Proceedings of the Second Curing Coma Campaign NIH Symposium: Challenging the Future of Research for Coma and Disorders of Consciousness.

This proceedings article presents actionable research targets on the basis of the presentations and discussions at the 2nd Curing Coma National Institutes of Health (NIH) symposium held from May 3 to May 5, 2021. Here, we summarize the background, research priorities, panel discussions, and deliverables discussed during the symposium across six major domains related to disorders of consciousness. The six domains include (1) Biology of Coma, (2) Coma Database, (3) Neuroprognostication, (4) Care of Comatose Patients, (5) Early Clinical Trials, and (6) Long-term Recovery. Following the 1st Curing Coma NIH virtual symposium held on September 9 to September 10, 2020, six workgroups, each consisting of field experts in respective domains, were formed and tasked with identifying gaps and developing key priorities and deliverables to advance the mission of the Curing Coma Campaign. The highly interactive and inspiring presentations and panel discussions during the 3-day virtual NIH symposium identified several action items for the Curing Coma Campaign mission, which we summarize in this article.

Proceedings of the First Curing Coma Campaign NIH Symposium: Challenging the Future of Research for Coma and Disorders of Consciousness.

Coma and disorders of consciousness (DoC) are highly prevalent and constitute a burden for patients, families, and society worldwide. As part of the Curing Coma Campaign, the Neurocritical Care Society partnered with the National Institutes of Health to organize a symposium bringing together experts from all over the world to develop research targets for DoC. The conference was structured along six domains: (1) defining endotype/phenotypes, (2) biomarkers, (3) proof-of-concept clinical trials, (4) neuroprognostication, (5) long-term recovery, and (6) large datasets. This proceedings paper presents actionable research targets based on the presentations and discussions that occurred at the conference. We summarize the background, main research gaps, overall goals, the panel discussion of the approach, limitations and challenges, and deliverables that were identified.

Anticoagulation strategy for patients presenting with ischemic strokes while using a direct oral anticoagulant: A systematic review and meta-analysis.

BACKGROUND: While direct-acting oral anticoagulants (DOACs) have established efficacy in reducing the risk of ischemic stroke, they still leave a residual risk of stroke, which may be greater in practice (0.7-2.3%) than in controlled clinical trial settings. This meta-analysis examines four therapeutic approaches following a stroke in patients already on DOACs: continuing with the same DOAC, changing to a different DOAC, increasing the current DOAC dosage, or switching to a vitamin K antagonist (VKA), such as warfarin. METHODS: Systematic review of literature from the MEDLINE, Embase, and Cochrane databases, was conducted in line with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The analysis focused on six studies with varied patient demographics, examining as outcomes as recurrent ischemic stroke, intracranial hemorrhage, other bleeding events, and mortality. RESULTS: Six studies comprising 12,159 patients were included, all of them were observational. Patients who remained on their initial DOAC regimen had a lower risk of experiencing ischemic strokes (risk ratio (RR) 0.55; 95% confidence interval (CI) 0.43-0.70; p < 0.001; I2 = 0%), intracranial hemorrhage (RR 0.37; 95% CI 0.25-0.55; p < 0.001; I2 = 0%), and hemorrhagic events (RR 0.44; 95% CI 0.30-0.63; p < 0.001; I2 = 6%) compared to those who were switched to warfarin, with an increase in mortality rates (hazard ratio (HR) 1.85; 95% CI 1.06-3.24; p = 0.03; I2 = 84%). In contrast, neither changing to a different DOAC nor adjusting the dose proved to be more effective than the original regimen. CONCLUSION: Post-stroke adjustments to anticoagulation therapy-whether altering the drug or its dosage-do not yield additional benefits. In addition, the results suggest that warfarin may be less effective than DOACs for preventing stroke recurrence, bleeding complications, and death in this patient population.

Cerebrovascular disease in patients with antiphospholipid antibody syndrome: a transcranial Doppler and magnetic resonance imaging study.

