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Stroke is a leading cause of death and disability. Some patients may present with atypical symptoms. One of the very rare presentations of stroke is initial neurogenic pain. Rare painful presentations include, amongst others, acute trigeminal neuralgia, atypical facial pain, hemi-sensory pain, and episodic pain. Based on the available literature, the pain at presentation may be episodic, transient, or persistent, and it may herald other debilitating stroke symptoms such as hemiparesis. Pain quality is often described as burning; less often as sharp. Patients often have accompanying focal symptoms and findings on neurological examination. However, in several of the reviewed cases, these were discrete or non-existent. In patients with pain located in the trunk and/or extremities, lesions may involve the thalamus, lateral medulla oblongata, insula, or parietal lobe. In patients with atypical facial or orbital pain (including the burning “salt and pepper” sensation), the stroke lesions are typically located in the pons. In this narrative review, we included studies/case series of patients who had pain at the time of onset, shortly before or within 24 h of stroke symptoms (on the day of admission). Cases with pain related to aortic or cervical vessel dissection, cerebral venous sinus thrombosis, subarachnoid hemorrhage, reversible cerebral vasoconstriction syndrome, and CNS vasculitis were excluded. With this review, we aim to summarize the current knowledge on stroke presenting with acute pain.

The determinants of blood pressure variability (BPV) are complex. We aimed to evaluate whether circulating high-sensitivity C-reactive protein (hsCRP) is associated with short-term BPV during the subacute stage of ischemic stroke. In this observational study, a consecutive series of acute ischemic stroke patients who underwent 24 h ambulator blood pressure monitoring (ABPM) during day 4 to 10 after onset were enrolled. Multivariable linear regression models were constructed to assess relationships between hsCRP and BPV. Among a total of 325 patients analyzed, the mean age was 60 years old and 72% were male. The SD, CV, ARV of 24 h SBP and DBP were more likely to be higher in patients with hsCRP ≥ 2 mg/L, and these predispositions remained unchanged in linear regression analyses after adjusting for possible confounding factors, with a dose-response relationship when patients were additionally categorized into quartiles according to hsCRP levels using the lowest quartile as a reference category. In contrast, similar results were observed for the mean of SBP but not the mean of DBP. These results indicate that hsCRP is dose-dependently associated with short-term BPV during the subacute stage of ischemic stroke. These findings suggested that patients with a higher level of hsCRP tended to have larger blood pressure fluctuations.

Cerebral cavernous malformation (CCM) or cavernoma is a major vascular disease of genetic origin, whose main phenotypes occur in the central nervous system, and is currently devoid of pharmacological therapeutic strategies. Cavernomas can remain asymptomatic during a lifetime or manifest with a wide range of symptoms, including recurrent headaches, seizures, strokes, and intracerebral hemorrhages. Loss-of-function mutations in KRIT1/CCM1 are responsible for more than 50% of all familial cases, and have been clearly shown to affect cellular junctions, redox homeostasis, inflammatory responses, and angiogenesis. In this study, we investigated the therapeutic effects of multidrug-loaded lipid nanoemulsions in rescuing the pathological phenotype of CCM disease. The pro-autophagic rapamycin, antioxidant avenanthramide, and antiangiogenic bevacizumab were loaded into nanoemulsions, with the aim of reducing the major molecular dysfunctions associated with cavernomas. Through Western blot analysis of biomarkers in an in vitro CCM model, we demonstrated that drug-loaded lipid nanoemulsions rescue antioxidant responses, reactivate autophagy, and reduce the effect of pro-angiogenic factors better than the free drugs. Our results show the importance of developing a combinatorial preventive and therapeutic approach to reduce the risk of lesion formation and inhibit or completely revert the multiple hallmarks that characterize the pathogenesis and progression of cavernomas.

Objective: to conduct a systematic review and meta-analyses of the effect of socio-behavioral cognitive reserve (CR) proxies on cognitive decline after stroke. Method: three journal search and indexing databases (PubMed, Scopus and Web of Sciences) were crossed to examine the scientific evidence systematically. In addition, meta-analytic techniques, using mixed-effect methods, were carried out to estimate the impact (pooled effect size) of CR proxies on either dementia incidence or cognitive decline after stroke. Results: twenty-two studies were included in the systematic revision, whereas nineteen of them were eligible for the meta-analysis. The findings showed that high education is associated with a decreased rate of post-stroke dementia. Moreover, other CR proxies (e.g., occupation, bilingualism or social interaction) demonstrate a protective effect against non-dementia cognitive decline after stroke, although some inconsistencies were found in the literature. Regarding the meta-analysis, occupational attainment and education) showed a protective effect against post-stroke cognitive impairment diagnosis in comparison with a mixed category of different CR proxies. Second, a main cognitive change effect was found, pointing to greater cognitive change after stroke in those with low vs. high CR. Conclusions: Our findings emphasize that CR may prevent cognitive decline after stroke, but this effect can be modulated by different factors such the CR proxy and individual characteristics such as age or type of lesion. The methodological divergences of the studies (i.e., follow-up intervals, cognitive outcomes) need unification to diminish external sources of variability for predicting rates of cognitive decline after stroke.

Background Physical inactivity is highly prevalent after stroke, increasing the risk of poor health outcomes including recurrent stroke. Tailoring of exercise programs to individual preferences can improve adherence, but no tools exist for this purpose in stroke. Methods We identified potential questionnaire items for establishing exercise preferences via: (i) our preliminary Exercise Preference Questionnaire in stroke, (ii) similar tools used in other conditions, and (iii) expert panel consultations. The resulting 35-item questionnaire (SEPI-35) was administered to stroke survivors, along with measures of disability, depression, anxiety, fatigue and self-reported physical activity. Exploratory factor analysis was used to identify a factor structure in exercise preferences, providing a framework for item reduction. Associations between exercise preferences and personal characteristics were analysed using multivariable regression. Results A group of 134 community-dwelling stroke survivors (mean age 64.0, SD 13.3) participated. Analysis of the SEPI-35 identified 7 exercise preference factors (Supervision-support, Confidence-challenge, Health-wellbeing, Exercise context, Home-alone, Similar others, Music-TV). Item reduction processes yielded a 13-item version (SEPI-13); in analysis of this version, the original factor structure was maintained. Lower scores on Confidence-challenge were significantly associated with disability (p = 0.002), depression (p = 0.001) and fatigue (p = 0.001). Self-reported barriers to exercise were particularly prevalent in those experiencing fatigue and anxiety. Conclusions The SEPI-13 is a brief instrument that allows assessment of exercise preferences and barriers in the stroke population. This new tool can be employed by health professionals to inform the development of individually tailored exercise interventions.

Introduction: Thyroid hormones affect the cardiovascular system, but the precise mechanisms of their effects on the development of atherosclerosis are not entirely clear. The relationship between subclinical hypothyroidism, dyslipidemia and carotid atherosclerosis has been widely investigated, but the findings were controversial. The aim of the present study was to determine whether female subjects with subclinical hypothyroidism (SHypo) have increased carotid intima-media thickness (IMT) compared with euthyroid subjects, as well as to examine the association of SHypo, carotid atherosclerosis and dyslipidemia. Methods: This research included 100 women aged 30 to 70 years who were divided into two groups: the SHypo group including subjects with signs of subclinical hypothyroidism and the control group of euthyroid subjects. Carotid IMT thickness using B mode ultrasound was determined and its correlation with serum concentrations of fT4, TSH, CRP, and lipid profile including small dense LDL (sdLDL) was analysed. Results: Subjects with SHypo had significantly increased carotid IMT (IMT ≥ 75th centile) in all three measured segments of the right (p p = 0.001) carotid artery compared to the control group, with a significantly more frequent appearance of plaque (25% vs. 9%; p = 0.05). Significant positive correlations were found between higher TSH and higher IMT values. Increased age, LDL cholesterol, and TSH predicted thickening of the carotid artery IMT. Conclusions: It is important to screen people showing early, subclinical signs of thyroid gland dysfunction due to its impact on carotid atherosclerosis development.

Type 2 diabetes (Т2DM) both directly and indirectly impacts the development of morphological and functional changes of the central nervous system.The study was to determine clinical and neurophysiological patterns of cognitive impairment (CI) in patients with chronic cerebrovascular diseases (CCD) and Т2DM.We examined 132 patients with CCD. First group included 58 patients without Т2DM aged 64.5 [58; 72], second group 74 patients with CCD and Т2DM 63 [57; 70]. Clinical, neurological, neuropsychological, neurophysiological (cognitive evoked potentials (EP) and neurovisualisation (brain MRI) examination was carried out to all patients.Somatic and neurological characteristics of the patients were similar in both groups with the exception of more distinct metabolic changes in Т2DM patients. Neurovisualisation study of the brain MRI in Т2DM patients revealed more distinct changes in the form of white matter hyperintensity and subarachnoidal spaces enlargement. Neuropsychological examination in patients revealed the reduction of intellectual flexibility, constructive praxis disruption, optical spatial dysfunction and deteoration of delayed word recall. Significant disorders in the way of overall cognitive impairment, lobar dysfunction and impaired verbal associative productivity, proved by statistically lower amplitude and higher latency of P300 EP peak were noted in Т2DM patients. Correlation links were detected: for P300 amplitude and direct and inverse number listing test (r=0.366 and r=0.520; p=0.006 and p0.001 respectively); P300 latency and HbA1c (r=0.32; р0.05) in group 2 and glucose levels in both groups (r=0.30; p0.05); inverse relationship of latency with control functions evaluation (r=-0.34; p=0.008).CCD especially with Т2DM manifests with neurocognitive imbalance, including control functions disruption and are accompanied by neurophysiological and neurovisualistion changes.Обоснование. Сахарный диабет (СД) оказывает влияние на развитие морфологических и функциональных изменений центральной нервной системы. Цель. Определение клинико-нейрофизиологического паттерна когнитивных нарушений у пациентов с хроническими цереброваскулярными заболеваниями (ХЦВЗ) и СД 2. Материалы и методы. Обследовали 132 пациента с ХЦВЗ, в 1-ю группу вошли 58 человек без СД 2 в возрасте 64,5 [58; 72] года, во 2-ю 74 с сочетанием ХЦВЗ и СД 2 (63 [57; 70] года). Всем пациентам проводилось общеклиническое, неврологическое, нейропсихологическое, нейрофизиологическое (когнитивные вызванные потенциалы) и нейровизуализационное обследование (магнитно-резонансная томография головного мозга). Результаты. Общесоматическая и неврологическая характеристика обследованных значимо не различалась в группах. При исследовании вещества головного мозга у пациентов с СД 2 чаще отмечались более выраженные изменения гиперинтенсивности белого вещества, наличие лакунарных инфарктов и расширение ликворных пространств. Нейропсихологическое тестирование выявило снижение интеллектуальной гибкости, нарушение конструктивного праксиса, оптико-пространственные нарушения и ухудшение отстроченного воспроизведения слов. Нарушения когнитивных функций при СД 2 подтверждены изменением амплитуды и латентности пика когнитивных вызванных потенциалов Р300. Обнаружены корреляционные взаимосвязи: для амплитуды Р300 с тестом перечисления цифр в прямом и обратном порядке (r=0,366 и r=0,520; р=0,006 и р0,001 соответственно); латентности пика Р300 и уровня гликированного гемоглобина (r=0,32; р0,05) во 2-й группе и глюкозой плазмы в обеих группах больных (r=0,30; p0,05); обратная взаимосвязь латентности с оценкой управляющих функций (r=-0,34; p=0,008). Заключение. ХЦВЗ, особенно в сочетании с СД 2, проявляются нейрокогнитивным дисбалансом, включая нарушение управляющих функций, и сопровождаются нейрофизиологическими и нейровизуализационными изменениями.

