Thrombus histology does not predict stroke etiological subtype but influences recanalization.

BACKGROUND: There is conflicting data on whether clot retrieved from mechanical thrombectomy can predict stroke etiology or the success of recanalization. We aimed to analyse the relation between thrombus histology and stroke aetiology as well as recanalization. METHODOLOGY: Histopathological analysis of clots retrieved from patients with acute ischemic stroke and large vessel occlusion was done. Quantification of the amount of fibrin, red blood cells(RBC), platelets and white blood cells (WBC) in the clots were done. The clinical, imaging data and recanalization parameters were collected. The correlation between clot composition and stroke etiology as well as recanalization were analysed. RESULTS: Of the 77 patients, the mean age was 58. 67 ± 12.96 years. The stroke etiology were cardioembolism 44(57.1 %), large artery atherosclerosis 13(16.8 %), other determined aetiology 4(5.1 %) and undetermined in 16(20.7 %) patients. There was no significant correlation between the proportions of RBC-rich, platelet-rich and fibrin-rich thrombi and the stroke etiology. The susceptibility vessel sign was associated with RBC-rich clot(92.3 % vs 7.7 %, p = .03). All RBC-rich clots(100 %) had good recanalization(p = .05). Platelet-rich clots needed less number of passes(64.7 % vs 35.3 %, p = .006) and reduced groin puncture to recanalization time(87.9 % vs 12.1 %, p = .033). WBC-rich clots required lesser number of passes(57.5 % vs 42.5 %, P = .044). In multivariate analysis, WBC-rich clots (OR 0.230, CI 0.07-0.78, p = .018) showed an independent association with reduced recanalization attempts, while platelet-rich clots showed reduced recanalization time(OR 0.09, CI 0.01-0.63, p = .016). CONCLUSION: There was no correlation between thrombus histology and the etiological stroke subtype. However, clot composition predicted the degree of recanalization and number of passes.

A randomized controlled trial of medication adherence and management of risk factors for secondary prevention of stroke (MaMoRS) using a smartphone-based application.

BACKGROUND: There are little data on the use of smartphone-based applications for medication adherence and risk-factor control for the secondary prevention of stroke in low-and-middle-income countries (LMICs). AIMS: The aim was to determine whether a smartphone-based app improved medication adherence, risk-factor control, and provided health education to stroke survivors for lifestyle and behavioral modifications. METHODS: An unblinded, single-center randomized controlled double arm trial with 1:1 allocation among stroke survivors was performed in South India. The primary outcome was medication adherence, with co-primary outcomes of lifestyle and behavioral factors and control of vascular risk factors, at 3 and 6 months. RESULTS: Among 351 stroke survivors screened, 209 were recruited. The mean (standard deviation (SD)) age of the intervention (n = 105) group was 60 (12) years and that of the control (n = 104) group was 60 (10) years. In the primary outcome, mean medication adherence significantly improved in the intervention group with a between group difference of 0.735 (95% confidence interval (CI) = 0.419 to 1.050), p < 0.001. Being in intervention group (OR = 4.5; 95% CI = 2.3 to 8.9), stroke recurrence (OR = 3.3 (95% CI = 1.9 to 7.8)), and regular physician visits (OR = 2.1; 95% CI = 1.0 to 4.4) were significant predictors of good medication adherence. Considering the co-primary outcomes, compared to the control group, participants in the intervention group had a greater improvement in self-reported healthy diet intake (p = 0.003), intake of fruits (p = 0.005), and were physically more active (p = 0.001). At 6 months, mean fasting blood sugar (p = 0.005) and high-density lipoprotein cholesterol higher (p = 0.024) in the intervention group. CONCLUSIONS: The use of a mobile app is an effective method to improve medication adherence and risk-factor control in stroke survivors and is feasible in LMICs like India. DATA ACCESS STATEMENT: Data used during the study are available from the corresponding author on request. TRIAL REGISTRATION: The study is registered in Clinical Trial Registry of India (CTRI/2022/06/042980).

STENOSIS: Long-term single versus dual antiplatelet therapy in patients with ischaemic stroke due to intracranial atherosclerotic disease - a randomised trial.

