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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.

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.

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.

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: 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 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.

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 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.

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.

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.

Background— Carotid artery stenting (CAS) has become an alternative treatment for patients presenting symptomatic carotid artery stenosis. The improvement in clinical outcomes with CAS has been associated with the development of embolic protection devices. The trial aim is to compare flow reversal versus filter protection during CAS through femoral access. Methods and Results— Patients were randomly enrolled in CAS using flow reversal or filter protection. The primary end points were the incidence, number, and size of new ischemic brain lesions after CAS. The secondary end points included major adverse cardiac and cerebrovascular events, transient ischemic attack, and definitive ischemic brain lesions on fluid-attenuated inversion recovery magnetic resonance image at a 3-month follow-up. Ischemic brain lesions were assessed by a 3T magnetic resonance image. Neurological outcomes were evaluated by means of the National Institutes of Health Stroke Scale and the modified Rankin Scale (mRS). Forty consecutive patients were randomly assigned. Compared with flow reversal (n=21), filter protection (n=19) resulted in a significant reduction in the incidence (15.8% versus 47.6%, P =0.03), number (0.73 versus 2.6, P =0.05), and size (0.81 versus 2.23 mm, P =0.05) of new ischemic brain lesions. Two patients, 1 from each group, presented transient ischemic attack at 3-month follow-up. There were no major adverse cardiac and cerebrovascular events in the hospital or at 3-month follow-up. Conclusions— In this small sample size trial, filter protection was more effective than flow reversal in reducing ischemic brain lesions during CAS through femoral approach. Clinical Trial Registration— URL: http://portal2.saude.gov.br/sisnep/ . Unique identifier: 0538.0.004.000-10.

Introduction: After the results of the new endovascular trials that demonstrated a robust effect of endovascular treatment for acute ischemic stroke (AIS), early detection of proximal artery occlusion (PAO) has become a fundamental task during the initial assessment of acute stroke patients at the emergency department. Nevertheless, an accurate identification of PAO may be particularly challenging in smaller hospitals and in developing countries, areas with restricted assess to vascular neuroimaging modalities such as CTA and MRA. Hypothesis: Algorithms based on NIHSS and non-contrasted CT (NCCT) findings can be accurately used to detect PAO in patients with AIS of the anterior circulation. Method: We retrospectively evaluated 194 consecutive patients with AIS of the anterior circulation from a prospective stroke registry of patients admitted to an academic tertiary emergency unit in Brazil during 2014 that had a NCCT and a CTA at admission. NIHSS scores and attenuation of major intracranial arteries of the anterior circulation on NCCT were collected by two experienced investigators that were blind to the CT angiography findings. We used a ratio between two ROIs (rVA) that were drawn on NCCT blinded to CT angiography: (i) on the region of highest vessel attenuation ipsilateral to the involved hemisphere and (ii) mirror ROI on the corresponding vessel segment of the contralateral hemisphere. We used ROC curve analysis and C-statistics to predict CT angiography PAO. Results: NIHSS and vessel attenuation values were highly associated with the PAO with an area under the curve (AUC) of 0.88 (p < 0,001) and 0.83 (p < 0,001), respectively. An NIHSS of 10 at admission had a sensitivity, and negative predictive value of 97% and 97%, respectively. The rVA ≥ 1.50 had a specificity and positive predictive value 96% and 85%, respectively. The POA score was then built by logistic regression from NIHSS and rVA and showed even higher accuracy for the presence of POA on CTA, with an AUC of 0.93 (p < 0,001). Conclusion: The PAO score based on admission NIHSS and proximal vessel attenuation on NCCT can be accurately used to detect PAO in patients with AIS of the anterior circulation. Further studies are necessary to validate this score in a multicenter setting.

