Federal Center of Brain Research and Neurotechnologies

The emergence of SARS-CoV-2 and its worldwide spread has become a challenge for healthcare professionals related to rapid diagnosis of infection caused by the new coronaviruses, provision of specialized medical care, rehabilitation and secondary prevention. Currently, there is limited information on primary, secondary prevention and medical rehabilitation of this disease. The most common clinical manifestation of the new variant of coronavirus infection is bilateral pneumonia, with 34% of patients developing acute respiratory distress syndrome (ARDS). Given the unusual pandemic situation and the peculiar COVID-19 pathogenesis, the stereotyped application of generally accepted methods may be unsafe or ineffective. The Union of Rehabilitologists of Russia has prepared Temporary guidelines that are based on the advice on medical rehabilitation of patients with COVID-19 at various stages of special medical care published by WHO specialists, analysis of reports from clinics currently involved in rehabilitation of COVID-19 patients, as well as on the results of clinical studies conducted earlier on the rehabilitation of patients with Post-intensive care syndrome and adult respiratory distress syndrome (ARDS) of non-coronavirus etiology, regulatory documents of the Russian Ministry of Health and Federal Service on Surveillance for Consumer rights protection and human well-being. A syndrome-based approach to the use of means and methods of physical and rehabilitation medicine is also considered. The guidelines are intended for heads of medical organizations and their structural divisions, general practitioners, physicians, infectious disease doctors, pediatricians, emergency physicians of intensive care units in infectious hospitals, physiotherapy and sports medicine doctors, physiotherapists, medical psychologists, physical therapy instructors, nurses and other specialists of multidisciplinary rehabilitation teams working in the field of medical care for patients with COVID-19 at various stages.

We reviewed the role of oxidative stress (OS) in the pathogenesis of ischemic (IS) and hemorrhagic stroke (HS). OS plays a major role in programmed cell death, increased permeability of the blood-brain barrier, astroglial and microglial activation, and local inflammatory response. We also reviewed the current state of neuro- and cytoprotection studies and their translation in clinical practice. With respect to experimental and clinical data the efficacy of long term administration of multimodal cytoprotective drug with antioxidant effect - ethylmethylhydroxypyridine succinate (Mexidol) is discussed during the acute and early recovery period after stroke.

The expert consensus of the Russian communities discusses the issues of comprehensive medical rehabilitation of patients with coronavirus disease 2019 (COVID-19). COVID-19 is a contagious infectious disease that can cause pulmonary, cardiac, motor, metabolic, neurocognitive and mental disorders, that is, multiple organ dysfunction. COVID-19 survivors, especially after a severe clinical course, face serious psychological and physical problems, posttraumatic stress, cognitive dysfunction, nutritional deficiencies and exacerbation of concomitant chronic diseases. Some patients, regardless of the COVID-19 severity, have a long clinical course of the disease (“chronic-COVID”, “long COVID”). There is evidence of post-acute COVID-19 syndrome. In this regard, patients after COVID-19 will need rehabilitation measures. The expert consensus of the Russian communities presents general principles, stages and aspects of medical rehabilitation after COVID-19, indications and contraindications for rehabilitation interventions. The paper includes recommendations on comprehensive cardiac and pulmonary rehabilitation, as well as specifics of rehabilitation care for different COVID-19 courses within the national three-stage rehabilitation system.

