Introduction:Myeloproliferative neoplasms (MPN) may contribute to cerebrovascular disease via cellular and endothelial pathology leading to impairment at the neurovascular unit (NVU) level. Studies targeting this patient cohort form a neuroscientific viewpoint are scarce. Objective:We aimed at elucidating possible neuroimaging correlates of NVU alterations in MPNs patients. Materials and methods:We initially included 187 patients with MPNs in this study, retaining 39 patients as per eligibility criteria (25.6% males, median age - 43 years), who were matched with a control group of 11 healthy subjects (36.4% males, median age - 41 years). Structural and task-based (motor paradigm) functional MRI were performed in both groups, along with the evaluation of baseline blood parameters (hemoglobin, hematocrit and platelet count), comorbidities (arterial hypertension, diabetes mellitus, atherosclerosis) and antiplatelet use: these factors were then used as covariates in statistical analysis. Results:fMRI data analysis in the group of MPN patients revealed activation in the left primary sensorimotor cortex (pre- and post-central gyri); the right supramarginal gyrus showed significant activation (T = 5.99, pFWEcorr = 0.015) in the MPN group only. Group fMRI data analysis in healthy volunteers showed two main clusters of activation in the left precentral gyrus and right hemisphere of the cerebellum during task execution. Second-level analysis of activation differences between MPN patients and healthy volunteers showed greater activation in the right primary sensorimotor cortex in MPN (Puncorr = 0.014 and <0.001 at cluster and peak level respectively). Conclusion:Additional task-specific cortical activation in MPN patients may be potentially linked to NVU disturbance, even in otherwise unchanged cerebral activation patterns. Our findings also suggest that fMRI data in MPN may be confounded by higher blood cell count that needs to be controlled for in this cohort of patients.

Introduction. Cerebral atherosclerosis (CA) remains a leading cause of ischemic cerebrovascular diseases, while molecular markers characterizing the activity and mechanisms of atherogenesis in cerebral arteries are insufficiently studied. Exosomal microRNA expression may serve as a promising biomarker for CA, reflecting the level of epigenetic regulatory burden. The study aimed to identify the CA-associated exosomal microRNA profile and evaluate its potential as biomarkers through comparative profiling. Materials and methods. This prospective study included inpatients of the Research Center of Neurology and Neurosciences: a CA group (n = 43; median age 68 years) with extra-/intracranial atherosclerosis confirmed by angiographic imaging, and a control group with non-atherosclerotic cerebrovascular diseases (n = 17; median age 46 years). Exosomes and exosomal RNA were isolated from blood serum (ExoQuick), followed by amplification (SeraMir) and profiling of 384 microRNAs via real-time PCR. After quality control, 337 endogenous microRNAs were retained for analysis. Normalization was performed using the global mean method with ΔCt calculation; differential expression was assessed with limma (empirical Bayes correction), with significance thresholds set at adjusted p-value 0.1 and |log2FC| 0.5. Additionally, a network analysis of microRNA-target genes (miRTarBase/MIENTURNET) with functional annotation was conducted. Results. Patients with CA exhibited 9 exosomal microRNAs with statistically significant differential expression, with all changes being unidirectional — a decrease of microRNA levels in the CA group: hsa-miR-18a, hsa-miR-539, hsa-miR-20a, hsa-miR-100, hsa-miR-10b, hsa-let-7f, hsa-miR-148b, hsa-miR-187, hsa-miR-374a. Visualization of the top 30 microRNAs with the smallest adjusted p-value revealed a consistent trend toward lower expression in patients with CA, and sample clustering generally corresponded to clinical groups. Network analysis identified hub genes potentially involved in endothelial dysfunction and epigenetic regulation (DNMT1, MSL3, SMCHD1), lipid metabolism and anti-inflammatory signaling (RORA, NCOA6), oxidative stress/macrophage activation (SESN3), vascular smooth muscle cell proliferation (CCND1, CTDSPL2), and cell migration and vascular remodeling (PAFAH1B1, BTBD7). Conclusion. Cerebral atherosclerosis is associated with a unidirectional decrease in the expression of several microRNAs in circulating exosomes. These findings indicate the potential role of exosomal microRNAs in the CA molecular mechanisms and justify further investigation into their diagnostic and pathogenetic significance.

