Social Distancing, Stroke Admissions and Stroke Mortality During the COVID-19 Pandemic: A Multicenter, Longitudinal Study.

OBJECTIVES: We aimed to evaluate the relationship between social distancing, stroke admissions and stroke mortality during the COVID-19 pandemic, while accounting for the rate of COVID-19 admissions. METHODS: We performed a longitudinal analysis of a multicenter, prospective, hospital-based registry of intensive care units from 19 hospitals from Brazil, comprising a 14-month period of the COVID-19 pandemic. We investigated whether the daily rate of admissions (DRAstroke) and daily mortality rate for stroke were associated with the social distancing index (SDI), taking into account the daily rate of admissions for COVID-19 (DRACOVID) in univariate and multivariate regression models. We also compared the clinical characteristics of patients with stroke admitted before and during the pandemic. RESULTS: We found that DRAstroke decreased significantly in association with a strong rise in the SDI during the early months of the pandemic. However, in the latter period of the pandemic, only minor changes were observed in the SDI, and still, DRAstroke was inversely associated with the DRACOVID. Throughout the pandemic, higher SDI and DRACOVID were associated with higher in-hospital mortality for stroke. CONCLUSIONS: The severity of surges of the COVID-19 pandemic were independently and persistently associated with declines in stroke admissions, even during periods when social distancing policies were not intensified.

Intravenous thrombolysis in unwitnessed stroke onset: MR WITNESS trial results.

OBJECTIVE: Most acute ischemic stroke (AIS) patients with unwitnessed symptom onset are ineligible for intravenous thrombolysis due to timing alone. Lesion evolution on fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) correlates with stroke duration, and quantitative mismatch of diffusion-weighted MRI with FLAIR (qDFM) might indicate stroke duration within guideline-recommended thrombolysis. We tested whether intravenous thrombolysis ≤4.5 hours from the time of symptom discovery is safe in patients with qDFM in an open-label, phase 2a, prospective study (NCT01282242). METHODS: Patients aged 18 to 85 years with AIS of unwitnessed onset at 4.5 to 24 hours since they were last known to be well, treatable within 4.5 hours of symptom discovery with intravenous alteplase (0.9mg/kg), and presenting with qDFM were screened across 14 hospitals. The primary outcome was the risk of symptomatic intracranial hemorrhage (sICH) with preplanned stopping rules. Secondary outcomes included symptomatic brain edema risk, and functional outcomes of 90-day modified Rankin Scale (mRS). RESULTS: Eighty subjects were enrolled between January 31, 2011 and October 4, 2015 and treated with alteplase at median 11.2 hours (IQR = 9.5-13.3) from when they were last known to be well. There was 1 sICH (1.3%) and 3 cases of symptomatic edema (3.8%). At 90 days, 39% of subjects achieved mRS = 0-1, as did 48% of subjects who had vessel imaging and were without large vessel occlusions. INTERPRETATION: Intravenous thrombolysis within 4.5 hours of symptom discovery in patients with unwitnessed stroke selected by qDFM, who are beyond the recommended time windows, is safe. A randomized trial testing efficacy using qDFM appears feasible and is warranted in patients without large vessel occlusions. Ann Neurol 2018;83:980-993.