Patients with a new coronavirus infection (COVID-19) need rehabilitation. Rehabilitation approaches of patients with another pathology also require to be reviewed under the conditions of the SARS-CoV-2 epidemic. It is necessary to develop clinical recommendations for the rehabilitation care delivery in patients with COVID-19 and other diseases during a pandemic. A group of experts analyzed the data of current reviews on rehabilitation with COVID-19, as well as previous studies on rehabilitation in patients with Post-intensive care syndrome (PICS) and acute respiratory distress syndrome of non-coronavirus etiology, and developed thereupon the main positions of clinical recommendations. We discuss the main rehabilitation problems in patients with COVID-19, in particular structures and functions impairments, leading to limitations and restrictions of self-care, mobility, domestic life, communication, interpersonal interactions and relationships, professional activities and those determining care requirement. The article also provides general recommendations on medical rehabilitation management in a pandemic at all three stages, including patients routing, ensuring the infectious safety of medical personnel and patients. The necessary individual rehabilitation program components for patients with COVID-19 at all stages of rehabilitation have been identified, including patients examination, nutritional deficiency correction, restoration of respiratory function, exercise tolerance, muscle strength, self-monitoring and training in new movement conditions, psychoemotional state disorders and cognitive functions, as well as independence in everyday life recovery. Medical rehabilitation during the COVID-19 epidemic should include all rehabilitation care components and helps to optimize vital functions, to prevent complications and to improve the patients life quality.

The blood-brain barrier (BBB) regulates the exchange of metabolites and cells between the blood and brain, and maintains central nervous system homeostasis. Various factors affect BBB barrier functions, including reactive oxygen species (ROS). ROS can act as stressors, damaging biological molecules, but they also serve as secondary messengers in intracellular signaling cascades during redox signaling. The impact of ROS on the BBB has been observed in multiple sclerosis, stroke, trauma, and other neurological disorders, making blocking ROS generation a promising therapeutic strategy for BBB dysfunction. However, it is important to consider ROS generation during normal BBB functioning for signaling purposes. This review summarizes data on proteins expressed by BBB cells that can be targets of redox signaling or oxidative stress. It also provides examples of signaling molecules whose impact may cause ROS generation in the BBB, as well as discusses the most common diseases associated with BBB dysfunction and excessive ROS generation, open questions that arise in the study of this problem, and possible ways to overcome them.

Abstract Neurons are highly vulnerable to conditions of hypoxia-ischemia (HI) such as stroke or transient ischemic attacks. Recovery of cognitive and behavioral functions requires re-emergence of coordinated network activity, which, in turn, relies on the well-orchestrated interaction of pyramidal cells (PYRs) and interneurons. We therefore modelled HI in the mouse hippocampus, a particularly vulnerable region showing marked loss of PYR and fast-spiking interneurons (FSIs) after hypoxic-ischemic insults. Transient oxygen-glucose deprivation (OGD) inex vivohippocampal slices led to a rapid loss of neuronal activity and spontaneous network oscillations (sharp wave-ripple complexes; SPW-Rs), and to the occurrence of a spreading depolarization. Following reperfusion, both SPW-R and neuronal spiking resumed, but FSI activity remained strongly reduced compared with PYR. Whole-cell recordings in CA1 PYR revealed, however, a similar reduction of both EPSCs and IPSCs, leaving inhibition-excitation (I/E) balance unaltered. At the network level, SPW-R incidence was strongly reduced and the remaining network events showed region-specific changes including reduced ripple energy in CA3 and increased ripple frequency in CA1. Together, our data show that transient hippocampal energy depletion results in severe functional alterations at the cellular and network level. While I/E balance is maintained, synaptic activity, interneuron spiking and coordinated network patterns remain reduced. Such alterations may be network-level correlates of cognitive and functional deficits after cerebral HI.