Rationale: Intracranial atherosclerotic disease (ICAD) is a pathological process that causes progressive stenosis and cerebral hypoperfusion, leading to stroke occurrence and recurrence around the world. The exact duration of dual antiplatelet therapy (DAPT) for ICAD is unclear in view of long-term risk of bleeding complications. Aim: The current study aims to study the efficacy and safety of long-term DAPT (up to 12 months) in patients with ICAD. Sample size: Using 80% power and an alpha error of 5 %, presuming a 10%-15% drop-out rate, a total of 2200 patients will be recruited for the study. Methodology: This is a prospective, randomised, double-blind, placebo controlled trial. Study outcomes: The primary outcomes include recurrent ischaemic stroke (IS) or transient ischaemic attack and any intracranial haemorrhage (ICH), major or minor systemic bleeding at the end of 12 months. Secondary outcomes include composite of any stroke, myocardial infarction or death at the end of 12 months. The safety outcomes include any ICH, major or minor bleeding as defined using GUSTO (Global Use of Streptokinase and tPA for occluded Coronary Arteries) classification at the end of 12 months and 1 month after completion of the drug treatment phase. Discussion: The study will provide level I evidence on the duration of DAPT among patients with IS due to ICAD of more than or equal to 50%.

RE-OPEN: Randomised trial of biosimilar TNK versus TPA during endovascular therapy for acute ischaemic stroke due to large vessel occlusions.

Rationale: Rapid and timely treatment with intravenous thrombolysis and endovascular treatment (EVT) in patients with acute ischaemic stroke (AIS) and large vessel occlusion (LVO) significantly improves patient outcomes. Bridging therapy is the current standard of care in these patients. However, an incompletely answered question is whether one thrombolytic agent is better than another during bridging therapy. Aim: The current study aims to understand if one thrombolytic agent is superior to the other during bridging therapy in the treatment of AIS and LVO. Sample size estimates: Using 80% power and an alpha error of 5 %, presuming a 10% drop out rate, a total of 372 patients will be recruited for the study. Methods and design: This study is a prospective, randomised, multicentre, open-label trial with blinded outcome analysis design. Study outcomes: The primary outcomes include proportion of patients who will be independent at 3 months (modified Rankin score (mRS) ≤2 as good outcome) and proportion of patients who achieve recanalisation modified thrombolysis in cerebral infarction grade 2b/3 at first angiography run at the end of EVT. Secondary outcomes include proportion of patients with early neurological improvement, rate of symptomatic intracerebral haemorrhage (ICH), rate of any ICH, rate of any systemic major or minor bleeding and duration of hospital stay. Safety outcomes include any intracranial bleeding or symptomatic ICH. Discussion: This trial is envisioned to confirm the theoretical advantages and increase the strength and quality of evidence for use of tenecteplase (TNK) in practice. Also, it will help to generate data on the efficacy and safety of biosimilar TNK. Trial registration number: CTRI/2022/01/039473.

CT angiographic patterns predict carotid pseudo-occlusion in acute ischemic stroke.

Background: Identifying carotid pseudo-occlusion (PO) from true occlusion (TO) has implications in determining the candidacy and feasibility of successful endovascular thrombectomy (EVT) in acute ischemic stroke (AIS). Purpose: We reviewed the computed tomography angiographic (CTA) patterns differentiating a PO from a TO and analyzed the rate of successful recanalization after EVT. Materials and Methods: Patients with AIS and proximal internal carotid artery (ICA) occlusion who underwent EVT from 2014 to 2021 were identified. The patterns of carotid occlusion in CTA were classified into beak, dome, and flat patterns and correlated with microcatheter digital subtraction angiography (DSA) as PO and TO. The rates of successful recanalization in PO and TO were analyzed. Results: Of the 24 patients, 16 (66%) had ICA PO and eight (33%) had TO in DSA. A beak pattern of the proximal ICA on CTA was significantly higher among the PO group patients (87.5% vs. 25%, P = 0.005), and a flat pattern was significantly higher among the TO group patients (50% vs. 12%, P = 0.005). A gradual contrast decline of the proximal ICA on CTA images was seen only in PO group patients (85.7% vs. 0%, P = 0.05). There was no significant difference in the rate of successful recanalization between PO and TO group patients (81.25% vs. 62.5%, P = 0.362). Conclusion: Beak pattern and gradual contrast decline at the proximal ICA occlusion site in CTA are suggestive of carotid PO. Identification of PO in CTA can help in planning intervention strategies and prognostication.