Structural Integrity of Normal Appearing White Matter and Sex-Specific Outcomes After Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Women have worse poststroke outcomes than men. We evaluated sex-specific clinical and neuroimaging characteristics of white matter in association with functional recovery after acute ischemic stroke. METHODS: We performed a retrospective analysis of acute ischemic stroke patients with admission brain MRI and 3- to 6-month modified Rankin Scale score. White matter hyperintensity and acute infarct volume were quantified on fluid-attenuated inversion recovery and diffusion tensor imaging MRI, respectively. Diffusivity anisotropy metrics were calculated in normal appearing white matter contralateral to the acute ischemia. RESULTS: Among 319 patients with acute ischemic stroke, women were older (68.0 versus 62.7 years; P=0.004), had increased incidence of atrial fibrillation (21.4% versus 12.2%; P=0.04), and lower rate of tobacco use (21.1% versus 35.9%; P=0.03). There was no sex-specific difference in white matter hyperintensity volume, acute infarct volume, National Institutes of Health Stroke Scale, prestroke modified Rankin Scale score, or normal appearing white matter diffusivity anisotropy metrics. However, women were less likely to have an excellent outcome (modified Rankin Scale score <2: 49.6% versus 67.0%; P=0.005). In logistic regression analysis, female sex and the interaction of sex with fractional anisotropy, radial diffusivity, and axial diffusivity were independent predictors of functional outcome. CONCLUSIONS: Female sex is associated with decreased likelihood of excellent outcome after acute ischemic stroke. The correlation between markers of white matter integrity and functional outcomes in women, but not men, suggests a potential sex-specific mechanism.

Clinical Outcomes of Patients with Acute Basilar Artery Occlusion in Brazil: An Observational Study.

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 Ribeirão 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.

Subtle white matter intensity changes on fluid-attenuated inversion recovery imaging in patients with ischaemic stroke.

Leukoaraiosis is a neuroimaging marker of small-vessel disease that is characterized by high signal intensity on fluid-attenuated inversion recovery MRI. There is increasing evidence from pathology and neuroimaging suggesting that the structural abnormalities that characterize leukoaraiosis are actually present within regions of normal-appearing white matter, and that the underlying pathophysiology of white matter damage related to small-vessel disease involves blood-brain barrier damage. In this study, we aim to verify whether leukoaraiosis is associated with elevated signal intensity on fluid-attenuated inversion recovery imaging, a marker of brain tissue free-water accumulation, in normal-appearing white matter. We performed a cross-sectional study of adult patients admitted to our hospital with a diagnosis of acute ischaemic stroke or transient ischaemic attack. Leukoaraiosis was segmented using a semi-automated method involving manual outlining and signal thresholding. White matter regions were segmented based on the probabilistic tissue maps from the International Consortium for Brain Mapping 152 atlas. Also, normal-appearing white matter was further segmented based on voxel distance from leukoaraiosis borders, resulting in five normal-appearing white matter strata at increasing voxel distances from leukoaraiosis. The relationship between mean normalized fluid-attenuated inversion recovery signal intensity on normal-appearing white matter and leukoaraiosis volume was studied in a multivariable statistical analysis using linear mixed modelling, having normal-appearing white matter strata as a clustering variable. One hundred consecutive patients meeting inclusion and exclusion criteria were selected for analysis (53% female, mean age 68 years). Mean normalized fluid-attenuated inversion recovery signal intensity on normal-appearing white matter was higher in the vicinity of leukoaraiosis and progressively lower at increasing distances from leukoaraiosis. In a multivariable analysis, the mean normalized fluid-attenuated inversion recovery signal intensity on normal-appearing white matter was positively associated with leukoaraiosis volume and age (B = 0.025 for each leukoaraiosis quartile increase; 95% confidence interval 0.019-0.030). This association was found similarly across normal-appearing white matter strata. Voxel maps of the mean normalized fluid-attenuated inversion recovery signal intensity on normal-appearing white matter showed an increase in signal intensity that was not adjacent to leukoaraiosis regions. Our results show that normal-appearing white matter exhibits subtle signal intensity changes on fluid-attenuated inversion recovery imaging that are related to leukoaraiosis burden. These results suggest that diffuse free-water accumulation is likely related to the aetiopathogenic processes underlying the development of white matter damage related to small-vessel disease.

Association between obesity and COVID-19 mortality and length of stay in intensive care unit patients in Brazil: a retrospective cohort study.