Objective: Transcranial Doppler (TCD) and brain MRI may be useful in evaluating patients with APS, helping to stratify the risk of cerebrovascular ischaemic events in this population. This study aimed to assess the frequency of brain MRI abnormalities in patients with primary antiphospholipid syndrome, secondary antiphospholipid syndrome and SLE and correlate to TCD findings. Methods: The study, conducted over four years at two autoimmune disease referral centres, included 22 primary antiphospholipid syndrome patients, 24 secondary antiphospholipid syndrome patients, 27 SLE patients without APS and 21 healthy controls. All participants underwent TCD to assess cerebral haemodynamics, detect microembolic signals and evaluate right-to-left shunts, followed by brain MRI and magnetic resonance angiography. MRI scans were reviewed for acute microembolism, localized cortical infarctions, border infarctions, lacunar infarctions, ischaemic lesions, white matter hyperintensity, micro and macro haemorrhages and arterial stenosis ≥50% of the cervical carotid artery, by two neuroradiologists blinded to the clinical data. Results: Brain MRI findings were similar between the groups, except for lacunar infarction, more frequent in patients with secondary antiphospholipid syndrome (P = 0.022). Patients with intracranial stenosis detected by TCD had a higher frequency of territorial infarction (40% vs 7.5%, P = 0.02), lacunar (40% vs 11.3%, P = 0.075) and border zone infarcts (20% vs 1.9%, P = 0.034). Conclusions: Patients with intracranial stenosis presented a higher frequency of territorial, lacunar and border zone infarcts, suggesting that evaluating the intracranial vasculature should not be neglected in patients with APS and stroke.

The MAPSTROKE project: A computational strategy to improve access to acute stroke care.

BACKGROUND: Global access to acute stroke treatment is variable worldwide, with notable gaps in low and middle-income countries (LMIC), especially in rural areas. Ensuring a standardized method for pinpointing the existing regional coverage and proposing potential sites for new stroke centers is essential to change this scenario. AIMS: To create and apply computational strategies (CSs) to determine optimal locations for new acute stroke centers (ASCs), with a pilot application in nine Latin American regions/countries. METHODS: Hospitals treating acute ischemic stroke (AIS) with intravenous thrombolysis (IVT) and meeting the minimum infrastructure requirements per structured protocols were categorized as ASCs. Hospitals with emergency departments, noncontrast computed tomography (NCCT) scanners, and 24/7 laboratories were identified as potential acute stroke centers (PASCs). Hospital geolocation data were collected and mapped using the OpenStreetMap data set. A 45-min drive radius was considered the ideal coverage area for each hospital based on the drive speeds from the OpenRouteService database. Population data, including demographic density, were obtained from the Kontur Population data sets. The proposed CS assessed the population covered by ASCs and proposed new ASCs or artificial points (APs) settled in densely populated areas to achieve a target population coverage (TPC) of 95%. RESULTS: The observed coverage in the region presented significant disparities, ranging from 0% in the Bahamas to 73.92% in Trinidad and Tobago. No country/region reached the 95% TPC using only its current ASCs or PASCs, leading to the proposal of APs. For example, in Rio Grande do Sul, Brazil, the introduction of 132 new centers was suggested. Furthermore, it was observed that most ASCs were in major urban hubs or university hospitals, leaving rural areas largely underserved. CONCLUSIONS: The MAPSTROKE project has the potential to provide a systematic approach to identify areas with limited access to stroke centers and propose solutions for increasing access to AIS treatment. DATA ACCESS STATEMENT: Data used for this publication are available from the authors upon reasonable request.

An automated flowchart for the Modified Rankin Scale assessment: A multicenter inter-rater agreement analysis.

