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Introduction The benefits of mechanical thrombectomy in the treatment of patients with acute stroke due to large vessel occlusions (LVOs) have been extensively demonstrated by randomized trials and registries in developed countries. However, data on thrombectomy outside controlled trials are scarce in developing countries. The aim of this study was to assess the safety and efficacy, and to investigate the predictors for good and poor outcomes of thrombectomy for treatment of AIS due to anterior circulation LVOs in Brazil. Materials and Methods This was a single center registry of thrombectomy in the treatment of stroke caused by anterior circulation LVOs. Between 2011 and 2019, a total of 565 patients were included. Results the mean baseline NIHSS score on admission was 17.2. The average baseline ASPECTS was 8, and 91.0% of patients scored ≥6. Half of the patients received intravenous thrombolysis. The mean time from symptom onset to arterial puncture was 296.4 minutes. The mean procedure time was 61.4 minutes. The rates of the main outcomes were recanalization (TICI 2b-3) 85.6%, symptomatic intracranial hemorrhage (sICH) 8,1%, good clinical outcome (mRS=0-2) 43,5%, and mortality 22.1% at three months. Conclusions This study demonstrates the efficacy and safety of mechanical thrombectomy for treatment of patients with AIS of the anterior circulation in real-life conditions under limited facilities and resources. The results of the present study were relatively similar to those of large trials and population registers of developed countries.

Background The RESILIENT trial demonstrated the clinical benefit of mechanical thrombectomy in patients presenting acute ischemic stroke secondary to anterior circulation large vessel occlusion in Brazil. Aims This economic evaluation aims to assess the cost-utility of mechanical thrombectomy in the RESILIENT trial from a public healthcare perspective. Methods A cost-utility analysis was applied to compare mechanical thrombectomy plus standard medical care (n = 78) vs. standard medical care alone (n = 73), from a subset sample of the RESILIENT trial (151 of 221 patients). Real-world direct costs were considered, and utilities were imputed according to the Utility-Weighted modified Rankin Score. A Markov model was structured, and probabilistic and deterministic sensitivity analyses were performed to evaluate the robustness of results. Results The incremental costs and quality-adjusted life years gained with mechanical thrombectomy plus standard medical care were estimated at Int$ 7440 and 1.04, respectively, compared to standard medical care alone, yielding an incremental cost-effectiveness ratio of Int$ 7153 per quality-adjusted life year. The deterministic sensitivity analysis demonstrated that mRS-6 costs of the first year most affected the incremental cost-effectiveness ratio. After 1000 simulations, most of results were below the cost-effective threshold. Conclusions The intervention's clear long-term benefits offset the initially higher costs of mechanical thrombectomy in the Brazilian public healthcare system. Such therapy is likely to be cost-effective and these results were crucial to incorporate mechanical thrombectomy in the Brazilian public stroke centers.

Transcranial color-coded Doppler (TCCD) is an ultrasonographic technique used to obtain and evaluate images of the cerebral parenchyma and to assess blood flow velocities of the intracranial vessels. One of the major limitations of TCCD is the failure to insonate through the transtemporal window, which occurs in about 5%-44% of patients. Temporal bone thickness has been strongly associated with transtemporal window failure (TWF). The aims of the study were to evaluate the association between TWF on TCCD and radiologic findings on computed tomography of the skull along with the demographic characteristics of patients with acute stroke or transient ischemic attack (TIA), and to propose a classification for transcranial window quality (TWQ) on B-mode scan of TCCD. A total of 187 consecutive patients with acute stroke or TIA were included. Among them, 21.9% had TWF and 34.8% had TWQ categorized as insufficient on B-mode scan of TCCD. On logistic regression, age (odds ratio [OR] = 1.07, 95% confidence interval [CI]: 1.03-1.12, p0.001), female sex (OR = 5.99, 95% CI: 2.09-17.16, p = 0.001), pneumatized temporal bone (OR = 7.90, 95% CI: 1.95-32.03, p = 0.004) and temporal bone thickness (OR = 3.04, 95% CI: 1.73-5.35, p0.001) were independent predictors of TWF, even after adjusting for confounders. These findings may help to select patients in whom echogenic contrast or even other imaging methods could be used to assess intracranial vessels.

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.