Introduction. Cerebrovascular diseases are a medical and social problem for developed countries in the second half of the 20th century and the beginning of the 21st century. The study of special mortality rates makes it possible to study in depth the nature of this pathology, its intensity among the population and to formulate reasoned program solutions aimed at reducing its frequency in the population.The aim of the research is to identify trends and features of the dynamics of mortality in connection with cerebrovascular diseases in different age and sex groups of Irkutsk Region population.Materials and methods. The subject of the research is deaths from cerebrovascular diseases among Irkutsk Region population for the period of 2000–2020. A continuous method of statistical observation was used; the grouping of the material was carried out by distributing the deceased by sex and five-year age interval, with subsequent calculation of mortality tables. The dynamics of the quantitative measure of mortality was determined by calculating the matrix of time series indicators.Results and discussion. For the period of 2000–2020, in the Irkutsk Region, there was a decrease in mortality rates from cerebrovascular diseases both among the male and female population. Mortality rates by sex are higher among the male population, as indicated by the ratio of the ratio of mortality between men and women in all age intervals. The multiplicity of the ratio of indicators increases during the research period from the maximum values of 2.1 times in 2000 to 5.0 times in 2020. The maximum difference shifts from the age of 55–59 to the age group of 40–44. The intensity of mortality reduction in the dynamics of 2000–2020 among the female population is higher than the male. Based on the results of the analysis of the time series, it was found that the age-specific exponent of mortality in the content of 1 % of the mortality increase has a more pronounced quantitative measure for the male population.Conclusion. As the result of the research, for twenty-year observation period a decrease in mortality rates from cerebrovascular diseases was revealed. The age-specific mortality rate from cerebrovascular diseases in the male population is higher than in the female population. The maximum intensity of the difference in mortality between men and women is reached in the working age groups. The content of the indicator 1% of increase in deaths in the male population is higher than that of the female. State policy in the development and implementation of target-oriented programs for reduction of mortality should be based on thorough analysis of data of administrative districts.

4D flow magnetic resonance imaging allows for quantitative measurements of blood flow and velocities that may be useful for early diagnosis and treatment monitoring of neurovascular pathologies. To validate the potential of this technique in clinical applications, its accuracy and reproducibility need to be investigated. Hence, the goal of this thesis was to assess the test-retest reproducibility of 4D flow results in intracranial arteries. On two occasions, 24 hours apart, and on a population of 10 healthy volunteers, the pulsatility index, flow volume pulsatility, cross-sectional area, and minimum, mean, and maximum blood flow velocities were measured in the internal carotid artery, of both the left and right sides, the middle cerebral artery, of both hemispheres, and basilar artery. To evaluate the accuracy of the results, a series of analyses were performed, which included the calculation of intraclass correlation coefficients, Wilcoxon signed-rank tests, Bland-Altman plots, and Pearson correlations, between data collected at both time stamps. A correlation analysis was also employed to evaluate heart rate and blood pressure associations with the obtained vascular function recordings. In general, good test-retest reproducibility was observed for all arteries. Higher reliabil- ity was verified for the internal carotid arteries and the basilar artery than for the middle cerebral arteries. Worse results were found for the pulsatility index and flow volume pulsatility, when compared to flow velocities and cross-sectional area. Several correlations were found between neurovascular data and physiological parameters, especially for the middle cerebral arteries. A ressonância magnética de fluxo 4D permite medições quantitativas de fluxo sanguíneo e velocidades que podem ser úteis para o diagnóstico precoce e monitorização do tratamento de patologias neurovasculares. Para validar o potencial desta técnica para aplicações clínicas é necessário analisar a sua exatidão e reprodutibilidade. Assim, o objetivo desta tese é avaliar a reprodutibilidade das medições de ressonância magnética de fluxo 4D em artérias intracranianas. O índice de pulsatilidade, pulsatilidade do volume de fluxo, área da secção transversal, e velocidades mínimas, médias e máximas de fluxo sanguíneo foram medidas nas artérias carótidas internas, artérias cerebrais médias e artéria basilar em duas ocasiões espaçadas 24 horas numa população de 10 voluntários saudáveis. Para a avaliação da precisão, foi calculado o índice de correlação intraclasse e realizados um teste de Wilcoxon, uma análise de Bland-Altman e , por fim, uma análise de correlação de Pearson. Foi também realizada uma análise de correlação para avaliar as associações de frequência cardíaca e pressão arterial com os valores obtidos. Em geral, observou-se uma boa reprodutibilidade entre as duas medidas para todas as artérias. Foi verificada uma maior fiabilidade para as artérias carótidas internas e artéria basilar do que para as artérias cerebrais médias. Foram encontrados piores resultados para o indíce de pulsatilididade e pulsatilidade de volume de fluxo quando comparados com as velocidades de fluxo e a área da secção transversal. Por fim, verificaram-se várias correlações entre os resultados e os parâmetros fisiológicos, especialmente para as artérias cerebrais médias.

Resumo Introdução A doença cerebrovascular (DCBV) é a segunda principal causa de morte no mundo e no Brasil. Objetivo Avaliar as tendências da mortalidade por DCBV em duas cidades brasileiras (Maceió e Florianópolis) com diferenças socioeconômicas extremas, entre 1981 e 2015, estimando os efeitos idade, período e coorte. Método Estudo de séries temporais da mortalidade por DCBV em indivíduos com ≥ 40 anos, empregando a ferramenta Web tool. Resultados A mortalidade por DCBV diminuiu com o tempo, aumentou com a idade e foi menor para gerações mais novas. O efeito foi igual para ambos os sexos. Houve diminuição da mortalidade nas duas cidades, mas a diferença foi grande e a mortalidade continua alta em Maceió. Com base na amplitude dos efeitos estimados, foi possível verificar que o efeito de coorte foi o termo mais significativo para explicar a variabilidade temporal das taxas de mortalidade por DCBV no período. Conclusão A comparação da tendência temporal nas duas cidades mostrou a importância da melhora das condições de vida, do acesso a serviços de saúde para prevenção e controle dos fatores de risco, assim como assistência hospitalar aos casos para diminuirmos a mortalidade por DCBV em todo o território nacional. Abstract Background Cerebrovascular disease (CBVD) is the second leading cause of death in the world and Brazil. Objective To evaluate trends in mortality from CBVD in two Brazilian cities (Maceió and Florianópolis) with extreme socioeconomic differences, between 1981 and 2016, estimating the age, cohort effect. Method Study of CBVD mortality time series in individuals aged ≥40 years, using the Age, Period, Cohort (APC) analysis and the Web tool. Results CBVD mortality decreased with time, increased with age and was lower for younger generations. The effect was the same for both sexes. There was a decrease in mortality in both cities, but the difference was large, and mortality remains high in Maceió. Based on the amplitude of the estimated effects, it was possible to verify that the cohort effect was the most significant term to explain the temporal variability of mortality rates due to CVD in the period. Conclusion The comparison of the time trend in the two cities showed the importance of improving living conditions, access to health services for the prevention and control of risk factors, as well as hospital care for cases to reduce mortality from CVD nationwide.

Background: Enteral nutrition is often prescribed in acute stroke to meet energy and fluid needs in patients with dysphagia. Tubes clogging represent a common complication of enteral formula delivery, requiring substitution and influencing nutrition administration. Frequent water flushes are recommended as one of the most effective procedures to prevent tube occlusion, but it might be time demanding and not consistently performed by the healthcare staff. This study aimed to assess the efficacy of an automatic flush pump, compared to a manual flush system, to prevent tubes’ occlusions in acute-stroke patients, as this might affect nutrition and hydration. Methods: Gastrointestinal symptoms, nutrition and hydration biomarkers were also monitored to determine the different devices’ safety. Sixty-two patients were included in the study and allocated to the “manual” or “automatic” flushes device. Results: The mean duration of data collection was 7 ± 2 days. Tube occlusions occurred in 22.6% of the patients in the “manual” group, whereas only one tube clogging was reported in the “automatic” group (p = 0.023). No significant differences between groups were reported for constipation and diarrhea frequency nor nutrition and hydration status. When the nurses were asked to simulate manual flush administration at the same frequency of the automatic device, they were able to meet the recommendations only 10% of the time. Conclusion: This preliminary study suggests the efficacy of automatic flush systems to prevent enteral tube clogging, without affecting health status compared to standard manual flush systems.

Background: Vertigo is an uncommon symptom among acute stroke victims. Knowledge about the clinical profile, the brain location, and the early outcome in stroke patients with cerebrovascular diseases and vertigo remains limited. Objectives: In this study, the effects of vertigo on cerebral topography and early prognosis in cerebrovascular diseases were investigated. Methods: A comparative analysis in terms of demographics, risk factors, clinical characteristics, stroke subtypes, cerebral and vascular topography, and early outcome was performed between patients with presence or absence of vertigo on a sample of 3743 consecutive acute stroke patients available from a 24-year ongoing single-center hospital-based stroke registry. Results: Vertigo was present in 147 patients (3.9%). Multiple logistic regression analysis showed that variables independently associated with vertigo were: location in the cerebellum (OR 5.59, CI 95% 3.24–9.64), nausea or vomiting (OR 4.48, CI 95% 2.95–6.82), medulla (OR 2.87, CI 95% 1.31–6.30), pons (OR 2.39, CI 95% 1.26–4.51), basilar artery (OR 2.36, CI 95% 1.33–4.17), ataxia (OR 2.33, CI 95% 1.41–3.85), and headache (OR 2.31, CI 95% 1.53–3.49). Conclusion: The study confirmed that the presence of vertigo was not related with increased in-hospital mortality or poor prognosis at hospital discharge. Vertigo is mainly related to non-lacunar vertebrobasilar stroke with topographic localization in the cerebellum and/or brainstem.

Endothelial dysfunction is a universal pathological mechanism underlying or contributing to the development/progression of many diseases, including cerebrovascular disease and multiple sclerosis. Von Willebrand factor is a multimeric glycoprotein synthesized by endothelial cells and megakaryocytes that participates in a range of physiological and pathological processes, including primary hemostasis and coagulation. It also regulates secretion and transport of a variety of molecules, exerts a proinflammatory effect, modulates angiogenesis and smooth muscle mitotic activity, influences atherogenesis. In this review, we discuss the synthesis, secretion, and regulation of the von Willebrand factor within the context of endothelial dysfunction and other common mechanisms that play a significant role in brain tissue damage in cerebrovascular diseases and multiple sclerosis.