Background and Purpose— Functional MRI is a powerful tool to investigate recovery of brain function in patients with stroke. An inherent assumption in functional MRI data analysis is that the blood oxygenation level-dependent (BOLD) signal is stable over the course of the examination. In this study, we evaluated the validity of such assumption in patients with chronic stroke. Methods— Fifteen patients performed a simple motor task with repeated epochs using the paretic and the unaffected hand in separate runs. The corresponding BOLD signal time courses were extracted from the primary and supplementary motor areas of both hemispheres. Statistical maps were obtained by the conventional General Linear Model and by a parametric General Linear Model. Results— Stable BOLD amplitude was observed when the task was executed with the unaffected hand. Conversely, the BOLD signal amplitude in both primary and supplementary motor areas was progressively attenuated in every patient when the task was executed with the paretic hand. The conventional General Linear Model analysis failed to detect brain activation during movement of the paretic hand. However, the proposed parametric General Linear Model corrected the misdetection problem and showed robust activation in both primary and supplementary motor areas. Conclusions— The use of data analysis tools that are built on the premise of a stable BOLD signal may lead to misdetection of functional regions and underestimation of brain activity in patients with stroke. The present data urge the use of caution when relying on the BOLD response as a marker of brain reorganization in patients with stroke.

To determine the rate of symptomatic intracranial hemorrhage (SIH) and in-hospital mortality among patients with acute ischemic stroke related to Chagas disease (CD) treated with IV tissue plasminogen activator (TPA).In this retrospective cohort study, consecutive stroke patients treated with IV TPA and routinely tested for CD were retrospectively selected from a single-center, hospital-based, prospective registry of acute stroke patients from 2001 to 2012. Demographic and clinical data were obtained from the registry as well as in-hospital mortality. CT scans were blindly reviewed to assess the occurrence of hemorrhagic transformation. Among acute stroke patients who received IV TPA, we compared those with and without a positive serology for CD.Among 240 patients treated with IV TPA, 174 had serologic testing for CD available. Of those, 24 patients (13.8%) had positive serology for CD. Patients with CD more frequently had heart failure (45.8% vs 14.7%; p0.01) and higher admission NIH Stroke Scale scores (19 [15-21] vs 13 [8-19]; p0.01) than patients with negative serology. The rates of SIH (4.2% vs 5.3%; odds ratio: 0.77; 95% confidence interval: 0.09-6.46; p = 0.99) and in-hospital death (16.7% vs 11.3%; odds ratio: 1.57; 95% confidence interval: 0.48-5.12; p = 0.50) were not higher among patients with CD.In the largest published series of patients with CD-related stroke treated with IV TPA, we have observed that IV thrombolysis was safely performed and showed no increase of SIH. The diagnosis of CD should not preclude IV thrombolysis in these patients.

Mexico has had the Advanced Trauma Life Support (ATLS) program since 1986. We assessed the attrition of ATLS skills among ATLS providers and instructors in this country.Three groups (S, 16 students [new medical graduates enrolled for an ATLS course]; P, 33 providers; and I, 26 instructors [who had completed courses previously]) were evaluated. Group S read the manual before pretesting. Groups P and I were subdivided based on the length of time since the course had been completed: P1, less than 2 years (n = 22); P2, more than 2 years (n = 11); I1, less than 2 years (n = 16); and I2, more than 2 years (n = 10). Multiple-choice and psychomotor testing using ATLS scoring criteria were used. Affect was assessed post-ATLS for motivational factors, interactivity, and attitude toward trauma care.Multiple-choice test scores (means +/- SD) out of a maximum of 40 were as follows: S, 24.3 +/- 2.6; P1, 24.0 +/- 5.7; P2, 21.3 +/- 8.0; I1, 23.2 +/- 8.2; and I2, 24.0 +/- 7.2. Group S all passed the post-ATLS multiple-choice test (with correct answer percentages of 60.3% +/- 6.6% pre-ATLS versus 88.8% +/- 5.6% post-ATLS). An ATLS passing score of 80% correct answers was achieved in 2 of 33 for group P and 8 of 26 for group I (p0.05), with no statistically significant differences between groups P1 and P2 or between groups I1 and I2. For the psychomotor skills testing component, 5 of 16 in the S group passed, 15 of 22 in P1 passed, 9 of 11 in P2 passed, 14 of 16 in I1 passed, and 6 of 10 in I2 passed. The pass rate was significantly lower in the S pre-ATLS group than in the P and I groups (p0.05, Fisher's exact test). More than 60% preferred interactive components and enrolled for professional improvement, and more than 90% reported improved post-ATLS attitude to trauma care.Reading the manual alone yields similar cognitive but inferior psychomotor performance compared with subjects who completed the course previously. The majority of previous providers and instructors did not obtain a passing score (80%) in the multiple-choice test, but all the new providers passed the post-ATLS multiple-choice test, suggesting major attrition of cognitive skills but maintenance of psychomotor skills. Instructors had superior cognitive performance versus providers with worsening performance over time, but clinical skills performance was maintained at an equally high level by all groups. A very positive attitude toward ATLS prevailed among all participants.