Limited data exist on the optimum level of SBP in thrombolyzed patients with acute ischemic stroke (AIS). We aimed to determine the effects of intensive blood pressure (BP) lowering, specifically in patients with severe AIS who participated in the international, Enhanced Control of Hypertension and Thrombolysis Stroke Study.Prespecificed subgroup analyzes of the BP arm of Enhanced Control of Hypertension and Thrombolysis Stroke Study, a multicenter, partial-factorial, open, blinded outcome assessed trial, in which 2227 thrombolysis-eligible and treated AIS patients with elevated SBP (150 mmHg) were randomized to intensive (target 130-140 mmHg) or guideline-recommended (180 mmHg) BP management. Severe stroke was defined by computed tomography or magnetic resonance angiogram confirmation of large-vessel occlusion, receipt of endovascular therapy, final diagnosis of large artery atheromatous disease, or high (10) baseline neurological scores on the National Institutes of Health Stroke Scale. The primary efficacy outcome was death or any disability (modified Rankin scale scores 2-6). The key safety outcome was intracranial hemorrhage (ICH). Treatment effects estimated in logistic regression models are reported as odds ratios (ORs) with 95% confidence intervals (CIs).There were 1311 patients [mean age 67 years; 37% female; median baseline National Institutes of Health Stroke Scale of 11 (range 6.0-15.0)] with severe AIS. Overall, there was no significant difference in the primary outcome of death or disability. However, intensive BP lowering significantly increased mortality (OR 1.52, 95% CI 1.09-2.13; P = 0.014) compared with guideline BP lowering, despite significantly lowering clinician-reported ICH (OR 0.63, 95% CI 0.43-0.92; P = 0.016).Intensive BP lowering is associated with increased mortality in patients with severe AIS despite lowering the risk of ICH. Further randomized trials are required to provide reliable evidence over the optimum SBP target in the most serious type of AIS.ClinicalTrials.gov Identifier: NCT01422616.

Improving the readout for arterial spin labeling with multiple post-labeling delays (multi-PLD ASL) through a flip angle (FA) sweep towards increasing contrast-to-noise ratio for long PLD images. Images were acquired from 20 healthy subjects and 14 patients with severe, asymptomatic carotid artery stenosis (ACAS) in a 3T MRI scanner. Multi-PLD ASL images with conventional and proposed (FA sweep) readouts were acquired. For patients, magnetic resonance angiography was used to validate the multi-PLD ASL results. Perfusion values were calculated for brain regions irrigated by the main cerebral arteries and compared by analysis of variance. For healthy subjects, better contrast was obtained for long PLDs when using the proposed multi-PLD method compared to the conventional. For both methods, no hemispheric difference of perfusion was observed. For patients, the proposed method facilitated the observation of delayed tissue perfusion, which was not visible for long PLD using the conventional multi-PLD ASL. We successfully assessed brain perfusion of patients with asymptomatic CAS using multi-PLD ASL with FA sweep. We were able to show subtle individual differences. Moreover, prolonged arterial transit time in patients was observed, although they were considered asymptomatic, suggesting that it may not be an adequate term to characterize them.

O Brasil é um país emergente com crescente desenvolvimento econômico nos últimos 20 anos e com a sétima economia mais rica do mundo. No entanto, o ranking do Brasil no Índice de Desenvolvimento Humano das Nações Unidas (79ª posição, com base em dados de 2014) é paradoxalmente baixo em comparação com seu status econômico. As dimensões continentais do Brasil ampliam as desigualdades entre suas regiões, e a Amazônia é a área menos desenvolvida do país. Neste artigo, discutimos algumas das razões para a escassez de neurologistas na Amazônia brasileira. Além disso, discutimos possíveis novas estratégias para diminuir essas desigualdades em saúde pública em um futuro próximo.