The present study aimed to evaluate the association between obesity and COVID-19 mortality and length of stay in ICU patients, and how these associations were modified by age groups. We performed a retrospective multicenter cohort study with data obtained from a hospital-based registry. The sample consisted of 8183 ICU hospitalized patients who tested positive for SARS-CoV-2. Cox proportional models were used to evaluate the association between BMI categories and COVID-19 mortality and generalized linear models for the length of stay in the ICU. After adjusting for confounders, those in the younger group with severe obesity had an increased risk of COVID-19 mortality compared to those with normal/overweight (HR 1.27; 95% CI 1.01-1.61). An increased risk of death was also observed for patients with underweight (HR 3.74; 95% CI 1.39-10.07). For patients aged ≥ 60 year, mild/moderate obesity was associated with reduced mortality risk (HR 0.87; 95% CI 0.78-0.97). For the age group < 60 year, the length of stay in ICU for those patients with severe obesity was 35% higher compared to the normal/overweight category (eß 1.35; 95% CI 1.21-1.51). Conversely, for the survivors in the underweight category, the length of stay in ICU was 51% lower compared to the normal/overweight group (eß 0.49; 95% CI 0.31-0.78). In the age group ≥ 60 year, mild/moderate obesity was associated with an increased length of stay in the ICU (eß 1.10; 95% CI 1.01-1.21), adjusting for confounders. These findings could be helpful for health professionals to identify subgroups at higher risk for worse outcomes.

Sex-specific differences in white matter microvascular integrity after ischaemic stroke.

Background and purpose: Functional outcomes after ischaemic stroke are worse in women, despite adjusting for differences in comorbidities and treatment approaches. White matter microvascular integrity represents one risk factor for poor long-term functional outcomes after ischaemic stroke. The aim of the study is to characterise sex-specific differences in microvascular integrity in individuals with acute ischaemic stroke. Methods: A retrospective analysis of subjects with acute ischaemic stroke and brain MRI with diffusion-weighted (DWI) and dynamic-susceptibility contrast-enhanced (DSC) perfusion-weighted imaging obtained within 9 hours of last known well was performed. In the hemisphere contralateral to the acute infarct, normal-appearing white matter (NAWM) microvascular integrity was measured using the K2 coefficient and apparent diffusion coefficient (ADC) values. Regression analyses for predictors of K2 coefficient, DWI volume and good outcome (90-day modified Rankin scale (mRS) score <2) were performed. Results: 105 men and 79 women met inclusion criteria for analysis. Despite no difference in age, women had increased NAWM K2 coefficient (1027.4 vs 692.7×10-6/s; p=0.006). In women, atrial fibrillation (ß=583.6; p=0.04) and increasing NAWM ADC (ß=4.4; p=0.02) were associated with increased NAWM K2 coefficient. In multivariable regression analysis, the K2 coefficient was an independent predictor of DWI volume in women (ß=0.007; p=0.01) but not men. Conclusions: In women with acute ischaemic stroke, increased NAWM K2 coefficient is associated with increased infarct volume and chronic white matter structural integrity. Prospective studies investigating sex-specific differences in white matter microvascular integrity are needed.

Incidence and Etiology of Microinfarcts in Patients with Ischemic Stroke.

BACKGROUND AND PURPOSE: Cerebral microinfarcts (CMI) are associated with intracerebral hemorrhage due to small vessel disease (SVD) in studies not including an ischemic etiologic workup. We aimed to determine their incidence and potential causes in a large ischemic stroke (IS) cohort. METHODS: Consecutive patients with MRI-confirmed IS within 72 hours of onset were enrolled. Subjects had either single high-risk embolic source (cardioembolic or large vessel disease) or no embolic source. CMIs were classified by their relationship to the primary infarct as within or outside the same vascular territory. White matter hyperintensities (WMH) and microbleeds were markers SVD severity. Multivariable regression tested the association between CMIs and potential etiologies. RESULTS: We analyzed 946 IS patients, mean age 69 ± 15 years, 46% female. We detected CMI (≤5 mm) on diffusion-weighted imaging in 269 (28%) subjects, 190 (71%) within the vascular territory of the primary infarct. Large-vessel atherosclerosis (P <.001), cardioembolic source (P <.001), higher WMH (P = .032) and lower systolic blood pressure (SBP, P = .024) were independently associated with the presence of CMI. While SBP was associated with CMI in any location (P <.05), WMH was only associated with CMI outside the territory of the primary infarct (P = .033), and large vessel atherosclerosis with CMI within the primary infarct territory (P = .004). CONCLUSIONS: CMIs occurring within the vascular territory of a larger infarct are more likely embolic, but those occurring outside are probably related to SVD. Our findings suggest a role for SVD in pathogenesis of CMIs and emphasize the importance of etiologic workup to identify alternate etiologies.