Introduction: We evaluated the association between carotid compliance, a measure of arterial stiffness, to parahippocampal volume (PHV) and hippocampal volume (HV) over 20 years later in the Atherosclerosis Risk in the Community study. Methods: We included participants with common carotid compliance measurements at visit 1 (1987–1989) and volumetric brain MRI at visit 5 (2011–2013). The primary outcomes are pooled bilateral PHV and HV. We performed linear regression models adjusting for age, sex, vascular risk factors, and total brain volume. Results: Of the 614 participants, higher compliance was correlated with higher PHV (R = 0.218[0.144–0.291], p < 0.001) and HV (R = 0.181 [0.105–0.255, p < 0.001]). The association was linear and significant after adjusting for confounders. At follow-up MRI, 30 patients with dementia had lower PHV and HV than patients without dementia (p < 0.001 and p < 0.001, respectively). Conclusion: Carotid compliance is associated with higher PHV and HV when measured 20 years later, further supporting the link between arterial stiffness and cognitive decline.

Bone morphogenetic protein belongs to transcription growth factor superfamily β; bone morphogenetic protein signal pathway regulates cell proliferation, differentiation, and apoptosis among different tissues. Cerebrovascular system supplies sufficient oxygen and blood into brain to maintain its normal function. The disorder of cerebrovascular system will result into serious cerebrovascular diseases, which is gradually becoming a major threat to human health in modern society. In recent decades, many studies have revealed the underlying biology and mechanism of bone morphogenetic protein signal pathway played in cerebrovascular system. This review will discuss the relationship between the two aspects, aiming to provide new perspective for non-invasive treatment and basic research of cerebrovascular diseases.

Background: In a recent Italian study, 30% of patients with reversible cerebral vasoconstriction syndrome (RCVS) presented without thunderclap headache (TCH), and tended to present more severe forms of RCVS than patients with TCH. We aimed to analyze the risk for complications of RCVS in patients with and without TCH at onset. Methods: In a pooled cohort of 345 French patients with RCVS, we compared patients with and without TCH at onset regarding rates of neurological complications, and the functional outcome at 3 months. Results: As compared to the 281 patients with TCH at onset, the 64 patients without TCH had a higher risk for any neurological complication (61% vs. 24%, OR 4.9, 95% CI 2.8-8.7, p < 0.001). The association was strongest for cervical artery dissections (28% vs. 5%, OR 8.1, 95% CI 3.7-17.6, p < 0.001), followed by posterior reversible encephalopathy syndrome (17% vs. 3%, OR 7.1, 95% CI 2.7-18.4, p < 0.001), seizures (9% vs. 2.5%, OR 4.1, 95% CI 1.3-12.5, p = 0.019), and subarachnoid hemorrhage (41% vs. 16%, OR 3.5, 95% CI 1.9-6.3, p < 0.001). In multivariable analysis, the risk for any neurological complication remained significantly elevated in the absence of TCH (OR 3.5, 95% CI 1.8-6.8, p < 0.001). The functional outcome was equal in both groups, with a modified Rankin scale score of 0-1 in ≥90% of patients. Conclusions: Absence of TCH at onset might predict a higher risk of complications in RCVS. Our results warrant further multicentric studies to prove this finding.

Cerebral Cavernous Malformation (CCM) is a cerebrovascular disease of genetic origin affecting 0.5% of the population and characterized by abnormally enlarged and leaky capillaries that predispose to seizures, neurological deficits, and intracerebral hemorrhage (ICH). CCM occurs sporadically or is inherited as dominant condition with incomplete penetrance and highly variable expressivity. Three disease genes have been identified: KRIT1 (CCM1), CCM2 and CCM3. Previous results demonstrated that loss-of-function mutations of CCM genes cause pleiotropic effects, including defective autophagy, altered reactive oxygen species (ROS) homeostasis, and enhanced sensitivity to oxidative stress and inflammatory events, suggesting a novel unifying pathogenetic mechanism, and raising the possibility that CCM disease onset and severity are influenced by the presence of susceptibility and modifier genes. Consistently, genome-wide association studies (GWAS) in large and homogeneous cohorts of patients sharing the familial form of CCM disease and identical mutations in CCM genes have led to the discovery of distinct genetic modifiers of major disease severity phenotypes, such as development of numerous and large CCM lesions, and susceptibility to ICH. This review deals with the identification of genetic modifiers with a significant impact on inter-individual variability in CCM disease onset and severity, including highly polymorphic genes involved in oxidative stress, inflammatory and immune responses, such as cytochrome P450 monooxygenases (CYP), matrix metalloproteinases (MMP), and Toll-like receptors (TLR), pointing to their emerging prognostic value, and opening up new perspectives for risk stratification and personalized medicine strategies.

In the last 20 years, ultra-high field (UHF) magnetic resonance imaging (MRI) has become an outstanding research tool for the study of the human brain, with 90 of these scanners installed today, worldwide. The recent clearances from regulatory bodies in the USA and Europe to 7-T clinical systems have set the ground for a transition from pure research applications to research and clinical use of these systems. As today, UFH neuroimaging is demonstrating clinical value and, given the importance of this topic for both preclinical scientists and clinical neuroradiologists, European Radiology Experimental is launching a thematic series entitled “7-T neuro MRI: from research to clinic”, consisting of peer-reviewed articles, invited or spontaneously submitted, on topics selected by the guest editors, describing the state of the art of UHF MRI neuroimaging across different pathologies, as well as related clinical applications. In this editorial, we discuss some of the challenges related to the clinical use of 7-T scanners and the strengths and weaknesses of clinical imaging at UHF.

Background and purpose The aim of this study was to determine the differences in life expectancy and causes of death after primary intracerebral hemorrhage (ICH) relative to general population controls. Methods In a population-based setting, 963 patients from Northern Ostrobothnia who had their first-ever ICH between 1993 and 2008 were compared with a cohort of 2884 sex- and age-matched controls in terms of dates and causes of death as extracted from the Causes of Death Register kept by Statistics Finland and valid up to the end of 2017. Results Of our 963 patients, 781 died during the follow-up time (mortality 81.1%). Cerebrovascular disease was the most common cause of death for these patients, 37.3% compared with 8.2% amongst the controls. The most common reasons for cerebrovascular mortality in the ICH patients were late sequelae of ICH in 12.8% (controls 0%) and new bleeding in 10.6% (controls 1.0%). The long-term survivors had a smaller ICH volume (median 12 ml) than those patients who died within 3 months (median 39 ml). The mortality rate of ICH patients during a follow-up between 12 and 24 years was still higher than that of their controls (hazard ratio 2.08, 95% confidence interval 1.58-2.74, p < 0.001). Conclusions Very long-term ICH survivors have a constant excess mortality relative to controls even 10 years after the index event. A significantly larger proportion of patients died of cerebrovascular causes and fewer because of cancer relative to the controls.

A unique structure of care for neurological inpatients with significant palliative care (PC) needs was established in the Department of Neurology at the Charite-Universitatsmedizin Berlin in 2021: a specialized neuropalliative care (NPC) unit. After one year, we provide an overview of the concept and the patients' characteristics. Methods: We retrospectively analyzed the characteristics of patients treated in our NPC unit between February 2021-February 2022. Data were extracted from medical records and PC assessment including diagnosis, mode of admission and discharge, length of stay, and palliative symptoms. Data are presented as averages with a 95% confidence interval [lower limit; upper limit] or percentage (absolute number). Results: We included 143 patients (52% (75) female, 67.9 years [65.6; 70.2]). Patients were admitted from general wards (48%; 68), their homes (22%; 32), intensive care units (16%; 23) or emergency departments (14%; 20). The main diagnoses were tumors of the nervous system (39%; 56), neurodegenerative diseases (30%; 43), neurologic complications (13%; 19) and cerebrovascular diseases (12%; 17). Complaints most frequently rated as severely to overwhelmingly burdensome were motor- or fatigue-associated problems, problems communicating, dysphagia and pain. The average length of stay was 13.7 days [12.2; 15.2]. Forty-five percent (64) of patients were discharged without further PC, 17% (24) were referred to a hospice and 13% (18) were discharged with outpatient PC. Five percent (7) were referred to neurorehabilitation and 21% (30) of patients died. Conclusions: Our NPC unit is a new model of care for neurological patients with substantial PC needs especially within the structures of a highly specialized and individualized medicine.

Cerebrovascular disease is one of the leading causes of disability and death worldwide, and seeking a potential treatment is essential. Trilinolein (TriL) is a natural triacylglycerol presented in several plants. The effects of TriL on cerebrovascular diseases such as cerebral ischemia and carotid stenosis have never been studied. Accordingly, we investigated the protection of TriL on cerebral ischemia/reperfusion (I/R) and vascular smooth muscle cell (VSMC) migration in vivo and in vitro. The cerebral infarction area, the intima to media area (I/M ratio), and proliferating cell nuclear antigen (PCNA)-staining of the carotid artery were measured. Platelet-derived growth factor (PDGF)-BB-stimulated A7r5 cell migration and potential mechanisms of TriL were investigated by wound healing, transwell, and Western blotting. TriL (50, 100, and 200 mg/kg, p.o.) reduced: the cerebral infarction area; neurological deficit; TUNEL-positive apoptosis; intimal hyperplasia; and PCNA-positive cells in rodents. TriL (5, 10, and 20 µM) significantly inhibited PDGF-BB-stimulated A7r5 cell migration and reduced matrix metalloproteinase-2 (MMP-2), Ras, MEK, and p-ERK protein levels in PDGF-BB-stimulated A7r5 cells. TriL is protective in models of I/R-induced brain injury, carotid artery ligation-induced intimal hyperplasia, and VSMC migration both in vivo and in vitro. TriL could be potentially efficacious in preventing cerebral ischemia and cerebrovascular diseases.

