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Aim. To study the efficacy and safety of a drug product based on the succinic acid complex with trimethylhydrazine used to treat patients with asthenic syndrome after a new coronavirus infection (COVID-19). Materials and methods. A prospective, multicenter, comparative, randomized, double-blind, placebo-controlled study of the safety and efficacy of sequential therapy with Brainmax enrolled 160 patients 1216 weeks after coronavirus infection (no more than 12 months). The study was conducted at 6 healthcare centers in different regions of the Russian Federation. At the enrollment, clinical and neurological examination and the following tests were performed: complete blood count, urinalysis, blood chemistry, coagulation test, pulse oximetry, electrocardiography, glomerular filtration rate calculation (according to CockcroftGault formula) were performed. Also, the patients were assessed using the following tools: VAS headache rating scale, MFI-20 asthenia scale, PSQI index, FAS-10 fatigue assessment scale, Dizziness Handicap Inventory (DHI), MoCA-test for cognitive impairment assessment, Beck Anxiety Inventory, Krd Autonomic Index. Results. The primary endpoint was the mean reduction in the MFI-20 asthenia scale score after the therapy (Visit 5, 41st day of therapy) compared to data from Visit 0 (beginning of therapy). A clinically significant advantage of the study drug versus the placebo was demonstrated, with a median absolute change in the MFI-20 score of -19.5 [-27; -11] points in the Brainmax drug group and -3 [-7; 1] score in the placebo group (p0.001). A significant sleep quality improvement according to the PSQI index was shown in the study group: by -2.5 [-4; -1] points versus no improvement in the placebo group (0 [-3; 0], p0,001). Significant differences were also noted for the following secondary endpoints: PSQI sleep quality scale, FAS-10 fatigue assessment scale, DHI, and Beck Anxiety and Depression Inventory. There was also a decrease in patients' complaints of cognitive deterioration according to the CGI scale. Conclusion. Our study clearly demonstrated the efficacy and high safety profile of Brainmax in a representative sample of patients with the post-COVID syndrome.

Introduction. Carotid atherosclerosis (CA) is one of the main causes of ischaemic stroke. MicroRNA is a relatively new group of biomarkers, some of which are associated with atherogenesis. The aim of the study was to evaluate the expression of several microRNAs in patients with cerebrovascular disease, depending on the severity of CA. Materials and methods. The study included 50 people (median age 66 [61; 71] years, 58% men) with cerebrovascular disease secondary to CA. The patients were divided into two groups: 16 patients (32%) had 70% internal carotid artery (ICA) stenosis (main group), while the remaining 34 patients had 70% stenosis and formed the comparison group. Expression of the following microRNAs was measured: miR-126-5p, miR-126-3p, miR-29-5p, miR-29-3p, miR-33a-5p, miR-33a-3p, miR-21-5p and miR-21-3p. Results. Compared to the comparison group, patients with a high degree of CA had reduced expression of miR-126-5p/-3p (4.8 and 5.9 vs. 8.5 and 7.6, respectively; p 0.001) and miR-29-3p (7.6 vs. 10.3; p 0.001), while miR-33a-5p expression was elevated (46.3 vs. 40.0; p 0.05). Cluster analysis confirmed typical expression patterns of these microRNAs in patients with varying degrees of ICA stenosis. Significant negative correlations were also found between the degree of stenosis and expression of miR-126-5p ( = 0.83; р 0.05), miR-126-3p ( = 0.64; р 0.05) and miR-29-3p ( = 0.62; р 0.05). Conclusion. Based on an analysis of patients with cerebral atherosclerosis, the studied microRNAs can be divided into proatherogenic (miR-33a-5p/-3p) and atheroprotective (miR-126-5p/-3p, miR-29-3p, and mir-21-5p/-3p). These biomarkers can be diagnostically useful in predicting the risk of both CA progression and acute cerebrovascular accidents, yet prospective studies are required.