Background: Cardioembolic (CE) stroke carries significant morbidity and mortality. Current risk stratification tools such as CHADS2 score do not include any imaging parameters and are based on clinical features, which have limitations. Left atrial (LA) enlargement and remodeling may be associated with CE risk due to predisposition for atrial arrhythmias and thrombus formation. Left atrial cross sectional area (LACSA), a novel echo measure which reflects both LA size and shape, may improve CE stroke risk assessment. Aim: This study examined the value of LACSA in predicting CE stroke risk and the improvement in risk prediction when added to CHADS2 score. Methods: Clinical and echo parameters were examined in a prospective cohort of 1275 consecutive patients with ischemic stroke. Strokes were classified using the Causative Classification of Strokes and 259 (20%) were classified as CE stroke. LACSA was calculated using the formula: π/4*largest measured LA diameter*smallest measured LA diameter where mid LA diameter was measured in the parasternal long axis, 4 chamber and 2 chamber views. Results: Patients with CE stroke had greater LACSA (8.6 ± 2.3 vs 6.4 ± 1.8 cm2/m2; p Conclusion: LACSA is a novel measure of LA remodeling and associated with CE stroke. LACSA, an imaging parameter, enhances the risk prediction of the CHADS2 score, a clinical measure of risk, improving risk stratification for CE stroke and impacting therapeutic strategies.

Background: The modified Rankin Scale (mRS) is the most commonly used scale to asses functional outcome after stroke. Several studies on mRS have shown good reliability, feasibility and interrater agreement of this scale using a face-to-face assessment and by telephone assessment in developed countries. Nevertheless, it is still uncertain with the culture-adapted and translated version of the scale to Portuguese could also be reliably applied by telephone assessment in Brazil. The aim of this study was to validate the telephone assessment of a Portuguese version of the mRS using a structured interview in a sample of Brazilian stroke patients. Methods: We evaluated 50 stroke outpatients twice. The first interview was face-to-face and the second was made by telephone and the time between the two assessments was at most 14 days. Four web-certified raters evaluated the patients using a structured interview as reported in the literature. Raters were blinded for the mRS score given by the other rater. For both assessments, the rater could also interview a caregiver if necessary. Results: The patients’s mean age was 62.8±14.7; mean duration of education was 5.2±3.4 years; 52% were males and 55.2% needed caregiver assistance to answer the questions. The majority of caregivers were female (85%), mean age 49.1±15 years old, and mean number of years of study 8.3±3.4. Perfect agreement between the telephone and face-to-face assessments was obtained for 27 (54%) patients, corresponding to an unweighted Kappa of 0.44 (95% CI 0.27 - 0.61) and a Kappa with quadratic weighting of 0.89. A difference of 1 level occurred in 21 (42%) patients. The median of telephone assessment mRS was 3.5 (interquartile range= 2-4) and of face-to-face assessment was 4 (interquartile range= 2-5). There was no difference between the two assessments (Wilcoxon test, p=0.35). Conclusion: Despite the low education level of our sample, telephone assessment of using a translated and culturally adapted Portuguese version of the mRS showed good validity, reliability and reproducibility in Brazil. The use of a structured interview is recommended for this purpose.

