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Objectives: to investigate exosome-derived transfer RNAs (tRNAs) in the plasma of patients in the chronic phase of ischemic stroke (IS). tRFs may be disease biomarkers, especially for disorders linked to hypoxic and extracellular stress. Material and methods: We assessed samples from ten patients who had ischemic stroke (IS), collected them six months after the ictus, and compared to samples obtained from ten controls. We used small RNA sequencing for tRNA identification and quantification. Results: We found that the most abundant class of tRFs identified in the patients’ samples were 3′ fragments (37.7%). Most interestingly, we found increased levels of two tRFs in patients, namely Phe-GAA (p = 0.0146) and Leu-TAG (p = 0.0331). These two fragments originate from mitochondrial tRNAs and may be related to mechanisms leading to abnormal regulation of cellular energy, DNA transcription, and oxidative stress. We also identified decreased tRNA-Gly and tRNA-Val derivatives in patients. Furthermore, we found that the expression signature of tRNA Phe-GAA differentiates patients from controls with an area under the receiver operating characteristics (ROC) curve (AUC) = 0.78. Conclusions: Our results indicate differential expression of circulating exosome-derived tRFs in the chronic stages of IS. The tRFs with the greatest differences in expression identified in this study may be linked to the mechanisms leading to disease, most likely related to underlying risk factors that may persist after the acute event. Thus, we provide suggestive evidence that tRFs may assist in risk stratification for individuals with increased susceptibility to IS.

Introduction: Although the 2019 severe acute respiratory syndrome coronavirus 2 infection (SARS-CoV-2, COVID-19) pandemic poses new challenges to the healthcare system to provide support for thousands of patients, there is special concern about common medical emergencies, such as stroke, that will continue to occur and will require adequate treatment. The allocation of both material and human resources to fight the pandemic cannot overshadow the care for acute stroke, a time-sensitive emergency that with an inefficient treatment will further increase mortality and long-term disability. Objective: This paper summarizes the recommendations from the Scientific Department on Cerebrovascular Diseases of the Brazilian Academy of Neurology, the Brazilian Society of Cerebrovascular Diseases and the Brazilian Society of Neuroradiology for management of acute stroke and urgent neuro-interventional procedures during the COVID-19 pandemic, including proper use of screening tools, personal protective equipment (for patients and health professionals), and patient allocation.

Background: Atrial fibrillation (AF) is a widely accepted risk for causing stroke. However, recent studies show AF as a risk factor for dementia, even without causing stroke. The mechanisms by which dementia develops in stroke-free patients with AF are still poorly understood and the association of AF with abnormal function of brain networks activities, such as the default mode network (DMN), has not been previously studied. We aimed to determine whether, in the absence of stroke and dementia, patients with AF have abnormal resting-state brain networks compared to controls without AF. Methods: Twenty-one stroke-free patients with AF and 21 age- and sex-matched controls without AF underwent brain functional magnetic resonance imaging acquired at a 3.0 Tesla scanner. During the exam, the subjects were instructed to lie still with eyes closed. At first-level analysis, connectivity of the DMN was obtained for all subjects. Second-level analysis compared the DMN connectivity between AF patients and controls with a general linear model (two-sample t test, p < 0.05, False Discovery Rate corrected, minimum of 50 contiguous voxels). Results: Patients with AF compared with controls showed decreased connectivity in regions of the DMN including the frontal lobe (left medial frontal gyrus, left superior frontal gyrus and anterior cingulate), left angular gyrus, and bilateral precuneus. Conclusions: Stroke-free patients with AF have evidence of abnormal DMN connectivity. This study adds evidence to the occurrence of cerebral dysfunction in patients with AF.

