The possibilities of antithrombotic therapy to prevent thromboembolic events in non-valvular atrial fibrillation (AF) have substantially expanded after the design and clinical introduction of direct oral anticoagulants (DOACs). The start of clinical use of these agents has opened a new page in oral anticoagulant therapy for the prevention of thromboembolic events in AF. Dabigatran etexilate is the first DOAC that underwent clinical trial registration 6 years ago. After completion of the RE-LY  trial, the positive safety and efficacy profile of dabigatran has been confirmed over the last 6 years of its clinical use in actual practice in more than 250 thousand patients in nearly 100 countries around the world. The risk of ischemic stroke, intracranial and intracerebral hemorrhages, and death was shown to be simultaneously statistically significantly lower only in the dabigatran 150 mg group than in the warfarin group. The rate of major bleeding and all bleedings requiring hospitalization and that of myocardial infarction were comparable. Massive gastrointestinal bleeding (GIB) was more commonly recorded in the patients taking dabigatran; the RE-LY  trial investigating the reduced dabigatran dose used in Europe and Russia has shown that it may be used in a group of patients at higher bleeding risk.

The results of the investigation in the Medicare system have indicated that treatment with dabigatran 150 mg versus rivaroxaban reduces the risk of intracranial hemorrhage by 40%, major hemorrhage by 33%, and massive GIB by 39%. Thus, dabigatran demonstrates a favorable benefit-risk ratio in real world practice and requires no additional modifications in the current instruction and recommendations for its use.

A protocol for EEG biological feedback (BFB) at infra-low frequencies (<0.01 Hz) corresponding to those of the brain default mode network has been devised in recent years.

Objective: to evaluate the therapeutic features of an EEG BFB technique in the rehabilitation of patients with a decreased level of consciousness.

Patients and methods. The study included 11 patients with a decreased consciousness level (Glasgow coma scores of 7.4±2.5).  The patients were examined using the specialized clinical scales before and every 3 weeks during BFB therapy (5 BFB sessions per week).

Results. According to the neuropsychological scales, the patients' level of consciousness and mental activity were noted to become obviously increased just after 3 weeks of therapy, which was observed until the neurorehabilitation course was completed.

Conclusion. The minimally conscious patients using EEG BFB showed a significant clinical improvement. The infra-low frequency EEG BFB method deserves attention as a promising tool for increasing the patients' level of consciousness in accessible form.

Objective: to provide a dynamic assessment of cognitive functions in hypertensive patients in relation to the cerebral perfusion reserve and passive transmembrane ion transport velocity.

Patients and methods. The investigation enrolled 79 hypertensive patients (the mean age at the start of examination was 54 years), including 44 women (mean age, 58±16.2 years) and 35 men (mean age, 60±9.8 years). During a screening, the mean duration of hypertension was more than 5 years in 60% of the patients and less than 5 years in 40%. 55% of the patients had adequate antihypertensive therapy and normal blood pressure (BP) (<140/90 mm Hg), 45% were not on this therapy and they failed to achieve normal BP. The investigators evaluated a variety of factors, such as gender, age, BP, duration of hypertension, indicators of cerebrovascular reactivity (CVR), and levels of passive transmembrane ion transport, by using a model of Na+-Li+  countertransport (NLCT)  in the erythrocyte membrane as an example.

Results. Some risk factors were ascertained to influence cognitive functions in hypertension, but to a greater extent on CVR values in different vascular beds. A correlation was found between CVR and genetically determined NLCT velocity.

Conclusion. The indicators CVR and NLCT may be used as predictors for the development and progression of vascular cognitive impairment.

Objective: to study of the emotional features in patients with myasthenia.

Patients and methods. 52 myasthenic patients (11 men and 41 women; mean age, 50.5±13.8 years) were examined. The investigators determined the level of situational and personal anxiety (SA and PA) by the Spielberger-Hanin questionnaire and that of depression by the Zung scale. They  clarified the association of these indicators with gender, age, myasthenia duration and severity by the Myasthenia Gravis Foundation of America (MGFA) scale, and with the presence of crises.

Results and discussion. The patients with myasthenia showed a higher level of SA than those with depression. There was an increase in the indicators depending on age and disease duration and severity according to the MGFA scale, and on the group of disability. A number of patients who were critically ill and had high MGFA scores were noted to have low PA levels, which may contribute to the decreased level of protective psychological mechanisms.

Conclusion. Most myasthenic patients have high levels of anxiety. In these patients, the absence of depression or the presence of its mild form and the prevalence of anxiety determine the choice of therapy with a preference being given to psychotherapy.

