Primary progressive aphasia (PPA) is a heterogeneous group of neurodegenerative diseases related to focal degenerations of the brain and mainly manifested by a gradual loss of speech functions. This symptom is characterized by specific speech disorders. The article presents the etiopathogenic features of PPA, systematizes the clinical criteria for its diagnosis, and describes the modern neuroimaging characteristics of different types of PPA. The proposed PPA severity point scale allows clinicians to record the very early manifestations of aphasia. Modified scales, such as the Frontal Behavioral Inventory (FBI-mod) and the Clinical Dementia Rating (CDR), are also important for specifying the type of PPA.

Objective: to determine the impact of social support on the risk of stroke in an open population aged 25–64 years in Russia/Siberia.

Patients and methods. A random representative sample of a Novosibirsk population aged 25–64 years (657 men; mean age, 44.3±0.4 years; response rate, 82.1%; 689 women; mean age, 45.4±0.4 years; response rate, 72.5%) was examined within Screening III of the WHO MONICApsychological program. The screening program included: registration of sociodemographic data and determination of social support (the index of close contacts (ICC) and the social network index (SNI). The prospective follow-up study period was 16 years. The study identified the following end-point: new-onset stroke cases.

Results and discussion. The open population aged 25–64 years showed a low ICC in 62% of men and in 56.8% of women (χ2=22.603; df=2; p=0.0001) and a low SNI in 43.5% of men and in 33.9% of women (χ2=21.546; df=2; p=0.0001). During a 16-year follow-up, the risk of stroke in the people with a low ICC was 3.5 times higher for men (95% confidence interval (CI), 1.42–7.69; p<0.05), and that was 3.6 times higher for women (95% CI, 1.5–8.7; p<0.01). Over the same follow-up period, the risk of stroke in the patients having a low SNI was 3.4-fold higher for men (95% CI 1.28–5.46, p<0.001) and 2.3-fold higher for women (95% CI 1.18–4.49, p<0.05). Application of a multivariate model revealed an increase in the risk of stroke in people with a low level of social support: in men with an unfavorable family status, manual labor and in women with a low level of education.

Conclusion. Social support is a protective risk factor for stroke in both men and women.

Objective: to assess the structural and functional state of skeletal muscles in the hip, as well as changes in the content of the sarcomere cytoskeleton proteins titin and nebulin and their phosphorylation level in patients with chronic alcohol intoxication.

Patients and methods. Thirteen patients (4 men and 9 women; mean age, 38.9±9.9 years) with chronic alcohol intoxication were examined. The average duration of regular consumption of alcoholic beverages was 7.6±3.7 years. The mean amount of alcohol consumed per week was 48.2±13.1 units. A control group included 10 healthy volunteers matched for age and sex. A neurological examination was performed according to the generally accepted scheme. Laboratory tests involved blood biochemical analysis estimating the levels of liver enzymes, creatine phosphokinase (CPK), and insulin-like growth factor-1 (IGF-1). All the patients underwent hip magnetic resonance imaging (MRI), followed by assessment of the degree of muscle tissue damage and by determination of the volume of anterior and posterior thigh muscles. The content of titin and nebulin and their phosphorylation level were determined in the muscle tissue samples obtained by an open biopsy from the lateral head of the quadriceps femoris muscle.

Results and discussion. Four (30.8%) patients were found to have proximal leg muscle weakness; the degree of paresis was the same in the anterior and posterior thigh muscles. There was a significant increase in the plasma level of liver enzymes; the CPK level remained within the reference values; there was a tendency towards lower IGF-1 levels. Analysis of MRI data showed that 7 (53.8%) patients had fatty degeneration in the thigh muscles. Quantitative evaluation ascertained a significant symmetrical decrease in the volume of anterior thigh muscles and a tendency towards a symmetrical reduction in that in the posterior thigh muscle compared to the control. Analysis of the content of titin and nebulin in the lateral head of the quadriceps femoris muscle revealed a significant decrease in the percentage of nebulin (81.1%; p < 0.01) and intact titin-1 (T1) isoforms (83.6%; p < 0.01). The percentage of proteolytic titin-2 (T2) fragments in the muscle of patients did not differ significantly from that in the control group. Estimating the phosphorylation level of the structural muscle proteins showed no significant differences when compared to the control.

Conclusion. Anterior and posterior thigh muscle weakness should be considered as the main clinical manifestation of chronic alcoholic myopathy (CAM) in the absence of biochemical and neurophysiological markers of the disease. Lower extremity muscle MRI that can reveal a lower muscle volume concurrent with fatty degeneration is a non-invasive informative diagnostic technique for CAM. The pathogenesis of skeletal muscle atrophy in chronic alcohol intoxication involves the sarcomere structural proteins titin and nebulin, which regulate the interaction of the major contractile proteins actin and myosin, and whole muscle contraction.