Background. The International Classification of Functioning, Disability and Health (ICF) is a universal system for assessing the health of the body as a whole, as well as problems that limit life. Using the ICF, it is possible at the level of the body, personality and society to quite accurately investigate the nature and severity of disabilities. Subsequently, this will make it possible, on a scientific basis, to substantiate the need and volume of rehabilitation measures and social protection. For medical professionals, one of the main criteria for using the ICF is the ability to formulate a rehabilitation diagnosis, which in turn makes it possible to determine the goal, objectives, rehabilitation program, and in the future to assess the effectiveness of rehabilitation measures. In the formulation of a rehabilitation diagnosis, the coding for the ICF domains is used. Rehabilitation diagnosis is a description of structural and functional disorders that have arisen in a patient as a result of a stroke, which entailed a restriction of activity and participation, the possibility of using environmental factors that may facilitate or hinder the performance of the described functions by the patient. Clinical case description. The patient, 65 years old, was admitted to the rehabilitation department with complaints of decreased muscle strength, instability when walking, limited mobility, dizziness, impaired pronunciation of words. Directional diagnosis: Ischemic stroke. After the rehabilitation diagnosis was made, the patient had an average rehabilitation potential and a relatively favorable prognosis. During rehabilitation, medical treatment, individual sessions with a psychologist, methods of rehabilitation of violations of regulatory functions, etc. were used. Upon discharge, the evaluation of the scales revealed the positive dynamics of the medical rehabilitation. Conclusion. The ICF evaluates all components of a post-stroke patient's health. The ICF is used in the preparation of a rehabilitation diagnosis and justifies the use of methods of medical rehabilitation. Formation of a rehabilitation diagnosis based on the principles of ICF is a key point in determining short-term and long-term goals for the patient, as well as assessing the rehabilitation potential and prognosis, drawing up an individual plan for medical rehabilitation and further recommendations upon discharge. Our experience of rehabilitation in the post-stroke period has shown that the use of the international classification of functioning in the formulation of a rehabilitation diagnosis in this category of patients allows for a higher efficiency of medical rehabilitation in general.

We review the current and emerging topics in ischemic stroke (IS) and intracerebral hemorrhage (ICH). We discuss the association of genetic predisposition and healthy lifestyle, ambient particulate air pollution, weather parameters, variations in the anatomy of cerebral blood vessels, psychological stress, depression, insonmia with the development of IS or ICH. Also, the role of oral anticoagulants (AC) as a new risk factor for ICH is presented. The issues of pathophysiology of IS and ICH are considered, in particular, the discrepancy between blood flow and metabolism and penumbra stability in IS and changes in perfusion and cerebral blood flow (CBF) in stroke, autoimmune mechanisms of brain damage. Widening of therapeutic window, introduction of new generation of thrombolytic medications, tele-thrombolysis and thrombolysis in mobile stroke units are discussed. In patients taking AC, the tactics of prescribing IIa and Xa factor blockers during telethrombolysis and thrombolysis are discussed. The issues of urgent correction of hemostasis in the development of ICH while taking AC, as well as the resumption of their use in the future, are considered. The issues of neuroprotection, including the combination of neuroprotection and telethrombolysis and thrombolysis, and the translation of experimental studies into clinical practice, as well as the implementation of immunomodulatory therapy are discussed.

Objective: to compare the results of staging the severity of viral pneumonia in patients with COVID-19 based on the results of chest computed tomography (CT) using the empirical visual scale CT 0–4 and chest CT severity score (CT-SS) point scale, as well as to assess their prognostic value. Material and methods. Chest CT scans and anamnestic data in patients hospitalized to a non-specialized center repurposed for the treatment of new coronavirus infection, were analyzed. Chest CT analysis was performed by two radiologists using CT 0–4 and CT-SS scales. Results. The time course of changes in the severity of lung parenchymal lesions, by using both scales, was found to be similar: the maximum magnitude of lung tissue changes was recorded on day 5 of the disease. In cases of death, there was a significantly more extensive lung parenchymal involvement at admission to the center than in recovered patients, which was also true for both CT data assessment systems. Bothscales demonstrated comparable diagnostic and prognostic value: there were no statistically significant differences in sensitivity, specificity, and predictive value of a fatal outcome. Both the CT 0–4 scales and the CT-SS are based on the estimation of the volume of the affected lung tissue, but when the CT 0–4 scale was employed, additional criteria were used in some cases: the presence of hydrothorax and the determination of the maximum score for the most affected lung. Not all patients with a pronounced CT picture of viral pneumonia had a fatal outcome, which may indicate the presence of other factors that increase its risk. Conclusion. Both CT 0–4 and CT-SS scales have similar predictive values. The greater severity of parenchymal damage assessed by these CT scales was associated with the higher mortality rate.

