Acute stroke is the second leading cause of death and the third leading cause of disability in the world. Ischemic stroke (IS) the most common type of stroke. In acute cerebral ischemia, damage to the brain tissue is complex and includes blood-brain barrier (BBB) dysfunction, neuroinflammation, oxidative stress, activation of intracellular and extracellular signaling pathways, expression of neurotoxic agents, excitotoxicity, and apoptosis. In acute IS, reperfusion therapy (RT), is one of the most prominent treatment options. Most of the randomized clinical trials demonstrated the efficacy and safety of RT. The use of novel neuroimaging techniques (CT-perfusion and new MRI modalities) significantly expanded the RT selection criteria in patients with IS. One of the possible ways to further expand the RT is to combine it with neurocytoprotection. According to many researchers, this could potentially significantly improve the efficacy and safety of RT. This opinion is based on the concept of preserving brain tissue in the ischemic penumbra region. The aim of this review was to analyze the current trials of neurocytoprotection in combination with RT in IS patients.

Posterior reversible encephalopathy syndrome (PRES) is characterized by nonspecific symptoms, including not only pronounced non-focal and various focal neurological signs but also specific neuroimaging features, including vasogenic edema affecting predominantly the posterior area. PRES usually develops in the setting of acute arterial hypertension. However, it is not uncommon for PRES to develop in non-hypertensive patients, including people with autoimmune disorders (multiple sclerosis, neuromyelitis optica spectrum disorder, etc). PRES could also be due to the toxic effects of drugs or other substances. The pathophysiological mechanisms of PRES include impaired autoregulation of cerebral blood flow due to acute arterial hypertension and toxic endotheliotropic effects of endogenous and exogenous factors.

OBJECTIVE:To evaluate the relationship between the severity of post-stroke cognitive impairment (PSCI) and coagulation parameters assessed using the dynamic thrombophotometry.MATERIAL AND METHODS:Thirty-five patients with hemispheric ischemic stroke (IS) with moderate neurological deficit at admission were included. All patients underwent a comprehensive clinical and instrumental assessment according to the current guidelines. On days 10-14, the cognitive status of patients was assessed using the Montreal Cognitive Assessment (MoCA). Coagulation parameters were assessed using the dynamic thrombophotometry at admission, on 6-8th days and 13-15th days from the onset of the disease. A database of laboratory studies of 30 apparently healthy volunteers was used as a comparison group.RESULTS:Data analysis revealed that a number of spatial and temporal parameters were within the reference values, and there were no significant changes over time. Nevertheless, though the optical density of the fibrin clot (D) was within the reference values, it showed a steady increase from the admission by the end of the 1st week of the disease (p=0.007) and by 13-15th days (p=0.009). Correlation and multivariate linear regression, including baseline stroke symptom severity, showed significant associations (p<0.01 in all tests) between the higher optical density of the fibrin clot (D) on days 6-8 and 13-15 and lower MoCA score, confirming the negative effect of altered hemostatic parameters on cognitive function in IS patients.CONCLUSION:The increase of optical density of the fibrin clot (D) by 6-8th and 13-15th days is a potential prognostic biomarker for the early development of PSCI.

In the paper, we analyze the state policy of Russia and the practical implementation of projects aimed to support and promote the Russian language abroad. Within the study, we use research methods, such as observations, interviews, and experimental testing, to improve the effectiveness of promoting the Russian language outside Russia. Moreover, we analyze Russian and foreign forms of promoting the language abroad. Additionally, we provide a detailed description of the advantages and disadvantages of the most appropriate forms to support and promote the language abroad and the forms tested in foreign schools. The paper presents the forms divided into those conducted abroad with the assistance of Russian native speakers and those conducted in Russia for foreigners. Furthermore, we describe the forms proposed and based on our experience of working with native speakers and organizing activities to support foreign languages in the Altai Republic, Russia, and Western Mongolia. These forms are relevant for supporting Russian as a foreign language in Western Mongolia.