BACKGROUND AND OBJECTIVE: The Modified Rankin Scale (mRS) is a widely adopted scale for assessing stroke recovery. Despite limitations, the mRS has been adopted as primary outcome in most recent clinical acute stroke trials. Designed to be used by multidisciplinary clinical staff, the congruency of this scale is not consistent, which may lead to mistakes in clinical or research application. We aimed to develop and validate an interactive and automated digital tool for assessing the mRS-the iRankin. METHODS: A panel of five board-certified and mRS-trained vascular neurologists developed an automated flowchart based on current mRS literature. Two international experts were consulted on content and provided feedback on the prototype platform. The platform contained five vignettes and five real video cases, representing mRS grades 0-5. For validation, we invited neurological staff from six comprehensive stroke centers to complete an online assessment. Participants were randomized into two equal groups usual practice versus iRankin. The participants were randomly allocated in pairs for the congruency analysis. Weighted kappa (kw) and proportions were used to describe agreement. RESULTS: A total of 59 professionals completed the assessment. The kw was dramatically improved among nurses, 0.76 (95% confidence interval (CI) = 0.55-0.97) × 0.30 (0.07-0.67), and among vascular neurologists, 0.87 (0.72-1) × 0.82 (0.66-0.98). In the accuracy analysis, after the standard mRS values for the vignettes and videos were determined by a panel of experts, and considering each correct answer as equivalent to 1 point on a scale of 0-15, it revealed a higher mean of 10.6 (±2.2) in the iRankin group and 8.2 (±2.3) points in the control group (p = 0.02). In an adjusted analysis, the iRankin adoption was independently associated with the score of congruencies between reported and standard scores (beta coefficient = 2.22, 95% CI = 0.64-3.81, p = 0.007). CONCLUSION: The iRankin adoption led to a substantial or near-perfect agreement in all analyzed professional categories. More trials are needed to generalize our findings. Our user-friendly and free platform is available at https://www.irankinscale.com/.

Telemedicine networks for acute stroke: an analysis of global coverage, gaps and opportunities.

BACKGROUND: Despite the proven efficacy of telestroke in improving clinical outcomes by providing access to specialized expertise and allowing rapid expert hyperacute stroke management and decision-making, detailed operational evidence is scarce, especially for less developed or lower - income regions. AIM: We aimed to map the global telestroke landscape and characterize existing networks. METHODS: We employed a four-tiered approach to comprehensively identify telestroke networks, primarily involving engagement with national stroke experts, stroke societies, and international stroke authorities. A carefully designed questionnaire was then distributed to the leaders of all identified networks to assess these networks' structures, processes, and outcomes. RESULTS: We identified 254 telestroke networks distributed across 67 countries. High-income countries (HICs) concentrated 175 (69%) of the networks. No evidence of telestroke services was found in 58 (30%) countries. From the identified networks, 88 (34%) completed the survey, being 61 (71%) located in HICs. Network set-up was highly heterogenous, ranging from 17 (22%) networks with more than twenty affiliated hospitals, providing thousands of annual consultations using purpose-built highly specialized technology, to 11 (13%) networks with fewer than 120 consultations annually using generic videoconferencing equipment. Real-time video and image transfer was employed in 64 (75%) networks, while 62 (74%) conducting quality monitoring. Most networks established in the last three years were located in low- and middle-income countries (LMICs). CONCLUSIONS: This comprehensive global survey of telestroke networks found significant variation in network coverage, set-up, and technology use. Most services are in HICs, and few services are in LMICs, although an emerging trend of new networks in these regions marks a pivotal moment in global telestroke care. The wide variation in quality monitoring practices across networks, with many failing to report key performance metrics, underscores the urgent need for standardized, resource-appropriate quality assurance measures that can be adapted to diverse settings.

Safety and efficacy of factor XIa inhibition with milvexian for secondary stroke prevention (AXIOMATIC-SSP): a phase 2, international, randomised, double-blind, placebo-controlled, dose-finding trial.