Objective. Evaluation of the comparative efficacy and safety of ethylmethylhydroxypyridine succinate therapy with Mexidol, solution for intravenous and intramuscular administration, 50 mg/ml, and Mexidol FORTE 250, film-coated tablets, 250 mg, during their sequential use in patients in the acute and early recovery periods of ischemic stroke (IS) compared to placebo. Material and methods. The clinical trial was conducted as a prospective international multicenter randomized double-blind placebo-controlled parallel-group trial. Data from the randomized patients in the acute and early recovery periods of ischemic stroke were collected at 4 visits. Patients were divided into two equal groups: the main group (standard therapy+Mexidol at a dose of 500 mg twice a day administered intravenously in 100—200 ml of 0.9% NaCl solution for 10 days, followed by Mexidol FORTE at a dose of 250 mg three times a day for 60 days) and the placebo group (standard therapy+placebo administered following the same scheme as the main group). The primary efficacy endpoint was the amount of change in patient status assessed with the Modified Rankin Scale (mRS) at the end of the therapy compared to the baseline level (measured in scores). Results. A total of 304 patients in the acute and early recovery periods of IS were randomized into the trial. The trial groups were matched for sex, age and anthropometric characteristics. The statistically significant differences confirming the efficacy of therapy with Mexidol were obtained. The Mexidol group showed a significant reduction in the degree of disability, according to the Modified Rankin Scale (mRS), a neurological improvement, according to the National Institutes of Health Stroke Scale (NIHSS), an increase in mobility, according to the Rivermead Mobility Index, and a strong tendency to the reduction of cognitive deficit, according to the Montreal Cognitive Assessment (MoCA). Statistically significant differences in favor of Mexidol compared to placebo were observed for the difference in median mRS scores at Visit 4 against the baseline level (p=0.003), the difference in median NIHSS scores (p<0.001) and in median Rivermead Mobility Index scores (p=0.014). Treatment with Mexidol was also associated with a reduction in the number of disabled patients (p=0.016) and an increase of patients with scores of 0—1 on the mRS at Visit 4 (p=0.002) when compared to placebo. Adverse events (AEs) were reported in 35 patients (23%) in the Mexidol group (42 AEs in total) and in 35 patients (23%) in the placebo group (43 AEs in total) (p=1.000). Conclusion. According to the clinical trial results, statistically significant differences were obtained, which confirm the greater efficacy of therapy using Mexidol compared to placebo in patients in the acute and early recovery periods of IS of moderate severity. This was observed in terms of reducing the degree of patients’ disability and the severity of neurological symptoms, in terms of improving motor capabilities and increasing mobility. A similar safety profile was demonstrated for the long-term sequential therapy with Mexidol and Mexidol FORTE 250 and placebo.

The aging of the population and the associated increase in the share of cognitive impairments in the structure of a wide range of diseases are a serious challenge for modern healthcare. Difficulties in the treatment of cognitive disorders are determined by many factors, including the age of patients, comorbidity, forced polypragmasia and the adequacy of the dosage of drugs that restore cognitive activity. The experts discussed information about the therapeutic potential of the drug Cerebrolysin in the treatment of cognitive disorders of various origins, stated significant experience of its effective and safe use in many clinical studies in mild and moderate forms of dementia. At the same time, there was a lack of consistent and systematic data on the dosage regimen, frequency, and duration of use of the drug in different forms of cognitive impairment and the degree of their severity. The aim of the international council of experts was to determine the optimal dosage regimens of the drug Cerebrolysin in patients with various etiologies and severity of cognitive impairment. The result of the work was the approval of a unified scheme for the use of the drug Cerebrolysin, considering the severity of the disease and its duration.