This review presents recent data on one of the most promising neuroimaging techniques, pharmacological functional magnetic resonance imaging (phFMRI). PhFMRI technologies are described as well as task-based approaches inducing neuronal activation in the areas of interest when evaluating the effects of neuroactive agents. We reviewed the potential use of phFMRI in various neurological disorders such as cerebrovascular disease and epilepsy, as well as in the management of metabolic disorders, cognitive impairment, pain syndrome, etc. Limitations of phFMRI and possible ways to address them in designing and conducting studies are presented. The potential uses of phFMRI for the objective assessment of the targeted effects of pharmacological agents are suggested.

Introduction. Atherosclerosis is a complex pathophysiological process with a wide range of clinical manifestations. Active research is underway to determine the prevalence of intracranial atherosclerosis across different ethnic groups, the role of modifiable and non-modifiable risk factors in its pathogenesis, and the advances in diagnostic algorithms for patients with extra-/intracranial atherosclerosis. The aim was to evaluate manifestations of intracranial atherosclerosis (patterns of intracranial artery lesions, including pathomorphological findings) and identify potential associations between known risk factors and intracranial atherosclerosis in patients with cerebrovascular disease. Materials and methods. During the first phase, a retrospective analysis of autopsy protocols was conducted for 166 patients (66% men) hospitalized at the Research Center of Neurology between 1976 and 2007. The second phase involved clinical, laboratory, and imaging data from 120 patients (59% men) with atherosclerotic disease of the brachiocephalic arteries. These patients were divided into two subgroups: a main subgroup with intracranial artery involvement combined with extracranial atherosclerosis (n = 60) and a control subgroup with isolated extracranial artery involvement (n = 60). Results. Pathomorphological assessment revealed a high rate of atherosclerotic lesions in the carotid artery system at both extra- and intracranial levels. One-third of patients had ≥50% atherosclerotic stenosis in intracranial arteries without significant extracranial stenosis. Multivariate logistic regression analysis identified obesity (odds ratio [OR] 3.22), male sex (OR 6.17), and low-density lipoprotein levels (OR 2.5) as the most significant independent clinical laboratory factors associated with intracranial atherosclerosis. Conclusion. The role of intracranial atherosclerosis in cerebrovascular events is underestimated. Overlapping neurological and generalized manifestations of isolated intra- and extracranial atherosclerosis may give a misleading impression of the true prevalence of intracranial atherosclerosis.

Background: Intracranial atherosclerosis (ICAS) is a major cause of ischemic stroke, yet fundamental studies regarding epigenetic regulation of ICAS are lacking. We hypothesized that, due to anatomical and/or functional differences, extracranial atherosclerosis is distinct from ICAS, which may explain the clinical variability as well. Methods: We chose a number of miRNAs involved in various steps of atherogenesis (namely, miR-712/205-5p/-3p, miR-106b-3p/-5p, miR-146a-3p/-5p, miR-100-3p/miR-5p, miR-200c-3p/-5p, miR-532-3p/-5p, and miR-126-3p/-5p) and examined their plasma levels in a cohort of patients with carotid stenosis > 50% (n = 35, mean age: 65 years, 54% male; 12 patients had ICAS). Results: A differential pattern of circulating miR expression was found in ICAS patients: there was an overexpression of miR-712/205-5p, miR-106b-5p, miR-146a-5p, miR-200c-5p, miR-532-3p, and miR-126-3p. The following miRs were underexpressed in intracranial atherosclerosis—miR-712/205-3p and miR-100-3p. These changes represent a plethora of atherogenic mechanisms: smooth muscle cell migration (miR-712/205, miR-532), foam cell formation (miR-106b, miR-146a), endothelial dysfunction (miR-200c), low-density lipoprotein-induced vascular damage (miR-100), and leukocyte recruitment (miR-126). In symptomatic ICAS patients, we observed a statistically significant upregulation of miR-712/205-3p and miR-146a-5p. Conclusions: Overall, the findings of our pilot study revealed several new and interesting associations: (1) intracranial atherosclerosis seems to have a different epigenetic profile (regarding circulating microRNA expression) than isolated extracranial vessel involvement; (2) ischemic stroke in ICAS may be potentiated by other pathophysiologic mechanisms than in extracranial-only atherosclerosis (ECAS). Certain miRs (e.g., miR-712/205) seem to have a larger impact on ICAS than on extracranial atherosclerosis; this may be potentially linked to difference between extra- and intracranial artery morphology and physiology, and/or may lead to the said differences. This underscores the importance of making a distinction in future epigenetic studies between ECAS and ICAS, as the mechanisms of atherogenesis are likely to vary.