Resumo Contexto A espectroscopia próxima ao infravermelho (NIRS) é uma técnica não invasiva que detecta as alterações hemodinâmicas teciduais. A NIRS pode monitorar de forma contínua as informações fisiológicas vasculares intracranianas. Por ser portátil, ela pode ser utilizada à beira do leito e no centro cirúrgico. Objetivos Avaliar as possíveis alterações hemodinâmicas cerebrais durante a endarterectomia em pacientes com estenoses maiores que 70% utilizando NIRS. Métodos Foram avaliados 10 voluntários portadores de doença carotídea aterosclerótica com indicação de endarterectomia. Após a seleção dos pacientes, que responderam um questionário com dados epidemiológicos e informações referentes à presença de comorbidades, a doença foi confirmada por métodos diagnósticos. No procedimento cirúrgico, utilizou-se a NIRS para monitorização. Foram avaliadas as variáveis saturação de oxigênio (SatO2), hemoglobina total (HbT), hemoglobina reduzida (HbR) e hemoglobina oxigenada (HbO) nos três tempos cirúrgicos pré-, trans e pós-clampeamento carotídeo. Utilizou-se p < 0,05 como nível de significância. Resultados A avaliação dos resultados obtidos por meio das medidas registradas pela NIRS permite afirmar que HbR e SatO2 variam ao longo das etapas da cirurgia. Durante o clampeamento, a variável HbR mostra valores mais elevados que nas outras duas etapas da cirurgia. Por outro lado, a variável SatO2 mostra redução durante o clampeamento. Conclusões A NIRS é um método viável e aplicável de monitorização intracerebral, não invasivo e em tempo real, durante a endarterectomia carotídea, capaz de medir de forma precisa as mudanças das condições hemodinâmicas capilares intracerebrais. Abstract Backgrounds Near-infrared spectroscopy (NIRS) is non-invasive technique that detects hemodynamic alterations in tissues. It enables continuous monitoring of intracerebral vascular physiologic information. Due to its portable nature, NIRS may be used bedside or in the operating room. Objectives To evaluate use of NIRS for intraoperative monitoring of the brain hemodynamic response, during carotid endarterectomy. Methods 10 patients with atherosclerotic carotid disease scheduled for endarterectomy were evaluated. After patients had been selected, they answered a questionnaire on epidemiological data and information about comorbidities and then carotid disease was confirmed with diagnostic methods. NRIS monitoring was used during the surgical procedure. The variables analyzed before, during and after carotid clamping were oxygen saturation (SatO2), total hemoglobin (THb), reduced hemoglobin (RHb), and oxyhemoglobin (OHb). A p value of

Ischemic stroke (IS) is one of the most common causes of mortality worldwide and represents 80% of all stroke cases. Previous studies have shown that some metabolites can be markers of oxidative injury to vascular endothelial cells and neuromodulation after brain ischemia. Biomarkers are small molecules that are dysregulated during diseases and that can be used to improve diagnosis and to determine prognosis, including responses to treatment. This study aims to identify if there are specific metabolites in the plasma of patients with IS in the acute and chronic stages. Currently, we have evaluated plasma samples of 21 individuals, using proton Nuclear Magnetic Resonance (1H NMR). The samples were divided into 4 groups: 6 samples from patients in the acute phase of IS (less than 24 h after the event), 6 samples from patients in the chronic phase of IS (more than 3 months after the acure event), 5 samples from healthy and agematched individuals and 4 samples from asymptomatic patients with severe internal carotid artery stenosis. Samples were evaluated using 1 H NMR spectra, recorded under the same conditions in a 600 MHz spectrometer.

Background: The role of patent foramen ovale is a field of debate and current publications have increasing controversies about the patients’ management in young undetermined stroke. Work up with echocardiography and transcranial Doppler (TCD) can aid the decision with better anatomical and functional characterization of right-to-left shunt (RLS). Medical and interventional strategy may benefit from this information. Summary: a group of experts from the Latin American participants of the Neurosonology Research Group (NSRG) of World Federation of Neurology created a task force to review literature and describe the better methodology of contrast TCD (c-TCD). All signatories of the present consensus statement have published at least one study on TCD as an author or co-author in an indexed journal. Two meetings were held while the consensus statement was being drafted, during which controversial issues were discussed and voted on by the statement signatories. The statement paper was reviewed and approved by the Executive Committee of the NSRG of the World Federation of Neurology. The main objective of this consensus statement is to establish a standardization of the c-TCD technique and its interpretation, in order to improve the informative quality of the method, resulting in expanding the application of TCD in the clinical setting. These recommendations optimize the comparison of different diagnostic methods and encourage the use of c-TCD for RLS screening and complementary diagnosis in multicenter studies.