Development and effect of a coordinated Community Health Worker (CHW) Intervention (C-CHW-I) model for the stroke survivors in Kerala, South India.

INTRODUCTION: Structured models for secondary prevention of stroke in community settings are scarce. We aimed to develop and evaluate a model for improving medication adherence and enhanced risk factor monitoring. METHODS: We developed a multimodal C-CHW-I model for stroke survivors. Following training, all patients received a minimum of three CHW home visits, and once in 3-month telephone-call and health education for six months by CHWs. Seven blocks from 16 blocks of the study area were randomised to additionally receive an SMS alert for six months to reinforce CHW involvement. The primary outcomes were medication adherence and risk factor monitoring, and the secondary outcome was risk factor control. RESULTS: The mean age of the study population was 64+12 years, 765(85%) had ischaemic stroke. In the overall study cohort receiving the CHW intervention, mean medication adherence significantly improved from 3.56(0.88) at baseline to 3.78(0.61) at 6 months; p<0.001. Overall risk factor monitoring improved from 42.7% to 49.7%, and mean (standard deviation) systolic blood pressure (SBP) significantly reduced from 138(21) mmHg to 132(15) mmHg at 6-months; p<0.001. In patients additionally receiving SMS-based intervention, a statistically significant improvement in medication adherence was seen at 3 months (3.76+0.64 versus 3.61+0.81; p=0.008) however no difference persisted at 6 months. The proportion of smokers and alcohol users reduced in both groups with a trend to greater reduction in the intervention group (smokers:5.9% versus 2.8% (p=0.446) and alcohol users: 1.6% versus 1.4%(p=0.474)). At six months, the SBP did not differ (SBP (132.1(16.2) in the SMS group versus 133.2(15.8) mmHg in the control group, p=0.409). CONCLUSION: Our model improved medication adherence and risk factor monitoring of stroke survivors in community settings, and this can reduce stroke burden in the community.

Diabetes mellitus and obesity among South Asians with ischemic stroke across three countries.

BACKGROUND: Diabetes mellitus and central obesity are more common among South Asian populations than among White British people. This study explores the differences in diabetes and obesity in South Asians with stroke living in the United Kingdom, India, and Qatar compared with White British stroke patients. METHODS: The study included the UK, Indian, and Qatari arms of the ongoing large Bio-Repository of DNA in Stroke (BRAINS) international prospective hospital-based study for South Asian stroke. BRAINS includes 4580 South Asian and White British recruits from UK, Indian, and Qatar sites with first-ever ischemic stroke. RESULTS: The study population comprises 1751 White British (WB) UK residents, 1165 British South Asians (BSA), 1096 South Asians in India (ISA), and 568 South Asians in Qatar (QSA). ISA, BSA, and QSA South Asians suffered from higher prevalence of diabetes compared with WB by 14.5% (ISA: 95% confidence interval (CI) = 18.6-33.0, p < 0.001), 31.7% (BSA: 95% CI = 35.1-50.2, p < 0.001), and 32.7% (QSA: 95% CI = 28.1-37.3, p < 0.001), respectively. Although WB had the highest prevalence of body mass index (BMI) above 27 kg/m2 compared with South Asian patients (37% vs 21%, p < 0.001), South Asian patients had a higher waist circumference than WB (94.8 cm vs 90.8 cm, p < 0.001). Adjusting for traditional stroke risk factors, ISA, BSA, and QSA continued to display an increased risk of diabetes compared with WB by 3.28 (95% CI: 2.53-4.25, p < 0.001), 3.61 (95% CI: 2.90-4.51, p < 0.001), and 5.24 (95% CI: 3.93-7.00, p < 0.001), respectively. CONCLUSION: South Asian ischemic stroke patients living in Britain and Qatar have a near 3.5-fold risk of diabetes compared with White British stroke patients. Their body composition may partly help explain that increased risk. These findings have important implications for public health policymakers in nations with large South Asian populations.

Thrombus Attenuation Gradient Can Predict Successful First-Pass Recanalization Following Stentriever Thrombectomy.