Hemianopia and unilateral spatial neglect are the most common visual-spatial disorders that occur after a right hemisphere stroke. Due to the similarity of their symptoms, health care professionals often need to establish a differential diagnosis between these two disorders. This article is the first part of the literature review and is devoted to the discussion of the phenomenology and diagnostic methods of homonymous hemianopia and neglect. For the first time in the Russian literature, the use of the eytracking method in patients with homonymous hemianopia and neglect is highlighted. The article also provides criteria for the differences between the two disorders. The article contains useful information for health care professionals to make an appropriate diagnosis, which implies subsequent rehabilitation procedures. Rehabilitation methods will be described in detail in the second part of the literature review.

Multimodal nonlinear microscopy combining third-harmonic generation (THG) with two- and three-photon-excited fluorescence (2PEF and 3PEF) is shown to provide a powerful resource for high-fidelity imaging of nucleoli and nucleolar proteins. We demonstrate that, with a suitably tailored genetically encoded fluorescent stain, the 2PEF/3PEF readout from specific nucleolar proteins can be reliably detected against the extranucleolar 2PEF/3PEF signal, enabling high-contrast imaging of the key nucleolar ribosome biogenesis components, such as fibrillarin. THG is shown to provide a versatile readout for unstained nucleolus imaging in a vast class of biological systems as different as neurons in brain slices and cultured HeLa cells.

Hyperuricemia is most often combined with lipid metabolism disorders, modifiable risk factors for coronary heart disease, stroke, abdominal obesity, type 2 diabetes mellitus, arterial hypertension, urolithiasis, chronic kidney disease. Current data indicate the presence of pro-inflammatory, pro-oxidant and vasoconstrictive effects of uric acid, which may contribute to the development of cardiometabolic disorders. Normal serum uric acid levels are 6 mg / dl (360 mmol / l) for women and 7 mg / dl (420 mmol / l) for men. Currently, the role of hyperuricemia as an independent biomarker of the risk of cardiovascular events is emphasized. Both gout and subclinical hyperuricemia are associated with unfavorable cardiovascular outcomes. Patients should be informed about the risk factors of hyperuricemia; the need for lifestyle modification, diet compliance, and correction of drug therapy for comorbid conditions. According to international and domestic recommendations, urate-lowering therapy is indicated for asymptomatic hyperuricemia (360 mmol / l) and high cardiovascular risk. The data available today allow us to consider the target serum uric acid level 5 mg / dl (300 mmol / l) for patients with high cardiovascular risk, including at least 2 of the following risk factors: hypertension, diabetes mellitus, dyslipidemia, stroke, heart attack, chronic disease kidneys, and 6 mg / dl for patients who do not have these risk factors. The urate-lowering drug is selected taking into account the concomitant pathology and the presence or absence of liver or kidney dysfunction. Xanthine oxidase inhibitors are still the first-line drugs for the correction of hyperuricemia. The superiority of xanthine oxidase inhibitors is due to the potential inhibition of the production of reactive oxygen species and their antioxidant effect. Treatment of gout is aimed at achieving clinical improvement in acute and chronic arthritis, preventing recurrence of arthritis and damage to internal organs, as well as reducing the risks of negative effects on comorbid pathology. Clinicians are faced with the task of controlling cardiovascular diseases in patients with asymptomatic hyperuricemia and gout. Further studies are needed to investigate the relationship between gout, hyperuricemia and increased risk of cardiovascular diseases, as well as to establish a more complete picture of the prevalence of a wide range of comorbid conditions.