BACKGROUND: People with factor XI deficiency have lower rates of ischaemic stroke than the general population and infrequent spontaneous bleeding, suggesting that factor XI has a more important role in thrombosis than in haemostasis. Milvexian, an oral small-molecule inhibitor of activated factor XI, added to standard antiplatelet therapy, might reduce the risk of non-cardioembolic ischaemic stroke without increasing the risk of bleeding. We aimed to estimate the dose-response of milvexian for recurrent ischaemic cerebral events and major bleeding in patients with recent ischaemic stroke or transient ischaemic attack (TIA). METHODS: AXIOMATIC-SSP was a phase 2, randomised, double-blind, placebo-controlled, dose-finding trial done at 367 hospitals in 27 countries. Eligible participants aged 40 years or older, with acute (<48 h) ischaemic stroke or high-risk TIA, were randomly assigned by a web-based interactive response system in a 1:1:1:1:1:2 ratio to receive one of five doses of milvexian (25 mg once daily, 25 mg twice daily, 50 mg twice daily, 100 mg twice daily, or 200 mg twice daily) or matching placebo twice daily for 90 days. All participants received clopidogrel 75 mg daily for the first 21 days and aspirin 100 mg daily for the first 90 days. Investigators, site staff, and participants were masked to treatment assignment. The primary efficacy endpoint was the composite of ischaemic stroke or incident covert brain infarct on MRI at 90 days, assessed in all participants allocated to treatment who completed a follow-up MRI brain scan, and the primary analysis assessed the dose-response relationship with Multiple Comparison Procedure-Modelling (MCP-MOD). The main safety outcome was major bleeding at 90 days, assessed in all participants who received at least one dose of the study drug. This trial is registered with ClinicalTrials.gov (NCT03766581) and the EU Clinical Trials Register (2017-005029-19). FINDINGS: Between Jan 27, 2019, and Dec 24, 2021, 2366 participants were randomly allocated to placebo (n=691); milvexian 25 mg once daily (n=328); or twice-daily doses of milvexian 25 mg (n=318), 50 mg (n=328), 100 mg (n=310), or 200 mg (n=351). The median age of participants was 71 (IQR 62-77) years and 859 (36%) were female. At 90 days, the estimates of the percentage of participants with either symptomatic ischaemic stroke or covert brain infarcts were 16·8 (90·2% CI 14·5-19·1) for placebo, 16·7 (14·8-18·6) for 25 mg milvexian once daily, 16·6 (14·8-18·3) for 25 mg twice daily, 15·6 (13·9-17·5) for 50 mg twice daily, 15·4 (13·4-17·6) for 100 mg twice daily, and 15·3 (12·8-19·7) for 200 mg twice daily. No significant dose-response was observed among the five milvexian doses for the primary composite efficacy outcome. Model-based estimates of the relative risk with milvexian compared with placebo were 0·99 (90·2% CI 0·91-1·05) for 25 mg once daily, 0·99 (0·87-1·11) for 25 mg twice daily, 0·93 (0·78-1·11) for 50 mg twice daily, 0·92 (0·75-1·13) for 100 mg twice daily, and 0·91 (0·72-1·26) for 200 mg twice daily. No apparent dose-response was observed for major bleeding (four [1%] of 682 participants with placebo, two [1%] of 325 with milvexian 25 mg once daily, two [1%] of 313 with 25 mg twice daily, five [2%] of 325 with 50 mg twice daily, five [2%] of 306 with 100 mg twice daily, and five [1%] of 344 with 200 mg twice daily). Five treatment-emergent deaths occurred, four of which were considered unrelated to the study drug by the investigator. INTERPRETATION: Factor XIa inhibition with milvexian, added to dual antiplatelet therapy, did not substantially reduce the composite outcome of symptomatic ischaemic stroke or covert brain infarction and did not meaningfully increase the risk of major bleeding. Findings from our study have informed the design of a phase 3 trial of milvexian for the prevention of ischaemic stroke in patients with acute ischaemic stroke or TIA. FUNDING: Bristol Myers Squibb and Janssen Research & Development.

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.

Predictors of hemorrhagic transformation differences between patients treated or not with reperfusion therapy.

BACKGROUND: Hemorrhagic transformation (HT) is a dreaded complication in stroke patients who were treated or not with recombinant tissue plasminogen activator (tPA). There are many predictive scores of HT, but all of them included patients treated with tPA. Molecular effects of tPA and clinical aspects of eligible patients for tPA therapy may imply specific HT's risk factors. We aimed to describe HT's characteristics and risk factors in patients treated or not with tPA. METHODS: We included 1565 consecutive stroke patients admitted to a Comprehensive Stroke Center, from 2015 to 2017. All included patients underwent a follow-up neuroimaging within seven days after admission. From a logistic regression model, we derived a score based on the beta-coefficients. The accuracy of the models was attested by Receiver Operating Characteristic analysis. RESULTS: Low ASPECTS, blood glucose ≥ 180 mg/dL, tPA treatment, and cardio-aortic embolism were predictors of HT. Male sex, leukoaraiosis, and hyperdense MCA sign were associated with HT in non-treated patients. Diastolic blood pressure ≥ 105 mmHg was a risk factor only in non-treated patients. The cutoff of our predictive score of HT was higher in patients not treated with tPA (5 vs 2 points). CONCLUSIONS: High arterial blood pressure was associated with HT only in patients treated with tPA. Different cutoffs and accuracy measurements suggest that scoring systems derived from patients treated with tPA may not be efficient to predict HT in non-treated patients. Further directions indicate considering the use of reperfusion therapies to select the most accurate predictive variables of HT.