OBJECTIVE: Computed tomography angiography (CTA) derived thrombus enhancement characteristics can predict first-pass recanalization. We studied whether dynamic contrast kinetics within the clot in multiphase CTA can predict first-pass recanalization following stentriever thrombectomy. METHODS: Patients with acute large vessel occlusive stroke evaluated with multiphasic CTA who underwent stentriever thrombectomy were selected. Thrombus perviousness on various phases including arterial, venous, and delayed phases was calculated. Thrombus attenuation gradient (TAG), defined as average attenuation difference between adjacent phases, was also evaluated and correlated with successful first-pass outcome (modified Treatment in Cerebral Ischemia score ≥2b). RESULTS: Of 69 patients, 32 (47%) had successful first-pass recanalization (group 1), and 37 (53%) required >1 attempt (group 2). TAG showed significant differences in arterial-plain and venous-arterial phases. The early increase in TAG was seen in group 1 in the arterial-plain phase, as opposed to group 2 (12.6 vs. 9, P = 0.01), which plateaued in the venous-arterial phase for group 1 and showed a further increase in group 2 (2.1 vs. 5.1, P = 0.02). A cutoff value of 9.2 HU for arterial-plain phase (P = 0.001) and 4.2 HU (P = 0.001) for venous-arterial phase was predictive of first-pass effect. Combining 2 metrics had an odds ratio of 2.8 for first-pass recanalization (P = 0.035). Accuracy evaluated in a validation cohort yielded 74%. Other features including histology were not significant. CONCLUSIONS: TAG evaluated from multiphase CTA can predict first-pass effect in stentriever thrombectomy.

Stroke awareness among community health workers from rural health blocks of Thiruvananthapuram, India.

Objectives: Secondary prevention of stroke largely depends on risk factor control and lifestyle modification. Optimal secondary prevention strategies are limited in rural settings due to the shortage of primary care physicians and neurologists. Awareness of community health workers (CHWs) regarding stroke and its management remains largely unexplored. The current cross-sectional study aimed at assessing the knowledge, attitude, and practice (KAP) of CHWs regarding stroke care. Materials and Methods: A structured KAP questionnaire was administered among 510 CHWs from randomly selected rural health blocks of Thiruvananthapuram, Kerala, India. Results: Knowledge assessment showed that the CHWs possessed an average knowledge of stroke care. The mean attitude and practice scores were higher, indicating a favorable attitude and good practice. The overall mean (standard deviation) KAP scores of CHWs were 13.54 (4.43) against a total score of 23. The KAP scores were highest among palliative care nurses. The stroke awareness of the accredited social health activists was comparatively lower than other CHWs. Factors such as age and years of work experience were not correlated to the KAP scores. Conclusion: Recurrent strokes remain a major challenge in primary care. Overall, the health workers demonstrated average knowledge, favorable attitudes, and positive practices. The study highlights the importance of training accredited social health activists (ASHAs) and other CHWs in stroke to improve secondary prevention strategies.

Recurrence of Cryptogenic (ESUS) Strokes in the First Year: Predictors and Outcome-A South Indian Study.

Introduction: Around 9-25% of ischemic strokes are embolic stroke of undetermined source (ESUS) with an annual recurrence risk of 4.5-5%. Regarding ESUS, studies from India are limited. Here, we studied the prevalence of cryptogenic ESUS among stroke subtypes, recurrence risk and outcome at 1 year, and their predictors. Materials and Methods: We performed a single-center study of ambispective nature. Patients above 18 years of age with a diagnosis of cryptogenic (ESUS) strokes from January 1, 2017, to December 31, 2020 (4 years), with a 1-year follow-up were recruited in our study. All the patients underwent neuroimaging computerised tomography/magnetic resonance tomography (CT/MRI) with angiography, electrocardiogram (ECG), transthoracic echo (TTE), and rhythm monitoring. Functional outcome was measured using the modified Rankin scale with scores 0-2 taken as good outcome. Results: We had 234 (11.21% of total ischemic strokes) subjects satisfying the criteria for ESUS over the study period with a mean age of 58.2 ± 12.8 years. 46 patients had a history of stroke/transient ischemic attack (TIA) at admission. 9.4% had a recurrent event at 1 year. The most important neuroimaging predictor of recurrent strokes was multiple embolic followed by superficial watershed pattern. Around 10% had more than one marker of atrial cardiopathy positive. While the risk factors, coronary artery disease (CAD), and neuroimaging pattern showed an association with recurrent events at 1 year on bivariate analysis, only the latter two remained significant on multivariate analysis. Conclusions: Our cohort of ESUS had a higher annual recurrence risk than reported before. Though vascular risk factors and ipsilateral vessel abnormalities were more in the recurrent ESUS group, it did not significantly affect the recurrence risk at 1 year. CAD and multiple embolic patterns on imaging showed an association with recurrent strokes, suggesting a possible cardiac substrate in our ESUS population as well.