Made available in DSpace on 2020-12-12T01:26:10Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-09-01 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) A common characteristic of sex chromosomes is the accumulation of repetitive DNA, which accounts for their diversification and degeneration. In grasshoppers, the X0 sex-determining system in males is considered ancestral. However, in some species, derived variants like neo-XY in males evolved several times independently by Robertsonian translocation. This is the case of Ronderosia bergii, in which further large pericentromeric inversion in the neo-Y also took place, making this species particularly interesting for investigating sex chromosome evolution. Here, we characterized the satellite DNAs (satDNAs) and transposable elements (TEs) of the species to investigate the quantitative differences in repeat composition between male and female genomes putatively associated with sex chromosomes. We found a total of 53 satDNA families and 56 families of TEs. The satDNAs were 13.5% more abundant in males than in females, while TEs were just 1.02% more abundant in females. These results imply differential amplification of satDNAs on neo-Y chromosome and a minor role of TEs in sex chromosome differentiation. We showed highly differentiated neo-XY sex chromosomes owing to major amplification of satDNAs in neo-Y. Furthermore, chromosomal mapping of satDNAs suggests high turnover of neo-sex chromosomes in R. bergii at the intrapopulation level, caused by multiple paracentric inversions, amplifications, and transpositions. Finally, the species is an example of the action of repetitive DNAs in the generation of variability for sex chromosomes after the suppression of recombination, and helps understand sex chromosome evolution at the intrapopulation level. Departamento de Biologia Geral e Aplicada UNESP-Univ Estadual Paulista Instituto de Biociências/IB Department of Organismal Biology Uppsala University Evolutionary Biology Centre Department of Ecology and Genetics Uppsala University Evolutionary Biology Centre Departamento de Biologia Geral e Aplicada UNESP-Univ Estadual Paulista Instituto de Biociências/IB

According to previous epidemiological studies, we can reduce the thickness of epicardial fat and improve cardiovascular risk factors through exercise, and the changes may depend on the form of exercise. We systemically reviewed published studies that evaluated exercise intervention on epicardial adipose tissue (EAT) levels. We included randomized controlled trials (RCTs) comparing one exercise with another exercise or diet for the treatment to reduce EAT. We used fixed effects models for meta-analyses; effects of exercise on outcomes were described as mean differences (MD) or standardized difference of means (SMD) was used, their 95% confidence intervals (CI). Five RCTs were included (n = 299), 156 in exercise group and 143 in the control. In comparison to the control group, exercise significantly reduced EAT (SMD − 0.57, 95%CI − 0.97 to − 0.18) and waist circumference (MD − 2.95 cm, 95%CI − 4.93 to − 0.97). Exercise did not have an effect on BMI (MD − 0.23 kg/m2, 95%CI − 0.73 to 0.27), weight (MD − 0.06 kg, 95%CI − 1.46 to 1.34), or HDL (SMD 0.26, 95%CI − 0.06 to 0.57).VO2 was significantly increased by exercise (SMD 1.58, 95%CI 1.17 to 1.99). Risk of bias was high for 3 studies, and GRADE quality of evidence was very low to moderate. Exercise reduced epicardial adipose tissue and waist circumference, and did not have effect on weight, BMI, or HDL. Newer trials with better design and methods are necessary to improve the quality of the evidence. PROSPERO registration number (CRD42018096581)