Uvod: Klinična uporaba magnetno resonančnih (MR) tomografov gostote magnetnega polja 7 Tesla (T) prinaša tako prednosti, kot so boljše razmerje signal-šum (RSŠ), boljša prostorska in kontrastna ločljivost ter krajši čas meritve, kot tudi slabosti, na primer nehomogenosti, povezane z zunanjim magnetnim poljem (B0), nehomogenosti, povezane z dodanimi radiofrekvenčnimi pulzi (B1) ter večjo specifično absorpcijsko stopnjo (SAR). Prednosti, povezane s 7 T MR tomografom po svetu izkoriščajo za diagnostiko različnih možganskih obolenj, kot so multipla skleroza (MS) (odkrivanje kortikalnih lezij), možgansko-žilne bolezni (vizualizacija majhnih intrakranialnih žil in submilimetrskih okluzivnih lezij), možganski tumorji (natančnejše načrtovanje zdravljenja in odkrivanje možganskih krvavitev) in nevrodegenerativne bolezni (odkrivanje sprememb v črni snovi in prepoznavanje amiloidnih plakov). Namen: Namen diplomskega dela je preučiti ključne prednosti in slabosti ter oceniti pomen implementacije MR tomografa gostote magnetnega polja 7 T na področje diagnosticiranja pogostih možganskih patologij. Metode dela: Uporabili sva deskriptivno metodo dela s sistematičnim pregledom literature. Članke sva iskali v različnih podatkovnih bazah in v pregled literature vključili le tiste, ki so v celoti ustrezali vnaprej zastavljenim vključitvenim faktorjem. Rezultati: Našli sva 15 ustreznih člankov na temo klinične uporabe MR tomografa z gostoto magnetnega polja 7 T, ki sva jih predstavili v dveh tabelah. V prvi tabeli so predstavljeni avtorji člankov in leto izdaje, število udeležencev in naloga le-teh v raziskavi ter predmet opazovanja, medtem ko druga tabela navaja glavne ugotovitve člankov, predstavljenih v prvi tabeli. Razprava in zaključek: Ugotovili sva, da uporaba MR tomografov z ultra visoko gostoto magnetnih polj pripomore k bolj natančnemu diagnosticiranju možganskih patologij. Pri MS gre za natančnejše razlikovanje med belo in sivo možganovino ter lezijami, ki so vidne na SWI (magnetno dovzetno poudarjeno slikanje), FLAIR (pulzno zaporedje z zasičenjem signala iz tekočine) ali T2 (transverzalna relaksacija) poudarjenih slikah. Za prikaz možganskega žilja je ključna Time-of-Flight (TOF) tehnika. Pri ultra visokih gostotah magnetnih polj je T1 (longitudinalna relaksacija) relaksacijski čas daljši (boljše razmerje kontrast-šum) in posledično je mogoče oceniti zelo majhne intrakranialne žile (npr. lentikulostriatne arterije). Pri diagnosticiranju možganskih tumorjev si pomagamo z MR spektroskopijo. Ta nam pri gostoti magnetnega polja 7 T omogoča tudi merjenje metabolitov nizkih koncentracij (npr. 23Na). Boljše RSŠ in večji učinek magnetne dovzetnosti pri ultra visoki gostoti magnetnega polja vplivata na natančen prikaz prekrvavljenosti tumorjev na slikah, ki jih pridobimo s pomočjo SWI pulznega zaporedja. Pri diagnosticiranju nevrodegenerativnih bolezni se pri Alzheimerjevi bolezni (AB) osredotočamo na oceno hipokampusa, kjer je za natančno oceno ključni kontrast med sivo in belo možganovino, prikaz le-tega pa je pri gostoti magnetnega polja 7 T izboljšan. Pri Parkinsonovi bolezni (PB) pa pri ultra visoki gostoti magnetnega polja dosežemo boljšo kontrastno in prostorsko ločljivost in z uporabo T2* sekvenc odkrijemo prisotnost amiloidnih plakov. Introduction: The clinical use of magnetic resonance imaging tomographs with the magnetic field strength of 7 Tesla (T) has both advantages, such as a higher signal-to-noise ratio, increased spatial and contrast resolution and shorter acquisition times, and disadvantages, for instance: inhomogeneities of the main magnetic field (B0), inhomogeneities of the applied radiofrequency field (B1) and a higher specific absorption rate. The benefits related to 7 T magnetic resonance imaging tomographs are used worldwide to diagnose the various brain pathologies, such as multiple sclerosis (detection of cortical lesions), cerebrovascular diseases (visualisation of small intracranial vessels and submilimeter oclusive lesions), brain tumors (a more careful planning of a medical treatment and detecting brain haemorrhages) and neurodegenerative disorders (detecting changes in black substance and identifying amyloid plaques). Purpose: The purpose of the diploma work is to examine the key advantages and disadvantages of the 7 T magnetic resonance imaging scanner and further more to evaluate its importance in establishing a diagnosis of the most common brain pathologies. Methods: A descriptive method together with a systematic literature review has been used. We searched for articles in different data bases and finally included only those that fully suited the pre-set inclusion factors. Results: We found 15 appropriate articles, related to the topic of the clinical use of magnetic resonance imaging tomographs with the magnetic field strength of 7 T, which are presented in two charts. The first one lists the authors' names and the year of publication, the number of participants and the task of the research and the subject of observation, while the second one reveals the main research findings of the articles presented in the first chart. Discussion and conclusion: We figured out that the use of magnetic resonance imaging tomographs with ultra high magnetic field strengths helps to confirm a more accurate diagnosis of brain pathologies. Diagnosing the multiple sclerosis, there is a more accurate distinction between grey and white matter and lesions that are visible on SWI, FLAIR or T2-weighted images, using 7 T magnetic resonance imaging scanner. The Time-of-Flight (TOF) is an important imaging technique to visualise intracranial vessels. TOF imaging benefits from longer T1 relaxation times at ultra high fields (better contrast-to-noise ratio) and consequently, tiny intracranial vessels can be visualised (for example: lenticulostriate arteries). Magnetic resonance spectroscopy plays an important role in diagnosing brain tumors. Magnetic resonance spectroscopy at ultra high fields allowes the assesment of low concentration metabolites, such as 23Na. A higher signal-to-noise ratio and a stronger susceptibility contrast at ultra high fields enables the visualisation of tumor microvascularity on SWI images. In diagnosing neurodegenerative disorders, in Alzheimer's disease, we focus on the evaluation of the hippocampus. Using the 7 T magnetic resonance imaging scanner, there is a better contrast between grey and white matter. In Parkinson's disease, at ultra high fields, there is an increased contrast and spatial resolution, and consequently, amyloid plaques can be detected using T2* sequences.

Günümüzde kronik hastalıkların sıklığının artması; hastada yaşam kalitesinin düşmesi, erken ölümlerin görülmesi gibi durumlara sebep olurken aynı zamanda sağlık sistemi ve topluma olan yükün artmasına yol açmaktadır. Bin dokuz yüz doksan yılından beri devam eden, Türk Erişkinlerindeki Kalp Hastalığı ve Risk Faktörleri (TEKHARF) çalışmasında; koroner kalp hastalığının 45-54 yaş grubunda %6, 55-64 yaş grubunda %17 ve 65 yaş ve üzerindeki bireylerde %28 oranında olduğu ortaya konulmuş olup, 45-74 yaş aralığı ele alındığında, 24 takip yılı boyunca koroner mortalite prevalanslarının erkeklerde binde 7.3 ve kadınlarda binde 3.8 düzeyinde olduğu tespit edilmiştir. Türkiye İstatistik Kurumu verilerine göre 2019 yılında ölüm nedenleri arasında, %36.8 ile dolaşım sistemi hastalıkları ilk sırada yer alırken, ikinci sırada %18.4 ile tümörler, üçüncü sırada %12.9 ile solunum sistemi hastalıkları gelmektedir. Dolaşım sistemi hastalıkları kaynaklı ölümlerin %39.1’ini iskemik kalp hastalığı, %22.2’sini serebrovasküler hastalıklar, %25.7’sini diğer kalp hastalıkları oluşturmaktadır. Bu veriler ışığında, çözünebilir epoksit hidrolaz (EPHX2) geninin kardiyovasküler hastalıklar, kanser, serebrovasküler hastalıklar ve diğer hastalıklar ile olan ilişkisi düşünüldüğünde bu gen üzerinde yapılan çalışmaların, daha önce sayılan hastalıkların mekanizmalarına ışık tutacağına, onlara bağlı ölümlerin, sakat kalmaların azalabileceği aynı zamanda tedavi maliyetlerinin de düşebileceği öngörülmektedir. Buradan yola çıkarak EPHX2 geni ve bu genle ilişkilendirilen hastalıklar taranarak literatüre bir derleme kazandırılması amaçlanmıştır., The increasing frequency of chronic diseases today; while it causes situations such as decreased quality of life and premature death in patients, it also causes an increase in the burden on the health system and society. In the study of Heart Disease and Risk Factors in Turkish Adults (TEKHARF), which has been going on since 1990; it has been revealed that coronary heart disease is 6 % in the 45-54 age group, 17 % in the 55-64 age group, and 28 % in the individuals aged 65 and over. Considering the age range of 45-74 years, the prevalance of coronary mortality was found to be 7.3 per thousand in men and 3.8 per thousand in women during 24 follow-up years. According to the data of the Turkish Statistical Institute, among the causes of death in 2019, circulatory system diseases ranked first with 36.8 %, tumors came in the second place with 18.4 %, and respiratory system diseases came in the third place with 12.9 %. 39.1 % of deaths due to circulatory system diseases are caused by ischemic heart disease, 22.2 % by cerebrovascular diseases, and 25.7 % by other heart diseases.Based on these data, when the relationship of the EPHX2 gene with cardiovascular diseases, cancer, cerebrovascular diseases and other diseases is considered, studies on this gene will shed light on the mechanisms of the previously mentioned diseases, deaths and disability due to themlt is predicted that the cost of treatment may also decrease. From this point of view, it is aimed to provide a review to the literatüre by screening the EPHX2 gene and the diseases associated with this gene.

Serebrovasküler hastalıklar dünyada ölüm nedenleri arasında kardiyovasküler hastalıklar sonrası ikinci sırada bulunan hayatı tehdit eden hastalıklar arasında olup, sıklıkla hastane öncesi acil sağlık hizmetlerinin konusu olmaktadır. Hastane öncesi acil sağlık hizmetlerinde tanı, tedavi ve transportta oluşan gecikmeler yüksek mortalite ve morbiditeye neden olan sonuçlar doğurabilmektedir. Serebrovasküler hastalıklar en çok iskemik daha az ise hemorajik kaynaklı karşımıza çıkmaktadır. Hastane öncesi acil sağlık hizmetleri sağlık çalışanlarının serebrovasküler hastalıkları erken tanıma ve doğru müdahale donanımına sahip olmaları hastalar için son derece önemlidir. Bu derlemenin amacı literatür bilgileri ışığında serebrovasküler hastalıkların hastane öncesi tanı ve tedavisi ile ilgili güncel bilgileri gözden geçirmektir., Cerebrovascular diseases are among the second leading causes of death in the world, after cardiovascular diseases, and are frequently the subject of prehospital emergency health services. Delays in diagnosis, treatment and transportation in pre-hospital emergency health services can lead to high mortality and morbidity outcomes. Cerebrovascular diseases are mostly ischemic and less hemorrhagic. Early recognition of cerebrovascular diseases and the right intervention equipment of pre-hospital emergency health care providers is extremely important for patients. The aim of this review is to review the current information about the prehospital diagnosis and treatment of cerebrovascular diseases in the light of the literature.

