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Introduction: Poststroke apathy (PSA) is a common neuropsychiatric disorder that may affect up to 30% of stroke patients. Despite the difficulties of investigating this condition (overlapping with depression, heterogeneity of diagnostic criteria, a small number of studies), some recent diffusion tensor imaging studies have suggested that widespread microstructural white matter (WM) disruption plays a key role in the development of PSA. Therefore, we intended to investigate this hypothesis by evaluating the relationship between WM hyperintensities (WMH) and apathy in patients with cerebrovascular disease. Methods: We studied patients with apathy (n = 7), depression (n = 13), comorbid apathy and depression (n = 13), and controls (n = 20), and we investigated the variables associated with the volume of WMH measured by an automated brain MRI segmentation software. Results: The overall prevalence of PSA was 37.7% (pure and comorbid). Patients with apathy presented a higher volume of WMH in comparison to controls. Mini-Mental State Examination (MMSE), NPI-A, and the number of cerebral microbleeds were the only variables associated with WMH. Conversely, NPI-D did not correlate to WMH. Discussion/Conclusion: This is an exploratory study that supports the view of PSA as a distinct syndrome from PSD mediated mainly by diffuse white matter hyperintensities, which suggests that WM disruption is an important pathway to the development of apathy in stroke patients.

Introduction: Cerebral small vessel disease (cSVD) involves a myriad of pathogenic mechanisms affecting small vessels of the brain, leading to a significant impact on motor and cognitive functions, and it is the main cause of Vascular cognitive impairment (VCI). The endothelial glycocalyx (EG), the layer lining the vascular endothelium, has a pivotal player in maintaining the proper function of neurovascular unit, and its degradation may be involved in VCI due to cSVD. Objectives: to investigate the relationship between markers of EG damage and VCI related to cSVD. Methods: Cross-sectional study based on clinical data and serum samples for the quantification of EG damage markers (syndecan-1, hyaluran) of VCI related to cSVD patients and of a control group derived from a dataset of healthy workers from the same institution. We used an automatic logarithm for segmentation and volumetric evaluation of white matter lesions on brain MRI of the patients. Logistic regression models and c-statistics were used to identify the independent variables related to VCI and investigate the accuracy of syndecan-1 to detect VCI. We studied the association of thebiomarkers and MoCA scores, index of independence in activities of daily living and whitematter lesion burden respectively. Results: Between July 2019 and March 2020, we studied 22 patients with VCI associated with cSVD and compared them with a dataset of 22 healthy workers from the same institution. Patients with VCI were older, had a higher prevalence of diabetesmellitus and hypertension, had a worse index of independence for daily activities, and higherlevels of syndecan-1 (78,4 vs 24; p < 0,01). There was no difference in hyaluran levels between both groups. In multivariate analysis, only age (OR 1,35;CI 1,04 - 1,76; p = 0,02) and syndecan-1 levels (OR 1,08;CI 1,01 - 1,15;p = 0,01) related to VCI. The ROC curve ofsyndecan-1 levels to predict VCI had a area under de curve of 0,78 (CI 0,64 - 0,92) and there was a correlation between syndecan-1 levels and MoCA scores (rho = - 0,34;p = 0,02). There were no correlations between syndecan-1 and hyaluran levels and index of independence and white matter lesion burden respectively. Conclusions: Syndecan-1, but not hyaluran, is a potential biomarker for VCI associated with cSVD.

Background: Simulations are becoming widely used in medical education, but there is little evidence of their effectiveness on neurocritical care. Because acute stroke is a neurological emergency demanding prompt attention, it is a promising candidate for simulation training. Objective: To assess the impact of a stroke realistic simulation course on clinicians’ self-perception of confidence in the management of acute stroke. Methods: We conducted a controlled, before-after study. For our intervention, 17 healthcare professionals participated in a stroke realistic simulation course. As controls, participants were chosen from a convenience sample of attendees to the courses Emergency Neurologic Life Support (ENLS) (18 participants) and Neurosonology (20 participants). All participants responded pre- and post-test questionnaires evaluating their self-perception of confidence in acute stroke care, ranging from 10 to 50 points. We evaluated the variation between pre- and post-test results to assess the change on trainees’ self-perception of confidence in the management of acute stroke. Multivariate analysis was performed to control for potential confounders. Results: Forty-six (83.63%) subjects completed both questionnaires. The post-test scores were higher than those from the pretests in the stroke realistic simulation course group [pretest median (interquartile range - IQR): 41.5 (36.7-46.5) and post-test median (IQR): 47 (44.7-48); p=0.033], but not in the neurosonology [pretest median (IQR): 46 (44-47) and post-test median (IQR): 46 (44-47); p=0.739] or the ENLS [pretest median (IQR): 46.5 (39-48.2), post-test median (IQR): 47 (40.2-49); p=0.317] groups. Results were maintained after adjustment for covariates. Conclusions: This stroke realistic simulation course was associated with an improvement on trainees’ self-perception of confidence in providing acute stroke care. RESUMO Introdução: Simulações são amplamente utilizadas na educação médica, mas há pouca evidência de sua eficácia no tratamento de pacientes neurocríticos. Como o acidente vascular cerebral agudo (AVC) é uma patologia que requer atendimento imediato, o uso de simulação pode ser uma ferramenta útil no treinamento do manejo desses pacientes. Objetivo: Avaliar o impacto do uso de simulação realística na autopercepção de segurança no atendimento a pacientes vítimas de AVC agudo. Métodos: Estudo antes-depois controlado. No grupo da intervenção, 17 profissionais da área de saúde participaram de um curso de simulação realística de atendimento a pacientes com AVC. Como controles, os participantes foram escolhidos a partir de uma amostra de conveniência composta por 18 participantes do curso Emergency Neurologic Life Support (ENLS) e 20 participantes de um curso de Neurossonologia. Foram respondidos questionários antes e após o curso para avaliar a autopercepção de segurança no atendimento a pacientes vítimas de AVC agudo, variando de 10 a 50 pontos. Foi avaliada a variação entre os resultados pré- e pós-teste, para avaliar a mudança na autopercepção de confiança do trainee no manejo do AVC agudo. Análise multivariada foi realizada para controlar possíveis fatores de confusão. Resultados: Quarenta e seis (83,63%) participantes responderam aos questionários. A pontuação no questionário pós-curso foi maior do que a obtida no questionário pré-curso no grupo de participantes do curso de simulação realística em AVC [mediana do questionário pré-curso: 41,5 (36,7-46,5) e mediana do questionário pós-curso: 47,0 (44,7-48,0); p=0,033]. Essa diferença não foi observada no curso de Neurossonologia [mediana pré-curso (IQR): 46,0 (44,0-47,00), mediana pós-curso (IQR): 46,0 (44,0-47,0); p=0,739] nem no ENLS [mediana pré-curso (IQR): 46,5 (39,0-48,2) mediana pós-curso (IQR): 47,0 (40,2-49,0); p=0,317]. Esses resultados persistiram após ajuste das variáveis. Conclusão: O curso de simulação realística em AVC foi associado a um aumento na autopercepção de segurança dos participantes em atender pacientes vítimas de AVC agudo.

Ischemic stroke is a leading cause of morbidity and mortality worldwide. Embolic stroke of undetermined source has been recently proposed to categorize nonlacunar ischemic strokes without confirmed etiology after adequate investigation with a likely embolic stroke mechanism. A strategy of empirical anticoagulation for embolic stroke of undetermined source patients is attractive but may only be beneficial in a select subset of patients. Strategies which would help identify the subset of embolic stroke of undetermined source patients most likely to have cardioembolic origin of stroke, and hence benefit from anticoagulation, are needed. This article will review current evidence which may be useful in the development of a risk stratification approach based on arrhythmia monitoring, cardiac imaging, and clinical risk stratification. This approach may be beneficial in clinical practice in improving patient outcomes and reducing stroke recurrence in this population; however, further work is required with active trials underway.

Background and Purpose: In thrombolysis-eligible patients with acute ischemic stroke, there is uncertainty over the most appropriate systolic blood pressure (SBP) lowering profile that provides an optimal balance of potential benefit (functional recovery) and harm (intracranial hemorrhage). We aimed to determine relationships of SBP parameters and outcomes in thrombolyzed acute ischemic stroke patients. Methods: Post hoc analyzes of the ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study), a partial-factorial trial of thrombolysis-eligible and treated acute ischemic stroke patients with high SBP (150–180 mm Hg) assigned to low-dose (0.6 mg/kg) or standard-dose (0.9 mg/kg) alteplase and intensive (target SBP, 130–140 mm Hg) or guideline-recommended (target SBP Results: Among 4511 included participants (mean age 67 years, 38% female, 65% Asian) lower attained SBP and smaller SBP variability were associated with favorable shift on the modified Rankin Scale (per 10 mm Hg increase: odds ratio, 0.76 [95% CI, 0.71–0.82]; P P =0.025) respectively, but not for magnitude of SBP reduction (0.98, [0.93–1.04]; P =0.564). Odds of intracranial hemorrhage was associated with higher attained SBP and greater SBP variability (1.18 [1.06–1.31]; P =0.002 and 1.34 [1.11–1.62]; P =0.002) but not with magnitude of SBP reduction (1.05 [0.98–1.14]; P =0.184). Conclusions: Attaining early and consistent low levels in SBP Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01422616.