Made available in DSpace on 2020-12-12T01:56:44Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-12-01 Introduction: The presence of microembolic signals (MES) during the acute phase of stroke is poorly understood, and its role and clinical application in relation to risk stratification and prognosis in patients remain uncertain. We assessed the prevalence of spontaneous MES in acute stroke and their relationship with risk stratification, stroke recurrence, morbidity, and mortality. Patients and methods: This was a prospective cohort study conducted in the Stroke Unit. The MES presence was evaluated by transcranial Doppler (TCD) in patients with ischemic stroke within 48 h. The outcomes (risk stratification, morbidity, mortality, and recurrence of a stroke) were followed up for 6 months. The relationship between risk stratification and MES was obtained by odds ratios and that between MES and stroke recurrence, morbidity, and mortality using multiple logistic regression; considering statistical significance at P < 0.05. Results: Of the 111 patients studied, 70 were men (63.1%) and 90 were white (81.1%), with a median age of 68 years. The MES frequency was 7%. There was a significant relationship between MES and symptomatic carotid disease (OR = 22.7; 95% CI 4.1–125.7; P < 0.001), a shorter time to monitoring (OR = 12.4; 95% CI 1.4–105.4; P = 0.02), and stroke recurrence (OR = 16.83; 95% CI 2.01–141; P =.009). Discussion: It was observed that the stroke recurrence adjusted for prior stroke was higher and earlier among patients with MES detection. In conclusion, MES demonstrated a significant correlation with symptomatic carotid disease and a shorter DELAY until monitoring, and could be a predictor for the early recurrence of stroke in the long term. Department of Neurology Psychology and Psychiatry Botucatu Medical School UNESP–Univ Estadual Paulista, Campus de Botucatu, Distrito de Rubião Jr, s/n Department of Applied Physical Therapy Institute of Health Sciences UFTM–Univ Federal do Triângulo Mineiro Department of Internal Medicine Botucatu Medical School UNESP–Univ Estadual Paulista Department of Tropical Diseases and Imaging Diagnosis Botucatu Medical School UNESP–Univ Estadual Paulista Department of Surgery and Orthopedics Botucatu Medical School UNESP–Univ Estadual Paulista Department of Neuroscience and Behavior Ribeirão Preto School of Medicine USP–Univ São Paulo Department of Neurology Psychology and Psychiatry Botucatu Medical School UNESP–Univ Estadual Paulista, Campus de Botucatu, Distrito de Rubião Jr, s/n Department of Internal Medicine Botucatu Medical School UNESP–Univ Estadual Paulista Department of Tropical Diseases and Imaging Diagnosis Botucatu Medical School UNESP–Univ Estadual Paulista Department of Surgery and Orthopedics Botucatu Medical School UNESP–Univ Estadual Paulista

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)

ObjectiveCardioembolic (CE) stroke carries significant morbidity and mortality. Left atrial (LA) size has been associated with CE risk. We hypothesised that differential LA remodelling impacts on pathophysiological mechanism of major CE strokes.MethodsA cohort of consecutive patients hospitalised with ischaemic stroke, classified into CE versus non-CE strokes using the Causative Classification System for Ischaemic Stroke were enrolled. LA shape and remodelling was characterised by assessing differences in maximal LA cross-sectional area (LA-CSA) in a cohort of 40 prospectively recruited patients with ischaemic stroke using three-dimensional (3D) echocardiography. Flow velocity profiles were measured in spherical versus ellipsoidal in vitro models to determine if LA shape influences flow dynamics. Two-dimensional (2D) LA-CSA was subsequently derived from standard echocardiographic views and compared with 3D LA-CSA.ResultsA total of 1023 patients with ischaemic stroke were included, 230 (22.5%) of them were classified as major CE. The mean age was 68±16 years, and 464 (45%) were women. The 2D calculated LA-CSA correlated strongly with the LA-CSA measured by 3D in both end-systole and end-diastole. In vitro flow models showed shape-related differences in mid-level flow velocity profiles. Increased LA-CSA was associated with major CE stroke (adjusted relative risk 1.10, 95% CI 1.04 to 1.16; p2DS2-VASc score. Specifically, the inclusion of LA-CSA in a model with traditional risk factors for CE stroke resulted in significant improvement in model performance with the net reclassification improvement of 0.346 (95% CI 0.189 to 0.501; p=0.00001) and the integrated discrimination improvement of 0.013 (95% CI 0.003 to 0.024; p=0.0119).ConclusionsLA-CSA is a marker of adverse LA shape associated with CE stroke, reflecting importance of differential LA remodelling, not simply LA size, in the mechanism of CE risk.

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.

Introduction: The damage in the endothelium and the neurovascular unit appears to play a key role in the pathogenesis of vascular cognitive impairment (VCI). Although there have been many advances in understanding the physiopathology of this disease, several questions remain unanswered. The association with other degenerative diseases and the heterogeneity of its clinical spectrum establish a diagnostic problem, compromising a better comprehension of the pathology and halting the development of effective treatments. The investigation of biomarkers is an important movement to the development of novel explicative models and treatment targets involved in VCI. Methods: We searched MEDLINE considering the original research based on VCI biomarkers in the past 20 years, following prespecified selection criteria, data extraction, and qualitative synthesis. Results: We reviewed 42 articles: 16 investigated plasma markers, 17 analyzed neuropathological markers, 4 studied CSF markers, 4 evaluated neuroimaging markers (ultrasound and MRI), and 1 used peripheral Doppler perfusion imaging. Conclusions: The biomarkers in these studies suggest an intrinsic relationship between endothelial dysfunction and VCI. Nonetheless, there is still a need for identification of a distinctive set of markers that can integrate the clinical approach of VCI, improve diagnostic accuracy, and support the discovery of alternative therapies.