Introduction. Philadelphia-negative myeloproliferative neoplasms (MPNs) are a rare blood disorder characterized by pancytosis and thrombohemorrhagic complications. The aim of this article is to describe clinical and neuroimaging patterns of brain changes in patients with MPN. Materials and methods. The study included 152 patients with an established diagnosis of MPN (according to WHO criteria 2008, 2016). A clinical and neurological examination, laboratory tests, and magnetic resonance imaging of the brain were performed. Results. In patients with polycythemia vera and primary myelofibrosis, neuroimaging patterns are represented by small (up to 1.5 cm) post-infarction lesions in the brainstem, cerebellum, and cortex in adjacent perfusion territories after hemorheological microocclusive stroke. In patients with essential thrombocythemia, the neuroimaging pattern is more often represented by massive post-infarction changes in cortical-subcortical brain tissue with atherosclerotic lesions of the major head arteries, which appear to be atherothrombotic. Stroke preceded hematologic diagnosis in 30% of polycythemia vera cases, 40% of essential thrombocythemia cases, and 25% of primary myelofibrosis cases.

Introduction . Myeloproliferative neoplasms (MPNs) are a rare but significant cause of strokes. Aim . To describe risk factors for stroke development, as well as prevention strategies based on available literature data on patients with MPN. Main findings . Online databases (PubMed, E-Library) were searched for studies on cerebral thrombotic complications in the setting of myeloproliferative disorders. Induction of specific cytoreductive treatment with low doses of acetylsalicylic ac id should be considered as a mandatory component of secondary prevention of noncardioembolic stroke.

The development of National clinical guidelines on diagnosis and treatment of Ph-negative myeloproliferative neoplasms provides the knowledge basis for decision making in diagnosis, therapy, prevention, and rehabilitation in compliance with evidence-based medicine principles in order to ensure appropriate medical care in a particular clinical setting. The clinical guidelines underly the choice of optimal methods of diagnosis, therapy, prevention, and rehabilitation as part of a patient’s medical care, the development of criteria for the assessment of medical care quality, medical care standards, medical care procedures, setting standards on equipment and management of diagnostic and therapeutic procedures, and provision of continuous medical education and advanced training for healthcare professionals. In 2013, a working group was formed to develop and formulate clinical guidelines on the treatment of myeloproliferative neoplasms. These guidelines were first published in 2014, afterwards they were revised and republished. The dynamic development of current hematology presupposes constant updating of knowledge and implementation of new diagnosis and treatment methods in clinical practice. In this context, clinical guidelines present a dynamic document to be continuously amended, expanded, and updated in accordance with scientific findings and new requirements of specialists who are directly involved in treatment activities. The present edition is an upgraded version of clinical guidelines with updated information on classification, diagnosis, prognosis, current methods of therapy, and their efficacy and tolerability assessment. The guidelines are intended for oncologists, hematologists, healthcare executives, and medical students.

The article is devoted to the study of the role of microRNAs in the progression of atherosclerotic cerebrovascular pathology. The work includes the results of a clinical and laboratory examination of 80 people with cerebrovascular pathology and atherosclerotic lesions of the brachiocephalic arteries, who were divided into two groups according to the degree of stenosis of the internal carotid artery: less than 50% (n=36) and more than 50% (n=44). Real-time PCR was used to quantify the selected panel of microRNA in all patients (hsa-miR-126-5p, hsa-miR-126-3p, hsa-miR-29-5p, hsa-miR-29-3p, hsa-miR-33a-5p, hsa-miR-33a-3p, hsa-miR-21-5p, hsa-miR-21-3p). Bioinformatic tools were used both for selection (using databases for predicting potentially significant microRNAs) and for evaluating the association of selected microRNAs with clinical data on the progression of atherosclerosis (bioinformatic analysis and visualization of the results were performed using the R programming language version 4.0.5 (2021-03-31). Based on a bioinformatic study on the prediction of microRNAs, 8 potentially significant microRNAs associated with the progression of atherosclerosis were selected, the expression level of which can and is available to determine in a clinical laboratory. The result of the study of patients with varying degrees of cerebral atherosclerosis was the description of the expression microRNAs pattern associated with various pathogenetic stages of atherogenesis. The demonstrated patterns determine the need for further investigation of the role of microRNAs in the progression of atherosclerotic cerebrovascular pathology, the expansion of the cohort of patients and the increased use of bioinformatic methods.