Background Carotid endarterectomy (CEA) and carotid artery stenting (CAS) have both been proposed for treatment of critical atherosclerotic stenosis located at the carotid bifurcation. Monitoring of hyperintense microembolic signals (MES) by transcranial Doppler ultrasound (TCD) is considered a method of quality control, both in CEA and in CAS. Objective To analyze temporal distribution of MES throughout both semi-eversion CEA and CAS procedures and to evaluate changes in mean velocity of blood flow through the ipsilateral middle cerebral artery (MCA). Method Thirty-three procedures (17 CEA and 16 CAS) were prospectively monitored using TCD and the data were related to three different stages of surgery (pre-cerebral protection, during cerebral protection and post-cerebral protection). Chi-square, Mann-Whitney, ANOVA and contrast tests were used for statistical analysis. Results The MES were uniformly distributed in the CEA group, but not in the CAS group (p = 0.208). The number of MES was higher in the CAS group in all stages. The average flow in the MCA was similarly lower in both groups during the protection stage. Conclusion CEA provoked a lower incidence of MES per procedure than CAS in all stages. The behavior of the averages of the mean of blood flow through the MCA was similar in both groups. Resumo Contexto A endarterectomia carotídea (EC) e a angioplastia carotídea (AC) são propostas para o tratamento de estenoses críticas localizadas na bifurcação carotídea. O monitoramento dos sinais de microembolias (SMs) pela ultrassonografia Doppler transcraniana (UDT) é considerado um método de controle de qualidade para ambas as técnicas. Objetivos Analisar a distribuição temporal dos SMs ao longo de diferentes estágios da EC por semieversão e da AC, e avaliar o significado das mudanças nas médias das velocidades médias do fluxo na artéria cerebral média ipsilateral (ACM). Método Trinta e três procedimentos (17 ECs e 16 ACs) foram monitorados com UDT, e os dados foram coletados prospectivamente para diferenciar os diferentes estágios cirúrgicos (pré, durante e pós-proteção cerebral). Para análise estatística foram usados os testes qui-quadrado, Mann-Whitney, análise de variância (ANOVA) e contraste. Resultados Em ambos os grupos, os SMs foram distribuídos uniformemente (p = 0,208). Em todos os tempos, o número de SMs foi superior no grupo AC. A média das velocidades médias do fluxo na ACM foi menor durante o tempo de proteção em ambos os grupos. Conclusão A EC teve uma menor incidência de SMs que a AC em todos os estágios. A média das velocidades médias na ACM teve comportamento similar em ambos os grupos.

Embolic stroke of undetermined source (ESUS) is an important group of cryptogenic strokes that are in evidence due recent ongoing trials. We reviewed medical records at discharge from the stroke unit of all patients who met ESUS criteria and attended our institution between February 2016 and July 2017. Among 550 stroke patients, 51 had ESUS. We found that hypertension (60%), diabetes mellitus (34%), and smoking (36%) were the most prevalent risk factors. The mean National Institutes of Health Stroke Scale (NIHSS) scores were 7 at admission and 4 at discharge, while median scores on the modified Rankin scale were 0 and 2 at admission and discharge, respectively. Our sample had similar ages, risk factors prevalence and NIHSS scores at admission and discharge when compared with European and North American cohorts. Although a small cohort, our study suggests that the ESUS population is similar in countries with different health financing. RESUMO Acidentes vasculares cerebrais (AVC) embólicos de fonte indeterminada (ESUS) é um grupo importante de pacientes com AVC criptogênico que estão em evidência devido a recentes ensaios clínicos. Foram revisados os prontuários médicos na alta da unidade de AVC de todos os pacientes que preencheram os critérios para ESUS atendidos em nossa instituição entre fevereiro de 2016 e julho de 2017. Entre 550 AVCs, 51 eram pacientes com ESUS. Hipertensão (60%), diabetes mellitus (34%) e tabagismo (36%) foram os fatores de risco mais prevalentes. Os escores médios do National Institutes of Health Stroke Scale (NIHSS) foram 7 na admissão e 4 na alta, enquanto os escores médios na escala de Rankin modificada (mRs) foram 0 e 2 na admissão e alta, respectivamente. Nossa amostra teve idade, prevalência de fatores de risco, escores NIHSS na admissão e alta, quando comparados com coortes europeias e norte-americanas semelhantes. Apesar de ser uma pequena coorte, nosso estudo sugere que a população ESUS é semelhante em países com diferentes níveis de financiamento em saúde.