Introduction The benefits of thrombectomy for occlusion of M2 segments remain controversial. The aim of this study is to assess thrombectomy’s efficacy and safety in patients with M2 segment occlusion and associations between occlusion sites and anatomic variations of M1 division. Materials and methods A prospective series of 30 patients with acute ischemic stroke (AIS) resulting from M2 segment occlusion of the middle cerebral artery (MCA) who underwent thrombectomy was analyzed. The primary endpoint was assessed by the Extended Treatment in Cerebral Infarction scale (eTICI). The secondary endpoints were the incidence of symptomatic hemorrhagic transformation (sICH), mortality and good functional outcome at three months. Results The mean patient age was 69.2 years. The mean National Institutes Health Stroke Scale score (NIHSS) upon hospital admission was 16. The recanalization rates were eTICI 2b/3 in 90% and 2c/3 in 60% of the patients. Total recanalization of the M2 branch was achieved in 53% of patients. sICH incidence was 6.6%, the mortality rate was 30%, and a good functional outcome (mRS ≤2) was observed in 50% of the patients. Twenty-seven patients (90%) had a dominant M2 branch and all were occluded. Regarding the site of M2 occlusions, 74% of patients had proximal M2 occlusions. Conclusions Thrombectomy appears to be a safe and effective method for the treatment of acute M2 segment occlusions of the MCA. Most of the cases had a dominant M2 branch, and all of them were occluded. Larger studies are needed to verify the benefits of thrombectomy for different settings of M2 occlusions.

Background Randomized controlled trials provide high-level evidence, but the necessity to include selected patients may limit the generalisability of their results. Methods Comparisons were made of baseline and outcome data between patients with acute ischemic stroke (AIS) recruited into the alteplase-dose arm of the international, multi-center, Enhanced Control of Hypertension and Thrombolysis Stroke study (ENCHANTED) in the United Kingdom (UK), and alteplase-treated AIS patients registered in the UK Sentinel Stroke National Audit Programme (SSNAP) registry, over the study period June 2012 to October 2015. Results There were 770 AIS patients (41.2% female; mean age 72 years) included in ENCHANTED at sites in England and Wales, which was 19.5% of alteplase-treated AIS patients registered in the SSNAP registry. Trial participants were significantly older, had lower baseline neurological severity, less likely Asian, and had more premorbid symptoms, hypertension and atrial fibrillation. Although ENCHANTED participants had higher rates of symptomatic intracerebral hemorrhage than those in SSNAP, there were no differences in onset-to-treatment time, levels of disability (assessed by the modified Rankin scale) at hospital discharge, and mortality over 90 days between groups. Conclusions Despite the high level of participation, equipoise over the dose of alteplase among UK clinician investigators favored the inclusion of older, frailer, milder AIS patients in the ENCHANTED trial. Clinical trial registration Clinical Trial Registration-URL: http://www.clinicaltrials.gov . Unique identifier: NCT01422616

The Head Positioning in Acute Stroke Trial (HeadPoST) is a pragmatic, international, cluster crossover randomized trial of 11,093 patients with acute stroke assigned to a lying-flat (0°) or sitting-up (head elevated ≥30°) position. This post hoc analysis aimed to determine the association between blood pressure variability (BPV) and outcomes for patients from a wide range of international clinical settings and how the association was modified by randomized head position. BPV was defined according to the standard criteria, with the key parameter considered the coefficient of variation (CV) of systolic BP (SBP) over 24 h. Outcome was ordinal 90-day Modified Rankin Scale (mRS) score. The association was analyzed by ordinal, logistic regression, hierarchical, mixed models with fixed intervention (lying flat vs. sitting up), and fixed period, random cluster, and random cluster-period, effects. Nine thousand one hundred and fifty six (8324 acute ischemic stroke and 817 intracerebral hemorrhage; mean age 68.1 years; 39.2% women) were included in the analysis. CV of SBP had a significant linear association with unfavorable shift of mRS at 90 days (adjusted odds ratio 1.06, 95% confidence interval 1.02–1.11; P = 0.01). There was no heterogeneity of the association by randomized head positioning. In addition, CV of diastolic BP (DBP) (1.08, 1.03–1.12; P = 0.001) over 24 h post stroke was significantly associated with 3-month poor outcome. The association was more apparent in sitting-up position (1.12, 1.06–1.19) compared with lying-flat position (1.03, 0.98–1.09) (P interaction = 0.005). BPV was associated with adverse stroke outcome, and the magnitude of the association was greater with sitting-up head positioning in terms of DBP variability.