Aim. Evaluation of various methods for determining the effectiveness of aspirin therapy and aspirin resistance in patients with cerebrovascular disease (CVD) depending on the presence of type 2 diabetes mellitus (T2DM).Materials and methods. The prospective study included 78 patients with various manifestations of CVD. All patients received acetylsalicylic acid (ASA) 75 mg daily. Along with a comprehensive clinical examination, a laboratory assessment of platelet function with the usage of Born method with aggregometer, a detailed biochemical blood test (including the determination of the small subunit of low density lipoprotein [s-LDL]), as well as therapeutic drug monitoring of salicylates were performed on a gas chromatograph-mass spectrometer.Results. In 53% of cases, the absence or insufficiency of the effect of ASA on platelet aggregation was noted. Two subgroups were separately identified: with T2DM; (n=40) and without T2DM (n=38). Insufficient effect of the drug on platelet aggregation characteristics were observed in 65% of patients with T2DM and in 38% without T2DM. The differences were revealed between the groups in triglycerides, s-LDL, glycemic and glycated hemoglobin (p – 0.20 [0; 0.39] μg/ml, while in patients without T2DM higher values were noted: ASA 0.29 [0.15; 0.55] μg/ml, SA – 0.33 [0.05; 0.73] μg/ml. A decrease in the concentration of ASA was associated with an increase in the level of ADP-induced platelet aggregation. There was an increase in the levels of ADPand adrenaline-induced platelet aggregation with a decrease in the concentration of ASA (p=0.004) and SA (p=0.006). Therapeutic drug monitoring revealed a more significant decrease in ASA level in T2DM than in the comparison group (p=0.025).Conclusion. It is advisable to monitor aspirin therapy both with the assessment of platelet aggregation and with therapeutic drug monitoring. The relationship between the level of ASA and SA in the blood plasma and the functional activity of platelets was confirmed. The presence of T2DM is associated with a decrease in the concentration of ASA and aspirin resistance detected in therapeutic drug monitoring.

Carotid atherosclerosis (CA) is an important risk factor for ischemic stroke. We described the miRNA and hemostasis profile of patients with moderate and advanced stages of carotid atherosclerosis and elucidated potential correlations with hemostatic activation. A prospective case-control study included 61 patients with evidence of carotid atherosclerosis (via ultrasound). The study population was divided into groups depending on the degree of carotid artery stenosis: 60% or more (advanced) and

Cerebrovascular diseases are one of the main causes of death and permanent disability. Effective and timely neuroprotective therapy can reduce the burden of cerebrovascular disease. The possibilities of neuroprotection as a method of prevention and medical rehabilitation of acute and chronic cerebrovascular diseases are addressed.Цереброваскулярная патология различной этиологии является одной из основных причин летальных исходов и стойкой инвалидизации. Снижение бремени цереброваскулярных заболеваний возможно при обеспечении эффективной и своевременной нейропротективной терапии. Анализируются возможности нейропротекции как важного мероприятия, направленного на предупреждение и реабилитацию острых и хронических церебровкскулярных заболеваний.

Atherosclerosis is a chronic inflammatory disease with a complex, multifactorial pathogenesis, which includes lipid metabolism alterations. miR-33a is a microRNA that plays a key role in cholesterol efflux and promotes atherosclerosis, yet its relationship with lipid markers in carotid atherosclerosis (CA) remains unclear. The objective is to evaluate possible associations between miR-33a expression and lipid biomarkers in patients with CA. This was a prospective study that included 61 patients (median age 66.0 years, 55.7% male) with evidence of CA. Lipid profile (total cholesterol, triglycerides [TG], high-density lipoprotein [HDL] and low-density lipoprotein [LDL] cholesterol) was analyzed. Extraction and quantification of miR-33a-5p/3p was performed according to protocol. Patients were further divided depending on the target LDL level (

Atherosclerosis is a multifactorial disease and one of the leading causes of ischaemic stroke. In recent years, microRNA has become an important factor to consider in the pathogenesis of atherosclerosis. MicroRNAs are non-coding RNA sequences that are divided into proatherogenic and atheroprotective. This study evaluated the leukocyte expression of certain microRNAs (miR-126-(5p/3p), miR-29a-(5p/3p), miR-33a-5p and miR-21-(5p/3p)) in patients with carotid atherosclerosis. Statistically significant differences were found between patient groups in regard to the molecular levels, as well as correlations between several microRNAs. This indicates the potential use of microRNA in diagnosis and treatment, and confirms the role of microRNAs as important regulators of carotid atherosclerosis.