OBJECTIVE:To evaluate the efficacy and safety of using Cellex for the treatment of cognitive impairment as part of the complex therapy of patients with chronic cerebral ischemia (CCI) compared with placebo.MATERIAL AND METHODS:The study randomized 300 patients with a reliable diagnosis of CCI stage 1-2, all participants were divided into two groups, 150 participants in each - main and control. The study drug Cellex or placebo was administered as two 10-day treatment courses, 1 ml once a day. The duration of the study was 90±5 days for each participant. The primary end point for evaluating the effectiveness of the therapy was the degree of improvement in the state of cognitive functions relative to the initial state according to the Montreal Cognitive Dysfunction Scale (MoCA) on the 31st and 60th days from the start of therapy in the compared groups. Secondary endpoints were the assessment of the degree of improvement in the state of cognitive functions according to psychometric testing scales (MoCA, Correction Test, Frontal Dysfunction Test Battery) relative to the initial state on the 31st, 60th and 90th days from the start of therapy. Also, a dynamic assessment of the systemic concentration of markers of brain damage - S100β, GFAP, MMP9 and neurotrophins - BDNF and GDNF was carried out.RESULTS:The primary endpoint of the study was achieved-the MoCA score in each group increased uniformly after baseline. However, in the main group, this indicator was significantly higher starting from visit 3 - 23.4±2.8 points in the main group, in the placebo group 22.7±2.3 (p<0.001), a statistically significant difference also remained at visit 5 (p<0.001). When analyzing the secondary endpoints according to the battery of frontal dysfunction tests and the correction test, a more pronounced positive trend was also noted in the main group. Changes in the emotional sphere in both groups remained within the normal range. The dynamics of the systemic concentration of markers of brain damage and neurotrophins was multidirectional, the assessment of which was possible only at the trend level.CONCLUSION:Based on the statistical analysis of the results of the study, Cellex was confirmed to be superior to Placebo in the degree of improvement in cognitive functions measured by the MoCA scale after the 1st and 2nd treatment courses.

The COVID-19 pandemic has had significant influences on the incidence of acute cerebrovascular accidents and the structure of mortality. SARS-CoV-2 increases the risks of developing both ischemic and hemorrhagic stroke. The key pathogenetic element underlying the development of cerebral stroke in COVID-19 consists of impairments to the operation of angiotensin 2 receptors, which are accompanied by accumulation of excess quantities of angiotensin 2, endothelial dysfunction, hypercoagulation, overproduction of proinflammatory cytokines, and an oxidative storm. In patients with stroke and COVID-19, lesion severity is associated with dual mechanisms of ischemia – systemic and cerebral. The possibilities of medication-based correction of both systemic impairments associated with coronavirus infection and local impairments due to ischemic or hemorrhagic brain damage, are limited. Substances with antioxidant activity may potentially be effective in patients with stroke and COVID-19. Data from a number of clinical rials indicate that Mexidol significantly improves functional outcomes in ischemic stroke. Use of Mexidol in patients with stroke and COVID-19 is advised.

Post-stroke cognitive impairment (PCI) contributes greatly to the global stroke burden. In recent years, the role of hemostasis in PCI is acknowledged more and more. This study aimed to evaluate the connection between PCI and coagulation/fibrinolysis balance.

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.

Interleukin-6 (IL-6) and interleukin-8 (IL-8), produced by macrophages, are major inflammatory cytokines. It is known that M1 macrophage activity (indicated by IL-6 upregulation) plays a major role in ischemic stroke. However, this subject is less studied in intracerebral hemorrhage (ICH). The goal of this pilot study was to investigate the role of IL-6, IL-8, and M1 macrophage activity in acute hypertensive ICH.

Small penetrating vessels are a major source of bleeding in acute hypertensive intracerebral hemorrhage (ICH). The goal of this study was to evaluate the role of platelet aggregation in hematoma formation and evolution.

The COVID-19 pandemic had a significant impact on both the incidence of acute cerebral circulatory disorders and the structure of mortality. SARS-CoV-2 increases the risk of both ischemic and hemorrhagic stroke. The key pathogenetic links underlying the development of cerebral stroke in COVID-19 are impaired functioning of angiotensin 2 receptors, accompanied by the accumulation of excess angiotensin 2, endothelial dysfunction, hypercoagulation, hyperproduction of proinflammatory cytokines and oxidative storm. In patients with stroke and COVID-19, the severity of the lesion is associated with a dual mechanism of ischemia - systemic and cerebral. The possibilities of medical correction of systemic disorders associated with coronavirus infection, as well as local ones caused by ischemic or hemorrhagic brain damage, are limited. Substances with antioxidant activity could potentially be effective in patients with stroke and COVID-1.