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.

Background RESILIENT is a prospective, multicenter, randomized phase III trial to test 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. Methods Subjects must fulfill the following main inclusion criteria: symptom onset ≤8 h, age ≥18 years, baseline NIHSS ≥8, evidence of intracranial ICA or proximal MCA (M1 segment) occlusion, ASPECTS ≥6 on CT or >5 on DWI-MRI and be either ineligible for or unresponsive to intravenous alteplase. The primary end-point is the distribution of disability levels (on the modified Rankin Scale, mRS) at 90 days under the intention-to-treat principle. Randomization Randomization is performed under a minimization process using age, baseline NIHSS, intravenous alteplase use, occlusion site and center. Design The trial is designed with an expectation of a 10% difference in the proportion of favorable outcome (mRS 0–2 at 90 days) common odds ratio of 1.615. Primary outcome Projected sample size is 690 subjects with pre-planned interim analyses at 174, 346, and 518 subjects. Secondary outcomes Secondary end-points include: 90-day functional independence (mRS ≤2), mRS shift stratified for treatment with IV rt-PA at 90 days, infarct volume on 24 h CT or MRI, early dramatic response (NIHSS 0–2 or improvement ≥8 points) at 24 h, vessel recanalization evaluated by CTA or MRA at 24 h, and the post-procedure rate of successful reperfusion (defined as a modified Treatment in Cerebral Infarction 2b or greater). Safety variables are mortality at 90 days, symptomatic intracranial hemorrhage at 24 h and procedure-related complications.

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.

Supplemental Digital Content is available in the text., Objectives: 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.

Introduction: Moving toward evidence-based care protocols is key to reduce the burden of cardiovascular diseases. Hypothesis: We assessed the hypothesis that a multifaceted intervention could improve the adherence to evidence-based therapies for coronary artery disease patients. Methods: The BRIDGE Cardiovascular Prevention study was a cluster randomized trial including 1,619 patients with ischemic stroke, coronary artery disease or peripheral artery disease from 40 outpatient clinics in Brazil. Clusters were randomized to receive a multifaceted quality improvement intervention or to routine practice. The intervention included reminders, care algorithms, training of a case manager, audit and feedback reports, and distribution of educational materials to health care providers. The primary endpoint was the adherence to combined use of statins, antiplatelets and ACEi or ARBs, using an “all or none” approach at 12 months in patients without contra-indications. Results: Among the 1619 patients enrolled in the original sample, 1327 (81.9%) were coronary artery disease patients. The mean age was 65.7 (SD=10.4) and 880 (66.3 %) were men. There was a significant difference in the combined prescription of evidence-based therapies between the intervention and the control groups (75.4% versus 61.8 % respectively, Odds Ratio, 2.33 [95% CI, 1.29 - 4.21], p Conclusions: Among coronary artery disease patients treated in Brazil, a quality improvement intervention resulted in improved prescription of evidence-based therapies for cardiovascular prevention.

Background Assessment of the impact of the thrombectomy learning curve on clinical outcomes is essential for developing healthcare system protocols. Aims The aim of this study was to assess the effect of thrombectomy case volume on procedural and clinical outcomes in a Brazilian registry. Methods A total of 645 patients with acute ischemic stroke treated by thrombectomy were included in the analysis. Patients were divided into two groups regarding the period of treatment: the early period group and the late period group. Results In the adjusted analysis, treatment in the late period was an independent predictor of recanalization (odds ratio 1.91, 95% CI 1.28–2.86) and excellent neurologic outcomes at three months (odds ratio 1.77, 95% CI 1.04–3.01). Treatment in the late period had no significant association with mortality (odds ratio 0.88, 95% CI 0.55–1.41). Conclusions An increase in thrombectomy case volume for the treatment of AIS over time was an independent predictor of recanalization and excellent neurologic outcome.