The promising approaches to determining the rehabilitation potential of ischemic stroke (IS) patients include an assessment of the microstructural integrity of the brain matter by diffusion tensor imaging (DTI), the main indicator of which is fractional anisotropy (FA). The role of the intact hemisphere in the rehabilitation process after IS remains a controversial subject. The hypothesis for the investigation is that the development of a diffusion and perfusion model (DPM) based on the assessment of FA in combination with data on cerebral blood flow velocity (CBFV) and the impact of the focus will be able to predict the patients' neurological status by the end of the acute period of IS.

Objective: to investigate the role of diffusion and perfusion characteristics of the intact hemisphere in determining the rehabilitation potential in the acute period of IS and to develop a prognostic DPM.

Patients and methods. The investigation enrolled 100 patients with IS and 10 individuals in the control group. All the examinees underwent brain MRI. Perfusion-weighted sequence without bolus injection of a contrast agent was used to quantify CBFV in 10 areas according to the Alberta stroke program early CT score (ASPECTS). Values for FA in 10 areas of both hemispheres were calculated using DTI findings. Neurological and functional statuses were evaluated over time with the National Institute of Health Stroke Scale (NIHSS) and the modified Rankin scale.

Results. The NIHSS score at discharge was associated with FA and CBFV in 4 and 6 of the 10 areas of the intact hemisphere, respectively. DPM for predicting the rehabilitation potential included the key parameters correlating with a discharge NIHSS score (in order of decreasing the significance): admission NIHSS value (r = 0.55; p < 0.001), the size of a focus (r = 0.42; p < 0.001), FA in the contralateral cingulum bundle FA (r = -0.28; p = 0.007), and CBFV in M2 white matter [r = -0.24; p = 0.025; R2 = 0.642; p(F) <0.001].

Conclusion. In addition to the NIHSS score at admission, the size of a focus, DPM values (FA in the contralateral cingulum bundle and CBFV in the white matter) allow prediction of the rehabilitation potential in IS.

Complaints of dizziness are common in patients diagnosed with chronic cerebrovascular insufficiency (CCVI). Effective therapy of these patients is one of the most urgent problems of outpatient neurological practice.

Objective: to evaluate the efficiency and safety of long-term administration of vinpocetine (Cavinton Comforte) in the treatment of dizziness in patients with CCVI.

Patients and methods. A total of 139 patients took part in an open-label parallel-group clinical study. Vinpocetine (Cavinton Comforte) and vestibular exercises were prescribed in Group 1 (n=69); vestibular exercises were used in Group 2 (n=70). The efficiency of treatment was evaluated using a visual analog scale (VAS) in assessing vertigo and dizziness, the Dizziness Handicap Inventory (DHI), the Drug Attitude Inventory (DAI), the Montreal Cognitive Assessment (MoCA), the 5-point Likert scale, and videonystagmographic tests. Plasma brain-derived neurotrophic factor (BDNF) concentrations were analyzed before and after treatment. The total duration of the investigation was 8 months (6 months of therapy and 2 months of follow-up after therapy discontinuation).

Results and discussion. The administration of vinpocetine significantly decreased the subjective intensity of vertigo and dizziness (on the VAS) and improved daily activities in patients (on the DHI) and a number of parameters according to the video nystagmographic tests: pursuit and saccadic eye movement tests. According to the DNI scores, the improvement changes in the patients' condition significantly correlated with increased plasma BDNF expression throughout the follow-up (Pearson's correlation coefficient>0.5). The use of vinpocetine could improve cognitive functions (on the MoCA and the 5-point Likert scale) and increase patient adherence to the therapy performed (on the DAI). The clinically significant effect in improving the statodynamic function was shown by vinpocetine at 2 months of its administration and was highest at 5 months; there was a significant improvement in cognitive function at 6 months. The long-term use of vinpocetine was not associated with the risk of serious adverse events.

Conclusion. The findings allow vinpocetine to be recommended for long-term (at least 5 months) treatment of vertigo, dizziness, and cognitive impairment in patients with CCVI, in this case, the clinical effect is achieved through stimulating neuroplasticity, inducing BDNF synthesis in particular.

Objective: to evaluate the impact of surgical treatment for drug-resistant temporal lobe epilepsy in children on seizure frequency and quality of life.