AutoML accurately predicts endovascular mechanical thrombectomy in acute large vessel ischemic stroke.

Background and objective: Automated machine learning or autoML has been widely deployed in various industries. However, their adoption in healthcare, especially in clinical settings is constrained due to a lack of clear understanding and explainability. The aim of this study is to utilize autoML for the prediction of functional outcomes in patients who underwent mechanical thrombectomy and compare it with traditional ML models with a focus on the explainability of the trained models. Methods: A total of 156 patients of acute ischemic stroke with Large Vessel Occlusion (LVO) who underwent mechanical thrombectomy within 24 h of stroke onset were included in the study. A total of 34 treatment variables including clinical, demographic, imaging, and procedure-related data were extracted. Various conventional machine learning models such as decision tree classifier, logistic regression, random forest, kNN, and SVM as well as various autoML models such as AutoGluon, MLJAR, Auto-Sklearn, TPOT, and H2O were used to predict the modified Rankin score (mRS) at the time of patient discharge and 3 months follow-up. The sensitivity, specificity, accuracy, and AUC for traditional ML and autoML models were compared. Results: The autoML models outperformed the traditional ML models. For the prediction of mRS at discharge, the highest testing accuracy obtained by traditional ML models for the decision tree classifier was 74.11%, whereas for autoML which was obtained through AutoGluon, it showed an accuracy of 88.23%. Similarly, for mRS at 3 months, the highest testing accuracy of traditional ML was that of the SVM classifier at 76.5%, whereas that of autoML was 85.18% obtained through MLJAR. The 24-h ASPECTS score was the most important predictor for mRS at discharge whereas for prediction of mRS at 3 months, the most important factor was mRS at discharge. Conclusion: Automated machine learning models based on multiple treatment variables can predict the functional outcome in patients more accurately than traditional ML models. The ease of clinical coding and deployment can assist clinicians in the critical decision-making process. We have developed a demo application which can be accessed at https://mrs-score-calculator.onrender.com/.

Surveillance of stroke: a South-East Asia Region (SEAR) perspective.

Surveillance of stroke is critical to track its burden and assess progress in prevention and treatment. We reviewed the literature to evaluate stroke surveillance efforts in the South-East Asia Region (SEAR) countries, identify progress and assess gaps. Epidemiological data on all the major parameters such as the incidence, prevalence and mortality of stroke were available for India and Thailand but for none of the other SEAR countries. Most of the epidemiological data came from investigator-initiated studies. National stroke surveillance was present only in India in the form of a National Stroke Registry Programme and Thailand has a national database that was used to obtain epidemiological data for stroke. Research on novel methods for stroke registration, such as using information technology, was absent. This review identified serious gaps in the monitoring and surveillance of stroke in SEAR countries. Systematic efforts are needed to fill those gaps.

Progressive lacunar strokes behave differently from stable ones even at one year-An observational study.

BACKGROUND AND AIMS: Small fraction of lacunar stroke patients have an early fluctuating course, described as progressive lacunar syndrome [PLS].We studied the predictors and short term outcome of progressive lacunar strokes in comparison with those with an early stable course. MATERIALS AND METHODS: Single centre retrospective study where patients with lacunar strokes from 2016 to 2020 were included in the study. Progression was defined as increase in stroke severity [NIHSS] by ≥2 points from baseline without imaging evidence of new infarcts or haemorrhagic transformation. We compared the clinical variables, risk factors, imaging, treatment received and 1 year outcome of subjects with PLS with those with a stable course, with modified Rankin score 0-2 taken as good outcome. RESULTS: Of the 216 patients with a mean age 63.17 years, progressive course was noted in 56 subjects [26 %].Majority of the fluctuations occurred within 24 h of onset of symptoms. Though stroke severity at admission was comparable between the 2 groups, discharge and 1 year outcome was poorer in those with an early progressive course. We found that presentation as pure motor syndrome, hypertriglyceridemia and thrombolytic therapy were predictors of poor outcome in progressive lacunar strokes, while age, risk factors, infarct location or leukoaraiosis failed to show an association. Thalamic infarcts and atypical lacunar syndromes were associated with a stable course. CONCLUSION: Progressive course is seen in a quarter of lacunar strokes and they have poorer outcome at 1 year. Our finding of thrombolysis being associated with worse outcome in PLS patients, should alert physicians regarding need for more definitive therapies for this condition.