Objective: Uncertainty exists over the prognostic significance of low arterial oxygen saturation (SaO(2)) in acute stroke. We aimed to determine the strength of association of SaO(2) and adverse outcomes among participants of the international Head Positioning in acute Stroke Trial (HeadPoST). Methods: Post-hoc analyzes of HeadPoST, a pragmatic cluster-crossover randomized trial of lying flat versus sitting up head positioning in 11,093 patients (age >= 18 years) with acute stroke at 114 hospitals in 9 countries during 2015-2016. Associations of the lowest recorded SaO(2) level, as a continuous measure and as a cut-point for desaturation (SaO(2)

The corneal reflex assesses the integrity of the trigeminal and facial cranial nerves. This brainstem reflex is fundamental in neuroprognostication after cardiac arrest and in brain death determination. We sought to investigate corneal reflex testing methods among neurologists and general critical care providers in the context of neuroprognostication following cardiac arrest. This is an international cross-sectional study disseminated to members of the Neurocritical Care Society, Society of Critical Care Medicine, and American Academy of Neurology. We utilized an open Web-based survey (Qualtrics®, Provo, UT, USA) to disseminate 26 questions regarding neuroprognostication practices following cardiac arrest, in which 3 questions pertained to corneal reflex testing. Descriptive statistical measures were used, and subgroup analyses performed between neurologists and non-neurologists. Questions were not mandatory; therefore, the percentages were relative to the number of respondents for each question. There were 959 respondents in total. Physicians comprised 85.1% of practitioners (762 out of 895), of which 55% (419) identified themselves as non-neurologists and 45% (343) as neurologists. Among physicians, 85.9% (608 out of 708) deemed corneal reflex relevant for prognostication following cardiac arrest (neurologists 84.4% versus non-neurologists 87.0%). A variety of techniques were employed for corneal reflex testing, the most common being “light cotton touch” (59.2%), followed by “cotton-tipped applicator with pressure” (23.9%), “saline or water squirt” (15.9%), and “puff of air” (1.0%). There were no significant differences in the methods for testing between neurologists and non-neurologists (p = 0.52). The location of stimulus application was variable, and 26.1% of physicians (148/567) apply the stimulus on the temporal conjunctiva rather than on the cornea itself. Corneal reflex testing remains a cornerstone of the coma exam and is commonly used in neuroprognostication of unconscious cardiac arrest survivors and in brain death determination. A wide variability of techniques is noted among practitioners, including some that may provide suboptimal stimulation of corneal nerve endings. Imprecise testing in this setting may lead to inaccuracies in critical settings, which carries significant consequences such as guiding decisions of care limitations, misdiagnosis of brain death, and loss of public trust.

Since neuronal activity is coupled with neurovascular activity, we aimed to analyze the cerebral blood flow hemodynamics during and following high-definition transcranial direct current stimulation (HD-tDCS). We assessed the mean middle cerebral artery blood flow velocity (MCA-BFv) bilaterally using transcranial doppler ultrasound, during and after HD-tDCS, in eleven right-handed healthy adult participants (6 women, 5 men; mean age 31 ± 5.6 years old), with no evidence of brain or cardiovascular dysfunction. The HD-tDCS electrode montage was centered over the right temporo-parietal junction. The stimulation protocol comprised 3 blocks of 2 min at each current intensity (1, 2, and 3 mA) and an inter-stimulus interval of 5 min between blocks. Participants received three electrical stimulation conditions (anode center, cathode center, and sham) on three different days, with an interval of at least 24 h. Stimulation was well tolerated across HD-tDCS conditions tested, and the volunteers reported no significant discomfort related to stimulation. There was no significant difference in the right or the left MCA-BFv during or after the stimulation protocol across all stimulation conditions. We conclude that at a range of intensities, vascular reaction assessed using middle cerebral artery blood flow is not significantly altered during or after HD-tDCS both locally and remotely, which provides further evidence for the safety of HD-tDCS.

COVID-19 may be associated with neurologic complications. Patients with COVID-19 may develop an acute inflammatory painful polyradiculoneuritis that seems to respond to intravenous human immunoglobulin.

BackgroundDuring the COVID-19 pandemic, decreased volumes of stroke admissions and mechanical thrombectomy were reported. The study’s objective was to examine whether subarachnoid haemorrhage (SAH) hospitalisations and ruptured aneurysm coiling interventions demonstrated similar declines.MethodsWe conducted a cross-sectional, retrospective, observational study across 6 continents, 37 countries and 140 comprehensive stroke centres. Patients with the diagnosis of SAH, aneurysmal SAH, ruptured aneurysm coiling interventions and COVID-19 were identified by prospective aneurysm databases or by International Classification of Diseases, 10th Revision, codes. The 3-month cumulative volume, monthly volumes for SAH hospitalisations and ruptured aneurysm coiling procedures were compared for the period before (1 year and immediately before) and during the pandemic, defined as 1 March–31 May 2020. The prior 1-year control period (1 March–31 May 2019) was obtained to account for seasonal variation.FindingsThere was a significant decline in SAH hospitalisations, with 2044 admissions in the 3 months immediately before and 1585 admissions during the pandemic, representing a relative decline of 22.5% (95% CI −24.3% to −20.7%, pInterpretationThere was a relative decrease in the volume of SAH hospitalisations, aneurysmal SAH hospitalisations and ruptured aneurysm embolisations during the COVID-19 pandemic. These findings in SAH are consistent with a decrease in other emergencies, such as stroke and myocardial infarction.

Background Acute basilar artery occlusion is a devastating life-threatening condition. Early recanalization is the therapeutic goal in patients with acute ischemic stroke. Despite the high rates of recanalization achieved with modern devices for basilar occlusions, many patients have had poor clinical outcomes. This study aimed to assess the predictors of good and poor outcomes among patients with basilar artery occlusion treated with thrombectomy. Methods A consecutive registry of 80 patients was included in this retrospective study. The primary end point was to access variables associated with neurologic outcomes defined by a modified Rankin Scale (mRS) score of 0–2, symptomatic intracranial hemorrhage (sICH), and mortality at 3 months follow-up. Results Recanalization was achieved in 86.2%, and the sICH rate was 8.7%. A good neurologic outcome (mRS score 0–2) was observed in 26.2% and a moderate outcome (mRS score 0–3) in 32.5% of patients. The mortality was 38.7% at 3 months follow-up. Conclusions After thrombectomy for posterior circulation strokes, young patients, V4–proximal basilar occlusion, (high) baseline posterior circulation Alberta Stroke Program Early CT Score, and complete recanalization were independent predictors of good neurologic outcomes. Failure to recanalize was strongly related to sICH and mortality. In addition, diabetes, atrial fibrillation, and baseline National Institutes of Health Stroke Scale scores ≥10 had an independent association with mortality. This study contributes to the knowledge required to optimize recanalization treatments for posterior circulation strokes and may help to improve future clinical studies.

Made available in DSpace on 2020-12-12T00:07:54Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-08-01 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Background: Well studied in patients with ischemic stroke after reperfusion thera-pies (RT), hemorrhagic transformation (HT) is also common in patients not treated with RT and can lead to disability even in initially asymptomatic cases. The best predictors of HT in patients not treated with RT are not well established. Therefore, we aimed to identify predictors of HT in patients not submitted to RT and create a user-friendly predictive score (PROpHET). Material and Methods: Patients admitted to a Comprehensive Stroke Center from 2015 to 2017 were prospectively evaluated and randomly selected to the derivation cohort. A multivariable logistic regression modeling was built to produce a predictive grading score for HT. The external vali-dation was assessed using datasets from 7 Comprehensive Stroke Centers using the area under the receiver operating characteristic curve (AUROC). Results: In the derivation group, 448 patients were included in the final analysis. The validation group included 2,683 patients. The score derived from significant predictors of HT in the multivariate logistic regression analysis was male sex (1 point), ASPECTS = 180 mg/dL (1 point), cardioembolism (1 point) and lacunar syndrome (-3 points) as a protective factor. The grading score ranges from -3 to 7. A Score >= 3 had 78.2% sensitivity and 75% specificity, and AUROC of 0.82 for all cases of HT. In the validation cohort, our score had an AUROC of 0.83. Conclusions: The PROpHET is a simple, quick, cost-free, and easy-to-perform tool that allows risk stratification of HT in patients not submitted to RT. A cost-free computerized version of our score is available online with a user-friendly interface. Univ Fed Sao Paulo, Rua Napoleao Barros 715, Sao Paulo, SP, Brazil Columbia Univ, Doris & Stanley Tananbaum Stroke Ctr, Neurol Inst New York, 710 W 168th St,6TH Floor,NI 614, New York, NY 10032 USA Univ Fortaleza, Fortaleza, Cear, Brazil Hosp Geral Fortaleza, Fortaleza, Ceara, Brazil Univ Fed Ceara, Campus Quixada, Quixada, CE, Brazil Univ Fed Bahia, Salvador, BA, Brazil Univ Sao Paulo, Ribeirao Preto, Brazil Univ Estadual Paulista, Sao Paulo, Brazil Hosp Inst Neurol Curitiba, Curitiba, Parana, Brazil Hosp Geral Fortaleza, Rua Avila Goulart 900, Fortaleza, CE, Brazil Praca 15 Novembro SN, Salvador, BA, Brazil Hosp Clin, Floor 4th, Ribeirao Preto, SP, Brazil Av Prof Mario Rubens Guimaraes Montenegro, Botucatu, SP, Brazil R Jeremias Maciel Perretto 300, Curitiba, PR, Brazil Hosp Israelita Brasileiro Albert Einstein, Rua Albert Einstein 627, Sao Paulo, SP, Brazil Univ Estadual Paulista, Sao Paulo, Brazil

BackgroundAlthough the Head Positioning in acute Stroke Trial (HeadPoST) showed no effect of the flat head position (FP; vs sitting up head position (SUP)) on functional outcome, we hypothesised that it could still offer benefits if commenced early in those with acute ischaemic stroke (AIS) of at least moderate severity.MethodsSubgroup analysis of HeadPoST in participants with National Institutes of Health Stroke Scale (NIHSS) scores ≥7, ≥10 and ≥14, randomised to FP or SUP ResultsThere was no significant differential treatment effect in patient subgroups defined by increasing baseline NIHSS scores: adjusted OR and 95% CI for ordinal shift and binary (3–6) mRS scores: for NIHSS ≥7 (n=867) 0.92 (0.67 to 1.25) and 0.74 (0.52 to 1.04); NIHSS ≥ 10 (n=606) 0.80 (0.58 to 1.10) and 0.77 (0.49 to 1.19); NIHSS ≥14 (n=378) 0.82 (0.54 to 1.24) and 1.22 (0.69 to 2.14).ConclusionsEarly FP had no significant effect in patients with moderate–severe AIS.Trial registration numberNCT02162017.