Patients with intracranial artery stenosis show high incidence of stroke. Angiography reports contain rich but underutilized information that can enable the detection of cerebrovascular diseases. This study evaluated various natural language processing (NLP) techniques to accurately identify eleven intracranial artery stenosis from angiography reports. Three NLP models, including a rule-based model, a recurrent neural network (RNN), and a contextualized language model, XLNet, were developed and evaluated by internal–external cross-validation. In this study, angiography reports from two independent medical centers (9614 for training and internal validation testing and 315 as external validation) were assessed. The internal testing results showed that XLNet had the best performance, with a receiver operating characteristic curve (AUROC) ranging from 0.97 to 0.99 using eleven targeted arteries. The rule-based model attained an AUROC from 0.92 to 0.96, and the RNN long short-term memory model attained an AUROC from 0.95 to 0.97. The study showed the potential application of NLP techniques such as the XLNet model for the routine and automatic screening of patients with high risk of intracranial artery stenosis using angiography reports. However, the NLP models were investigated based on relatively small sample sizes with very different report writing styles and a prevalence of stenosis case distributions, revealing challenges for model generalization.

Objective: to analyze the diagnostic significance of clinical and phenomenological characteristics of affective disorders in patients with chronic somatic pathology.Patients and methods. The analysis included the results of a clinical evaluation of 131 patients with chronic somatic pathology, including 96 patients suffering from cardiovascular diseases and 35 patients with cerebral small vessel disease. Clinical assessment included Primary care evaluation of mental disorders (PRIME-MD) and Hamilton Depression Rating Scale.Results and discussion. Despite the significant frequency and transparent clinical symptoms, general practitioners diagnosed mental disorders in only 30% of patients with depression. We observed a higher prevalence of somatic rather than psychological complaints during the clinical survey. According to the screening using PRIME-MD, 74% of patients were diagnosed with mood disorders, anxiety, and somatoform disorders. We also noted their significant comorbidity with a predominance of a depression and anxiety combination (p < 0.001). Hypertensive patients had the highest depression prevalence (87%) and severity. Moderate depression was the most frequent diagnosis in the study participants, corresponding to major depressive disorder (61.5%).Conclusion. In general, the symptoms of anhedonia, depression, and anxiety were most pronounced in patients with affective disorders. The high prevalence of somatic symptoms complicates depression evaluation. It is possible to highlight depression and anhedonia as significant symptoms for the detection of depression in patients with somatic disorders.

COVID-19 patients have presented with a wide range of neurological disorders, among which stroke is the most devastating. We have reviewed current studies, case series, and case reports with a focus on COVID-19 patients complicated with stroke, and presented the current understanding of stroke in this patient population. As evidenced by increased D-dimer, fibrinogen, factor VIII and von Willebrand factor, SARS-CoV-2 infection induces coagulopathy, disrupts endothelial function, and promotes hypercoagulative state. Collectively, it predisposes patients to cerebrovascular events. Additionally, due to the unprecedented strain on the healthcare system, stroke care has been inevitably compromised. The underlying mechanism between COVID-19 and stroke warrants further study, so does the development of an effective therapeutic or preventive intervention.

Questions Does mechanically assisted walking improve walking speed, distance and participation compared with no/non-walking intervention or overground walking after stroke? Are any benefits maintained beyond the intervention period? Design Systematic review of randomised trials with meta-analysis. Participants Ambulatory adults at any time after stroke. Intervention Mechanically assisted walking (treadmill or gait trainer) without body weight support. Outcome measures Walking speed, walking distance and participation. Results Sixteen trials involving 713 participants were included. The mean PEDro score of the trials was 6.3 (range 4 to 8). Treadmill walking increased walking speed by 0.13 m/s (95% CI 0.08 to 0.19) and distance by 46 m (95% CI 24 to 68) compared with no/non-walking intervention; these effects were largely maintained beyond the intervention. Treadmill walking had a similar or better effect on walking speed (MD 0.07 m/s, 95% CI 0.00 to 0.13) and distance (MD 18 m, 95% CI 1 to 36) compared with overground walking. The estimate of the relative effect of treadmill walking compared with overground walking on participation was very imprecise (SMD 0.16, 95% CI −0.15 to 0.48). Conclusion This systematic review provides moderate-quality evidence that the effect of treadmill walking is the same as or better than the effect of overground walking for improving walking speed and distance in ambulatory people after stroke. Long-term effects and carryover benefits to participation remain uncertain. Review Registration PROSPERO (CRD42020162778).

Resumen: Introducción: El cannabis y sus análogos sintéticos corresponden actualmente a las sustancias ilícitas de mayor consumo a nivel mundial. Resultan múltiples las alteraciones con las cuales se ha relacionado su consumo, y dentro de estas se encuentra la enfermedad cerebrovascular (ECV) o ictus, cuya asociación con esta sustancia se ha fundamentado principalmente a través de la hipótesis de vasoconstricción transitoria, la cual explica una amplia proporción de los casos descritos. Sin embargo, los estudios epidemiológicos realizados no han desarrollado un análisis individual en los pacientes sin otros factores de riesgo cardiovascular, lo que puede limitar la estimación del riesgo que confiere por sí mismo el consumo de esta droga. Desarrollo: Se realizó una revisión sistemática de la literatura a través de Medline, EBSCOhost, EMBASE, Lilacs y Scielo hasta el 13 de mayo de 2016 considerando estudios de tipo «Caso clínico» que presentaran pacientes con diagnóstico de ECV o ataque isquémico transitorio e historia de consumo de cannabinoides sin otros factores de riesgo cardiovascular. Se utilizaron palabras clave como ictus; enfermedad cerebrovascular; cannabis; marihuana, entre otras. Finalmente, de las 566 referencias encontradas fueron seleccionados 18 casos clínicos. Conclusiones: Existe una amplia variedad de publicaciones de ictus asociado a consumo concomitante de cannabis en pacientes sin otros factores de riesgo, destacando una presentación a edad joven y una alta temporalidad, lo que, en concordancia con los estudios epidemiológicos y fisiopatológicos en esta área, ubica a esta sustancia como un potencial factor de riesgo para esta población. Abstract: Introduction: Cannabis and its synthetic analogues are currently the most widely consumed illicit substances worldwide. Multiple alterations have been linked to its use, including cerebrovascular disease (CVD) or stroke, whose association with the substance has been based mainly on the hypothesis of transient vasoconstriction, which explains a large proportion of the cases reported. However, epidemiological studies have not performed an individual analysis of patients without other cardiovascular risk factors, which may limit the estimation of the risk of stroke associated with cannabis use alone. Development: A systematic literature review was conducted through Medline, EBSCOhost, EMBASE, Lilacs, and Scielo to gather case reports published before 13 May 2016 presenting patients with a diagnosis of CVD or transient ischaemic attack, a history of cannabinoid use, and no other cardiovascular risk factors. Key words such as stroke, cerebrovascular disease, cannabis, and marijuana, among others, were used. A total of 18 case reports were selected from the 566 references found. Conclusions: There is a wide variety of reports of stroke associated with cannabis use in patients with no other risk factors. Noteworthy findings were presentation at young age and a strong temporal association, which place cannabis use as a potential risk factor for this population in line with the epidemiological and pathophysiological studies in this area.

Vascular diseases of the brain are one of the most important problems of modern neurology. Increasing prevalence, high mortality, deep disability in cerebral strokes determines the medical and social significance of this pathology. In Kyrgyzstan, the relevance is times greater due to high mortality and disability rates. According to the WHO, stroke is the second most common cause of death. Acute disorders of cerebral circulation reduce the duration of the upcoming life of more than half of patients who have suffered from it, and those who survived remain severely disabled, completely deprived of the ability to self-care. The article presents epidemiological indicators of cerebral strokes in residents of the city of Osh.

Cerebral small vessel disease (cSVD) accounts for 25% of ischemic strokes and is a major cause of cognitive decline. Inflammatory processes, involving immune cells and platelets might drive development and progression of cSVD. The aim of the study was to identify potential novel biomarkers for cSVD, gaining new insights into its pathophysiology. We measured inflammation and platelet and neutrophil activation markers in patients with cSVD and age-matched controls. It was hypothesized that cSVD is accompanied by altered levels of these markers. The levels of interleukin 1β, CX3CL1, CXCL4, CXCL7, myeloperoxidase (MPO), MPO-DNA complex and S100A8/A9 were measured by ELISA in plasma samples of patients with cSVD presenting with mild vascular cognitive impairment (mVCI, n = 36) or lacunar stroke (Laci, n = 44), and controls (n = 38). To determine the relevance of these ELISA markers compared with patient- and MRI-based characteristics, all characteristics were entered into three machine learning models. Among the ELISA markers measured, MPO levels were significantly elevated in patients with cSVD (48.3 (27.8-80.1, interquartile range) ng/mL) compared with controls (32.2 (19.6-47.4) ng/mL, P = 0.023), particularly in the Laci group (56.8 (33.3-84.7) ng/mL, P = 0.004). Regularized logistic regression and random forest algorithms returned MPO levels as an important feature in the detection and prediction of cSVD. Of note, logistic regression and random forest analysis also highlighted levels of CXCL4, CXCL7, MPO-DNA and S100A8/A9 as features associated with cSVD. Taken together, the neutrophil activation marker MPO is elevated in patients with Laci and machine learning indicates platelet and neutrophil markers as interesting molecules for future investigation. SHORTENED ABSTRACT: Cerebral small vessel disease (cSVD) is a major cause of cognitive decline and stroke. We aimed to identify potential novel biomarkers for cSVD and to obtain new insights into its pathophysiology. Levels of markers reflecting neutrophil activation, neutrophil extracellular trap (NET) formation, platelet activation and vascular inflammation were measured in plasma samples of patients with cSVD, and controls. Only myeloperoxidase (MPO) levels were significantly altered. Regularized logistic regression and random forest algorithms returned MPO levels as an important feature in the detection and prediction of cSVD and highlighted platelet- and NET markers as cSVD associated.

According to the World Health Organization (WHO), particulate matter (PM) contamination causes around 800,000 premature deaths per year, ranking 13th in the world in terms of mortality. However, several findings revealed that the correlation is much stronger and more complicated than previously believed. PM is an element of emissions comprised of very small, acidic, organic compounds, metals, and particulate soil or dust particles or fluid droplets. The most consistent air quality component linked to human illness is PM, which is categorized by size. PM is likely to develop cardiovascular and cerebrovascular disorders due to the mechanisms of inflammation, overt and indirect coagulation activation, and direct translocation to the systemic circulation. The evidence on the cardiovascular system that shows a PM effect is strong. Coronary incidence and mortality rates in populations prone to long-term PM toxicity were significantly higher. Short-term acute emissions increase coronary incidence rates subtly within days of the pollution peak. While some evidence and associated mechanisms show a smaller outcome, the findings for PM’s cortical disease symptoms are not as promising. Respiratory infections are aggravated by exposure to PM. More analysis is needed to clarify the effects of structure, chemistry, and PM for vulnerable groups. The existing research indicates that PM toxicity causes a minor but significant increase in human morbidity and mortality. Air conditioners and particulate matter filters reduced internal heating, and cooking combustion and smoking cessation will reduce indoor PM exposure. These fundamental improvements can be beneficial to patients with acute and chronic cardiovascular and respiratory symptoms. This article provides an overview of the effects of atmospheric airborne suspended particulate matter on population morbidity and mortality. This critical review concludes with public health recommendations based on a summary of the published literature’s findings.