Healthcare professionals' perspectives of the provision of, and challenges for, eating, drinking and psychological support post stroke: findings from semistructured interviews across India.

AIM: This qualitative study explores with health professionals the provision of, and challenges for, postdischarge stroke care, focussing on eating, drinking and psychological support across India. DESIGN: Qualitative semistructured interviews. SETTING: Seven geographically diverse hospitals taking part in a Global Health Research Programme on Improving Stroke Care in India. PARTICIPANTS: A purposive sample of healthcare professionals with current experience of working with patients who had a stroke. RESULTS: Interviews with 66 healthcare professionals (23 nurses (14 staff nurses; 7 senior nurse officers; 1 intensive care unit nurse; 1 palliative care nurse)); 16 doctors (10 neurologists; 6 physicians); 10 physiotherapists; 5 speech and language therapists; 4 occupational therapists; 4 dieticians; 2 psychiatrists; and 2 social workers resulted in three main themes: integrated inpatient discharge care planning processes; postdischarge patient and caregiver role and challenges; patient and caregiver engagement post discharge. CONCLUSIONS: Discharge planning was integrated and customised, although resources were limited in some sites. Task shifting compensated for a lack of specialists but was limited by staff education and training. Caregivers faced challenges in accessing and providing postdischarge care. Postdischarge care was mainly hospital based, supported by teleservices, especially for rural populations. Further research is needed to understand postdischarge care provision and the needs of stroke survivors and their caregivers.

Early versus Later Anticoagulation for Stroke with Atrial Fibrillation.

BACKGROUND: The effect of early as compared with later initiation of direct oral anticoagulants (DOACs) in persons with atrial fibrillation who have had an acute ischemic stroke is unclear. METHODS: We performed an investigator-initiated, open-label trial at 103 sites in 15 countries. Participants were randomly assigned in a 1:1 ratio to early anticoagulation (within 48 hours after a minor or moderate stroke or on day 6 or 7 after a major stroke) or later anticoagulation (day 3 or 4 after a minor stroke, day 6 or 7 after a moderate stroke, or day 12, 13, or 14 after a major stroke). Assessors were unaware of the trial-group assignments. The primary outcome was a composite of recurrent ischemic stroke, systemic embolism, major extracranial bleeding, symptomatic intracranial hemorrhage, or vascular death within 30 days after randomization. Secondary outcomes included the components of the composite primary outcome at 30 and 90 days. RESULTS: Of 2013 participants (37% with minor stroke, 40% with moderate stroke, and 23% with major stroke), 1006 were assigned to early anticoagulation and 1007 to later anticoagulation. A primary-outcome event occurred in 29 participants (2.9%) in the early-treatment group and 41 participants (4.1%) in the later-treatment group (risk difference, -1.18 percentage points; 95% confidence interval [CI], -2.84 to 0.47) by 30 days. Recurrent ischemic stroke occurred in 14 participants (1.4%) in the early-treatment group and 25 participants (2.5%) in the later-treatment group (odds ratio, 0.57; 95% CI, 0.29 to 1.07) by 30 days and in 18 participants (1.9%) and 30 participants (3.1%), respectively, by 90 days (odds ratio, 0.60; 95% CI, 0.33 to 1.06). Symptomatic intracranial hemorrhage occurred in 2 participants (0.2%) in both groups by 30 days. CONCLUSIONS: In this trial, the incidence of recurrent ischemic stroke, systemic embolism, major extracranial bleeding, symptomatic intracranial hemorrhage, or vascular death at 30 days was estimated to range from 2.8 percentage points lower to 0.5 percentage points higher (based on the 95% confidence interval) with early than with later use of DOACs. (Funded by the Swiss National Science Foundation and others; ELAN ClinicalTrials.gov number, NCT03148457.).