Maintaining stroke care during the COVID-19 pandemic in lower- and middle-income countries: World Stroke Organization Position Statement endorsed by American Stroke Association and American Heart Association.

For more than a year, the SARS-CoV-2 pandemic has had a devastating effect on global health. High-, low-, and middle-income countries are struggling to cope with the spread of newer mutant strains of the virus. Delivery of acute stroke care remains a priority despite the pandemic. In order to maintain the time-dependent processes required to optimize delivery of intravenous thrombolysis and endovascular therapy, most countries have reorganized infrastructure to optimize human resources and critical services. Low-and-middle income countries (LMIC) have strained medical resources at baseline and often face challenges in the delivery of stroke systems of care (SSOC). This position statement aims to produce pragmatic recommendations on methods to preserve the existing SSOC during COVID-19 in LMIC and propose best stroke practices that may be low cost but high impact and commonly shared across the world.

The Role of Transthoracic Echocardiography in the Evaluation of Patients With Ischemic Stroke.

Background: Ischemic stroke can be classified into five etiological types, according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification, and its adequate investigation and characterization can aid in its clinical management and in preventing new events. Transthoracic echocardiography (TTE) plays a key role in investigating its etiology; approximately one-third of the patients remain without an adequate definition of the etiology or are classified as the undetermined TOAST type. Objectives: To evaluate if the percentage of patients with indeterminate etiology according to the TOAST classification decreased after transthoracic echocardiography, to determine whether or not the prognosis after ischemic stroke is worse among patients classified as the undetermined TOAST type, and to verify the predictive capacity of echocardiography on the prognosis after ischemic stroke. Methods: In this retrospective cohort study, clinical, neurological, and echocardiographic examinations were conducted when the patient was hospitalized for stroke. In-hospital mortality and functional capacity were evaluated at hospital discharge and 90 days thereafter. Multiple linear regression and multiple logistic regression models were adjusted for confounding factors. The level of significance was 5%. Results: A total of 1,100 patients (men = 606; 55.09%), with a mean age of 68.1 ± 13.3 years, were included in this study. Using TTE, 977 patients (88.82%) were evaluated and 448 patients (40.7%) were classified as the undetermined TOAST type. The patients who underwent TTE were 3.1 times less likely to classified as the undetermined TOAST type (OR = 0.32; p < 0.001). Echocardiography during hospitalization was a protective factor against poor prognosis, and reduced the odds of in-hospital death by 11.1 times (OR: 0.090; p < 0.001). However, the presence of the undetermined TOAST classification elevated the chance of mortality during hospitalization by 2.0 times (OR: 2.00; p = 0.013). Conclusions: Echocardiography during hospitalization for ischemic stroke reduces the chances of an undetermined TOAST classification and the risk of in-hospital mortality. However, being classified as the undetermined TOAST type increases the chance of mortality during hospitalization, suggesting that evaluating patients using echocardiography during hospitalization for acute ischemic stroke is important.

Postcardiac Arrest Neuroprognostication Practices: A Survey of Brazilian Physicians.

End-of-life care and decisions on withdrawal of life-sustaining therapies vary across countries, which may affect the feasibility of future multicenter cardiac arrest trials. In Brazil, withdrawal of life-sustaining therapy is reportedly uncommon, allowing the natural history of postcardiac arrest hypoxic-ischemic brain injury to present itself. We aimed to characterize approaches to neuroprognostication of cardiac arrest survivors among physicians in Brazil. DESIGN: Cross-sectional study. SETTING: Between August 2, 2019, and July 31, 2020, we distributed a web-based survey to physicians practicing in Brazil. SUBJECTS: Physicians practicing in Brazil and members of the Brazilian Association of Neurointensive Care, who care for patients resuscitated following cardiac arrest. INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN RESULTS: Responses from 185 physicians were obtained. Pupillary reflexes, corneal reflexes, and motor responses were considered critical to prognostication, whereas neuroimaging and electroencephalography were also regarded as important. For patients without targeted temperature management, absent pupillary and corneal reflexes at 24 hours postarrest were considered strongly predictive of poor neurologic outcome by 31.8% and 33.0%, respectively. For targeted temperature management-treated patients, absent pupillary and corneal reflexes at 24-hour postrewarming were considered prognostic by 22.9% and 20.0%, respectively. Physicians felt comfortable making definitive prognostic recommendations at day 6 postarrest or later (34.2%) for nontargeted temperature management-treated patients, and at day 6 postrewarming (20.4%) for targeted temperature management-treated patients. Over 90% believed that improving neuroprognostic accuracy would affect end-of-life decision-making. CONCLUSIONS: There is significant variability in neuroprognostic approaches to postcardiac arrest patients and timing of prognostic studies among Brazilian physicians, with practices frequently deviating from current guidelines, underscoring a need for greater neuroprognostic accuracy. Nearly all physicians believed that improving neuroprognostication will impact end-of-life decision-making. Given the tendency to delay prognostic recommendations while using similar neuroprognostic tools, Brazil offers a unique cohort in which to examine the natural history of hypoxic-ischemic brain injury in future studies.