Background Cognitive deficits in patients with asymptomatic carotid stenosis have been reported. The ultimate mechanism of cognitive deficits remains unclear and might be related to subtle structural brain damage. Aims The aim of the present study was to evaluate the presence of subtle white and grey matter abnormalities associated with asymptomatic carotid stenosis. Methods Twenty-five patients with asymptomatic ≥70%/occlusion carotid stenosis and 25 healthy controls, matched for gender and age, underwent 3 Tesla brain magnetic resonance imaging. Gray and white matter macrostructural abnormalities were evaluated with voxel-based morphometry using spm8 software. White matter microstructural abnormalities were evaluated with diffusion tensor images with the Diffusion Toolbox package and tract-based spatial statistics from FMRIB Software Library. Results We observed significant macro- and microstructural white matter abnormalities, and these findings were diffuse and symmetrical in both hemispheres. In contrast, gray matter atrophy was observed in the areas corresponding to the anterior circulation of the hemisphere ipsilateral to the carotid stenosis. Conclusions Patients with asymptomatic carotid stenosis have different patterns of gray and white matter abnormalities. While the white matter damage is diffuse, the gray matter atrophy is localized in the territory of anterior circulation ipsilateral to the stenosis. The role of asymptomatic carotid stenosis in the gray matter damage must be further investigated with longitudinal studies and comparison with neuropsychological evaluation.

Atherosclerotic disease has been associated with increased risk of severe neurovascular consequences including transient ischemic attacks, ischemic strokes, and even mortality. Following the onset of carotid stenosis, the brain undergoes different compensatory mechanisms to provide adequate perfusion in order to maintain brain metabolism. In this study, we employed near-infrared spectroscopy (NIRS) to better comprehend how carotid stenosis affects cerebral hemodynamics, both at rest and during activity. Eighteen patients diagnosed with atherosclerotic disease were recruited for a protocol consisting of resting state and vasoreactivity testing performed with breath holding. Although the breath holding challenge induced global vasodilation in all patients, the extent of dilation varied according to the level of stenosis. Patients diagnosed with carotid stenosis have impaired hemodynamic response, with a median 77% vasoreactivity in the hemisphere ipsilateral to the stenotic vessel when compared to the healthy hemisphere. Hemodynamics of these patients differed at rest, with 33% fewer network links in the hemisphere ipsilateral to the stenosis than the healthy hemisphere. On the other hand, hemodynamic patterns were more heterogeneous with patients diagnosed with a carotid occlusion, which correlates with the opening of collateral circulation. Overall, our results suggest that NIRS can open new directions to the investigation of the effects of cerebrovascular atherosclerotic disease.