Background: The increasing demand and shortage of experts to evaluate and treat acute stroke patients has led to the development of remote communication tools to aid stroke management. We aimed to describe the experience of the Brazilian Stroke Network in the implementation of a telemedicine stroke program using a low-cost smartphone application system (JOIN App, Allm, Japan) for rapid sharing of clinical and neuroimaging patient data. Methods: We evaluated the initial experience of the telestroke program using a smartphone app measuring its feasibility, safety and speed in the acute stroke decision-making process, with a particular focus on intravenous thrombolysis. The App was implemented in hospitals without neurologists available for acute stroke evaluation and was connected with a stroke team to support the decision for thrombolysis. We analyzed the times of acute treatment and safety through the rate of symptomatic intracranial hemorrhage (sICH) in 24hours. The program was implemented as part of the partnership with the Angels Initiative in Brazil supported by Boehringer Ingelheim to improve stroke care across the globe. Results: The telestroke program started in May 2019 and since then 7 hospitals, in 5 Brazilian states, were included. Only 2 of these hospitals had previous experience with stroke thrombolysis. In all hospitals, the patients were assisted by emergency physicians with eventual support of local neurologists. The telestroke program was activated for 58 patients. The median age was 68yo (IQR58-72), 47% were female and the baseline NIHSS was 11 (IQR8-16). In 69% of the activation the diagnosis was ischemic stroke (IS), 7% hemorrhagic, 5% TIA and 28% other diagnosis. Thrombolysis was suggested in 48% of all evaluations (70% of IS patients). A total of 53% of IS were actually treated with thrombolys. The response-time of the stroke experts was 2.6 minutes (2-6), door-to-CT scan 20min (15-31) and door-needle time 59min (27-81). None of the patients had sICH. Conclusion: In a telestroke program using a smartphone App, thrombolysis performed by emergency physicians was feasible and safe. This mobile low cost technology can increase the possibility of patients with stroke to receive treatment in regions without neurologists across the globe.

Background and purpose: RESILIENT Trial was the first study in a developing country to demonstrate the benefit of mechanical thrombectomy (MT) in acute stroke patients. This economic evaluation aimed to access the cost-utility of MT under the perspective of the Brazilian Public Healthcare System. Methods: Analysis was based on a subset sample of the original study (151 of 221 patients) from 4 hospitals. We compared costs and utilities between MT plus standard care (n=78) vs. standard care alone (n=73). Direct medical costs were considered, and utilities were inputted according to each patient’s Utility-Weighted modified Rankin Score (UW-mRS). First-year survival was obtained from trial follow-up and modelled for a life-time horizon adjusted by National Mortality Data. Direct medical costs were converted to I$ using Purchasing Power Parity (PPP). A discount rate of 5% was used. Incremental cost-effectiveness ratio (ICER) is expressed in cost (I$) per Quality-Adjusted Life Year (QALY). Results: RESILIENT trial was stopped on its first interim analysis because of early efficacy. The incremental costs and QALYs gained with MT were estimated at I$ 8,369 and 0.75, respectively, compared with standard medical care, yielding an incremental cost-effectiveness ratio (ICER) of I$ 7,256 per QALY. Conclusion: The initially higher costs of MT were offset by the clear benefit of the intervention. RESILIENT trial demonstrated that such therapy is likely to be cost-effective despite the economical constraints in the Brazilian healthcare system.

Background: Mechanical thrombectomy (MT) in addition to intravenous thrombolysis (IVT) is now the recommended treatment for acute ischemic stroke (AIS) patients with large vessel occlusion (LVO). The positive trials also demonstrated that MT alone among patients ineligible for IVT is an effective therapy for AIS. Whether MT alone is as effective, worse, or better than pretreatment with IVT before MT among IVT-eligible AIS patients with LVO is debatable. We aimed to assess the effect of IVT on the clinical outcome of MT in the RESILIENT trial. Methods: RESILIENT was a randomized, prospective, multicenter, controlled trial evaluating the safety, efficacy, and cost-effectiveness of thrombectomy versus medical treatment alone. A total of 221 patient were enrolled. The trial showed a strong benefit to thrombectomy (90-day mRS ordinal shift, OR 95%CI). All eligible patients received intravenous tPA within the 4.5-hour-window. The primary end-point was the common odds ratio (cOR) of mRs at 90 days (shift analysis) and the main secondary endpoint was the rate of functional independence (mRS 0-2) at 90 days. Ordinal logistic and binary regression analyses with the use of intravenous tPA as an interaction term were performed with adjustments for potential confounders including age, baseline NIHSS score, occlusion site, IV tPA use and ASPECTS. A p value < 0.05 was considered statistically significant. Results: Among 221 randomized patients (median NIHSS, 18 IQR [14-21]), 155 (70%) were treated with IV tPA. The frequency of good recanalization (TICI 2b> ) and of hemorrhagic transformation was not affected by IVT. There was no significant difference in the treatment effect size across patients who received intravenous tPA versus those who did not in terms of overall functional disability (ordinal mRS shift: aOR: 2.63, 95%CI [1.48-4.69] vs. 1.54, 95%CI [0.63-3.74]; p=0.42) or functional independence (mRS 0-2: aOR: 3.06, 95%CI [1.37-6.48] vs. 1.71 95%CI [0.55-5.33], p=0.40) at 90 days. Conclusions: The large effect size of MT on LVO outcomes was not significantly affected by IVT. Further studies directly evaluating the role of IVT before MT are of utmost importance.

Background: Despite evidence supporting the overall efficacy of mechanical thrombectomy (MT) in acute ischemic stroke (AIS) due to large vessel occlusion (LVO) of the anterior circulation, it is unclear whether the treatment effect of MT differs by sex in different populations. We assessed the impact of sex differences in the treatment effect of MT in the RESILIENT trial. Methods: RESILIENT was a prospective, multicenter, randomized phase III trial that was designed to assess the safety, efficacy, and cost-effectiveness of mechanical thrombectomy as compared to medical treatment alone in patients treated under the less than ideal conditions typically found in the public healthcare system of a developing country. Results: Among 221 patients enrolled in the trial, 104 (47,1%) were female. Baseline characteristics were well balanced between sexes, except for a higher prevalence of hypertension (76% vs. 57.4%; p=0.004) and diabetes (34.3% vs. 21.7%; p=0.039) and a lower frequency of alcohol abuse (4% vs. 28.9%; p=0.001) in females. After adjustment for baseline characteristics, we found a significant interaction (p=0.026) between sex and the effect of MT with a lower efficacy of MT for functional independency at 90 days among women (aOR=1.13;95%CI:0.42-3.02) compared to men (aOR=4.78; 95%CI:1.88-12.15). Conclusions: In our study population of patients with AIS caused by LVO of the anterior circulation, women were less likely to benefit from MT than men. Further studies are necessary to investigate these findings.

Background: The RESILIENT randomized trial of endovascular therapy for anterior circulation stroke within 8 hours of symptom onset excluded subjects with poor collaterals. We analyzed the relationship of CTA collateral grade with respect to subsequent infarct growth over 24 hours, with and without revascularization. Methods: The independent RESILIENT imaging and angiography core lab scored baseline CTA Tan collateral grade (0-3) and CT ASPECTS scores at baseline and 24 hours in both arms. ASITN collateral grade (0-4) was adjudicated prior to revascularization in the interventional arm. Descriptive statistics, univariate, multivariate and ANOVA related CTA collateral grade with 24-hour infarct growth. Results: 210/221 (95%) subjects (median age 67 (53-76) years; 48% women) in RESILIENT had baseline single-phase CTA available to the core lab evaluation. CTA collateral grade was complete (grade 3) in 106 (50.5%), grade 2 (50-99%) in 68 (32.4%), grade 1 (1-49%) in 36 (17.1%), with no collaterals in 0. The extent of collaterals was more robust in the medical arm (55.0% grade 3, 31.4% grade 2, 13.3% grade 1) compared to the interventional arm (45.7% grade 3, 33.3% grade 2, 21.0% grade 1), although this finding was not statistically significant (p=0.11). In the interventional arm, the extent of CTA collaterals had a strong correlation with ASITN grade (ρ=0.59, p Conclusions: In RESILIENT, CTA collateral grade was linked with higher ASPECTS and less infarct growth over 24 hours. Despite more robust collaterals in the medical arm, greater infarct growth occurred without revascularization or endovascular therapy.

