcranial color-coded duplex sonography (TCCS) and confirmed by MR-angiography and/or CT-angiography. We set a neurosonological and clinical follow-up at 3, 6, 12, and 24 months (T0, T1, T2, T3, and T4). RESULTS: We observed that the hemodynamic effect of the stenosis changed during the 2-year follow-up, as revealed by the modifications of Peak Systolic Velocity (PSV) (Friedman-ANOVA test, p < 0.001). The pairwise post-hoc analysis showed a statistically significant difference between PSV at T0 and PSV at T3 (p = 0.005) and between PSV at T0 and PSV at T4 (p < 0.001) being PSV at T3 and T4 lower than PSV at T0. Seven patients had a new event in the first 12 months. CONCLUSIONS: The high rate of recurrent stroke or death among ICAD patients seems to be independent of progressive arterial narrowing. A wide multicenter follow-up study is needed in order to identify the factors that, alongside the hemodynamic features, contribute to the high risk of recurrent stroke among patient with symptomatic ICAD.

Socio-Demographic Characteristics of the Patients with a Post Stroke Depression from the Municipality of Tetovo, Republic of Macedonia.

BACKGROUND: Although post-stroke depression (PSD) is the most common neuro-psychiatric consequence after a stroke there is still some obscurity regarding its aetiology and risk factors, which complicates its management. A better knowledge of the predictors will enable better prevention and treatment. AIM: The aim of this work was the identification of the risk factors for PSD, typical for the Macedonian population, which will help in early prediction, timely diagnosis and treatment of the disease. MATERIALS AND METHODS: We carried out a prospective study at the Clinical Hospital in Tetovo, the Republic of Macedonia to determine the prevalence of PSD and to analyse the socio-demographic characteristics as possible risk factors in 100 patients on discharge and after 5 months. The depression symptoms were quantified using the Hamilton Depression Ranking Scale (HAM-d) and the Geriatric Depression Scale (GDS). RESULTS: The average age of the patients with PSD on the first examination is 65.0 ± 8.3, whereas on the second examination is 64.5 ± 9.2. According to the Mann-Whitney U test, the difference between the average ages on both examinations is statistically insignificant for p > 0.05. On both examinations, the statistically significant dependence of p > 0.05 between PSD and the occupational status and PSD and education is not recorded. On both examinations, the PSD in male patients was 78.0% and 62.7%, while in female patients it was 85.4% and 68.3% not recording the statistically significant dependence of p < 0.05 between PSD and the gender. CONCLUSION: The socio-demographic characteristics of the patients with PSD cannot be considered as predictors of the disease.

Prevalence and Predictors of Depression after Stroke - Results from a Prospective Study.

BACKGROUND: A depression following a stroke (Post Stoke Depression-PSD) is the most common complication of a stroke that has a negative effect on the result after the stroke. A better definition of the risk factors of the disease will provide for better prediction and treatment. AIM: To research identification of the risk factors for PSD, typical for the Macedonian population, which will help in early prediction, timely diagnosis and treatment of the disease? MATERIAL AND METHODS: We carried out a prospective study in order to determine the prevalence and the risk factors of PSD in 100 patients treated at the hospital in Tetovo. The severity, localisation and the functional outcome of the stroke have been examined as potential risk factors for discharge and after 5 months. The symptoms of depression were quantified using the Hamilton Depression Rating Scale (HAM-d). RESULTS: On discharge, 81% of the patients were diagnosed with PSD, and 67% had PSD after 5 months. A statistically significant codependence of p < 0.05 was registered between PSD and the level of functional dependence for activities of daily living (ADL); PSD and the severity of the stroke; and PSD and the level of disability on both examinations. In most patients with PSD, an ischemic stroke in the right middle cerebral artery has been diagnosed; the percentage difference between the other localisations is statistically significant (p = 0.0436; p = 0.0002). CONCLUSION: There is an increased risk of PSD for immobile patients, those incapable of activities of daily living (ADL), with ischemic stroke in the right middle cerebral artery. A PSD screening and additional studies for better prediction are required.

Are there opportunities for a closer collaboration on clinical stroke research in Europe?

INTRODUCTION: One of the aims of the European Stroke Organisation (ESO) is to facilitate academic, multinational clinical stroke research. However, despite examples of successful regional and national stroke research networks and collaborative groups, there is no organisational structure at a European level that can facilitate multinational clinical stroke research. MATERIALS AND METHODS: In a project including a survey and a workshop and involving stroke researchers in the ESO, we sought to identify the challenges faced by existing clinical stroke research networks, to define the purpose and roles of any future European stroke research collaboration, and to propose an organisational structure. RESULTS: The survey and workshop gave strong support for an alliance model with independent network members, with the purpose of facilitating clinical stroke research through improved coordination and communication, provision of support, education, and advocacy and communication with other stakeholders. The focus of a proposed European clinical stroke research alliance should be multinational randomised-controlled trials in acute care, prevention and rehabilitation, but the alliance could also support other forms of multi-national clinical stroke research. CONCLUSION: There is an interest for increased collaboration on multinational clinical stroke research in Europe, in the form of an alliance of independent research networks and collaborative groups. The ESO Trials Network Committee will continue consultation with existing stroke research networks and collaborative groups, and other key stakeholders, to assess the feasibility and support for development of an ESO Trials Alliance.