Diffuse microvascular dysfunction and loss of white matter integrity predict poor outcomes in patients with acute ischemic stroke.

We sought to investigate the relationship between blood-brain barrier (BBB) permeability and microstructural white matter integrity, and their potential impact on long-term functional outcomes in patients with acute ischemic stroke (AIS). We studied 184 AIS subjects with perfusion-weighted MRI (PWI) performed <9 h from last known well time. White matter hyperintensity (WMH), acute infarct, and PWI-derived mean transit time lesion volumes were calculated. Mean BBB leakage rates (K2 coefficient) and mean diffusivity values were measured in contralesional normal-appearing white matter (NAWM). Plasma matrix metalloproteinase-2 (MMP-2) levels were studied at baseline and 48 h. Admission stroke severity was evaluated using the NIH Stroke Scale (NIHSS). Modified Rankin Scale (mRS) was obtained at 90-days post-stroke. We found that higher mean K2 and diffusivity values correlated with age, elevated baseline MMP-2 levels, greater NIHSS and worse 90-day mRS (all p < 0.05). In multivariable analysis, WMH volume was associated with mean K2 ( p = 0.0007) and diffusivity ( p = 0.006) values in contralesional NAWM. In summary, WMH severity measured on brain MRI of AIS patients is associated with metrics of increased BBB permeability and abnormal white matter microstructural integrity. In future studies, these MRI markers of diffuse cerebral microvascular dysfunction may improve prediction of cerebral tissue infarction and functional post-stroke outcomes.

Vascular Spectrum of Imaging Findings in COVID-19: Ischemic, Hemorrhagic, and Thromboembolic Complications

Abstract Ischemic strokes secondary to occlusion of large vessels have been described in patients with COVID-19. Also, venous thrombosis and pulmonary thromboembolism have been related to the disease. Vascular occlusion may be associated with a prothrombotic state due to COVID-19-related coagulopathy and endotheliopathy. Intracranial hemorrhagic lesions can additionally be seen in these patients. The causative mechanism of hemorrhage could be associated with anticoagulant therapy or factors such as coagulopathy and endotheliopathy. We report on cases of ischemic, thrombotic, and hemorrhagic complications in six patients diagnosed with SARS-CoV-2 infection. Chest computed tomography (CT) showed typical SARS-CoV-2 pneumonia findings in all the cases, which were all confirmed by either serology or reverse transcription polymerase chain reaction (RT-PCR) tests.

Integrity of normal-appearing white matter and functional outcomes after acute ischemic stroke.