Background: Randomized trials performed in high income countries have shown similar effects of mechanical thrombectomy (MT) in elderly and non-elderly patients with large vessel ischemic strokes (LVO). We aimed to assess the effect of age on the clinical outcome of MT in RESILIENT (a randomized, prospective, multicenter, controlled, phase III, clinical trial with blinded outcome assessment performed in Brazil designed to assess the safety, efficacy, and cost-effectiveness of mechanical thrombectomy as compared to medical treatment alone). Methods: Patients were classified as elderly and non-elderly (≤ 70 vs. > 70 years). The end-points were the common odds ratio (cOR) of mRs (shift analysis) and the frequency of functional independence (mRS 0-2) at 90 days. Ordinal logistic regression analysis (unadjusted and adjusted for important potential confounders) with age group as an interaction term were performed. A p value < 0.05 was considered statistically significant. Results: Among 221 randomized patients (117- 52.9% males), 89 (40.2%) were classified as elderly. Age had an important effect modification of MT on the mRS shift analysis (elderly - cOR 1.20 95% CI [0.57-2.51] vs. non-elderly cOR 3.9, 95% CI [1.65-5.80], p-interaction = 0.003) and on the frequency of functional independence at 90 days (elderly - OR 0.92 95% CI [0.33 - 2.59] vs. non-elderly OR 3.56, 95% CI [1.64 - 7.75], p-interaction = 0.04). A similar effect modification was observed after adjusting for IV rt-PA, occlusion site, baseline NIHSS and ASPECTS on the mRS shift analysis (elderly - cOR 1.34, 95% CI [0.63 - 2.86] vs. non-elderly cOR 3.26, 95% CI [1.73 - 6.13], p-interaction = 0.06) and on the frequency of functional independence at 90 days (elderly - OR 1.08 95% CI [0.36 - 3.21] vs. non-elderly OR 4.26, 95% CI [1.85 - 9.82], p-interaction = 0.04) . Conclusion: The large effect size of MT on LVO outcomes is significantly diminished in the elderly population of patients treated under the less than ideal conditions typically found in the public healthcare system of a developing country.

Objective: To create an accurate and user-friendly pr edictive sc o re for he morrhagic t ransformation in patients not submitted to reperfusion therapies (PROpHET). Methods: We created a multivariable logistic regression model to assess the prediction of Hemorrhage Transformation (HT) for acute ischemic strokes not treated with reperfusion therapy. One point was assigned for each of gender, cardio-aortic embolism, hyperdense middle cerebral artery sign, leukoaraiosis, hyperglycemia, 2 points for ASPECTS ≤7, and -3 points for lacunar syndrome. Acute ischemic stroke patients admitted to the Fortaleza Comprehensive Stroke Center in Brazil from 2015 to 2017 were randomly selected to the derivation cohort. The validation cohort included similar, but not randomized, cases from 5 Brazilian and one American Comprehensive Stroke Centers. Symptomatic cases were defined as NIHSS ≥4 at 24 hours after the event. Results from the derivation and validation cohorts were assessed with the area under the receiver operating characteristic curve (AUC-ROC). Results: From 2,432 of acute ischemic stroke screened in Fortaleza, 448 were prospectively selected for the derivation cohort and a 7-day follow-up. From 1,847 not selected, 577 underwent reperfusion therapy, 734 were excluded due to inadequate imaging or refusal of consent, and 538 whose data were obtained retrospectively and were selected only for the validation cohort. A score ≥3 had 78% sensitivity and 75% specificity, AUC-ROC 0.82 for all cases of HT, Hosmer-Lemeshow 0.85, Brier Score 0.1, and AUC-ROC 0.83 for those with symptomatic HT. An AUC-ROC of 0.84 was found for the validation cohort of 1,910 from all 6 centers, and a score ≥3 was found in 65% of patients with HT against 11.3% of those without HT. In comparison with 8 published predictive scores of HT, PROpHET was the most accurate (p < 0.01). Conclusions: PROpHET offers a tool simple, quick and easy-to-perform to estimate risk stratification of HT in patients not submitted to RT. A digital version of PROpHET is available in www.score-prophet.com Classification of evidence: This study provides Class I evidence from prospective data acquisition.

Background: CT perfusion has been increasingly used as a selection tool in acute reperfusion therapies. However, it remains unknown whether its use is associated with a higher treatment benefit in patients undergoing thrombectomy. We sought to evaluate the interaction between imaging selection modalities and treatment effect in the RESILIENT Trial. Methods: RESILIENT was a randomized, prospective, multicenter, controlled trial evaluating the safety, efficacy, and cost-effectiveness of thrombectomy versus medical treatment alone in Brazil. A total of 221 patient were enrolled. The trial showed a strong benefit of thrombectomy (90-day mRS ordinal shift, OR 2.28 95%CI [1.41-3.70]; p=0.001). Key imaging selection criteria included ASPECTS ≥6 on non-contrast CT (NCCT) and the exclusion of malignant collateral profile on CT angiography. The use of automated CT perfusion software (RAPID, IschemaView) was optional but was made available in some centers with the pre-specified plan to compare imaging selection modalities. The primary end-point was the common odds ratio (cOR) of mRs at 90 days (shift analysis) and the main secondary endpoint was the rate of functional independence (mRS 0-2) at 90 days. Ordinal logistic and binary regression analyses with imaging selection modality (NCCT versus CTP) as an interaction term were performed with adjustments for potential confounders including age, baseline NIHSS score, occlusion site, IV tPA use and ASPECTS. A p value < 0.05 was considered statistically significant. Results: CTP was performed in 41% of the thrombectomy group and 45% in the control group. There was no significant difference in the treatment effect size for patients selected on the basis of NCCT and CTA only versus those submitted to CTP in terms of overall functional disability (ordinal mRS shift: aOR: 2.87, 95%CI [1.47-5.61] vs. 2.10, 95%CI [1.01-4.36]; p=0.390) or functional independence (mRS 0-2: aOR: 3.16, 95%CI [1.32-7.57] vs. 2.54 95%CI [0.86-7.49], p=0.40) at 90 days. Conclusion: In a randomized clinical trial of thrombectomy within 8 hours of stroke onset, there was no evidence of difference in the treatment effect size across patients selected with NCCT and CTA alone versus automated CT perfusion software.

Background Intravenous thrombolysis (IVT) and endovascular therapy (EVT) were proven safe and effective for anterior circulation proximal occlusions. However, the most appropriate recanalization strategy in patients with acute basilar artery occlusion (BAO) is still controversial. This study aimed to assess outcomes of patients with BAO at an academic stroke center in Brazil. Methods This is a retrospective analysis of consecutive patients with BAO from a prospective stroke registry at Ribeirao Preto Medical School. Primary outcomes were mortality and favorable outcome (modified Rankin score [mRS] ≤3) at 90 days. After univariate analyses, multivariate logistic regressions were used to identify independent predictors of primary outcomes. Results Between August 2004 and December 2015, 63 (65% male) patients with BAO and median National Institutes of Health Stroke Scale (NIHSS) score of 31 (interquartile range: 19-36) were identified. Twenty-nine (46%) patients received no acute recanalization therapy, 15 (24%) received IVT, and 19 (30%) received EVT (68% treated with stent retrievers). Twenty-four (83%) patients treated conservatively died, and only 2 (7%) achieved an mRS less than or equal to 3. Among patients treated with acute recanalization therapies, 15 (44%) died, and 9 (26.5%) had a favorable outcome. On multivariate analysis, baseline systolic blood pressure (odds ratio [OR] = .97; 95% confidence interval [CI]: .95-0.99; P = .023), posterior circulation Alberta Stroke Program Early CT score (OR = .62; 95% CI: .41-0.94; P = .026), and successful recanalization (OR = .18; 95% CI: .04-0.71; P = .015) were independent predictors of lower mortality. Baseline NIHSS (OR = 1.40; 95% CI: 1.08-1.82; P = .012), prior use of statins (OR = .003; 95% CI: .001-0.28; P = .012), and successful recanalization (OR = .05; 95% CI: .001-0.27; P = .009) were independent predictors of favorable outcome. There was no significant difference between the IVT group and the EVT group on primary outcomes. Conclusions BAO is associated with high morbidity and mortality in Brazil. Access to acute recanalization therapies may decrease mortality in those patients.

Background and Purpose— Many patients receiving thrombolysis for acute ischemic stroke are on prior antiplatelet therapy (APT), which may increase symptomatic intracerebral hemorrhage risk. In a prespecified subgroup analysis, we report comparative effects of different doses of intravenous alteplase according to prior APT use among participants of the international multicenter ENCHANTED study (Enhanced Control of Hypertension and Thrombolysis Stroke Study). Methods— Among 3285 alteplase-treated patients (mean age, 66.6 years; 38% women) randomly assigned to low-dose (0.6 mg/kg) or standard-dose (0.9 mg/kg) intravenous alteplase within 4.5 hours of symptom onset, 752 (22.9%) reported prior APT use. Primary outcome at 90 days was the combined end point of death or disability (modified Rankin Scale [mRS] scores, 2–6). Other outcomes included mRS scores 3 to 6, ordinal mRS shift, and symptomatic intracerebral hemorrhage by various standard criteria. Results— There were no significant differences in outcome between patients with and without prior APT after adjustment for baseline characteristics and management factors during the first week; defined by mRS scores 2 to 6 (adjusted odds ratio [OR], 1.01; 95% confidence interval [CI], 0.81–1.26; P =0.953), 3 to 6 (OR, 0.95; 95% CI, 0.75–1.20; P =0.662), or ordinal mRS shift (OR, 1.03; 95% CI, 0.87–1.21; P =0.770). Alteplase-treated patients on prior APT had higher symptomatic intracerebral hemorrhage (OR, 1.82; 95% CI, 1.00–3.30; P =0.051) according to the safe implementation of thrombolysis in stroke-monitoring study definition. Although not significant ( P -trend, 0.053), low-dose alteplase tended to have better outcomes than standard-dose alteplase in those on prior APT compared with those not using APT (mRS scores of 2–6; OR, 0.84; 95% CI, 0.62–1.12 versus OR, 1.16; 95% CI, 0.99–1.36). Conclusions— Low-dose alteplase may improve outcomes in thrombolysis-treated acute ischemic stroke patients on prior APT, but this requires further evaluation in a randomized controlled trial. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01422616.