Background and Purpose: The prognostic significance of interictal epileptiform discharges (IED) and periodic patterns (PP) after ischemic stroke has not been assessed. We sought to test whether IED and PP, detected on standard Electroencephalography (EEG) performed during the acute phase of ischemic stroke are associated with a worse functional outcome. Methods: One-hundred-fifty-seven patients 18 years or older with a diagnosis of acute ischemic stroke presenting within 72 h from stroke onset were prospectively enrolled and followed. Patients with a pre-stroke history of seizures or epilepsy, previous debilitating neurological disease or conditions that precluded the performance of EEG were excluded. Interpretation was performed by a blinded board certified neurophysiologist. IED and PP (grouped as epileptiform activity [EA]) were defined according to proposed guidelines. Univariable and multivariable analyses were used to identify predictors of outcome (modified Rankin Scale dichotomized ≤2 vs. ≥3) at 3 months. Results: In the univariable analysis, admission NIHSS (OR 1.20, 95% CI 1.12-1.28, p = 0.001), age (OR 1.03, 95% CI 1.01-1.05, p = 0.02), and presence of EA (OR 2.94, 95% CI 1.51-5.88, p = 0.001) were significantly associated with the outcome at 3 months. In the multivariable analysis, only admission NIHSS (OR 1.19, 95% CI 1.11-1.28, p < 0.001) and the presence of EA (OR 2.27, 95% CI 1.04-5.00, p = 0.04) were independently associated with the prognosis. Significance: The importance of EEG in the prognosis of acute ischemic stroke warrants additional research, examining the role of medication therapy on the outcome and the occurrence of seizures for those patients with specific EEG patterns.

Introduction: Seizures after acute ischemic stroke lead to a worse functional outcome. Interictal epileptiform discharges (IED) and periodic patterns (PP) after ischemic stroke increase the risk of seizures. However, their prognostic significance has not been assessed. Hypothesis: We sought to test whether IED and PP, detected on standard EEG performed during the acute phase of ischemic stroke are associated with a worse functional outcome. Methods: One-hundred-fifty-seven patients 18 years or older with a diagnosis of acute ischemic stroke presenting within 72 hours from stroke onset were prospectively enrolled and followed. Patients with a pre-stroke history of seizures or epilepsy, previous debilitating neurological disease or conditions that precluded the performance of EEG were excluded. Interpretation was performed by a board certified neurophysiologist blinded to clinical data. IED and PP (grouped as epileptiform activity - EA) were defined according to proposed guidelines. Univariable and multivariable analysis were used to identify predictors of outcome (modified Rankin Scale dichotomized ≤ 2 vs. ≥ 3) at 3 months. Results: In the univariable analysis, admission NIHSS (OR 1.20, 95% CI 1.12-1.28, p=0.001), age (OR 1.03, 95% CI 1.01-1.05, p=0.02) and presence of EA (OR 2.94, 95% CI 1.51-5.88, p=0.001) were significantly associated with the outcome at 3 months. In the multivariable analysis, only admission NIHSS (OR 1.19, 95% CI 1.11-1.28, p Conclusion: The importance of EEG in the prognosis of acute ischemic stroke warrants additional research examining the role of medication therapy on the outcome and the occurrence of seizures for those patients with specific EEG patterns.

Differently from previous studies that used Transcranial Doppler (TCD) and functional MRI (fMRI) for cerebral vasomotor reactivity (CVR) assessment in patients with carotid stenosis (CS), we assessed CVR using an identical stimulus, the Breath-Holding Test (BHT). We included 15 patients with CS and 7 age-matched controls to verify whether fMRI responded differently to BHT between groups and to calculate the agreement rate between tests. For TCD, impaired CVR was defined when the mean percentage increase on middle cerebral artery velocities was ≤31% on 3 consecutive 30-s apnea intercalated by 4-min normal breathing intervals. For fMRI, the percent variation on blood oxygen level-dependent (BOLD) signal intensity in the lentiform nucleus (LN) ipsilateral to the CS (or both LNs for controls) from baseline breathing to apnea was measured. The Euclidian differences between the series of each subject and the series of controls and patients classified it into normal or impaired CVR. We found different percent variations on BOLD-signal intensities between groups (P=0.032). The agreement was good in Controls (85.7%; κ=0.69) and overall (77.3%; κ=0.54). We conclude that BHT was feasible for CVR assessment on fMRI and elicited different BOLD responses in patients and controls, with a good overall agreement between the tests.

We read with interest the article by Li and Johnson in which they demonstrated that improvement initiatives were able to reduce alarm-to-needle time in acute stroke care by applying the Lean Six Sigma approach. In Brazil, the Unified Health System is challenged to improve efficiency with limited budgets by ensuring that the right things are done by the right people at the right time. Successful implementations in the National Health System (United Kingdom) have shown that Lean thinking contributes to [...]