Aim: to evaluate the efficacy and safety of the L-lysine escinate venotropic drug in the treatment of cephalgic, atactic and asthenic syndromes in patients with chronic cerebral ischemia, mainly caused by venous disorders. Patients and Methods: the study involved 60 patients with a diagnosis of chronic cerebral ischemia with signs of chronic venous insufficiency. All patients were randomly divided into two groups consisting of 30 people. Patients in the main group received L-lysine escinate, and the control group received Vinpocetine. The drugs were administered by intravenous drip for 10 days. A dynamic assessment was performed using a modified subjective scale of asthenia evaluation (MFI-20), 100 mm long visual analogue scale (VAS) for headache, subjective neurological impairment scale (SNIS), and Tinetti test. An ophthalmic examination with an assessment of the fundus vessels and an ultrasound duplex scanning of head vessels (veins) were also conducted. Results: it was shown that L-lysine escinate therapy showed a statistically more significant reduction in the severity of headache (according to VAS) and an improved stability measured by Tinetti test versus during Vinpocetine treatment. There were no significant differences in the level of asthenia (MFI-20), the severity of emotional disorders, and the SNIS score. Also, the number of patients with dilated fundus veins significantly decreased during treatment in the main group (p<0.05), which was not the case in the control group. According to ultrasound duplex scanning data, the venous flow velocity through the veins of Rosenthal and angular veins during L-lysine escinate therapy was significantly higher (p<0.05) than in patients receiving Vinpocetine. Conclusion: the inclusion of vasotropic drugs (in particular, the L-lysine escinate venotonic drug) in the treatment regimen of patients with chronic brain ischemia seems appropriate, especially if there are signs of venous insufficiency. KEYWORDS: systemic venous insufficiency, chronic cerebrovascular disease, venous dyscirculation, glymphatic system, L-lysine escinate, Vinpocetine. FOR CITATION: Schukin I.A., Fidler M.S., Koltsov I.A. Chronic cerebrovascular disease: the role of venous disorders and the possibility of pathogenetic correction. Russian Medical Inquiry. 2020;4(9):544–551. DOI: 10.32364/2587-6821-2020-4-9-544-551.

AIM:To study the changes in endothelial dysfunction and von Willebrand factor activity in acute and chronic stages of hemispheric intracerebral hemorrhage (ICH) and their influence on clinical severity and functional recovery.MATERIAL AND METHODS:Fifty patients with hemispheric ICH, aged 61.6±11.2 years, and 30 patients with AH, aged 59.6±6.2 years, (comparison group) were examined. Patients with ICH were examined on admission, 6-8th, 13-15th days, and 11.1±0.9 months after stroke onset. Patients with arterial hypertension (AH) were examined on admission. Changes in NIHSS, Glasgow coma scale, and modified Rankin scale were studied. Restocetin induced platelet aggregation (RIPA) was assessed by optical aggregometry (BIOLA LA230-2 AGGRWB) in modification by G. Born and Z. Gabbasov. von Willebrand factor (vWF) activity was examined as described by J. Olson.RESULTS:RIPA was significantly higher in acute ICH compared to chronic ICH, AH and reference values. RIPA values were negatively correlated with hematoma volume and midline shift (r≥ -0.308, p≤0.035). vWF activity was significantly higher in ICH patients than in AH and reference values. Patients with AH also had significantly higher vWF activity than reference values. In acute ICH, vWF activity steadily increased reaching maximal values by 13-15th day. In chronic ICH, vWF activity decreased compared to the acute phase, but still remained higher than in AH patients or reference values. In acute phase, 1% increment in vWF values resulted in 0.5% increase in the risk of death during the follow-up period (95% CI 1.001-1.008, p=0.007).CONCLUSION:Endothelial dysfunction assessed by vWF activity increases during the acute hemispheric ICH and remains elevated in the chronic stage. vWF activity may be used as a marker in assessing stroke outcome and prognosis.

The article reviews the etiological factors and pathophysiological mechanisms by which the cerebral vascular insufficiency develops and advances. It presents the main directions in the treatment of such patients including the combined use of polymodal drugs with neuroprotective, metabolic and vascular effects.