Objective: to investigate the impact of anticoagulant therapy on the indicators of arterial stiffness and endothelial dysfunction (ED) in patients with atrial fibrillation (AF) after cardioembolic stroke (CES).

Patients and methods. The investigation enrolled 93 patients with AF after CES. The patients were divided into two groups: a study group in which all patients (n=48) received anticoagulants and a comparison group (n=45) in which the patients did not take anticoagulants, although the latter had been prescribed. The follow-up duration was 180.5±5.5 days. During this time the patients visited their doctors twice: the first visit was at baseline, the second one was after 24 weeks.

All the patients underwent three-dimensional sphygmography. The levels of glucose, creatinine, total cholesterol, high-density lipoproteins, and triglycerides were determined. The markers of endothelial function, such as von Willebrand factor, plasminogen, antithrombin III,  and tissue plasminogen activator inhibitor-1, were estimated.

Results. All the patients in the study and comparison groups had a higher comorbidity index of obvious somatic pathology. The patients from both groups showed changes in all cardiac morphometric and functional parameters. It was noted that after 6 months of a follow-up, there was a statistically significant positive trend in the indicators of arterial stiffness in the patients taking anticoagulants. The study group showed a significant correlation of blood pressure with the argumentation index. The 6-month follow-up revealed a strong correlation between the cardioankle vascular index and all the indicators of ED in the study group. After 24 weeks, in both groups there were 12 (12.9%) deaths: 3 (6.25%) and 8 (17.8%) in the study and comparison groups, respectively.

Conclusion. The findings suggest that in patients with AF after CES, the indicators of arterial stiffness and endothelial function tend to improve during anticoagulant therapy.

Neurological disorders in hypertensive patients can be caused by both brain injury and concomitant diseases. The elucidation of the causes of neurological disorders and their effective treatment contribute to hypertensive patients’ better adherence to long-term antihypertensive therapy, which normalizes blood pressure (BP) and reduces the risk of cerebral complications Objective: to study of the causes of neurological disorders in hypertensive patients and the efficiency of their correction using a new dispersible vinpocetine formulation (Cavinton® Comforte) in combined therapy.

Patients and methods. A total of 80 patients (men (20%) and women (80%); mean age 63±12.3  years) with neurological complaints in the presence of hypertension were examined. All the patients were diagnosed with dyscirculatory encephalopathy or chronic brain ischemia, whether they had vascular cognitive impairment. The examination of patients revealed that the neurological complaints were mainly due to concomitant diseases, such as migraine (12%), tension-type headache (66%), and the latter concurrent with migraine (4%).

Results and  discussion. The  effective treatment of concomitant diseases in  combination with antihypertensive therapy contributed to normalization of BP and regression of complaints. The most pronounced effect was noted in 40 patients whose combination therapy included Vinpocetine (Cavinton® Comforte) 10 mg thrice daily.

Conclusion. The therapy resulted in the less severity of both the symptoms of cerebrovascular disease (vascular cognitive impairment) and comorbid neurological disorders (headache, dizziness, etc.).

The efficacy of ethylmethylhydroxypyridine succinate (EMHPS)  depends on the concentration and activity of proteomic proteins. To provide the body with magnesium and pyridoxine is an important condition for the efficacy of EMHPS because these micronutrients are essential for maintaining neuronal function.

Objective: to analyze the biological effects of pyridoxineand magnesium-dependent proteins providing the molecular mechanisms of multi-targeted action of EMHPS,  pyridoxine, and magnesium.

Material and methods. Proteins that interact with both pyridoxine and magnesium were found in the genomic and proteomic databases. A list of 78 vitamin B6-dependent proteins, which is based on the available human genome records in NCBIPROTEIN, EMBL,  UNIPROT,  and HumanProteomeMap databases, was analyzed using a functional binding assay. The same assay was also applied to analyze a list 720 magnesium-dependent proteins.

Results. The analysis has shown that 78 pyridoxine-dependent proteomic proteins are necessary for: 1) the synthesis and processing of amino acids; 2) cell energy metabolism (ATP synthesis), and 3) the synthesis of neurotransmitters and neuronal membranes. MexiB 6 has numerous synergistic interactions between the molecules of EMHPS,  pyridoxine, and magnesium. The combination of the components of EMHPS,  pyridoxine and magnesium in MexiB 6 (triple synergism) allows prediction that the drug has more pronounced clinical effects than the molecules of EMHPS,  which emerges in its antihypoxic and antioxidant activities, the improvement of synaptic transmission of a signal, the neutralization of homocysteine, and the regulation of lipid and carbohydrate metabolism (restoration of cell sensitivity to insulin and carbohydrates in patients with atherosclerosis and in those at risk for diabetes mellitus or obesity). Pyridoxineand magnesium-induced potentiation of the effects of EMHPS may enhance its activity.