Background Brazil is a developing country struggling to reduce its extreme social inequality, which is reflected on shortage of health-care infrastructure, mainly to the low-income class, which depends exclusively on the public health system. In Brazil, less than 1% of stroke patients have access to intravenous thrombolysis in a stroke unit, and constraints to the development of mechanical thrombectomy in the public health system increase the social burden of stroke. Objective Report the feasibility of mechanical thrombectomy as part of routine stroke care in a Brazilian public university hospital. Methods Prospective data were collected from all patients treated for acute ischemic stroke with mechanical thrombectomy from June 2011 to March 2016. Combined thrombectomy was performed in eligible patients for intravenous thrombolysis if they presented occlusion of large artery. For those patients ineligible for intravenous thrombolysis, primary thrombectomy was performed as long as there was no evidence of significant ischemia for anterior circulation stroke (Alberta Stroke Program Early CT score >6) within a 6-hour time window, and also for those patients with wake-up stroke or posterior circulation stroke, regardless of the time of symptoms onset. Results A total of 161 patients were evaluated, resulting in an overall successful recanalization rate of 76% and symptomatic intracranial hemorrhage rate of 6.8%. At 3 months, 36% of the patients had modified Rankin Scale score less than or equal to 2. The overall mortality rate was 23%. Conclusion Our study, the first ever large series of mechanical thrombectomy in Brazil, demonstrates acceptable efficacy and safety results, even under restricted conditions outside the ideal scenario of trial studies.

Background Mechanical thrombectomy (MT) is the standard of care for acute ischemic stroke (AIS) caused by large vessel occlusion of the anterior circulation within 6 hours of symptoms onset and can be performed with an extended window up to 24 hours in selected patients. Nevertheless, the outcomes of MT with extended window are unknown in developing countries. Objective Explore the safety and efficacy of MT for AIS performed beyond 6 hours from symptoms onset in Brazil. Methods We reviewed data from AIS patients treated with MT beyond 6 hours of stroke onset, from 2015 to 2018 in a Brazilian public hospital. Patients had an occlusion of the intracranial internal carotid artery and/or proximal segment of the middle cerebral artery. CT Perfusion mismatch was evaluated using the RAPID® software. We evaluated the modified Rankin scale (mRS) and mortality at 90 days, and rate of symptomatic intracranial hemorrhage (sICH). Results Fifty-four patients were included, with a mean age of 65.6 ± 16.1 years, 55.6% were male, and the median NIHSS score at presentation was 17. Successful recanalization (TICI 2b to 3) was obtained in 92.6% of patients and sICH rate was 11.1%. Overall, 34% of the patients had a good outcome (mRS ≤2) at 90 days and the mortality rate was 20.3%. Conclusion Our study, the first series of MT for AIS treated with extended window reported in Latin America, shows that MT can be performed with safety and lead to adequate functional outcomes in this context. Further studies should explore the barriers to broad implementation of MT for AIS in Latin America.

Objective Access to acute stroke unit (ASU) care is known to vary worldwide. We aimed to quantify regional variations in the various components of ASU care. Method Secondary analysis of the Head Positioning in acute Stroke Trial (HeadPoST), an international, multicentre, cluster crossover trial of head-up versus head-down positioning in 11,093 acute stroke patients at 114 hospitals in 9 countries. Patients characteristics and 11 standard components of processes of care were described according to ASU admission within and across four economically-defined regional groups (Australia/UK, China [includes Taiwan], India/Sri Lanka, and South America [Brazil/Chile/Colombia]). Variations in process of ASU care estimates were obtained in hierarchical mixed models, with adjustment for study design and potential patient- and hospital-level confounders. Results Of 11,086 patients included in analyses, 59.7% (n = 6620) had an ASU admission. In China, India/Sri Lanka and South America, ASU patients were older, had greater neurological severity and more premorbid conditions than non-ASU patients. ASU patients were more likely to receive reperfusion therapy and multidisciplinary care within regions, but the components of care varied across regions. With Australia/UK as reference, patients in other regions had a lower probability of receiving reperfusion therapy, especially in India/Sri Lanka (adjusted odds ratio [aOR] 0.27, 95% confidence interval [CI] 0.12–0.63) and multidisciplinary care (mainly in formal dysphagia assessment, physiotherapy and occupational therapy). Conclusion There is significant variation in the components of stroke care across economically-defined regions of the world. Ongoing efforts are required to reduce disparities and optimise health outcomes, especially in resource poor areas. Clinical trial registration HeadPoST is registered at ClinicalTrials.gov ( NCT02162017 ).

Supplemental Digital Content is available in the text., Background and Purpose: Among patients with a transient ischemic attack or minor ischemic strokes, those with ipsilateral atherosclerotic stenosis of cervicocranial vasculature have the highest risk of recurrent vascular events. Methods: In the double-blind THALES (The Acute Stroke or Transient Ischemic Attack Treated With Ticagrelor and ASA for Prevention of Stroke and Death) trial, we randomized patients with a noncardioembolic, nonsevere ischemic stroke, or high-risk transient ischemic attack to ticagrelor (180 mg loading dose on day 1 followed by 90 mg twice daily for days 2–30) or placebo added to aspirin (300–325 mg on day 1 followed by 75–100 mg daily for days 2–30) within 24 hours of symptom onset. The present paper reports a prespecified analysis in patients with and without ipsilateral, potentially causal atherosclerotic stenosis ≥30% of cervicocranial vasculature. The primary end point was time to the occurrence of stroke or death within 30 days. Results: Of 11 016 randomized patients, 2351 (21.3%) patients had an ipsilateral atherosclerotic stenosis. After 30 days, a primary end point occurred in 92/1136 (8.1%) patients with ipsilateral stenosis randomized to ticagrelor and in 132/1215 (10.9%) randomized to placebo (hazard ratio 0.73 [95% CI, 0.56–0.96], P=0.023) resulting in a number needed to treat of 34 (95% CI, 19–171). In patients without ipsilateral stenosis, the corresponding event rate was 211/4387 (4.8%) and 230/4278 (5.4%), respectively (hazard ratio, 0.89 [95% CI, 0.74–1.08]; P=0.23, Pinteraction=0.245). Severe bleeding occurred in 4 (0.4%) and 3 (0.2%) patients with ipsilateral atherosclerotic stenosis on ticagrelor and on placebo, respectively (P=NS), and in 24 (0.5%) and 4 (0.1%), respectively, in 8665 patients without ipsilateral stenosis (hazard ratio=5.87 [95% CI, 2.04–16.9], P=0.001). Conclusions: In this exploratory analysis comparing ticagrelor added to aspirin to aspirin alone, we found no treatment by ipsilateral atherosclerosis stenosis subgroup interaction but did identify a higher absolute risk and a greater absolute risk reduction of stroke or death at 30 days in patients with ipsilateral atherosclerosis stenosis than in those without. In this easily identified population, ticagrelor added to aspirin provided a clinically meaningful benefit with a number needed to treat of 34 (95% CI, 19–171). Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03354429.

Background and Purpose— Sleep apnea has been associated with a poor outcome in acute stroke patients. Polysomnography is the gold standard diagnostic method for sleep apnea, but it is not feasible as a routine in the acute stroke setting. The current generation of positive airway pressure (PAP) devices can detect the different types of respiratory events. This study aimed to compare the algorithms used in PAP device to manually scored events on polysomnography in patients with acute stroke. Methods— A sleep study was performed with standard polysomnography and PAP device, simultaneously, within the first 48 hours after acute stroke onset. Results— We prospectively evaluated 29 patients with acute stroke (59.5±12.1 years). The area under the receiver operating characteristic curve for each apnea-hypopnea index value was above 0.90 by PAP device. There was a good correlation of apnea-hypopnea index ( r s =0.92; P r s =0.89; P r s =0.70; P Conclusions— Given the high frequency of sleep apnea during the acute phase of stroke and the complexity of a full polysomnography study in this setting, PAP device on diagnostic mode can be used as an alternative tool for sleep apnea detection in acute stroke patients.

Importance Translating evidence into clinical practice in the management of acute ischemic stroke (AIS) and transient ischemic attack (TIA) is challenging, especially in low- and middle-income countries. Objective To assess the effect of a multifaceted quality improvement intervention on adherence to evidence-based therapies for care of patients with AIS and TIA. Design, Setting and Participants This 2-arm cluster-randomized clinical trial assessed 45 hospitals and 2336 patients with AIS and TIA for eligibility before randomization. Eligible hospitals were able to provide care for patients with AIS and TIA in Brazil, Argentina, and Peru. Recruitment started September 12, 2016, and ended February 26, 2018; follow-up ended June 29, 2018. Data were analyzed using the intention-to-treat principle. Interventions The multifaceted quality improvement intervention included case management, reminders, a roadmap and checklist for the therapeutic plan, educational materials, and periodic audit and feedback reports to each intervention cluster. Main Outcomes and Measures The primary outcome was a composite adherence score for AIS and TIA performance measures. Secondary outcomes included an all-or-none composite end point of performance measures, the individual process measure components of the composite end points, and clinical outcomes at 90 days after admission (stroke recurrence, death, and disability measured by the modified Rankin scale). Results A total of 36 hospitals and 1624 patients underwent randomization. Nineteen hospitals were randomized to the quality improvement intervention and 17 to routine care. The overall mean (SD) age of patients enrolled in the study was 69.4 (13.5) years, and 913 (56.2%) were men. Overall mean (SD) composite adherence score for the 10 performance measures in the intervention group hospitals compared with control group hospitals was 85.3% (20.1%) vs 77.8% (18.4%) (mean difference, 4.2%; 95% CI, −3.8% to 12.2%). As a secondary end point, 402 of 817 patients (49.2%) at intervention hospitals received all the therapies that they were eligible for vs 203 of 807 (25.2%) in the control hospitals (odds ratio, 2.59; 95% CI, 1.22-5.53;P = .01). Conclusions and Relevance A multifaceted quality improvement intervention did not result in a significant increase in composite adherence score for evidence-based therapies in patients with AIS or TIA. However, when using an all-or-none approach, the intervention resulted in improved adherence to evidence-based therapies. Trial Registration ClinicalTrials.gov identifier:NCT02223273

The present article provides the historical background of the Sociedade Brasileira de Doenças Cerebrovasculares (Brazilian Society for Cerebrovascular Diseases), including details on its function, structure, challenges and main achievements. RESUMO O presente texto apresenta um relato histórico da Sociedade Brasileira de Doenças Cerebrovasculares, incluindo detalhes da sua fundação, estruturação, dificuldades e principais realizações.