Atherosclerosis is a chronic inflammatory disorder which remains the main cause of cardiovascular morbidity and mortality, with carotid atherosclerosis (CA) being a major cause of ischemic stroke. Epigenetic regulation plays a significant role in CA progression and stroke, yet the impact of circulating microRNA expression, associated with atherogenesis, has not been clearly defined. We included 81 patients with moderate–severe CA (mean age 67 ± 7 years, 53% male), 42% of whom had prior ipsilateral ischemic stroke (i.e., were symptomatic). A total of 24 miRs were identified and their plasma expression levels were measured. We observed that several microRNAs were up-regulated in stroke survivors, namely miR-200c-3p (30.6 vs. 29.7, p = 0.047), miR-106b-3p (31.01 vs. 30.25, p = 0.004), and miR-494-5p (39 vs. 33, p < 0.001), while others (miR183-3p [25.5 vs. 28.6, p < 0.001], miR-126-5p [35.6 vs. 37.1, p = 0.03], and miR-216-3p [12.34 vs. 16.2, p < 0.001]) had lower plasma levels in symptomatic patients. In a multivariable logistic regression model for symptomatic CA, the only miRs showing statistical significance were miR-106b-5p, miR-183-3p, miR-216-3p, and miR-494-5p. Cluster analysis demonstrated differential miR expression in CA patients depending on their stroke status. Epigenetic modulation, represented as complex interplay between circulating miRs of different atherogenic potential, may play a significant role in CA development and progression. In our study, we show possible candidates for future research regarding CA and stroke.

Эссенциальная тромбоцитемия (ЭТ) – редкое заболевание крови, связанное с различными тромбогеморрагическими осложнениями. Представлен клинический случай пациентки с ЭТ, открытым овальным окном, на фоне которых развились транзиторные ишемические атаки. Как при ЭТ, так и приоткрытом овальном окне могут присутствовать сопутствующие факторы риска развития тромбозов различных локализаций, в том числе артерий головного мозга, которые подтверждают необходимость проведения детального скрининга у пациентов молодого возраста в данной когорте. Essential thrombocythemia (ЕТ) is a rare blood disorder associated with various thrombotic events. We present a clinical case of a female patient with ET, a patent foramen ovale, and transient ischemic attacks. In both ET and a patent foramen ovale, there may be concomitant risk factors for the development of thrombosis in various locations, including cerebral arteries. This highlights the need for detailed screening in young patients in this cohort.

Backgrounds and Purpose: Post-COVID syndrome is characterized by persistent symptoms, including fatigue and cognitive impairment. These symptoms may be experienced by up to 80% of patients. We aimed to identify possible patterns of brain activation underlying post-COVID fatigue. Methods: The study used functional MRI (Siemens MAGNETOM Prisma 3T scanner with a specially created protocol) of the brain in 30 patients with post-COVID fatigue syndrome and 20 healthy volunteers. Task functional MRI (fMRI) was performed using a cognitive paradigm (modified Stroop test). Eligible patients included adults aged 18–50 years with a >12 weeks before enrolment (less than 12 months) prior history of documented COVID-19 with symptoms of fatigue not attributable to any other cause, and with MFI-20 score > 30 and MoCA at first visit. Healthy control participants had no prior history of COVID-19 and negative tests for severe acute coronavirus respiratory syndrome with MFI-20 score < 30 and MoCA at first visit. Task fMRI data were processed using the SPM12 software package based on MATLAB R2022a. Results: Cognitive task fMRI analysis showed significantly higher activation in the post-COVID group versus healthy volunteers’ group. Between-group analysis showed significant activation differences. Using a threshold of T > 3 we identified eight clusters of statistically significant activation: supramarginal gyri, posterior cingulate cortex, opercular parts of precentral gyri and cerebellum posterior lobe bilaterally. Conclusions: Post-COVID fatigue syndrome associated with subjective cognitive impairment could show changes in brain functional activity in the areas connected with information processing speed and quality.

Aim. To study the features of post-COVID asthenic syndrome and evaluate the effectiveness of the drug containing the succinic acid complex with trimethylhydrazinium in its treatment. Materials and methods. A prospective, multicenter, comparative, randomized, double-blind, placebo-controlled study of the efficacy of sequential therapy with BRAINMAX included 160 patients with a history of coronavirus infection within 12 to 16 weeks (not more than 12 months). The study was conducted at 6 healthcare centers in different regions of the Russian Federation. Testing was performed on the following scores: VAS for headache score, MFI-20 asthenia score, PSQI test, FAS-10 fatigue score, DHI dizziness score, MoCA cognitive impairment score, Beck anxiety score, vegetative index of Kerdo. Results. PSQI questionnaire showed significant improvement in sleep quality in the study group: by -2.5 points [-4; -1] (p0.001); there was a more pronounced significant decrease in the MFI-20 score of -19.5 points [-27; -11] (p0.001); a significant decrease in the FAS-10 fatigue score by -9 [-13.5; -4] points (p0.001); DHI dizziness score showed a decrease by -6 [-12; 0] points in the BRAINMAX group (p=0.001); the score of Beck anxiety and depression scale decreased by -5 [-11; -2] points (p0.001). Multiple linear regression data showed a significant increase of 0.56 (p=0.02) in the MoCA score. Conclusion. Our study convincingly showed the effectiveness of therapy with BRAINMAX in a wide range of symptoms in patients with the post-COVID syndrome.