Acute treatment costs of stroke in Brazil.

BACKGROUND AND PURPOSE: Although stroke is the leading cause of death in Brazil, little information exist on the acute treatment provided for stroke and its associated costs. This study addresses this gap by both clinically and economically characterizing the acute treatment of first-ever intracerebral hemorrhage (ICH) and ischemic stroke (IS) in Brazil. METHODS: Retrospective medical chart review using data from two high-volume stroke centers in São Paulo, Brazil. Clinical and resource utilization data for all patients admitted to the stroke centers with a first-ever stroke between January 1, 2006 and May 31, 2007 were collected and the mean acute treatment costs per person were calculated by assigning appropriate unit cost data to all resource use. Cost estimates in Brazilian reals (BRL) were converted to US dollars (USD) using the 2005 purchasing power parity index. National costs of acute treatment for incident strokes were estimated by extrapolation of mean cost estimate per person to national incidence data for the two types of stroke. The mean costs of acute treatment on a national scale were examined in sensitivity analysis. RESULTS: A total of 316 stroke patients were identified and their demographic and clinical characteristics, patterns of care, and outcomes were examined. Mean length of hospital stay was 12.0 +/- 8.8 days for ICH and 13.3 +/-23.4 days for IS. Ninety-one percent of the ICH patients and 68% of the IS patients were admitted to an intensive care unit (ICU). Mean total costs of initial hospitalization were USD 4,101 (SD +/-4,254) for ICH and USD 1,902 (SD +/-1,426) for IS. In multivariate analysis, hemorrhagic stroke, development of pneumonia, neurosurgical intervention, stay in ICU, and physical therapy were all significant independent predictors of acute treatment costs. Aggregate national health care expenditures for acute treatment of incident ICH were USD 122.4 million (range 30.8-274.2) and USD 326.9 million for IS (range 82.4-732.2). CONCLUSION: Acute treatment costs of incident ICH and IS in Brazil are substantial and primarily driven by the intensity of hospital treatment and in-hospital complications. With the expected increase in the incidence of stroke in Brazil over the coming decades, these results emphasize the need for effective preventive and acute medical care.

Priorities to reduce the burden of stroke in Latin American countries.

The large and increasing burden of stroke in Latin American countries, and the need to meet the UN and WHO requirements for reducing the burden from non-communicable disorders (including stroke), brought together stroke experts and representatives of the Ministries of Health of 13 Latin American countries for the 1st Latin American Stroke Ministerial meeting in Gramado, Brazil, to discuss the problem and identify ways of cooperating to reduce the burden of stroke in the region. Discussions were focused on the regional and country-specific activities associated with stroke prevention and treatment, including public stroke awareness, prevention strategies, delivery and organisation of care, clinical practice gaps, and unmet needs. The meeting culminated with the adoption of the special Gramado Declaration, signed by all Ministerial officials who attended the meeting. With agreed priorities for stroke prevention, treatment, and research, an opportunity now exists to translate this Declaration into an action plan to reduce the burden of stroke.

Embolic Stroke of Undetermined Source in Latin America: A Review.