Obesity is a pathological condition caused by overweight and requiring medical intervention. The clinical and scientific experience gained over the past decades has allowed researchers to consider this problem as an independent disease with its own pathophysiological features, prevalence, incidence, approaches to therapy and prevention. One of the most important factors in the pathogenesis of obesity is disordered eating behavior, the central regulation of which is carried out with the active participation of the prefrontal cortex. Impact on this area (for example, using non-invasive brain stimulation) may be one of the promising ways to modulate eating behavior. The article describes clinical cases of treatment of morbid obesity using navigated rhythmic transcranial magnetic stimulation (rTMS). Different patterns of dorsolateral prefrontal cortex (DLPFC) activation before and after rTMS are demonstrated. Possible mechanisms of the influence of DLPFC on the formation of eating behavior are also considered. These data underline the important role of DLPFC dysregulation in obesity, as well as show potentially effective neuromodulation techniques.

Polycythemia vera (PV) is a Ph-negative myeloproliferative neoplasm (MPN) which is characterized by erythrocytosis and a high incidence of thrombotic complications, including stroke. The study aimed to evaluate red blood cell (RBC) morphodynamic properties in PV patients and their possible association with stroke. We enrolled 48 patients with PV in this cross-sectional study, 13 of which have a history of ischemic stroke. The control group consisted of 90 healthy subjects. RBC deformability and aggregation analysis were performed using a laser-assisted optical rotational red cell analyzer. The following parameters were calculated: aggregation amplitude (Amp), RBC rouleaux formation time constant (Tf), time of formation of three-dimensional aggregates (Ts), aggregation index (AI), rate of complete disaggregation (y-dis), and the maximal elongation of RBC (EImax). Statistical analysis was performed with the R programming language. There were significant differences in RBCs morphodynamics features between patients with PV and the control group. Lower EImax (0.47 (0.44; 0.51) vs. 0.51 (0.47; 0.54), p < 0.001) and γ-dis (100 (100; 140) vs. 140 (106; 188) s−1, p < 0.001) along with higher amplitude (10.1 (8.6; 12.2) vs. 7.7 (6.6; 9.2), p < 0.001) was seen in patients with PV compared with control. A statistically significant difference between PV patients with and without stroke in aggregation amplitude was found (p = 0.03). A logistic regression model for stroke was built based on RBC morphodynamics which performed reasonably well (p = 0.01). RBC alterations may be associated with overt cerebrovascular disease in PV, suggesting a possible link between erythrocyte morphodynamics and increased risk of stroke.

Backgrounds and Purpose. Philadelphia chromosome-negative myeloproliferative disorders (Ph-negative MPD) are a rare group of hematological diseases, including three distinct pathologies: essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF). They most often manifest with thrombotic complications, including cerebrovascular events. Covert brain infarcts (CBIs) are defin ed as predominantly small ischemic cerebral lesions that are detected using magnetic resonance imaging (MRI) in the absence of clinical stroke events. The relationship between MPD and CBIs remains unclear. Methods. Included in the study were 103 patients with the diagnosis of Ph-MPD (according to WHO 2016 criteria) (median age—47 (35; 54) years; 67% female). In total, 38 patients had ET, 42 had PV, and 23 had PMF. They underwent clinical examination, routine laboratory analyses (complete blood count), brain MRI, ultrasound carotid artery, flow-mediated dilatation (as a measure of endothelial dysfunction—FMD). Results. Overall, 23 patients experienced an ischemic stroke (as per MRI and/or clinical history), of which 16 (15.5%) could be classified as CBIs. The rate of CBIs per MPD subtype was statistically non-significant between groups (p = 0.35): ET–13.2%, PV–21.4%, and PMF–8.7%. The major vascular risk factors, including arterial hypertension, carotid atherosclerosis, and prior venous thrombosis, were not associated with CBIs (p > 0.05). Age was significantly higher in patients with CBIs compared to patients without MRI ischemic lesions: 50 (43; 57) years vs. 36 (29; 48) (p = 0.002). The frequency of headaches was comparable between the two groups. CBIs were associated with endothelial dysfunction (OR - 0.71 (95% CI: 0.49–0.90; p = 0.02)) and higher hemoglobin levels (OR—1.21 (95% CI: 1.06–1.55); p =0.03). Conclusions. CBIs are common in patients with Ph-negative MPD. Arterial hypertension and carotid atherosclerosis were not associated with CBIs in this group of patients. The most significant factors in the development of CBIs were endothelial dysfunction (as measured by FMD) and high hemoglobin levels. Patients with Ph-negative MPD and CBIs were older and had more prevalent endothelial dysfunction.