Today, chronic cerebral ischemia (CCI) is the most common diagnosis in our country, both in neurological and general medical practice. The high frequency of comorbid conditions and diseases predisposing to the development of CCI, and the association with the risk of stroke and dementia, which increase patient disability, make CCI an urgent medical and social problem. Proper diagnosis of CCI allows the prescription of effective treatment, prevents the disease progression, and the development of strokes and dementia. The article deals with the treatment principles for elderly and senile patients with headache and CCI in outpatient practice. It discusses the causes of headache in CCI patients and its treatment methods. It also covers in depth the spectrum of therapeutic effects of Neurox ® (ethylmethylhydroxypyridine succinate) and Neupilept ® (citicoline) in this category of patients.

COVID-19 worsens the course of cerebrovascular diseases (CVD), including chronic cerebral ischaemia (CCI). The Actovegin drug, which has long been widely used in CCI treatment, has an antioxidant and endothelium protective effect. It makes sense to study the effect of Actovegin therapy on the clinical manifestations of CCI in patients with a recent experience of COVID-19.Objective: to evaluate Actovegin efficacy in the treatment of CCI in patients with a recent experience of COVID-19.Patients and methods. The study included 440 patients (234 female; 206 male) with a recent experience of COVID-19, suffering from CCI, their average age being 67.8 years (from 54 to 85 years). All patients were broken down into two groups of 220 people (the patients in Group 1 were administrated Actovegin, the ones in Group 2 – were not). All patients were followed up for 90 days; their condition was assessed by the severity of clinical manifestations of CCI, using special scales and questionnaires.Results and discussion. After 90 days of follow-up, the frequency of complaints of cognitive impairment, sleep disorder, dizziness, fatigue, emotional disorders, and headache in Group 1 was significantly lower than in Group 2 (pConclusion. The observational study demonstrated the efficacy of Actovegin in the treatment of main clinical manifestations of CCI in patients with recent COVID-19 experience.

Cerebrovascular endothelial dysfunction is involved in the progression of leukoaraiosis. Asymmetric dimethylarginine is a competitive inhibitor of nitric oxide, which is highly expressed in patients with leukoaraiosis. Dimethylarginine dimethylaminohydrolase (DDAH) is a hydrolytic enzyme that is primarily responsible for eliminating asymmetric dimethylarginine, and it plays a role in the pathogenesis of cardiovascular and cerebrovascular diseases. The DDAH2 subtype is expressed in organs rich in induced nitric oxide synthase, including the heart, the placenta, and the cerebral endothelium during cerebral ischemia, in the stress state, or under neurotoxicity. Overexpression of the DDAH2 gene can inhibit asymmetric dimethylarginine-induced peripheral circulating endothelial cell dysfunction. However, it is unknown whether this polymorphism regulates plasma asymmetric dimethylarginine levels in patients with leukoaraiosis. In this double-blind study, we recruited 46 patients with leukoaraiosis and 46 healthy, matched controls. Plasma asymmetric dimethylarginine levels were determined using enzyme-linked immunoassays. Genomic DNA was isolated from whole blood samples, and polymerase chain reaction, SmaI restriction enzyme digestion, restriction fragment length polymorphisms, and agarose electrophoresis were used to detect DDAH2 (-449 G/C) gene polymorphisms. The results revealed that 95.65% of leukoaraiosis patients had recessive genetic models (GG and CG), while 89.13% of healthy control subjects had dominant genetic models (CC and CG). There was a significant difference in the genotype composition ratio between leukoaraiosis patients and healthy controls (P = 0.0002). The frequency of G alleles in the leukoaraiosis patients (71.74%) was significantly higher than in healthy controls, whereas the frequency of C alleles was lower (χ2 = 13.9580, P = 0.0002). Furthermore, asymmetric dimethylarginine concentrations in subjects with the GG genotype were significantly higher than in subjects with the CG and CC genotypes (Kruskal–Wallis H = 24.5955, P < 0.0001). In addition, the GG genotype of DDAH2 (-449 G/C) was more common in patients with leukoaraiosis. These findings suggest that the G allele of DDAH2 (-449 G/C) is a risk factor for leukoaraiosis morbidity and is correlated with high levels of asymmetric dimethylarginine. This study was approved by the Institutional Ethics Committee of the 2nd Affiliated Hospital of Harbin Medical University of China (approval No. KY2016-177) on July 28, 2016.

Background: There is a growing body of evidence suggesting a link between obstructive sleep apnea (OSA) and atrial fibrillation (AF). The primary objective of this study is to evaluate the association between OSA and AF in acute ischemic stroke. The secondary objective is to describe the clinical features of patients with acute ischemic stroke and concomitant OSA. Methods: We enrolled consecutive patients with acute ischemic stroke. All patients underwent full-night cardiorespiratory polygraphy. To determine if there is an association between AF and OSA, we compared the observed frequency of this association with the expected frequency from a random co-occurrence of the two conditions. Subsequently, patients with and without OSA were compared. Results: A total of 174 patients were enrolled (mean age 67.3 ± 11.6 years; 95 males). OSA and AF were present in 89 and 55 patients, respectively. The association OSA + AF was observed in 33/174 cases, which was not statistically different compared to the expected co-occurrence of the two conditions. Patients with OSA showed a higher neck circumference and body mass index, a higher prevalence of hypertension and dysphagia, and a higher number of central apneas/hypoapneas. In the multivariate analysis, dysphagia and hypertension were independent predictors of OSA. A positive correlation was observed between OSA severity, BMI, and neck circumference. The number of central apneas/hypoapneas was positively correlated with stroke severity. Conclusions: Our data suggest that OSA and AF are highly prevalent but not associated in acute stroke. Our findings support the hypothesis that OSA acts as an independent risk factor for stroke.

Acute spontaneous intracerebral hemorrhage (ICH) is the most severe stroke subtype, with a high risk of death, dependence, and dementia. Knowledge about the clinical profile and early outcomes of ICH patients with lobar versus deep subcortical brain topography remains limited. In this study, we investigated the effects of ICH topography on demographics, cerebrovascular risk factors, clinical characteristics, and early outcomes in a sample of 298 consecutive acute ICH patients (165 with lobar and 133 with subcortical hemorrhagic stroke) available in a single-center-based stroke registry over 24 years. The multiple logistic regression analysis shows that variables independently associated with lobar ICH were early seizures (OR 6.81, CI 95% 1.27–5.15), chronic liver disease (OR 4.55, 95% CI 1.03–20.15), hemianopia (OR 2.55, 95% CI 1.26–5.15), headaches (OR 1.90, 95% CI 1.90, 95% IC 1.06–3.41), alcohol abuse (>80 gr/day) (OR 0–10, 95% CI 0.02–0,53), hypertension (OR 0,41, 95% CI 0.23–0–70), sensory deficit (OR 0.43, 95% CI 0.25–0.75), and limb weakness (OR: 0.47, 95% CI 0.24–0.93). The in-hospital mortality was 26.7% for lobar and 16.5% for subcortical ICH. The study confirmed that the clinical spectrum, prognosis, and early mortality of patients with ICH depend on the site of bleeding, with a more severe early prognosis in lobar intracerebral hemorrhage.

Ischemic stroke seems to be one of the most serious neurologic complications in patients with COVID-19 infection. Herein, we report a series of 10 ischemic stroke patients with concomitant COVID-19 disease. Out of 10, 8 had large infarcts (3 massive middle cerebral artery, 2 basilar artery, 2 posterior cerebral artery, and 1 internal carotid artery infarct territory). Two had cardiogenic embolic stroke due to atrial fibrillation. Almost half of our patients did not have a vascular risk factor. Nine did not have fever and were diagnosed with COVID-19 upon admission for stroke. Stroke occurred in the first week of respiratory symptoms with moderate pulmonary involvement. Most Patients did not have hypoxia and did not establish respiratory failure or acute respiratory distress syndrome. The blood pressures were low and hemorrhagic transformation did not occur even after antiplatelet or anticoagulant therapy. Patients had markedly increased levels of lactate dehydrogenase, C-reactive protein, and D-dimer. Three patients died. It seems that ischemic strokes in COVID-19 patients tend to occur as large infarct and can be seen in patients with mild to moderate pulmonary involvement.

Purpose To assess whether an asymmetry exists in the prevalence of carotid artery intraplaque hemorrhage (IPH) between right- and left-sided arteries. Materials and methods The records of all patients with atherosclerotic carotid artery disease that underwent neck magnetic resonance angiography imaging with high-resolution plaque sequences between 2017 and 2020 at our institution were retrospectively reviewed. The prevalence of stenosis and IPH was determined for all patients and compared between the left and right carotid arteries of those with unilateral anterior circulation ischemic strokes. Multiple regression analysis was performed to determine potential independent associations of IPH laterality with ischemic strokes. Results A total of 368 patients were included overall and 241 were male (65.4%). There were a total of 125 asymptomatic patients and 211 patients with unilateral anterior circulation ischemic strokes. Of patients with ischemic strokes, 55.5% had left-sided strokes compared with 44.5% who had right-sided strokes ( p = 0.03). Patients with left-sided strokes had a higher prevalence of ipsilateral IPH than those with right-sided strokes (64.1% versus 36.2%, p Conclusions Left-sided plaques more frequently have IPH and may be more likely to result in ipsilateral ischemic strokes compared with right-sided plaques. The underlying mechanism of asymmetric distribution of IPH between right and left carotids remains unclear.

It is essential to know whether COVID-19 patients have a history of cerebrovascular disease, as it may be predictive of prognosis and useful for allocation of limited medical resources. This meta-analysis was performed to assess the incidence of cerebrovascular disease as a comorbidity in COVID-19 patients. The PubMed, Cochrane Library, Embase, CNKI, WFSD, and VIP databases were systematically searched. The pooled analysis of relevant data was conducted using RevMan 5.3 software. The primary outcome was incidence of cerebrovascular disease as a comorbidity. Forty-seven studies involving 16,143 COVID-19 patients were included in this analysis. The incidences of a history of cerebrovascular disease and hypertension in COVID-19 patients were estimated to be 3.0% (95% CI, 2.0%-4.0%; P

Purpose Dorsal arachnoid web (DAW) is a rare intradural abnormality which is associated with progressive myelopathy. Our objective was to review multi-modality imaging techniques demonstrating the scalpel sign appearance in evaluation of DAW. Methods We retrospectively reviewed various imaging modalities of patients found to have DAW at our institution during January 2015 to February 2020. Five patients underwent surgical decompression with pathological correlation. The remaining patients were presumptively diagnosed based on the characteristic finding of scalpel sign. Clinical data were evaluated and correlated to imaging findings. All imaging modalities demonstrated the characteristic scalpel sign. Results Sixteen patients (10 females, and six males) with multi-imaging modalities were evaluated. Their mean age was 52 year (range 23–74 years). Fifteen patients underwent conventional spine MRI. Further high-resolution MR imaging techniques, e.g. 3D T2 myelographic sequence, were utilized with two patients. MRI spine CSF flow study was performed to evaluate the flow dynamic across the arachnoid web in one patient. Eight patients were evaluated with CT myelogram. Syrinx formation was discovered in seven (44%) patients; five (71%) of them underwent surgical resection and decompression. Two patients underwent successful catheter-directed fenestration of the web with clinical improvement. We found a statically significant positive correlation between the degree of cord displacement and compression with syrinx formation (r = 0.55 and 0.65 with p-value of 0.03 and 0.009, respectively). Conclusion DAW has characteristic scalpel sign independent of imaging modality. Multi-modality imaging evaluation of DAW is helpful for evaluation and surgical planning.