Background: Basilar artery occlusion (BAO) is a rare stroke subtype with high mortality rates. Best BAO reperfusion strategy is still controversial. Objective: We aim to describe outcomes of BAO patients submitted to mechanical thrombectomy (MT) in a comprehensive stroke center in Brazil and analyze which previous published computed tomography angiography (CTA) collateral score better predict functional outcomes. Methods: Retrospective analysis of consecutive BAO patients. CTA was used to evaluate the posterior circulation collateral score (PC-CS), the basilar artery on CTA score, and for the presence of posterior communicating arteries. A favorable outcome was defined as modified Rankin Score ≤3 at 90-days. After univariate analyses, multivariate logistic regression was used to identify if any collateral score independently predicts favorable outcomes. Results: Between January 2011 and April 2017, 27 (85% male) BAO patients with median NIHSS 26 (IQR 15–32) were identified. Twenty-five (93%) patients were treated with MT devices, and only 2 (7%) patients were treated with angioplasty and stenting. Successful recanalization rate was 85%, and only 1 (3.7%) patient had symptomatic hemorrhagic transformation. Favorable outcomes were reached in 10 (37%) patients. In univariate analysis, female sex, NIHSS, Glasgow coma scale, mild-to-moderate symptoms on admission, onset-to-groin time, and PC-CS predicted favorable outcomes. In multivariate analysis, PC-CS (OR 1.69; 95% CI 1.10–2.60; p = 0.016) and NIHSS (OR 0.84; 95% CI 0.77–0.93; p = 0.001) remained the only independent predictors of favorable outcomes. The PC-CS AUC was 0.80 (95% CI 0.62–0.98; p = 0.012). Conclusions: MT is a promising strategy for BAO treatment. Among collateral scores, PC-CS was the only independent predictor of favorable outcomes in the present study.

Introduction: Supratentorial Intracerebral hemorrhage (ICH) main prognostic factors on admission are age, Glasgow coma scale (GCS), ICH volume and ventricular hemorrhage. Subsequent ICH expansion and associated elevated intracranial pressure (ICP) have also been linked to poorer outcomes. Dilatation of optic nerve sheath diameter (ONSD) by trans-orbital ultrasound examination is an increasingly recognized marker of elevated ICP. We sought to evaluate whether increased ONSD at hospital admission could be associated with mortality among patients with supratentorial ICH. Methods: Prospective cohort of consecutive acute supratentorial ICH patients admitted to a tertiary stroke center. Exclusion criteria: 1) last well seen > 24 hours; 2) immediate surgical intervention indicated by neurosurgery team; 3) Secondary ICH (anticoagulants and antiplatelets were allowed); 4) previous optic nerve pathology precluding accurate ONSD measurements. Ultrasound assessment and CT performed within the first hour after admission. Primary outcome was 90-days mortality. Multivariate logistic regression, ROC curve and c-statistics was used to identify independent predictors of mortality. Results: Between July 2014 and July 2017, 57 patients were evaluated. Among those, 13 were excluded and 44 were recruited into the trial. Their mean age was 62.3± 13.1 years and 32 (72.7%) were male. On univariate analysis, ICH volume on admission CT scan, ICH ipsilateral ONSD measurement on admission TCCD, diabetes and current smoking were predictors of mortality. After multivariate analysis, ipsilateral ONSD (OR:6.24;95CI%1.18-33.1;p=0.031) was an independent predictor of mortality, even after adjustment for ICH volume, age, GCS and intraventricular hemorrhage. The ONSD had an area under the curve (AUC) of 0.71 (p=0.021) for mortality at 3 months. Conclusion: ONSD is a non-invasively, bedside, low cost technique that could be used to estimate increased ICP in patients with acute supratentorial ICH. Among these patients, increased ONSD is an independent predictor of mortality at 3 months.

Background\ud \ud Few studies have assessed regional variation in the organisation of stroke services, particularly health care resourcing, presence of protocols and discharge planning. Our aim was to compare stroke care organisation within middle- (MIC) and high-income country (HIC) hospitals participating in the Head Position in Stroke Trial (HeadPoST).\ud \ud Methods\ud \ud HeadPoST is an on-going international multicenter crossover cluster-randomized trial of ‘sitting-up’ versus ‘lying-flat’ head positioning in acute stroke. As part of the start-up phase, one stroke care organisation questionnaire was completed at each hospital. The World Bank gross national income per capita criteria were used for classification.\ud \ud Results\ud \ud 94 hospitals from 9 countries completed the questionnaire, 51 corresponding to MIC and 43 to HIC. Most participating hospitals had a dedicated stroke care unit/ward, with access to diagnostic services and expert stroke physicians, and offering intravenous thrombolysis. There was no difference for the presence of a dedicated multidisciplinary stroke team, although greater access to a broad spectrum of rehabilitation therapists in HIC compared to MIC hospitals was observed. Significantly more patients arrived within a 4-h window of symptoms onset in HIC hospitals (41 vs. 13%; P < 0.001), and a significantly higher proportion of acute ischemic stroke patients received intravenous thrombolysis (10 vs. 5%; P = 0.002) compared to MIC hospitals.\ud \ud Conclusions\ud \ud Although all hospitals provided advanced care for people with stroke, differences were found in stroke care organisation and treatment. Future multilevel analyses aims to determine the influence of specific organisational factors on patient outcomes.

Background and Purpose— Noncontrast computed tomographic (CT) hypodensities have been shown to be associated with hematoma expansion in intracerebral hemorrhage (ICH), but their impact on functional outcome is yet to be determined. We evaluated whether baseline noncontrast CT hypodensities are associated with poor clinical outcome. Methods— We performed a retrospective review of a prospectively collected cohort of consecutive patients with primary ICH presenting to a single academic medical center between 1994 and 2016. The presence of CT hypodensities was assessed by 2 independent raters on the baseline CT. Unfavorable outcome was defined as a modified Rankin score >3 at 90 days. The associations between CT hypodensities and unfavorable outcome were investigated using uni- and multivariable logistic regression models. Results— During the study period, 1342 patients presented with ICH and 800 met restrictive inclusion criteria (baseline CT available for review, and 90-day outcome available). Three hundred and four (38%) patients showed hypodensities on CT, and 520 (65%) patients experienced unfavorable outcome. In univariate analysis, patients with unfavorable outcome were more likely to demonstrate hypodensities (48% versus 20%; P P =0.018). Conclusions— The presence of noncontract CT hypodensities at baseline independently predicts poor outcome and comes as a useful and widely available addition to our ability to predict ICH patients’ clinical evolution.

Verticality misperception after stroke is a frequent neurological deficit that leads to postural imbalance and a higher risk of falls. The posterior thalamic nuclei are described to be involved with verticality perception, but it is unknown if extra-thalamic lesions can have the same effect via diaschisis and degeneration of thalamic nuclei. We investigated the relationship between thalamic fractional anisotropy (FA, a proxy of structural integrity), and verticality perception, in patients after stroke with diverse encephalic extra-thalamic lesions. We included 11 first time post-stroke patients with extra-thalamic primary lesions, and compared their region-based FA to a group of 25 age-matched healthy controls. For the patient sample, correlation and regression analyses evaluated the relationship between thalamic nuclei FA and error of postural vertical (PV) and haptic vertical (HV) in the roll (PVroll/HVroll) and pitch planes (PVpitch/HVpitch). Relative to controls, patients showed decreased FA of anterior, ventral anterior, ventral posterior lateral, dorsal, and pulvinar thalamic nuclei, despite the primary lesions being extra-thalamic. We found a significant correlation between HVroll, and FA in the anterior and dorsal nuclei, and PVroll with FA in the anterior nucleus. FA in the anterior, ventral anterior, ventral posterior lateral, dorsal and pulvinar nuclei predicted PV, and FA in the ventral anterior, ventral posterior lateral and dorsal nuclei predicted HV. While prior studies indicate that primary lesions of the thalamus can result in verticality misperception, here we present evidence supporting that secondary degeneration of thalamic nuclei via diaschisis can also be associated with verticality misperception after stroke.