Abstract Most of the motor mapping procedures using navigated transcranial magnetic stimulation (nTMS) follow the conventional somatotopic organization of the primary motor cortex (M1) by assessing the representation of a particular target muscle, disregarding the possible coactivation of synergistic muscles. In turn, multiple reports describe a functional organization of the M1 with an overlapping among motor representations acting together to execute movements. In this context, the overlap degree among cortical representations of synergistic hand and forearm muscles remains an open question. This study aimed to evaluate the muscle coactivation and representation overlapping common to the grasping movement and its dependence on the stimulation parameters. The nTMS motor maps were obtained from one carpal muscle and two intrinsic hand muscles during rest. We quantified the overlapping motor maps in size (area and volume overlap degree) and topography (similarity and centroid’s Euclidean distance) parameters. We demonstrated that these muscle representations are highly overlapped and similar in shape. The overlap degrees involving the forearm muscle were significantly higher than only among the intrinsic hand muscles. Moreover, the stimulation intensity had a stronger effect on the size compared to the topography parameters. Our study contributes to a more detailed cortical motor representation towards a synergistic, functional arrangement of M1. Understanding the muscle group coactivation may provide more accurate motor maps when delineating the eloquent brain tissue during pre-surgical planning.

Arterial hypertension (AH) is a leading risk factor for cardiovascular diseases including cerebrovascular complications. Strokes and/or vascular cognitive impairment (VCI) are considered as a clinical sign of brain damage as a target organ in hypertension. To identify and assess the severity of VCI, patients with hypertension should undergo a neuropsychological assessment. Neuroimaging confirm the vascular origin of cognitive impairment. Patient management should include antihypertensive therapy along with neuroprotection. Among different neuroprotective therapy, ethylmethylhydroxypyridine succinate (mexidol) is one of medication with serious evidence of clinical efficacy.

Despite the success of modern conservative therapy of severe spinal instability, surgical methods still retain their importance in the treatment of this pathology, but even the most successful operation may be in vain without subsequent adequate rehabilitation. This report summarizes the features of rehabilitation of patients after surgery for injuries of the cervical spine using methods and means of physiofunctional treatment.

One of the urgent problems of modern health care is Alzheimer's disease (AD) and its early diagnosis. This is due to the rapid global spread of AD, the lack of pathogenetic therapy, and the ability to stabilize the progression of cognitive impairment in the early stages of the disease. Currently, only an autopsy can confirm the diagnosis of AD with 100% reliability, and classical laboratory and instrumental methods of diagnosis verification are difficult to implement in routine clinical practice due to several limitations. That is why the study of new and available biomarkers identified in human bodily fluids is promising for the early diagnosis of AD. The review addresses the problem of AD verification using markers in human bodily fluids, which can be obtained in a non-invasive way. Potential biomarkers of AD in saliva, tear fluid, urine, and nasal secretion are reviewed, and their prognostic values as AD indicators in the early stage are evaluated.

The guidelines describe modern approaches to equipping and ensuring endoscopic examinations of the digestive and respiratory systems in accordance with the objectives of improving their quality, safety and efficiency. The focus is on improving endoscopic diagnostics of precancerous diseases and early cancer of the gastrointestinal tract and bronchi. Based on the analysis of evidence-based medicine data, modern conditions for equipping and ensuring endoscopic examinations from the minimum necessary to the expert level are provided, including conditions for integrating digital solutions into protocols and reports, including conditions for creating databases for artificial intelligence systems, as well as conditions for ensuring epidemiological safety in endoscopy. The guidelines are based on risk-oriented approaches and serve as a basis for an objective assessment and analysis of the risks of compliance of equipment and provision in endoscopy with modern requirements for the quality and safety of medical activities. The components of equipment and provision are presented in summary tables, which in practice can serve as checklists. Each component is also an evaluation parameter and can be assessed by qualitative (present or absent) and/or quantitative (% provision) indicators. The methodological recommendations are designed in accordance with the requirements of the current GOST R 6.30-2003: “Unified documentation systems. Unified system of organizational and administrative documentation. Requirements for the execution of documents” (updated on 05/25/2017), which states that this type of methodological product, based on positive experience, reveals the order and logic of setting up any methodology. The objectives of such documents include the promotion of the most effective and rational examples of practical actions applicable to a certain type of activity, according to which the terminology, style and volume of methodological recommendations are regulated.

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.