Patients and methods. Examinations were made in 80 children aged 2–17 years with drug-resistant temporal lobe epilepsy, who had undergone surgery in 2011–2016. To assess its outcomes, the investigators used the Quality of Life Childhood Epilepsy, QOLCE questionnaire for patients' parents and the Engel Epilepsy Surgery Outcomes Scale.

Results and discussion. In the long-term period after surgical treatment, 54.5% of the children with drug-resistant temporal lobe epilepsy achieved a favorable outcome (Engel class I); there were significant (p<0.05) positive changes in quality of life subdomains, such as speech, physical limitations, energy levels/weakness, and overall quality of life. Comparison of quality of life before and after surgical treatment established its positive impact on subdomains, such as social contacts and activity, behavior, physical limitations, attentiveness, memory, and speech. In general, there was a neutral or beneficial effect of the treatment on most of the quality of life subdomains.

Conclusion. To make recommendations based on high-level evidence, there is a need for further multicenter prospective studies of large patient populations with a detailed analysis of the relationship of factors influencing the outcome of surgery and indicators of psychosocial well-being of a child. The preoperative and postoperative changes in health and quality of life indicators cannot be more accurately assessed in patients without standardizing their preoperative examination algorithm and using equivalent psychometric tools.

The diagnosis of idiopathic normal pressure hydrocephalus (iNPH) presents difficulties because of the same symptomatology in neurodegenerative diseases. The data of brain magnetic resonance imaging (MRI) and invasive techniques (tap test, external lumbar drainage, and infusion test) not always allow an accurate diagnosis of iNPH, especially when patients have comorbidity. This increases the role of cerebrospinal fluid (CSF) biomarkers in the differential diagnosis of iNPH and comorbidities at early stages.

Objective: to analyze the data available in the literature on current ideas about CSF biomarkers and their role in the differential diagnosis of iNPH and neurodegenerative diseases in the brain.

Material and methods. The literature data were sought in the internet resource PubMed by the keywords: normal pressure hydrocephalus, CSF biomarkers, neurodegeneration, Alzheimer's disease (AD), beta-amyloid protein, and tau protein. Fifty-three communications published in 1965 to 2018 were reviewed.

Results and discussion. In accordance with the data available in the literature, the most informative CSF biomarkers for the differential diagnosis of iNPH are beta-amyloid (Aβ) proteins β42, Aβ-40, Aβ -38, sAPPβ, sAPPβ, and t-tau and p-tau. The study of CSF biomarkers opens up prospects not only for the detection of iNPH, but also for its differential diagnosis with neurodegenerative diseases, primarily with AD. The detection of biomarkers can be used in addition to brain MRI and invasive techniques to improve the accuracy of diagnosis, as well as to predict the efficiency of bypass surgery, but provided that they are comprehensively assessed.

Conclusion. The analysis of the levels of specific CSF proteins holds promise for the differential diagnosis of iNPH.

One of the promising areas in the pathogenetic treatment of multiple sclerosis (MS) is anti-B-cell therapy using ocrelizumab, an anti-CD20 monoclonal antibody. The drug is indicated for primary progressive MS (PPMS), secondary progressive MS (SPMS) and exacerbations, and highly active MS.

Objective: to analyze the use of the drug in 32 patients with different types of MS in everyday neurological practice.

Patients and methods. The investigation included 32 patients diagnosed with MS using the 2017 McDonald criteria: 12 patients with PPMS, 12 with highly active MS and 8 with SPMS and exacerbations. The median Expanded Disability Status Scale (EDSS) score was 4.0; the most severe course of the disease was observed in patients with SPMS. All the patients received a treatment cycle of 600-mg intravenous ocrelizumab injections (with an infusion pump) every 6 months; the initial dose was by 300 mg every 2 weeks. The follow-up period was 6 to 18 months.

Results and discussion. During ocrelizumab therapy, the patients with PPMS showed stabilization of EDSS score; and 6 (50%) had even its slight decrease by 0.5–1.0 scores, which may be caused by compensation for the existing symptoms due to pathogenetic treatment. In highly active MS, only 1 of the 12 ocrelizumab-treated patients had an ongoing exacerbation of the disease. During a subsequent 6–18-month follow-up, magnetic resonance imaging revealed that none of the patients had manifestations of MS activity; the EDSS score decreased in all the patients, indicating their achievement of stable remission. Six (75%) of the 8 patients with SPMS and exacerbations also displayed a decrease in EDSS score in the absence of exacerbations. No adverse events, including infusion reactions, were recorded during drug administration. The drug has a good tolerance and safety profile and ease-to-use.

Conclusion. Ocrelizumab therapy with will be able to improve the quality of treatment in patients with different types of MS, which is of great medical and social importance

Management of patients with acute back pain is one of the urgent problems in modern medicine.