Background: Obstructive sleep apnea (OSA) is frequent in acute stroke patients and is associated with increased mortality and poor functional outcome. Polysomnography (PSG) is the gold standard diagnostic method for OSA, but it is impracticable as a routine for all acute stroke patients. We evaluated how OSA screening tools such as the Berlin Questionnaire (BQ) and the Epworth Sleepiness Scale (ESS) would perform when administered to relatives of stroke patients in the acute setting, and compared these individual tools against a combined screening score (SOS score). Methods: Ischemic stroke patients were submitted to a full PSG at the first night after symptoms onset. OSA severity was measured by apnea-hypopnea index (AHI). BQ and ESS were administered to relatives of stroke patients before the PSG. We combined elements of the BQ and ESS to create a new screening tool for OSA named Sleep Obstructive apnea score optimized for Stroke (SOS score). Results: Thirty-nine consecutives ischemic stroke patients were enrolled in our study. The mean age was 62.3 ±12.2 years. Age was significantly different between those with and without OSA (p=0.02). The mean body mass index and neck circumference were 26.7 ± 4.7 and 38.9 ± 4.0cm, respectively. OSA (AHI ≥ 10) was present in 76.9%. The area under the curve for SOS score (AUC:0.812; p=0.005) was superior to BQ (AUC:0.567; p=0.549) and also to ESS (AUC:0.646; p=0.119 vs. AUC:0.686; p=0.048) for severe OSA (IAH ≥ 30). The threshold of SOS ≤ 10 (present in 20.5% of patients) showed high sensitivity (90%) and negative predictive value (96.2%) for OSA; SOS ≥20 (17.9% of patients) showed high specificity (100%) and positive predictive value (92.5%) for severe OSA. Using SOS as a screening approach would decrease by around 40% the demand for PSG during the acute stroke setting. Conclusions: The SOS score when administered to relatives of stroke patients appears to be an appropriate tool to screen acute stroke patients for OSA, while decreasing the need for a formal sleep study during the acute stroke setting. The new derived SOS score is superior to BQ and ESS for identifying patients with OSA and Severe OSA during the acute phase of stroke.

Background: The role of microembolic signal (MES) detected by transcranial Doppler sonography in the acute phase of a stroke remains controversial in the medical literature. The prevalence of MES in the various sources of arterial brain embolism in patients in developing countries has been poorly studied. We investigated the prevalence of MES and whether MES detection is of proven use for risk stratification in the Brazilian population Methods: This was a transversal study with 45 ischemic stroke patients in acute phase at the Stroke Unit in a Brazilian hospital. All patients underwent monitoring of the middle cerebral arteries by transcranial doppler for at least 30 minutes. The examiner who conducted the monitoring was unaware of the risk stratification of the patient(single blinded). Then the record of the examination was independently analyzed by two neurologists to identify the MES. Prior to monitoring, risk stratification was carried out for all patients by complementary examinations. The independent variables were: age, NIHSS at admission, time of ictus, symptomatic carotid disease (stenosis > 60%), atrial fibrillation, intracranial stenosis, diseases of small arteries and other cardioembolic sources. The outcome was the presence or absence of MES with independent variables. The relationship between admission variables and MES was analyzed by Fisher’s Exact Test and logistic regression to estimate the odds ratio with significance defined as p Results: The prevalence of MES was 10%. A significant correlation was found between ictus < 24 hours before transcranial Doppler examination (p=0.04; OR=5.0) and symptomatic carotid disease (p=0.03; OR=15.6) with presence of MES. There was no statistical correlation between age (p=1.0), intracranial stenosis (p=1.0), atrial fibrillation (p=0.55), diseases of small arteries (p=0.56), other cardioembolic sources (p=0.55), and the association with atrial fibrillation and symptomatic carotid disease (p=1.0). Conclusions: MES detection showed higher correlation with symptomatic carotid disease and the precocity of monitoring in relation to time of ictus too. There was no relationship found between cardioembolic source and atrial fibrillation.

Background: While acute hypertensive response (AHR) predicts worse outcome in intracerebral hemorrhage (ICH), the INTERACT-2 trial recently failed to definitively demonstrate a major benefit of intensive blood pressure reduction on these patients. A possible explanation is that the detrimental effect of AHR on outcome may differ among ICH patients with and without previous chronic hypertension. Objective: to explore whether the prognosis of patients with AHR during the acute phase of ICH differs according to the presence or absence of left ventricle hypertrophy (LVH), which is a marker of chronic hypertensive organ damage. Method: we performed a retrospective analysis of a prospective cohort of patients with primary ICH presenting to an academic hospital between January/2000 and December/2012 with age > 18 years, who had a transthoracic echocardiogram available. LVH was defined according to Penn convention. AHR was defined as systolic blood pressure > 180 mmHg on admission. Mantel-Haenszel test was initially used to assess if LVH status influenced the effect of AHR on mortality. For subsequent analyses, ICH patients were divided in 3 groups: without AHR (reference); AHR without LVH; AHR with LVH. A multivariate logistic regression model was then used to identify independent predictors of mortality at 30-days. Results: 430 patients met inclusion criteria. AHR was present in 196 (46.6%), LVH was present in 233 (54.2%); 30-day mortality was 15.6%. On Mantel-Haenszel test, we found a trend (p=0.09) suggesting that absence of LVH increased AHR effect on mortality (OR:1.64; 95% CI: 0.95-2.8; p=0.07). On multivariate analysis, patients with AHR without LVH had significantly higher mortality (OR: 2.65; 95%CI: 1.15 to 6.1; p=0.022) when compared to patients without AHR, after adjusting for baseline characteristics. There was only a trend towards increased mortality in the group of patients with AHR and LVH (OR:2.22; 95% CI: 0.99-5.0; p=0.053). Conclusions: Patients without chronic hypertension appear to be more susceptible to the detrimental effects of AHR during the acute phase of ICH. Stratification of patients with ICH may help to identify those that will have greater benefit with intensive blood pressure reduction in the acute phase of ICH.