OBJECTIVE: To characterize the effect of white matter microstructural integrity on cerebral tissue and long-term functional outcomes after acute ischemic stroke (AIS). METHODS: Consecutive AIS patients with brain MRI acquired within 48 hours of symptom onset and 90-day modified Rankin Scale (mRS) score were included. Acute infarct volume on diffusion-weighted imaging (DWIv) and white matter hyperintensity volume (WMHv) on T2 fluid-attenuated inversion recovery MRI were measured. Median fractional anisotropy (FA), mean diffusivity, radial diffusivity, and axial diffusivity values were calculated within normal-appearing white matter (NAWM) in the hemisphere contralateral to the acute lesion. Regression models were used to assess the association between diffusivity metrics and acute cerebral tissue and long-term functional outcomes in AIS. Level of significance was set at p < 0.05 for all analyses. RESULTS: Among 305 AIS patients with DWIv and mRS score, mean age was 64.4 ± 15.9 years, and 183 participants (60%) were male. Median NIH Stroke Scale (NIHSS) score was 3 (interquartile range [IQR] 1-8), and median normalized WMHv was 6.19 cm3 (IQR 3.0-12.6 cm3). Admission stroke severity (ß = 0.16, p < 0.0001) and small vessel stroke subtype (ß = -1.53, p < 0.0001), but not diffusivity metrics, were independently associated with DWIv. However, median FA in contralesional NAWM was independently associated with mRS score (ß = -9.74, p = 0.02), along with age, female sex, NIHSS score, and DWIv. CONCLUSIONS: FA decrease in NAWM contralateral to the acute infarct is associated with worse mRS category at 90 days after stroke. These data suggest that white matter integrity may contribute to functional recovery after stroke.

Brazilian guidelines for endovascular treatment of patients with acute ischemic stroke.

These guidelines are the result of a joint effort from writing groups of the Brazilian Stroke Society, the Scientific Department of Cerebrovascular Diseases of the Brazilian Academy of Neurology, the Brazilian Stroke Network and the Brazilian Society of Diagnostic and Therapeutic Neuroradiology. Members from these groups participated in web-based discussion forums with predefined themes, followed by videoconference meetings in which controversies and position statements were discussed, leading to a consensus. This guidelines focuses on the implications of the recent clinical trials on endovascular therapy for acute ischemic stroke due to proximal arterial occlusions, and the final text aims to guide health care providers, health care managers and public health authorities in managing patients with this condition in Brazil.

Brazilian guidelines for endovascular treatment of patients with acute ischemic stroke / Diretrizes brasileiras para o tratamento endovascular de pacientes com acidente vascular cerebral isquêmico agudo

ABSTRACT These guidelines are the result of a joint effort from writing groups of the Brazilian Stroke Society, the Scientific Department of Cerebrovascular Diseases of the Brazilian Academy of Neurology, the Brazilian Stroke Network and the Brazilian Society of Diagnostic and Therapeutic Neuroradiology. Members from these groups participated in web-based discussion forums with predefined themes, followed by videoconference meetings in which controversies and position statements were discussed, leading to a consensus. This guidelines focuses on the implications of the recent clinical trials on endovascular therapy for acute ischemic stroke due to proximal arterial occlusions, and the final text aims to guide health care providers, health care managers and public health authorities in managing patients with this condition in Brazil.

RESUMO Estas diretrizes são o resultado de um esforço conjunto de membros da Sociedade Brasileira de Doenças Cerebrovasculares (SBDCV), Departamento científico de Doenças Cerebrovasculares da Academia Brasileira de Neurologia (ABN), Rede Brasil AVC (RBAVC) e da Sociedade Brasileira de Neurorradiologia Diagnóstica e Terapêutica (SBNR). Membros destas 4 entidades participaram de fórum de discussões por internet de temas pré-definidos, seguidos de encontros de videoconferência para discussão de pontos controversos e das recomendações, em busca de um consenso final. Estas diretrizes tem seu foco sobre as implicações dos recentes ensaios clínicos de tratamento endovascular do acidente vascular cerebral (AVC) isquêmico agudo relacionado a oclusão de artérias proximais. O texto final foi elaborado para servir de orientação no manejo destes pacientes AVC isquêmico pelos diferentes profissionais de saúde, gestores de saúde pública e de saúde complementar no Brasil.

Tumores intracranianos / Intracranial neoplasms

Os autores fazem uma breve revisäo sobre tumores intracranianos, abrangendo, de uma forma bem prática, a faixa etária, topodiagnóstico, terapêutica e prognóstico