Carotid atherosclerosis is a significant cause of cerebrovascular disease. However, with many candidate markers, precise assessment of its development and progression risks is still limited. This paper reviews state-of-the-art concepts of microRNA as an atherogenesis biomarker throughout various stages including endothelial dysfunction, cholesterol/lipid metabolism, inflammation, oxidative stress, angiogenesis regulation, and proliferation and migration of vascular smooth muscle cells. Based on the available literature, we have described most significant microRNAs for each stage characterized in brief. We have visualized interactions between microRNAs and validated target genes with MIENTURNET and suggest and justify a set of microRNAs for further pilot studies of carotid atherosclerosis.

Background and purpose: to assess executive network using resting-state fMRI and patterns of brain activation using task fMRI with a cognitive paradigm, against the background of taking the drug in comparison with placebo in patients with post-COVID asthenic syndrome.Methods: The study employed a prospective, randomized, double-blind, placebo-controlled trial approach to assess the efficacy of utilizing functional MRI of the brain as a neuroprotective therapy for treating patients with chronic fatigue syndrome following COVID-19. The study included 30 patients matched by sex and age with post-COVID asthenic syndrome. All patients were examined with MFI-20, MoCA, FAS-10 scales, MRI using a Siemens MAGNETOM Prisma 3 T scanner before and after a course of therapy with coordination complex with succinate acid anion (CCSA) or placebo (15 patients each) using resting state fMRI and with cognitive paradigm.Results: The changes obtained as a result of the treatment of post-Covid asthenic syndrome demonstrated clinical superiority in the reduction of asthenic symptoms for the group of patients treated with CCSA (MFI-20 scores:-20.0 points in the CCSA group compared to-12 points in the placebo group, p = 0.043). The data obtained also correlate with the analysis of task fMRI and resting state fMRI may indicate an increase in the functional cognitive status after a course of therapy with CCSA. Clinically, this correlates with a statistically significant improvement in the MoCA score (2 points in the CCSA group compared to 1 point in the placebo group, p < 0.05).Conclusions: the study demonstrates the potential effectiveness of CCSA therapy in relation to a wide range of symptoms (chronic fatigue syndrome/ asthenic syndrome and cognitive impairment) in patients with post-COVID syndrome. The first time demonstrated the effectiveness of neuroprotective therapy after post-COVID asthenic syndrome with the use of high-tech neuroimaging techniques.

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 (<1.8 mmol/L). Patients with CA had relatively favorable LDL levels with a median of 2.0 mmol/L. Both miR-33a-5p and miR-33a-3p levels were lower in patients with less than targeted LDL levels (37.4 and 38.3 vs. 41.8 and 42.5 respectively, p < 0.05). A significant positive correlation between expression levels of miR-33a-5p/3p and degree of carotid stenosis was found (r = 0.44 and r = 0.38 respectively, p < 0.05). In a univariate linear regression model miR-33a-3p/5p was positively associated with LDL cholesterol (p = 0.02). miR-33a up-regulation is associated with CA and may, in fact, be a key player by targeting cholesterol metabolism. A decrease in LDL cholesterol (<1.8 mmol/L) corresponded to lower levels of miR-33a, yet the direction and causality of this association remains unclear.

— Ischemic brain lesions are often observed in myeloproliferative disorders (MPDs), which are rare hematological pathologies and are commonly associated with an increase in the number of blood cells. A study was made to identify potential clinical and laboratory markers of vascular ischemic changes in brain matter in MPD patients. The study included 80 patients with an established diagnosis of MPD and no indication of past ischemic or hemorrhagic stroke in the history. A set of main factors associated with asymptomatic ischemic lesions of the brain in the MPD patients was found to include the age; cerebral atherosclerosis; and elevated levels of red blood cells, hemoglobin, hematocrit, and fibrinogen. Their predictive potential with respect to ischemic stroke should be evaluated in further prospective studies.