Background: AND AIM: Chagas disease (CD) is a common cause of stroke in undeveloped countries and has become more frequent in the US, where it is largely underestimated. CD related strokes are believed to be mainly cardioembolic but some studies have suggested concomitant cerebral vasculitis. Data on the safety of recanalization therapies in patients with acute stroke related to CD is still restricted to single case reports. We aimed to assess the rate of symptomatic intracranial hemorrhage (SIH) in a group of patients with CD-related stroke treated with intravenous tissue plasminogen activator (IV TPA) and/or endovascular therapy. METHODS: We performed a retrospective analysis of a prospective, single-center, hospital-based registry of acute stroke patients treated with IV TPA and/or endovascular therapy and routinely tested for CD. Demographics, medical history and clinical data were obtained from the registry. CT scans at admission and after 24-48 hours were blindly reviewed by two experienced stroke neurologists, who rated the presence of hemorrhage transformation according to the European Cooperative Acute Stroke Study criteria. RESULTS: From 2001 to 2012, 197 patients met the inclusion criteria for this study. CD was diagnosed in 30 patients (15.2%). Patients with CD had higher admission scores on the National Institute of Health Stroke Scale [median: 19; interquartile range (IR): 16-22; no CD: 14; IR: 9-19; P CONCLUSIONS: In the largest series of patients with acute stroke related to CD treated with recanalization therapies ever reported, we found that IV TPA appears to be safe in these patients. Further studies are necessary to confirm the safety and efficacy of endovascular recanalization strategies in patients with CD.

Background: A post-hoc analysis of the PROGRESS trial suggested that long-term anti-hypertensive therapy prevents intracerebral hemorrhage (ICH) in patients with cerebral amyloid angiopathy (CAA). However, the burden of underlying hypertension in patients with CAA is unclear, and it is also unclear whether this hypertensive burden contributes to long-term outcome in survivors of CAA-related ICH. Left ventricle (LV) hypertrophy is a measure of the chronicity and severity of hypertension and could be used to assess hypertensive end-organ damage in patients with CAA. Objective: To test the hypothesis that LV hypertrophy is common in patients with CAA-related ICH and is associated with increased long-term mortality and shorter survival in those patients. Methods: This was a retrospective analysis of a prospectively collected cohort of consecutive patients with primary ICH presenting to a single academic center. We included patients presenting between January/2000 to December/2010, age > 55 years, who received a transthoracic echocardiogram (echo) during follow-up and were diagnosed with definitive, probable or possible CAA according to the Boston criteria. LV mass index (10g/m2) was calculated according to Penn convention. Ninety-day survivors were followed prospectively for long-term mortality or censoring at January/2012. Cox proportional hazards models were used to identify predictors of mortality as time-dependent variables adjusting for potential confounders. Results: Among 211 patients who met inclusion criteria, the mean time to follow-up was 4.28 ± 2.7 years; the median time to echocardiogram was 3 days (IQR:49). The mean age was 75.7 ± 9.1 years; 103 (49%) were male. LV hypertrophy was present in 55 (31.8%) patients and 152 (72%) patients survived more than 90 days. In multivariate analysis, after adjusting for baseline characteristics, LV mass index (10g/m2) was associated with higher long-term mortality (HR: 1.20; 95%CI: 1.01-1.4; p=0.039). On Cox-regression, LV hypertrophy was independently associated with shorter long-term survival (HR 1.91; 95%CI 1.05-3.47; p=0.034). Conclusions: LV hypertrophy is common in patients with CAA-related ICH and is associated with increased risk of subsequent mortality among 90-day survivors.