Excessive daytime sleepiness (hypersomnia) is one of the clinically important, but inadequately studied symptoms of Parkinson’s disease (PD). It manifests as constant excessive sleepiness during the day and/or short unexpected (unintentional) naps. Hypersomnia negatively affects quality of life in patients; it is potentially dangerous in the situations requiring greater attention. The paper presents current approaches to diagnosing hypersomnia in PD. It discusses the multifactorial nature of its pathophysiology in patients with PD. The present-day ideas about the relationship of hypersomnia to degeneration of the brain structures involved in the regulation of sleep and wakefulness, to nocturnal sleep disorders and dopaminergic therapy are described. The paper gives the results of experimental and clinical studies confirming the role of circadian mechanisms in the manifestation of insomnia and hypersomnia in PD patients. It describes a clinical case of a patient with moderate motor and cognitive impairments, in whom hypersomnia is a leading factor in deteriorating daily life. The possible role of circadian disturbances in the development of hypersomnia and related mild manifestations of insomnia and parasomnia is discussed. A clinically significant effect in treating sleep and wakefulness disorders has been achieved in the prolonged use of melatonin and cognitive-behavioral therapy.

The paper provides a review of the works in which functional transcranial Doppler ultrasound is used in different areas of neurocognitive studies. It discusses the advantages and disadvantages of the technique in solving theoretical and practical problems and prospects of its use.

The paper considers the relationship between pain threshold and blood pressure (BP) in acute and chronic pain syndrome. Both experimental and clinical studies have established that elevated BP is accompanied by a higher pain threshold in acute pain (hypertension-related hypoalgesia). Epidemiological findings have shown that the prevalence of different pain syndromes is significantly lower in hypertensive patients than in individuals without hypertension. At the same time, there is evidence that elevated BP can, on the contrary, reduce pain thresholds and make prognosis worse in patients with chronic pain syndromes.

The review presents clinical and experimental data on the interaction between the nervous and immune systems during various systemic and inflammatory processes. It reflects the specificity of immune surveillance in the structures of the nervous system. The structural characteristics and varieties of S100 protein are shown. The role of S100 calcium-binding proteins as mediators of an inflammatory response and their participation in the mechanisms of pain syndrome are reflected.

Higher anxiety results in the decreased levels of various neurotrophic factors and enkephalins and in impaired production of proinflammatory cytokines. The anxiolytic etifoxine is used to treat anxiety states and adjustment disorders. Etifoxine modulates the GABAergic transmission and metabolism of neurosteroids. The latter determines the unique neurotrophic and neuroprotective properties of the drug, such as increased expression of neurotrophic factors, regeneration of nerve fibers, and preservation and regeneration of myelin sheaths. Other important pharmacological effects of an etifoxine molecule have been also discovered; these are to relieve allodynia related to 3α-steroids and GABA receptors and to effectively treat cerebral edema, experimental autoimmune encephalitis, and excessive nervous excitability in the presence of alcohol withdrawal. In addition, the chemoreactome simulation of the molecule of etifoxine has established that its attenuated side effects are due to its lower interaction with serotonin, acetylcholine, adrenergic and other neurotransmitter receptors than is shown by benzodiazepines. Etifoxine has been also found to have anti-inflammatory (due to antihistamine and antileukotriene effects) and antitumor activities and an ability to affect hemodynamics and vessel walls.

The paper presents a systematic analysis of the results of trials of the neurotrophic properties of etifoxine. It considers how the drug stimulates the expression of neurotrophic factors, accelerates the maturation and regeneration of nerve fibers, and regenerates myelin sheaths.

The neurotrophic effects of etifoxine along with its anxiolytic activity will accelerate the recovery of patients with different neurological diseases and enhance the quality of their neurorehabilitation.

Poststroke spasticity is common in many patients and frequently hampers the recovery of lost motor functions. Therapeutic exercises and a gradual increase in motion loads and social and daily living activities play a leading role in the treatment of spasticity. Botulinium toxin type A is recognized to offer a highly effective and safe treatment for poststroke spasticity, as confirmed by clinical trials conducted in accordance with the principles of evidence-based medicine. The application of a personalized poststroke rehabilitation program permits the maximum result to be achieved in a considerable number of patients. The paper reviews the literature on spasticity and a clinical case that demonstrates an individual approach to treating poststroke spasticity.