Mechanical Thrombectomy Global Access For Stroke (MT-GLASS): A Mission Thrombectomy (MT-2020 Plus) Study.

BACKGROUND: Despite the well-established potent benefit of mechanical thrombectomy (MT) for large vessel occlusion (LVO) stroke, access to MT has not been studied globally. We conducted a worldwide survey of countries on 6 continents to define MT access (MTA), the disparities in MTA, and its determinants on a global scale. METHODS: Our survey was conducted in 75 countries through the Mission Thrombectomy 2020+ global network between November 22, 2020, and February 28, 2021. The primary end points were the current annual MTA, MT operator availability, and MT center availability. MTA was defined as the estimated proportion of patients with LVO receiving MT in a given region annually. The availability metrics were defined as ([current MT operators×50/current annual number of estimated thrombectomy-eligible LVOs]×100 = MT operator availability) and ([current MT centers×150/current annual number of estimated thrombectomy-eligible LVOs]×100= MT center availability). The metrics used optimal MT volume per operator as 50 and an optimal MT volume per center as 150. Multivariable-adjusted generalized linear models were used to evaluate factors associated with MTA. RESULTS: We received 887 responses from 67 countries. The median global MTA was 2.79% (interquartile range, 0.70-11.74). MTA was <1.0% for 18 (27%) countries and 0 for 7 (10%) countries. There was a 460-fold disparity between the highest and lowest nonzero MTA regions and low-income countries had 88% lower MTA compared with high-income countries. The global MT operator availability was 16.5% of optimal and the MT center availability was 20.8% of optimal. On multivariable regression, country income level (low or lower-middle versus high: odds ratio, 0.08 [95% CI, 0.04-0.12]), MT operator availability (odds ratio, 3.35 [95% CI, 2.07-5.42]), MT center availability (odds ratio, 2.86 [95% CI, 1.84-4.48]), and presence of prehospital acute stroke bypass protocol (odds ratio, 4.00 [95% CI, 1.70-9.42]) were significantly associated with increased odds of MTA. CONCLUSIONS: Access to MT on a global level is extremely low, with enormous disparities between countries by income level. The significant determinants of MT access are the country's per capita gross national income, prehospital LVO triage policy, and MT operator and center availability.

A systematic review and synthesis of global stroke guidelines on behalf of the World Stroke Organization.

BACKGROUND: There are multiple stroke guidelines globally. To synthesize these and summarize what existing stroke guidelines recommend about the management of people with stroke, the World Stroke Organization (WSO) Guideline committee, under the auspices of the WSO, reviewed available guidelines. AIMS: To systematically review the literature to identify stroke guidelines (excluding primary stroke prevention and subarachnoid hemorrhage) since 1 January 2011, evaluate quality (The international Appraisal of Guidelines, Research and Evaluation (AGREE II)), tabulate strong recommendations, and judge applicability according to stroke care available (minimal, essential, advanced). SUMMARY OF REVIEW: Searches identified 15,400 titles; 911 texts were retrieved, 200 publications scrutinized by the three subgroups (acute, secondary prevention, rehabilitation), and recommendations extracted from most recent version of relevant guidelines. For acute treatment, there were more guidelines about ischemic stroke than intracerebral hemorrhage; recommendations addressed pre-hospital, emergency, and acute hospital care. Strong recommendations were made for reperfusion therapies for acute ischemic stroke. For secondary prevention, strong recommendations included establishing etiological diagnosis; management of hypertension, weight, diabetes, lipids, and lifestyle modification; and for ischemic stroke, management of atrial fibrillation, valvular heart disease, left ventricular and atrial thrombi, patent foramen ovale, atherosclerotic extracranial large vessel disease, intracranial atherosclerotic disease, and antithrombotics in non-cardioembolic stroke. For rehabilitation, there were strong recommendations for organized stroke unit care, multidisciplinary rehabilitation, task-specific training, fitness training, and specific interventions for post-stroke impairments. Most recommendations were from high-income countries, and most did not consider comorbidity, resource implications, and implementation. Patient and public involvement was limited. CONCLUSION: The review identified a number of areas of stroke care where there was strong consensus. However, there was extensive repetition and redundancy in guideline recommendations. Future guideline groups should consider closer collaboration to improve efficiency, include more people with lived experience in the development process, consider comorbidity, and advise on implementation.