BACKGROUND: Stroke is a major health concern throughout Latin America. As elsewhere, no precise cause can be determined for a substantial portion of strokes. In 6 studies since 2010 in the region, 16% to 43% of ischemic strokes were identified as cryptogenic. The term embolic stroke of undetermined source (ESUS) has been proposed as more clinically useful and positively defined than the vague term cryptogenic. The epidemiology of ESUS in Latin America is largely unknown. REVIEW SUMMARY: This article aims to provide a description of the epidemiology of ESUS in Latin America and practical information regarding available diagnostic procedures and current guidelines. Atrial fibrillation (AF) is a significant risk factor for stroke, observed in approximately 10% of Mexican and Brazilian stroke patients. Previously unknown AF has been detected through extended monitoring in numerous studies of stroke patients, including 8% of patients in an Argentinian study, and is a possible contributing cause of ESUS. External or implantable outpatient cardiac monitoring has shown increased diagnostic yield for the detection of intermittent AF versus standard cardiac monitoring, but is infrequently used in Latin America. CONCLUSIONS: Undiagnosed AF is likely to contribute significantly to cryptogenic stroke and ESUS. Research is needed to continue evaluation of the optimum means of identifying clinically relevant occult AF. In view of the thromboembolic mechanism of ESUS, anticoagulant therapy may prove useful in prevention of recurrence. Ongoing trials are evaluating use of dabigatran, rivaroxaban, or apixaban versus aspirin for reducing the risk of recurrent stroke in patients with previous ESUS.

Get with the guidelines stroke performance indicators in a brazilian tertiary hospital.

BACKGROUND: Stroke is the fourth leading killer in the US, the first in Brazil and a leading cause of adult long-term disability in both countries. In spite of widespread recommendation, clinical practice guidelines have had limited effect on changing physician behavior. Recognizing that both knowledge and acceptance of guidelines do not necessarily imply guideline adherence, the American Heart Association/American Stroke Association (AHA/ASA) developed a national stroke quality improvement program, the 'Get With The Guidelines (GWTG) stroke'. Even though GWTG has produced remarkable results in the US, other countries have not adopted the program. METHODS: We compared the stroke treatment quality indicators from a private Brazilian tertiary hospital to those published by the GWTG stroke program. Seven predefined performance measures selected by the GWTG stroke program as targets for stroke quality improvement were evaluated: (1) tissue plasminogen activator use in patients who arrived <2 h from symptom onset; (2) antithrombotic medication use within 48 h of admission; (3) deep vein thrombosis prophylaxis within 48 h of admission for nonambulatory patients; (4) discharge use of antithrombotics; (5) discharge use of anticoagulation for atrial fibrillation; (6) dosing of LDL and treatment for LDL >100 mg/dl in patients meeting the National Cholesterol Education Program Adult Treatment Panel (NCEP) III guidelines, and (7) counseling for smoking cessation. RESULTS: A total of 343 consecutive patients with acute ischemic stroke (70.8%) or transient ischemic attack (29.2%) were evaluated from August 2008 to December 2010. Antithrombotic medication within 48 h was used in 98.5% of the eligible patients and deep vein thrombosis prophylaxis in 100%. A total of 123 patients arrived within 2 h from symptoms onset, 23 were eligible for intravenous thrombolysis and 16 were treated (69.5%). All eligible patients were discharged using antithrombotic medication, and 86.9% of the eligible patients who had atrial fibrillation received anticoagulation. Only 56.1% of the eligible patients were treated according to the NCEP III guidelines. Counseling for smoking cessation was done in 63.6% of the eligible patients. CONCLUSIONS: Our study is the first in Brazil and the second outside the US to analyze compliance with the GWTG recommendations. Close attention to a better implementation of these measures may produce an improvement in such results similar to what happened after the full implementation of the program in the US. Whether or not a US disease-based registry such as GWTG can be adopted with success beyond the US is still a matter of debate.

The challenge of managing fusiform basilar artery aneurysms: from acute ischemic stroke to a massive subarachnoid hemorrhage.

We present the case of a patient with acute brain stem ischemic stroke who was found to have a fusiform basilar aneurysm with a thrombus within the dilated vessel. Three days after the ischemic stroke, the patient had a massive subarachnoid hemorrhage and died. This case illustrates the difficulties in the acute management of ischemic events in patients with basilar fusiform aneurysms, because the natural history of this disease encompasses both bleeding and thrombosis.