Objectives: Evidences from either small series or spontaneous reporting are accumulating that SARS-CoV-2 involves the Nervous Systems. The aim of this study is to provide an extensive overview on the major neurological complications in a large cohort of COVID-19 patients. Methods: Retrospective, observational analysis on all COVID-19 patients admitted from February 23rd to April 30th, 2020 to ASST Papa Giovanni XXIII, Bergamo, Italy for whom a neurological consultation/neurophysiological assessment/neuroradiologic investigation was requested. Each identified neurologic complication was then classified into main neurologic categories. Results: Of 1760 COVID-19 patients, 137 presented neurologic manifestations that manifested after COVID-19 symptoms in 98 pts and was the presenting symptom in 39. Neurological manifestations were classified as: (a) cerebrovascular disease [53 pts (38.7%)] including 37 ischemic and 11 haemorrhagic strokes, 4 transient ischemic attacks, 1 cerebral venous thrombosis; (b) peripheral nervous system diseases [31 (22.6%)] including 17 Guillain–Barrè syndromes; (c) altered mental status [49 (35.8%)] including one necrotizing encephalitis and 2 cases with RT-PCR detection of SARS-Cov-2 RNA in CSF; (d) miscellaneous disorders, among whom 2 patients with myelopathy associated with Ab anti-SARS-CoV-2 in CSF. Patients with peripheral nervous system involvement had more frequently severe ARDS compared to patients with cerebrovascular disease (87.1% vs 42%; difference = 45.1% 95% CI 42.0–48.2; χ2= 14.306; p < 0.0002) and with altered mental status (87.1% vs 55.6%; difference = 31.5% 95% CI 27.5–37.5%; χ2= 7.055; p < 0.01). Conclusion: This study confirms that involvement of nervous system is common in SARS-CoV-2 infection and offers clinicians useful information for prevention and prompt identification in order to set the adequate therapeutic strategies.

Angioreconstructive interventions are generally known to be of prophylactic value for cerebrovascular diseases (CVD). At the same time, their prognosis in comorbid patients, particularly in those with type 2 diabetes (T2D), have been insufficiently covered.Objective: to study the impact of T2D on cognitive functions after carotid angioplasty with stenting (CAS)Patients and methods. CAS was performed in 99 patients with chronic CVD. Group 1 consisted of 51 patients (median age, 64.5 years) without carbohydrate metabolism disorders. Group 2 included 48 patients (median age, 64 years) with T2D. Over time, all the patients underwent clinical, neurological, and neuropsychological examinations, general clinical and biochemical blood tests, duplex scanning of the brachiocephalic arteries, and magnetic resonance imaging (MRI) of the brain. Blood flow in the middle cerebral artery was monitored to assess the embolic and hemodynamic situation during a CAS procedure.Results and discussion. The baseline frequency of neurocognitive impairment was almost the same (75%) in both groups; however, the impairment was more obvious in patients with T2D. Re-examination in Group 1 patients immediately after intervention revealed slight positive cognitive changes, while the patients with T2D showed a decrease in the indicators of mental functions. The improved ability to abstract and increase the level of generalization of functions appeared in T2D patients only 2 months after intervention. Post-CAS MRI revealed ipsilateral acute ischemic foci (AIF) in the brain substance in 11 (22%) patients of Group 1 and in 24 (50%) with concomitant T2D. Comparison of neuroimaging data with cognitive function assessments for the entire group of the examinees established deterioration in the cognitive status in patients with new ischemic brain changes detected after intervention.Conclusion. CVD concurrent with T2D usually contributes to deterioration in the cognitive status. Angioreconstructive interventions, in particular CAS, are frequently accompanied by the identification of AIF (including «silent» ones) that can cause a transient deterioration in cognitive functions. When planning angioreconstructive interventions in patients with T2D, the question arises of predicting such risks and possible neuroprotective methods.

Amaç: Koronavirüs hastalığı 2019 (COVID-19) hastalarında merkezi ve periferik sinir sisteminin farklı mekanizmalarla tutulumuna bağlı olarak nörolojik semptomlar ortaya çıkmaktadır. COVID-19 enfeksiyonunda sitokin artışı ile birlikte protrombotik aktivasyon ile mikrovasküler tromboz gelişmektedir. Bu çalışmada COVID-19 pozitif hastalarda serebrovasküler hastalık insidansını ve eşlik eden risk faktörlerini araştırmayı amaçladık.Materyal ve Metot: COVID-19 tanısı alan hastalarda hastalıkla ilişkili olarak ortaya çıkan serebrovasküler hastalık durumu değerlendirildi. Serebrovasküler olaylar iskemik ve hemorajik olaylar, geçici iskemik ataklar ve serebral ven trombozu olmak üzere 4 grupta değerlendirildi. Bu hastalarda serebrovasküler hastalık için risk faktörleri ve bu risk faktörlerinin COVID-19 hastalarında serebrovasküler hastalık durumunda prognoza etkisi değerlendirildi.Bulgular: Çalışmada COVID-19 tanısı alan 1000 hasta değerlendirildi. On dört hastada (%1,4) iskemik serebrovasküler hastalık ve/veya geçici iskemik atak geliştiği görüldü. Bu durum COVID-19 tanısı alındıktan sonraki ilk hafta içinde izlendi. COVID-19 ile teşhis edilen akut iskemik inmeli 14 hastada COVID-19 ile ilgili en yaygın semptomlar ateş ve solunum sıkıntısı idi.Sonuç: COVID-19, birden fazla risk faktörü olan hastalarda inme riskini artırıyor. Özellikle pulmoner tutulumlu ve akut iskemik inmeli hastalarda mortalite daha yüksek olabileceğinden yakın takip daha dikkatli yapılmalıdır., Objective: Neurological symptoms occur due to central and peripheral nervous system involvement with different mechanisms in coronavirus disease 2019 (COVID-19). Microvascular thrombosis develops with prothrombotic activation along with the increase in cytokines in COVID-19 infection. We aimed to investigate the incidence of cerebrovascular disease and concomitant risk factors in COVID-19 positive patients.Materials and Methods: Acute and temporally related cerebrovascular diseases with a diagnosis of COVID-19 were evaluated. Cerebrovascular events were assessed in 4 groups as ischemic and hemorrhagic events, transient ischemic attacks, and cerebral venous thrombosis. Risk factors for cerebrovascular disease in these patients were also assessed, and which risk factors for cerebrovascular diseases in COVID-19 patients are high risk were examined.Results: Of the 1000 patients with COVID-19 disease were evaluated. Ischemic cerebrovascular disease and/or transient ischemic attack were found in 14 patients (1.4%). The most common symptoms related to COVID-19 were fever and respiratory distress in 14 patients with acute ischemic stroke diagnosed with COVID-19.Conclusion: COVID-19 increases the risk of stroke in patients with multiple risk factors. Close follow-up should be performed more carefully, especially in patients with pulmonary involvement and acute ischemic stroke, because mortality is likely to be higher.

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) High concentrations of matrix metalloproteinases-2 (MMP-2) and -9 (MMP-9) are associated with inflammation shortly after stroke and functional prognosis. It is proposed that during the chronic phase, post-stroke individuals exhibit a systemic inflammatory state that may be related to comorbidities. On the other hand, the muscular characteristics of this population are associated with the release of some cytokines that may enhance systemic inflammation, such as interleukin-6 and -10. The inclusion of aerobic exercises (AE) in the rehabilitation programs of these individuals has been suggested as an important strategy for recovery. AE improves mobility, cardiopulmonary conditions, cognition, regulates cardiovascular risk factors in these individuals, and has been associated with neuroplasticity, therefore motor recovery due to the increased concentration of Brain Derived Neurotrophic Factor (BDNF) mediated by the myokine Irisin. In this context, two studies were developed in this thesis, the first one aimed to quantify the serum activity of MMP-2 and MMP-9 in chronic post-stroke individuals and correlate these gelatinases with variables of physical activity level, body composition, functional capacity, and walking test, as well as with metabolic and inflammatory biomarkers. In addition, the activity of these gelatinases was characterized according to the motor impairment of these individuals. The second study, evaluated the changes in gelatinases activity in serum samples from chronic post-stroke subjects who received an intervention protocol for two-week, consisting of one session of high-intensity interval EA before the modified constraint-induced movement therapy (mCIMT). We also correlated the gelatinases with BDNF and Irisin concentrations, and with changes in manual dexterity and functional capacity. It was demonstrated with these studies that chronic post-stroke individuals have increased MMP-9 activity when compared to healthy individuals. Positive correlations were observed with time and steps at low cadence and negative correlations with medium cadence and peak activity index. According to motor impairment, MMP-2 activity is increased in the mild-moderate group compared to the control group. Furthermore, it was observed that the intervention protocol with the inclusion of AE, produces an acute response in MMP-9 increasing its activity. This increase was not correlated with manual dexterity nor with the functional capacity of these individuals, and there was also no relationship with BDNF and Irisin concentration. In conclusion, chronic post-stroke individuals present altered MMP-2 and -9 activity indicating a possible systemic inflammation, associated with the cardiovascular conditions of these individuals. In addition to showing, before an acute intervention, an increase in MMP-9 activity indicates a possible adaptive process prior to the modifications of vessels and muscle tissue to the AE. For long-term modifications in cardiovascular and/or muscular conditions, a change in the physical activity level of these individuals or the execution of longer duration intervention programs would be necessary. Altas concentrações das metaloproteinases de matriz-2 (MMP-2) e -9 (MMP-9) estão associadas à inflamação logo após o acidente vascular cerebral (AVC) e ao prognóstico funcional. É proposto que, durante a fase crônica, os indivíduos pós-AVC apresentem um estado inflamatório sistêmico que pode estar relacionada às comorbidades. Por outro lado, as características musculares desta população estão associadas à liberação de algumas citocinas que podem potencializar a inflamação sistêmica, tais como a interleucina-6 e -10. A inclusão de exercícios aeróbicos (EA) nos programas de reabilitação destes indivíduos, tem sido sugerida como uma importante estratégia para a recuperação. O EA melhora a mobilidade, as condições cardiopulmonares, a cognição e controla os fatores de risco cardiovascular destes indivíduos. Além disso, tem sido associado à neuroplasticidade e, portanto, à recuperação motora, em decorrência do aumento da concentração do Fator Neurotrófico Derivado do Cérebro (BDNF) que estaria mediado pela miocina Irisina. Diante disso, nesta tese foram desenvolvidos dois estudos, o primeiro teve como objetivo quantificar a atividade sérica da MMP-2 e da MMP-9 em indivíduos crônicos pós-AVC e correlacionar essas gelatinases com variáveis de nível de atividade física, composição corporal, capacidade funcional e de marcha, bem como, com biomarcadores metabólicos e inflamatórios. Além disso, a atividade das gelatinases foi caracterizada de acordo com o comprometimento motor desses indivíduos. O segundo estudo, avaliou as alterações na atividade destas gelatinases em amostras de soro de indivíduos pós-AVC crônicos, que receberam um protocolo de intervenção por duas semanas, que consistia em uma sessão de EA de alta intensidade e intervalado, antes da terapia por contensão induzida modificada (TCIm). Também correlacionamos as gelatinases com as concentrações de BDNF e Irisina, e com as mudanças na destreza manual e na capacidade funcional. Foi demonstrado com esses estudos que os indivíduos pós-AVC crônicos apresentam atividade aumentada da MMP-9 quando comparados com indivíduos saudáveis. Foram observadas correlações positivas com tempo e passos em cadência baixa e negativas com cadência média e índice de atividade de pico. De acordo com o comprometimento motor, a atividade da MMP-2 está aumentada no grupo leve-moderado em relação ao grupo controle. Além disso, foi observado que o protocolo de intervenção com a inclusão do EA, produz uma resposta aguda na MMP-9 aumentando sua atividade. Esse aumento não foi correlacionado com a destreza manual nem com a capacidade funcional destes indivíduos, e também não houve relação com o BDNF e a Irisina. Em conclusão, os indivíduos pós-AVC crônicos apresentam uma alteração na atividade das MMP-2 e -9 indicando uma possível inflamação sistêmica associada às condições cardiovasculares destes indivíduos. Além de apresentar, diante uma intervenção aguda, um aumento na atividade da MMP-9, indicando um possível processo adaptativo prévio às modificações dos vasos e tecido muscular frente ao EA. Para modificações a longo prazo nas condições cardiovasculares e/ou musculares seria necessária uma mudança no nível de atividade física destes indivíduos ou a execução de programas de intervenção de longa duração. 190413/2017-4