Introduction: Neurology is arguably one of the most difficult subjects to teach and study in the medical curriculum. Educational games (EG) may be a valid option to enhance motivation in neurology residents.Methods: We developed an educational board game (Neuropoly) to assist in teaching neurology. We present here an overview of the game, as well as the results of a pilot study aimed at determining: (a) the efficacy of the game in teaching certain neurological concepts; and (b) student compliance and satisfaction with the EG.Results: The pre- and post-play questionnaire scores differed significantly (3.2 ± 1.7 vs. 7.8 ± 1.6, p < 0.001). Our group of residents, showing an overwhelmingly positive response, very well received the game. The questions were rated as above average regarding difficulty.Conclusion: The “Neuropoly” educational board game has been shown to be interesting, efficient, and motivational among first- and second-year neurology residents. Novel educational methods for complex medical disciplines should be developed, with board games being a viable and inexpensive approach.

Myeloproliferative disorders (MPD) are accompanied by a high proportion of thrombotic complications, which may lead to cerebrovascular disease (CVD).To describe MRI-findings in patients with Ph - negative MPD and evaluate any cerebrovascular disease.We included 104 patients with Ph - negative MPD (age varied between 20 and 58) with clinical correlates of cerebrovascular pathology.Brain MRI showed post - stroke lesions in 20% of patients (7 hemispheric infarcts due to thrombotic occlusion of one of the large cerebral arteries, 14 - cortical infarcts). 37 patients (36%) had vascular cerebral lesions. Cerebral venous sinus thrombosis occurred in 5 patients - in 7% (n=3) of patients with polycythemia vera and 5% (n=2) - in patients with essential thrombocythemia. The incidence of vascular cerebral lesions was associated with higher levels of the following: erythrocyte, platelet count, fibrinogen, and with the decrease in fibrinolytic activity, as well.The pioneering results of the study include the description and analysis of brain MRI-findings in patients with Ph - negative MPD. The underlying mechanisms of cerebrovascular pathology in these patients are associated with certain blood alterations (particularly, hemorheology) which present a major risk factor.Цель. Оценка состояния вещества головного мозга при Ph-негативных миелопролиферативных заболеваниях (МПЗ) с целью выявления цереброваскулярной патологии. Материалы и методы. Проведено магнитно - резонансное томографическое (МРТ) исследование головного мозга у 104 пациентов с подтвержденным диагнозом Ph - негативное МПЗ в возрасте от 20 до 58 лет. Изучены гемостазиологические и гемореологические данные этих больных. Результаты. У 20% обследованных по данным МРТ головного мозга выявлялись ишемические изменения вещества головного мозга (7 полушарных инфарктов вследствии тромботической окклюзии одной из магистральных артерий головы, 14 инфарктов корковой локализации). В 36% случаев выявлялись очаговые изменения «сосудистого» генеза. Тромбозы венозных синусов развились у 5 пациентов: в 7% случаев (n=3) у пациентов с истинной полицитемией, в 5% (n=2) - у пациентов с эссенциальной тромбоцитемией. Развитие очаговых изменений «сосудистого» генеза ассоциировано с увеличением таких показателей, как эритроциты, тромбоциты, фибриноген, а также со снижением фибринолитической активности плазмы крови. Заключение. Впервые в когорте пациентов с Ph-негативными МПЗ продемонстрированы и описаны нейровизуализационные изменения вещества головного мозга. Полученные данные предполагают важную роль изменений характеристик крови (в том числе реологических) в формировании цереброваскулярной патологии при МПЗ.