Multiple sclerosis (MS) is the most common and potentially disabling disease of the central nervous system in young people. Not only inflammatory, but also neurodegenerative processes are involved in the pathogenesis of MS. The use of MS-modifying drugs (MSMDs)  has led to a substantial reduction in the frequency of MS exacerbations and to the slower development of irreversible neurological deficit. Glatiramer acetate is one of the MSMDs of first choice and has a dual (anti-inflammatory and neuroprotective) action. The drug has proven to be effective and safe if administered long-term. Therapy with glatiramer acetate has been established to promote the production of anti-inflammatory cytokines and neurotrophic factors, which prevent the development of a degenerative process and stimulate remyelination, and to slow the progression of cerebral atrophy. Experimental findings suggest that the drug improves the processes of neurogenesis.

The efficiency of treatment is known to be associated with patient medication adherence. This largely depends on the frequency and route of drug administration and on the development of adverse events (AEs). To improve treatment adherence to glatiramer acetate, its new 40-mg formulation has been designed, which allows it to be administered only thrice weekly. The use of the formulation has demonstrated its efficacy and safety and resulted in a considerable reduction in the incidence rate of AEs.

Obstructive sleep apnea/hypopnea syndrome (OSAHS) is the most common type of sleep apnea. OSAHS is due to upper airway obstruction. This condition is characterized by repetitive pauses in breathing during sleep despite the efforts of the respiratory muscles and it is generally associated with decreased blood oxygen saturation. The review presents the data available in the literature on the intermediate phenotypes of OSAHS, in the development of which there may be a genetic component. It is stated that a study of the genetic basis for various OSAHS phenotypes will give a better insight into the contribution of genetic factors to the development of the disease. The review describes the genes responsible for a predisposition to the development of four major phenotypes of OSAHS. It characterizes two basic approaches to a molecular genetic study in OSAHS; these are a genetic association analysis and a linkage analysis. Taking into account the wide prevalence and social importance of OSAHS, the latter should be timely prevented and diagnosed. The adequate treatment of OSAHS and its consequences is able not only to reduce the risk of fatal complications of the disease, but also to completely eliminate its symptoms.

The principle in the accounting of a weak neurotransmitter component is considered as one of the most specific and promising ones for the study and practical introduction of therapy for postcomatous states. The paper outlines problems in the accurate determination of the lack and excess of neurotransmitters by up-to-date techniques (biochemical and neurophysiological tests, magnetic resonance spectroscopy). It gives the reasons for clinical doubts and difficulties in the practical use of ideas about the relationship of the clinical picture to one or another disorder of neurotransmitter metabolism and to the feasibilities of its effective correction. It is concluded that the main method for the individualized therapy of postcomatous states is the clinical analysis of neurological and psychiatric symptoms, only upon its completion, the consideration of a weak neurotransmitter component can be taken into account. The main possible and currently preferable ways to correct cholinergic and GABAergic deficiency and redundancy and deficiency in glutamate and dopamine are considered.

Early diagnosis of Alzheimer's disease (AD) is one of the most important tasks of modern medicine. Even before its obvious clinical symptoms develop, AD can be now identified from the data of functional neuroimaging, including that with the Pittsburgh compound, which can detect amyloid protein accumulation in the brain structures, and from those of an analysis of biomarkers in the cerebrospinal fluid. If there are clinical symptoms, a diagnosis can be established by the correct evaluation of mnestic disorders; the latter in BA are so-called hippocampal. Treatment for AD should be initiated as early as possible; methods for pathogenetic therapy are being actively developed. When treating AD, one should adhere to a comprehensive approach involving the use of drugs for basic symptomatic treatment and those enhancing its efficiency, and non-drug treatments (cognitive and motor training). It is important to timely identify and eliminate potentially reversible conditions and to work with caregivers and guardians.

The paper presents a review of an update on the comparative pharmacoeconomic analysis of using dimethyl fumarate in the treatment of multiple sclerosis (MS) in European countries. A pharmacoeconomic evaluation was made to study the use of first-line oral dimethyl fumarate versus another first-line oral teriflunomide in the treatment of MS in the Russian Federation (for 1 year) and second-line natalizumab and fingolimod. Among first-line oral drugs, dimethyl fumarate was shown to be superior to teriflunomide in a cost-effectiveness ratio and to be slightly ahead of the MS-modifying drugs (MSMDs)  and the second-line drugs natalizumab and fingolimod. According to clinical and economic indicators, dimethyl fumarate is the drug of choise among other MSMDs in the treatment of MS.

On March 20, 2016 Moscow hosted the Second Annual Interuniversity Scientific and Practical Conference on Psychosomatic Medicine in Russia: Advances and Prospects-2016", which was attended by more than 330 physicians from 19 cities and regions of Russia: psychiatrists, narcologists, psychotherapists, neurologists, internists, family doctors, cardiologists, hematologists, gastroenterologists, dermatologists, plastic surgeons, beauticians, dentists etc.