Основными факторами риска развития цереброваскулярных заболеваний, так же как и возникновения когнитивных нарушений, являются артериальная гипертония, поражение церебральных артерий (атеросклероз, васкулит), сахарный диабет, гиперхолестеринемия, гипергомоцистеинемия, курение и наследственная отягощенность по сосудистым и нейродегенеративным заболеваниям. Большинство этих факторов поддаются контролю и требуют ранней профилактики и своевременной диагностики, а наличие нескольких факторов риска усиливает их неблагоприятное воздействие на когнитивные функции. В обзоре приводятся данные многочисленных исследований, в которых изучались особенности развития когнитивных нарушений на фоне цереброваскулярных заболеваний, и даются рекомендации по использованию препаратов, улучшающих мозговой кровоток и метаболизм, а также воздействующих на общие патогенетические механизмы повреждения головного мозга при патологии сосудов., High blood pressure, cerebral arteries damage (atherosclerosis, vasculitis), diabetes mellitus, hypercholesterolemia, hyperhomocysteinemia, smoking, and family history of vascular and neurodegenerative disorders are the main risk factors for cerebrovascular diseases, as well as cognitive impairment. Most of these risk factors are controllable and require early prevention measures and timely diagnosis, while simultaneous presence of multiple risk factors enhances their negative effects on cognitive functions. This review includes data from multiple studies focused on the features of the development of cognitive impairment in cerebrovascular diseases, and provides guidelines on the use of drugs that improve cerebral blood flow and metabolism, as well as influence the general pathogenic mechanisms of brain damage in vascular disorders.

Introduction Infection with SARS-CoV-2 is typically compared with influenza to contextualize its health risks. SARS-CoV-2 has been linked with coagulation disturbances including arterial thrombosis, leading to considerable interest in antithrombotic therapy for Coronavirus Disease 2019 (COVID-19). However, the independent thromboembolic risk of SARS-CoV-2 infection compared with influenza remains incompletely understood. We evaluated the adjusted risks of thromboembolic events after a diagnosis of COVID-19 compared with influenza in a large retrospective cohort. Methods We used a US-based electronic health record (EHR) dataset linked with insurance claims to identify adults diagnosed with COVID-19 between April 1, 2020 and October 31, 2020. We identified influenza patients diagnosed between October 1, 2018 and April 31, 2019. Primary outcomes [venous composite of pulmonary embolism (PE) and acute deep vein thrombosis (DVT); arterial composite of ischemic stroke and myocardial infarction (MI)] and secondary outcomes were assessed 90 days post-diagnosis. Propensity scores (PS) were calculated using demographic, clinical, and medication variables. PS-adjusted hazard ratios (HRs) were calculated using Cox proportional hazards regression. Results There were 417,975 COVID-19 patients (median age 57y, 61% women), and 345,934 influenza patients (median age 47y, 66% women). Compared with influenza, patients with COVID-19 had higher venous thromboembolic risk (HR 1.53, 95% CI 1.38–1.70), but not arterial thromboembolic risk (HR 1.02, 95% CI 0.95–1.10). Secondary analyses demonstrated similar risk for ischemic stroke (HR 1.11, 95% CI 0.98–1.25) and MI (HR 0.93, 95% CI 0.85–1.03) and higher risk for DVT (HR 1.36, 95% CI 1.19–1.56) and PE (HR 1.82, 95% CI 1.57–2.10) in patients with COVID-19. Conclusion In a large retrospective US cohort, COVID-19 was independently associated with higher 90-day risk for venous thrombosis, but not arterial thrombosis, as compared with influenza. These findings may inform crucial knowledge gaps regarding the specific thromboembolic risks of COVID-19.

BackgroundImpairments to comprehension and production of speech (aphasia, dysarthria) and swallowing disorders (dysphagia) are common sequelae of stroke, reducing patients' quality of life and social participation. Treatment oriented on evidence-based guidelines seems likely to improve outcomes. Currently, little is known about guideline adherence in stroke aftercare for the above-mentioned sequelae. This study aims to analyse guideline adherence in the treatment of aphasia, dysarthria and dysphagia after stroke, based on suitable test parameters, and to determine factors that influence the implementation of recommended therapies.MethodsSix test parameters were defined, based on systematic study of guidelines for the treatment of speech impairments and swallowing disorders (e.g. comprehensive diagnostics, early initiation and continuity). Guideline adherence in treatment was tested using claims data from four statutory health insurance companies. Multivariate logistic and linear regression analyses were performed in order to test the outcomes.Results4,486 stroke patients who were diagnosed with specific disorders or received speech therapy were included in the study. The median age was 78 years; the proportion of women was 55.9%. Within the first year after the stroke, 90.3% of patients were diagnosed with speech impairments and swallowing disorders. Overall, 44.1% of patients received outpatient speech and language therapy aftercare. Women were less frequently diagnosed with specific disorders (OR 0.70 [95%CI:0.55/0.88], p = 0.003) and less frequently received longer therapy sessions (OR 0.64 [95%CI:0.43/0.94], p = 0.022). Older age and longer hospitalization duration increased the likelihood of guideline recommendations being implemented and of earlier initiation of stroke aftercare measures.ConclusionsOur observations indicate deficits in the implementation of guideline recommendations in stroke aftercare. At the same time, they underscore the need for regular monitoring of implementation measures in stroke aftercare to address group-based disparities in care.

Background The evidence for rehabilitation interventions poststroke lack sufficient robustness. However, variation in treatment effects across countries have been given little attention. Objective To compare two identically protocolized trials conducted in different western countries in order to identify factors that may have caused variation in secondary trial outcomes. Methods Comparative study based on individual patient data (N = 129) from two randomized controlled trials, conducted in hospitals and rehabilitation facilities in the Netherlands (N = 66) and Australia (N = 63). Patients with stroke and their caregivers were randomly allocated to an 8-week caregiver-mediated exercises intervention (N = 63; 31 Australian and 32 Dutch) or to a control group (N = 66; 32 Australian and 34 Dutch). Patient characteristics, compliance, usual care and process measures were compared across countries. We examined if study setting significantly moderated the trial outcomes: Hospital Anxiety and Depression Scale, Fatigue Severity Scale and General Self-Efficacy Scale, measured at 8- and 12 weeks follow-up. In addition, we explored if factors that were significantly different across countries caused variation in these trial outcomes. Results Most patients suffered an ischemic stroke, were in the subacute phase and participated with their partner. Dutch patients were younger (P = 0.005) and had a lower functional status (P = 0.001). Australian patients were recruited earlier poststroke (PPPP = 0.040) among Dutch controls. No effect modification was observed and trial outcomes did not change after controlling for cross-country differences. Conclusions The present study highlighted important clinical differences across countries whilst using an identical study protocol. The observed differences could result in a different potential for recovery and variation in treatment effects across trials. We argue that we can proceed faster to evaluating interventions within international pragmatic trials.

Objective: Post-stroke epilepsy (PSE) is one of the most common causes of acquired epilepsy and accounts for about 10-15% of all newly diagnosed epilepsy cases. However, evidence about the clinical profile of antiseizure medications in the PSE setting is currently limited. Brivaracetam (BRV) is a rationally developed compound characterized by high-affinity binding to synaptic vesicle protein 2A. The aim of this study was to assess the 12-month effectiveness and tolerability of adjunctive BRV in patients with PSE treated in a real-world setting. Methods: This was a subgroup analysis of patients with PSE included in the BRIVAracetam add-on First Italian netwoRk Study (BRIVAFIRST). The BRIVAFIRST was a 12-month retrospective, multicentre study including adult patients prescribed adjunctive BRV. Effectiveness outcomes included the rates of seizure response (≥50% reduction in baseline seizure frequency), seizure‐freedom, and treatment discontinuation. Safety and tolerability outcomes included the rate of treatment discontinuation due to adverse events (AEs) and the incidence of AEs. Results: Patients with PSE included in the BRIVAFIRST were 75 and had a median age of 57 (interquartile range, 42-66) years. The median daily doses of BRV at 3, 6, and 12 months from starting treatment were 100 (100-150) mg, 125 (100-200) mg and 100 (100-200) mg, respectively. At 12 months, 32 (42.7%) patients had a reduction in their baseline seizure frequency by at least 50%, and the seizure freedom rates was 26/75 (34.7%). During the 1-year study period, 10 (13.3%) patients discontinued BRV. The reasons of treatment withdrawal were insufficient efficacy in 6 (8.0%) patients and poor tolerability in 4 (5.3%) patients. Adverse events were reported by 13 (20.3%) patients and were rated as mild in 84.6% and moderate in 15.4% of cases. Significance: Adjunctive BRV was efficacious and generally well-tolerated when used in patients with PSE in clinical practice. Adjunctive BRV can be a suitable therapeutic option for patients with PSE.