Soluble ST2 Predicts Poor Functional Outcome in Acute Ischemic Stroke Patients.

INTRODUCTION: There are very limited data on the role of biomarkers correlating with the outcome in acute ischemic stroke (AIS). We evaluated the predictive values of the plasma concentrations of soluble serum stimulation-2 (sST2), matrix metalloproteinase-9 (MMP-9), and claudin-5 in AIS. METHODS: The biomarker levels in the plasma samples of consecutive AIS patients collected at baseline, 12 h, and 24 h from stroke onset were quantified using immunoassays. Stroke severity was assessed using the National Institutes of Health Stroke Scale (NIHSS) and functional outcome at 90 days using the modified Rankin Scale (mRS), with scores above 3 defined as poor outcome. Receiver operating characteristic curve analysis and multiple logistic regression were performed for evaluating the discriminative power of each marker. RESULTS: We included 108 patients in the study (mean age 62.3 ± 11.7 years). Median NIHSS score was 12 (interquartile range 8-18). High baseline glucose levels, systolic blood pressure, baseline NIHSS, low Alberta Stroke Program Early CT Score, and hemorrhagic transformation were associated with poor outcomes. Elevated sST2 at 12 h (50.4 ± 51.0 ng/mL; p = 0.047) and 24 h (81.8 ± 101.3 ng/mL; p = 0.001) positively correlated with poor outcomes. MMP-9 (p = 0.086) and claudin-5 (p = 0.2) were not significantly associated with the outcome, although increased expressions of both markers were observed at 12 h. Multiple logistic regression showed that sST2 levels ≥71.8 ng/mL at 24 h, with a specificity of 96.9%, emerged as an independent predictor of poor functional outcome (OR: 6.44; 95% CI: 1.40-46.3; p = 0.029). CONCLUSION: Evaluation of sST2 may act as a reliable biomarker of functional outcome in AIS.

Biomarkers predict hemorrhagic transformation and stroke severity after acute ischemic stroke.

OBJECTIVES: Hemorrhagic transformation (HT) is a complication occurring in patients with acute ischemic stroke (AIS) either spontaneously or post-thrombolysis leading to significant morbidity and mortality. We assessed circulating matrix metalloproteinase-9 (MMP-9), Claudin-5, and soluble serum stimulation-2 (sST2) in HT and stroke severity in AIS based on their temporal distribution. MATERIALS AND METHODS: We prospectively enrolled 111 AIS patients within 12 h from onset. Patient demographic, clinical, and imaging details were documented. Follow-up imaging was conducted 24-48 h after admission. Blood samples were taken at three time-points from stroke onset. HT was classified according to the European Co-operative Acute Stroke Study-III(ECASS-III). Stroke severity was assessed using the National Institutes of Health Stroke Scale (NIHSS). Multiple logistic regression and receiver operating characteristic curve were conducted to determine the discriminative capacity. RESULTS: Mean age was 62.3 ± 11.7 years and median baseline NIHSS was 12[IQR 8.0-18.0]. HT was detected in 30(27%) patients. Biomarker levels at 12 h were elevated with median MMP-9 concentration of 153.9 ng/mL[IQR 110.6-309 ng/mL] indicating a trend toward significant positive correlation with HT(P = 0.05). Claudin-5 levels at 12 h was elevated but was not statistically significant (43.1 pg/mL[IQR:26.7-72.6 pg/mL] vs 59.4 pg/mL[IQR:24.5-100.8 pg/mL];P = 0.4). Multiple logistic regression indicated Claudin-5 levels at 12 h (OR 9.46;95% CI:1.97-64.6;P = 0.010) and baseline low ASPECTS score(OR 20.3;95% CI:3.46-193; P = 0.003) independently predicted HT. MMP-9 at 12 h was significantly elevated in patients with moderate to severe strokes (P = 0.04). CONCLUSIONS: Claudin-5 and low ASPECTS independently predicted HT. MMP-9 was positively correlated with baseline stroke severity.