Background: The results of recent trials of mechanical thrombectomy for acute ischemic stroke have increased the demand for identification of patients with large vessel occlusion (LVO) at the primary stroke center, where a prompt detection may expedite transfer to a comprehensive stroke center for endovascular treatment. However, in developing countries, a noncontrast computed tomography (NCCT) may be the only neuroimaging modality available at the primary stroke center scenario, what calls for a screening strategy accurate enough to avoid unnecessary transfers of noneligible patients for endovascular therapy. Algorithms based on National Institute of Health Stroke Scale (NIHSS) and NCCT findings can be used to screen for LVO in patients with anterior circulation stroke (ACS). Objective: To test the accuracy of a score based on NIHSS and NCCT to detect LVO in patients with ACS. Methods: We evaluated 178 patients from a prospective stroke registry of patients admitted to an academic tertiary emergency unit. NIHSS and vessel attenuation values of the middle cerebral artery on NCCT absolute vessel attenuation (VA) were collected by 2 investigators that were blind to CT angiography (CTA) findings. We used receiver operating characteristics curve analysis and C-statistics to predict LVO on CTA. Results: NIHSS and vessel attenuation were highly associated with LVO with an area under the curve (AUC) of .86 and .77. The LVO score, built by logistic regression coefficients of the NIHSS and VA, showed the highest accuracy for the presence of LVO on CTA (AUC of .91). Conclusion: The LVO score may be a useful screening approach to identify LVO in patients with ACS.

Summary 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.

Background: Debate exists as to whether statin pretreatment confers an increased risk of 90-day mortality and symptomatic intracranial haemorrhage (sICH) in acute ischaemic stroke (AIS) patients treated with intravenous thrombolysis. We assessed the effects of undifferentiated lipid-lowering pretreatment on outcomes and interaction with low-dose versus standard-dose alteplase in a post hoc subgroup ­analysis of the Enhanced Control of Hypertension and Thrombolysis Stroke Study. Methods: In all, 3,284 thrombolysis-eligible AIS patients (mean age 66.6 years; 38% women), with information on lipid-lowering pretreatment, were randomly assigned to low-dose (0.6 mg/kg) or standard-dose (0.9 mg/kg) intravenous alteplase within 4.5 h of symptom onset. Of the total number of patients, 615 (19%) received statin or other lipid-lowering pretreatment. The primary clinical outcome was combined endpoint of death or disability (modified Rankin Scale scores 2–6) at 90 days. Results: Compared with patients with no lipid-lowering pretreatment, those with lipid-lowering pretreatment were significantly older, more likely to be non-Asian and more likely to have a medical history including vascular co-morbidity. After propensity analysis assessment and adjustment for important baseline variables at the time of randomisation, as well as imbalances in management during the first 7 days of hospital admission, there were no significant differences in mortality (OR 0.85; 95% CI 0.58–1.25, p = 0.42), or in overall ­90-day death and disability (OR 0.85, 95% CI 0.67–1.09, p = 0.19), despite a significant decrease in sICH among those with ­lipid-lowering pretreatment according to the European Co-operative Acute Stroke Study 2 definition (OR 0.49, 95% CI 0.28–0.83, p = 0.009). No differences in key efficacy or safety outcomes were seen in patients with and without lipid-lowering pretreatment between low- and standard-dose alteplase arms. Conclusions: Lipid-lowering pretreatment is not associated with adverse outcome in AIS patients treated with intravenous alteplase, whether assessed by 90-day death and disability or death alone.

Background: Temporal trends on the incidence of stroke and its subtypes could help assess on-going public health policies and point to further targets for action among middle- and low-income countries, where the stroke burden is very high. This study aimed at evaluating longitudinal trends of stroke incidence in Joinville, Brazil. Methods: We ascertained the incidence of all first-ever strokes occurred in 1995, 2005-2006 and 2012-2013, which were extracted from Joinville Stroke Registry, a prospective epidemiological data bank, launched in 1995. Results: From 1995 to 2013, the age-adjusted incidence of all strokes decreased 37% (95% CI 32-42). From 2005 to 2013, the haemorrhagic stroke (HS) incidence decreased 60% (95% CI 13-86), ischemic stroke (IS) incidence decreased 15% (95% CI 1-28), and subarachnoid haemorrhage incidence remained stable. The proportion of IS and HS patients with regularly treated hypertension increased by 60% (p = 0.01) and 33% (p = 0.01), respectively. The proportion of IS and HS patients that quit smoking increased 8% (p = 0.03) and 17% (p = 0.03), respectively. Conclusions: Stroke incidence has been decreasing in Joinville over the last 18 years, more so for HS than IS. Better control of hypertension and tobacco use might explain these findings.

Summary Introduction Early carotid revascularization (≤ 14 days) is recommended for symptomatic carotid stenosis. Carotid artery stenting (CAS) has become an alternative to carotid endarterectomy (CEA); however, safety data on early CAS is controversial. The study aims to compare early versus late CAS, when CAS is performed as a first intention revascularization strategy. Methods A retrospective analysis of all symptomatic patients admitted to our stroke unit who underwent CAS was conducted. Patients were divided between two groups: patients who had undergone CAS within 14 days after symptoms and those who had undergone CAS later. Primary endpoints were ipsilateral ischemic stroke or ipsilateral parenchymal hemorrhage (iPH) at 30 days. The secondary endpoints were major adverse cardiac and cerebrovascular events (MACCE) at the 30-day and at the 12-month follow-up. Results One hundred twenty-seven consecutive patients were evaluated. Primary endpoints obtained in the early and late CAS groups were, respectively, ipsilateral stroke (2.0% vs. 2.6%, P = 1.00) and iPH (2.0% vs. 0.0%, P = 0.40). The rates of MACCE between the early and the late CAS groups were, respectively, (7.8% vs. 2.6%, P = 0.21) at the 30-day follow-up, and (12.2% vs. 10.5%, P = 0.77) at the 12-month follow-up. Conclusions In this study, CAS seems to be safe when used as first intention revascularization treatment within 2 weeks of symptoms, if infarcted area is less than one third of the middle cerebral artery territory. Our results need to be confirmed by larger studies.

Background: Obstructive sleep apnea (OSA) is very common in acute stroke patients and has been associated with a poor short-term and long-term outcome. Polysomnography (PSG) is the gold standard diagnostic method for OSA, but it is not feasible as a routine for all acute stroke patients. Therefore, it is essential to validade alternative methods to accurately diagnose OSA in acute stroke patients. The newest generation of automatic continuous positive airway pressure (auto-CPAP) devices innovates by the possibility of detecting the different types of respiratory events. However, the accuracy of auto-CPAP devices for OSA diagnosis has never been tested in comparison to PSG in the acute stroke setting. The main objective of this study was to evaluate the accuracy of an auto-CPAP device to diagnose OSA and to validate its algorithm of respiratory events detection to diagnose OSA in patients during the acute phase of stroke. Methods: A sleep study was performed with PSG and auto-CPAP device, simultaneously, within the first 48 hours after the acute stroke onset. The Receiver Operating Characteristic Curve (ROC), C-statistics, Spearman correlation coefficient, and intraclass correlation coefficient were analyzed. Results: We prospectively evaluated 31 adult patients with acute stroke. The mean age was 59.7 ± 12 years and 60% were males. All patients used auto-CPAP for longer than 4 hours. The PSG revealed an apnea-hypopnea index (AHI) mean of 34 ± 41 events/h, and the auto-CPAP showed an AHI of 18 ± 16 events/h. The area under the ROC curve for OSA diagnosis by the auto-CPAP was above 0.90, with sensitivity and specificity above 80% for each AHI value. The Spearman correlation coefficients (rs) of the AHI, of the hypopnea index, of the obstructive apnea index and of the central apnea index were 0.92; 0.89; 0.63 and 0.62, respectively. The intraclass correlation coefficients between device-detected and PSG manually scored events were 0.60 for AHI, 0.64 for hypopnea index, and 0.45 for apnea index. Conclusion: The auto-CPAP showed an excellent accuracy for the diagnosis of OSA and it was well tolerated by acute stroke patients. Our results suggest that auto-CPAP should be considered as the preferred diagnostic tool for OSA diagnosis during the acute phase of stroke.

Basilar artery occlusion (BAO) ischemic stroke is a relatively rare condition with high morbidity and mortality rates. To date, the best acute reperfusion therapy for BAO has still not been established, mainly due to the lack of randomized controlled trials in this field. In this article, we review the history of BAO diagnosis and treatment, and the impact of modern technological resources on the clinical evolution and prognosis of BAO over time. Furthermore, we describe historical events and nonmedical literature descriptions related to BAO. We conclude that BAO is a singular example of how art may help medical sciences with accurate descriptions of medical conditions. RESUMO O acidente vascular cerebral isquêmico secundário à oclusão aguda da basilar (OAB) é uma condição relativamente rara, que cursa com elevada morbimortalidade. Até o momento atual, a melhor estratégia de recanalização arterial na fase aguda da OAB não está definida, principalmente pela carência de ensaios clínicos randomizados e controlados neste contexto. Neste artigo, revisamos aspectos históricos do diagnóstico e do tratamento desta condição, assim como o impacto do avanço tecnológico na evolução clínica e prognóstico desta condição. Ademais, descrevemos fatos históricos e a literatura fictícia relacionados à OAB. Concluímos que a OAB é um exemplo peculiar de como a arte pode auxiliar a medicina na descrição acurada de condições médicas.

Aiming to contribute to studies that use detailed clinical and genomic information of biobanks, we present the initial results of the first Latin American Stroke Biobank. Methods: Blood samples were collected from patients included in the Joinville Stroke Registry and four Brazilian cities. Demographic socio-economic data, cardiovascular risk factors, Causative Classification System for Ischemic Stroke, Trial of Org 10172 in Acute Stroke Treatment and National Institutes of Health scores, functional stroke status (modified Rankin) and brain images were recorded. Additionally, controls from both geographic regions were recruited. High-molecular-weight genomic DNA was obtained from all participants. Results: A total of 2,688 patients and 3,282 controls were included. Among the patients, 76% had ischemic stroke, 12% transient ischemic attacks, 9% hemorrhagic stroke and 3% subarachnoid hemorrhage. Patients with undetermined ischemic stroke were most common according the Trial of Org 10172 in Acute Stroke Treatment (40%) and Causative Classification System for Ischemic Stroke (47%) criteria. A quarter of the patients were under 55 years of age at the first-ever episode. Conclusions: We established the Joinville Stroke Biobank and discuss its potential for contributing to the understanding of the risk factors leading to stroke.