Background. Cerebrovascular disorders continue to be among the most common and socially significant worldwide. Among multiple reasons for circulatory disturbances special importance is attached to hemorheology and hemostasis disorders occurring also in patients with Ph-negative myeloproliferative diseases (MPD). Aim. To investigate typical characteristics of the course of cerebrovascular disorders in patients with Ph-negative MPD. Materials & Methods. The trial included 169 adult patients with neurological diseases. Among them the main group consisted of 104 patients aged 34 to 55 years (median 48.5 years) with Ph-negative MPD diagnosed at the National Research Center for Hematology. The control group consisted of 65 patients aged 51 to 58 years (median 55.5 years) with cerebrovascular diseases without concomitant hematological pathology. Results. The incidence of acute ischemic strokes was 26.2 % in polycythemia vera (PV), 20.5 % in essential thrombocythe-mia (ET), and 8.7 % in primary myelofibrosis (PMF). Conclusion. An acute ischemic stroke with a concurrent thrombotic occlusion of one of the major head arteries is a criterion for ruling out Ph-negative MPD. To identify cerebral lesions in patients with Ph-negative MPD (PV, ET, PMF) MRI of the brain is recommended.

Aim. The study of Actovegin effectin clinical presentations and hemorheological characteristics in patients with chronic cerebrovascular pathology (CCVP) and mild cognitive impairment. Materials and methods. The study group included 47 patients (25 male and 22 female), aged 61-75 years (mean age 63.8±5.4) with CCVP who were treated with Actovegin. The control group comprised 28 patients matched by gender and age, without associated cerebrovascular pathology. All patients along with thorough neurological examination underwent laboratory analyses (platelet and erythrocyte rheology), neurovisualization studies (functional magnetic resonance imaging of the brain). Depending on the dosage all patients were divided in two groups: Actovegin 1000 mg and 160 mg daily. Results and discussion. Overall, with Actovegin treatment in 81% of cases positive dynamics both in subjective symptoms, and somatic status was observed. A favorable effect on cognitive function in patients with CCVP was noted. The dose-dependent drug effect was demonstrated. The effect of Actovegin on blood cell functioning included the formation of smaller (Tf and Ts; p=0.0096 and p=0.016) and less solid (γ dis) erythrocyte aggregates (p=0.0034) both in the study and control group. The increase in erythrocyte deformability during therapy was significantly associated with cognitive improvement (via MoCA test, r=0.28). Conclusion. Complex (including neuropsychological and neurovisualizational) examination may not only help determine the cognitive status in patients with CCVP, but also assess the efficacy of neurometabolic therapy. New facts of Actovegin’s influence on erythrocyte aggregation and deformability have been identified, which may enhance micro - and macrocirculation. The acquired data may prove the wide spectrum of Actovegin’s pharmacological effect, which allows to use it in all forms of cerebrovascular pathology.

Introduction. Hemorheological abnormalities in patients with Ph-negative myeloproliferative disorders (MPD) may lead to the development and/or progression ofcerebrovascular pathology. Adequate preventive therapy in such cases lowers the risk of cerebral thrombotic complications. Objective. Evaluation of the effect of dipiridamole and acetylsalicylic acid (ASA) on platelet and erythrocyte aggregation, as well as morphofunctional properties of erythrocytes in patients with cerebrovascular disease (CVD) on the background of MPD. Materials and methods. The study comprised 40 patients with various forms of CVD and Рh-negative MPD: 20 patients received dipyridamole, 20 – ASA for prevention of cerebral thrombotic complications. Mean study age was 44.6 years [35; 58.5]. A thorough clinical and neurological examination was performed, as well as neuroimaging studies, coagulation tests, analysis of platelet aggregation and rheological properties of erythrocytes. Results. Within the observation period (median – 6.3 months) no acute cerebrovascular events in both groups were observed. Platelet aggregation (induced by ADP or adrenaline) was similar in both groups. Dipyridamole and ASA were also similar in their effect on functional properties of erythrocytes. Conclusion. Our findings suggest that the therapeutic effect of dipyridamole concerning CVD is similar to that of ASA. Dipyridamole can be recommended for use in patients with Рh-negative MPD if other antiplatelet agents are contraindicated., №11 (2017)