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.

Given their copy number differences and unique modes of inheritance, the evolved gene content and expression of sex chromosomes is unusual. In many organisms the X and Y chromosomes are inactivated in spermatocytes, possibly as a defense mechanism against insertions into unpaired chromatin. In addition to current sex chromosomes, Drosophila has a small gene-poor X-chromosome relic (4th) that re-acquired autosomal status. Here we use single cell RNA-Seq on fly larvae to demonstrate that the single X and pair of 4th chromosomes are specifically inactivated in primary spermatocytes, based on measuring all genes or a set of broadly expressed genes in testis we identified. In contrast, genes on the single Y chromosome become maximally active in primary spermatocytes. Reduced X transcript levels are due to failed activation of RNA-Polymerase-II by phosphorylation of Serine 2 and 5., Sex chromosome gene content and expression is unusual. Here the authors use single cell RNA-Seq on Drosophila larvae to demonstrate that the single X and pair of 4th chromosomes are specifically inactivated in primary spermatocytes, while genes on the single Y chromosome become maximally active in primary spermatocytes.

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.

The burden of stroke in Brazil, as in other developing countries, has considerably increased over the past years. With incidence rates ranging from 105 to 137 cases per 100 000 persons per year and mortality reaching 24%, stroke is a major public health issue in this continental country. Although most strokes in Brazil can be attributed to classic treatable cardiovascular risk factors, infectious diseases such as Chagas disease, arboviruses hemorrhagic fevers, neurocysticercosis, and malaria are also important risk factors. Socioeconomic disparities and population unawareness about stroke symptoms are great challenges in Brazil. There was an improvement in stroke awareness after the Brazilian Stroke Society and the World Stroke Organization launched several campaigns throughout the country. Another important step was taken in 2012, when the Brazilian Ministry of Health published the Brazilian National Stroke Act, including reimbursement for rtPA, creation of stroke centers qualified according to the hospital complexity, integration of the Brazilian Emergency Medical System, establishment of a budget for the rehabilitation system, and education and training of healthcare professionals and of the population. Since these measures, the number of stroke centers increased from 35 in 2008 to 149 in 2017 and stroke mortality in public stroke centers decreased from 17.9% in 2010 to 12.8% in 2014. Although much has improved, Brazil still has major social inequalities and further measures are needed to guarantee a high-quality stroke care.

Background: Mirror therapy (MT) is becoming an alternative rehabilitation strategy for various conditions, including stroke. Although recent studies suggest the positive benefit of MT in chronic stroke motor recovery, little is known about its neural mechanisms. Purpose: To identify functional brain changes induced by a single MT intervention in ischemic stroke survivors, assessed by both transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI). Materials and methods: TMS and fMRI were used to investigate 15 stroke survivors immediately before and after a single 30-min MT session. Results: We found statistically significant increase in post-MT motor evoked potential (MEP) amplitude (increased excitability) from the affected primary motor cortex (M1), when compared to pre-MT MEP. Post-MT fMRI maps were associated with a more organized and constrained pattern, with a more focal M1 activity within the affected hemisphere after MT, limited to the cortical area of hand representation. Furthermore, we find a change in the balance of M1 activity toward the affected hemisphere. In addition, significant correlation was found between decreased fMRI β-values and increased MEP amplitude post-MT, in the affected hemisphere. Conclusion: Our study suggests that a single MT intervention in stroke survivors is related to increased MEP of the affected limb, and a more constrained activity of the affected M1, as if activity had become more constrained and limited to the affected hemisphere.

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.

Supplemental material, WSO908140 Supplemental material for Prognostic significance of early urinary catheterization after acute stroke: Secondary analyses of the international HeadPoST trial by Menglu Ouyang, Laurent Billot, Lili Song, Xia Wang, Christine Roffe, Hisatomi Arima, Pablo M Lavados, Maree L Hackett, Verónica V Olavarría, Paula Muñoz-Venturelli, Sandy Middleton, Octavio M Pontes-Neto, Tsong-Hai Lee, Caroline L Watkins, Thompson G Robinson and Craig S Anderson in International Journal of Stroke

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.