Importance A lower dose of intravenous alteplase appears to be a safer treatment option than the standard dose, reducing the risk of symptomatic intracerebral hemorrhage. There is uncertainty, however, over how this effect translates into an overall clinical benefit for patients with acute ischemic stroke (AIS). Objective To assess whether older, Asian, or severely affected patients with AIS who are considered at high risk of thrombolysis may benefit more from low-dose rather than standard-dose alteplase treatment. Design, Setting, and Participants This study is a prespecified secondary analysis of the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED), an international, randomized, open-label, blinded, end-point clinical trial of low-dose vs standard-dose intravenous alteplase for patients with AIS. From March 1, 2012, to August 31, 2015, a total of 3310 patients who had a clinical diagnosis of AIS as confirmed by brain imaging and who fulfilled the local criteria for thrombolysis treatment were included in the alteplase-dose arms. Patients were randomly assigned to receive low-dose (0.6 mg/kg; 15% as bolus and 85% as infusion over 1 hour) or standard-dose (0.9 mg/kg; 10% as bolus and 90% as infusion over 1 hour) alteplase. Of the 3310 randomized patients, 13 patients were excluded for missing consent, mistaken randomization, and duplicate randomization numbers. This secondary analysis was conducted between May 1, 2016, and April 28, 2017. Main Outcomes and Measures The primary end point was a poor outcome defined by the combination of death and any disability as scored by the modified Rankin Scale (scores range from 2 to 6, with the highest score indicating death) at 90 days. Results Of the 3297 patients included in the analysis, 1248 (37.9%) were women, and the mean (SD) age was 67 (13) years. No significant differences in the treatment effects were observed between low- and standard-dose alteplase for poor outcomes (death or disability) by age, ethnicity, or severity (all P > .37 for interaction). Similarly, the treatment effects of low- vs standard-dose alteplase on function outcome (ordinal shift of the modified Rankin Scale) in Asians (odds ratio, 1.05; 95% CI, 0.90-1.22) was consistent with non-Asians (odds ratio, 0.93; 95% CI, 0.76-1.14) (P = .32 for interaction). There were generally consistent reductions in rates of symptomatic intracerebral hemorrhage with low-dose alteplase, although this reduction was not statistically significant by age, ethnicity, or severity. Conclusions and Relevance This analysis found that the effects of low-dose alteplase were not clearly superior to the effects of standard-dose alteplase on death or disability in key demographic subgroups of patients with AIS. Further investigation is required to identify patients with AIS who may benefit from low-dose alteplase.

Mechanical thrombectomy using stent retrievers is the standard treatment for acute ischemic stroke that results from large vessel occlusions. The direct aspiration first pass technique (ADAPT) has been proposed as an efficient, fast, and cost-effective thrombectomy strategy. The aim of this study was to assess the safety and efficacy of ADAPT. Methods Recanalization was assessed using the modified thrombolysis in cerebral infarction (mTICI) score. Neurological outcomes were assessed using the National Institutes of Health Stroke Scale and modified Rankin Scale. Results Fifteen patients were evaluated. The mTICI score was 2b-3 in 80%, and it was 3 in 60% of patients. No intracranial hemorrhage was seen. At three months, modified Rankin Scale scores ≤ 2 were observed in 60% of patients and the mortality rate was 13.3%. Conclusions The ADAPT appears to be a safe, effective, and fast recanalization strategy for treatment of acute ischemic stroke resulting from large vessel occlusions. RESUMO A trombectomia mecânica com stent retrievers é o tratamento padrão ouro do acidente vascular cerebral isquêmico agudo (AVCi) por oclusão de grandes artérias. A técnica de aspiração primária (ADAPT) tem sido proposta como uma estratégia de trombectomia rápida e com boa custo-efetividade. O objetivo deste estudo foi avaliar a segurança e eficácia da técnica ADAPT. Métodos A recanalização foi avaliada utilizando a escala mTICI. Os desfechos neurológicos foram avaliados utilizando as escalas do NIHSS e mRS. Resultados Quinze pacientes foram avaliados. Foram obtidas taxas de mTICI = 2b-3 em 80% e TICI = 3 em 60% dos pacientes. Não ocorreram hemorragias intracranianas. Em 3 meses as taxas de mRS≤2 e mortalidade foram respectivamente 60% e 13.3%. Conclusão A técnica ADAPT parece ser uma estratégia de recanalização rápida, segura e efetiva para o tratamento do AVC por oclusão de grandes artérias.

BackgroundGlycogen phosphorylase is the key enzyme that breaks down glycogen to yield glucose-1-phosphate in order to restore depleted energy stores during cerebral ischaemia. We sought to determine whether plasma levels of glycogen phosphorylase BB (GPBB) isoform increased in patients with acute ischaemic stroke (AIS).MethodsWe studied plasma GPBB levels within 12 hours and again at 48±24 hours of symptom onset in 172 patients with imaging-confirmed AIS and 133 stroke-free individuals. We determined the ability of plasma GPBB to discriminate between cases and controls and examined the predictive value of plasma GPBB for 90-day functional outcome, 90-day survival and acute lesion volumes on neuroimaging.ResultsThe mean (SD) GPBB levels were higher in cases (46.3±38.6 ng/mL at first measurement and 38.6±36.5 ng/mL at second measurement) than in controls (4.1±7.6 ng/mL, pConclusionGPBB demonstrates robust response to acute ischaemia and high sensitivity for small infarcts. If confirmed in more diverse populations that also include stroke mimics, GPBB could find utility as a stand-alone marker for acute brain ischaemia.

IMPORTANCE The ability of present-day etiologic stroke classification systems to generate subtypes with discrete stroke characteristics is not known. OBJECTIVE To test the hypothesis that etiologic stroke subtyping identifies different disease processes that can be recognized through their different clinical courses. DESIGN, SETTING, AND PARTICIPANTS We performed a head-to-head evaluation of the ability of the Causative Classification of Stroke (CCS), Trial of Org 10172 in Acute Stroke Treatment (TOAST), and ASCO (A for atherosclerosis, S for small-vessel disease, C for cardiac source, and O for other cause) classification systems to generate etiologic subtypes with different clinical, imaging, and prognostic characteristics in 1816 patients with ischemic stroke. This study included 2 cohorts recruited at separate periods; the first cohort was recruited between April 2003 and June 2006 and the second between June 2009 and December 2011. Data analysis was performed between June 2014 and May 2016. MAIN OUTCOMES AND MEASURES Separate teams of stroke-trained neurologists performed CCS, TOAST, and ASCO classifications based on information available at the time of hospital discharge. We assessed the association between etiologic subtypes and stroke characteristics by computing receiver operating characteristic curves for binary variables (90-day stroke recurrence and 90-day mortality) and by calculating the ratio of between-category to within-category variability from the analysis of variance for continuous variables (admission National Institutes of Health Stroke Scale score and acute infarct volume). RESULTS Among the 1816 patients included, the median age was 70 years (interquartile range, 58-80 years) (830 women [46%]). The classification systems differed in their ability to assign stroke etiologies into known subtypes; the size of the undetermined category was 33% by CCS, 53% by TOAST, and 42% by ASCO (P < .001 for all binary comparisons). All systems provided significant discrimination for the validation variables tested. For the primary validation variable (90-day recurrence), the area under the receiver operating characteristic curve was 0.71 (95% CI, 0.66-0.75) for CCS, 0.61 (95% CI, 0.56-0.67) for TOAST, and 0.66 (95% CI, 0.60-0.71) for ASCO (P = .01 for CCS vs ASCO; P < .001 for CCS vs TOAST; P = .13 for ASCO vs TOAST). The classification systems exhibited similar discrimination for 90-day mortality. For admission National Institutes of Health Stroke Scale score and acute infarct volume, CCS generated more distinct subtypes with higher between-category to within-category variability than TOAST and ASCO. CONCLUSIONS AND RELEVANCE Our findings suggest that the major etiologic stroke subtypes are distinct categories with different stroke characteristics irrespective of the classification system used to identify them. We further show that CCS generates discrete etiologic categories with more diverse clinical, imaging, and prognostic characteristics than either TOAST or ASCO.

Background and Purpose: There is limited evidence on head positioning in acute ischemic stroke (AIS) or intracerebral hemorrhage (ICH). Potential benefits for lying flat (0°) include improved collateral blood flow in AIS and for head up (30°) reduced cerebral oedema in ICH. The Head Positioning in Stroke Trial (HeadPoST) aims to provide reliable evidence on the optimum head position in acute stroke. Methods: HeadPoST is a prospective, cluster randomised, crossover, blinded outcome assessed, clinical trial with consecutive patient recruitment who were positioned within 24 hours of admission. Hospitals were randomised to service organisation to compare lying flat vs. sitting up (≥30°) head positioning of stroke patients. An innovative centralized remote monitoring system was used to assess data quality across participating countries. Results: Over a 30 month study period, 10,000+ patients were recruited across 114 hospitals in 9 countries. A web-based monitoring system provided alerts for cross-over time points and achievement of cluster balance. Centralised reports included serious adverse events, protocol deviations, forms completion, data queries, entry delays and data validation, which were distributed to regional co-ordinating centres for action. Details of these procedures are outlined. Conclusions: Reliable, complete, and high quality data were required for this pragmatic international nursing care clinical trial, which used a novel cluster cross-over design.