Objective: to assess the management of patients with acute and subacute back pain in 2007–2008 and 2017–2018.

Patients and methods. The authors present their own experience in treating 140 patients (87 women and 53 men) (mean age, 50.7±17.6 years) at present and 70 patients (40 women and 30 men) (mean age, 46.5±15.0 years) 10 years ago.

Results and discussion. The experience shows the high efficiency of managing patients with acute back pain during information sharing (an educational conversation), a personalized approach (treatment of concomitant diseases and conditions) and, use of nonsteroidal anti-inflammatory drugs. However, these methods are not widely used in general clinical practice now, as 10 years ago.

Conclusion. To improve the quality of medical care, the additional education and training of physicians are required for the management of patients with back pain.

Objective: to assess changes in the vascular platelet component of hemostasis in patients in different recovery periods of ischemic stroke (IS).

Patients and methods. The investigation enrolled 73 patients with prior IS. According to the remoteness of stroke, the patients were divided into two groups: 1) 41 patients with a stroke remoteness of 1 to 6 months (an early recovery period); 2) 32 patients with that of 7 to 12 months (a late recovery period). In addition, a group of patients with recurrent stroke was identified to evaluate the efficiency of secondary prevention. A control group consisted of 30 healthy volunteers. All the patients took acetylsalicylic acid (ASA). Medical history data and laboratory and instrumental findings were analyzed. To assess the vascular platelet component of hemostasis, platelet aggregation with inductors was studied applying optical aggregometry; enzyme immunoassay was used to estimate the concentrations of the inflammatory marker myeloperoxidase and the endothelial dysfunction (ED) markers sICAM-1 and sE-selectin.

Results and discussion. The patients were found to have enhanced platelet aggregation with inductors; moreover, this was more pronounced in the patients with recurrent stroke than in those with new-onset IS. This suggests that the vascular platelet component of hemostasis contributes to the progression of the disease and its unfavorable course and necessitates the monitoring of these parameters to choose optimal secondary prevention methods, such as replacement of ASA with clopidogrel or use of its combination with dipyridamol. The activity of chronic immune inflammation processes and ED was ascertained to be enhanced, which can contribute to the aggravation of cerebrovascular insufficiency and to the development of acute cerebrovascular accident.

Conclusion. In the recovery period of stroke, the follow-up monitoring of hemostatic parameters and immune inflammatory and ED markers is of importance in evaluating the efficiency of secondary prevention. For the successful prevention of recurrent strokes, it is necessary to prescribe adequate antiplatelet therapy, as well as drugs that have anti-inflammatory properties, affect intercellular interaction processes (ASA, clopidogrel, and statins), and suppress oxidative stress associated with endothelial inflammation (alpha-lipoic acid and succinic acid preparations).

Hashimoto's encephalopathy (HE) is a steroid-responsive encephalopathy associated with autoimmune thyroiditis; it is based on the inflammatory brain process associated with a cross-reaction to anti-thyroid autoantibodies. HE is manifested by impaired consciousness and focal neurological symptoms. The determination of the serum and cerebrospinal fluid levels of antithyroid autoantibodies plays a main role in diagnosing HE. The latter is treated with glucocorticoids and other immunosuppressive agents. The prognosis is favorable providing that the treatment of the disease is initiated in time.

The paper describes two cases of adolescent-onset anti-MOG (myelin oligodendrocyte glycoprotein) syndrome. One case had an onset of optic neuritis, followed by myelitis; a recurrence of the syndrome occurred during interferon-β therapy. In the other case the syndrome also began with optic neuritis; and after a long latent period it was manifested as unilateral encephalitis with contralateral hemiparesis and rare epileptic seizures. Detection of anti-MOG syndrome is of great importance, because its management tactics is different from that for multiple sclerosis; furthermore, the laboratory diagnosis of this syndrome can be made in our country now.

Deprescribing is the opposite of prescribing drugs, the purpose of which is to improve quality of life and reduce the risk of adverse drug reactions. The paper considers the process of deprescribing benzodiazepines. It analyzes relevant studies on this problem, as well as recommendations to help decide whether it is a need for deprescribing and how to accurately do this. There are also the results of original investigations demonstrating the tapering of benzodiazepine tranquilizers: comparison of simple tampering, use of psychotherapy, or replacement pharmacotherapy. The use of a deprescribing algorithm is the safest way to discontinue benzodiazepines in patients who do not have serious indications for their long-term use.

The main forms of cognitive impairment (CI) are characterized by a significant variability in the relationship between morphological changes and clinical manifestations. One of the promising concepts, which explains these features, is a modern model of cognitive reserve. The cognitive reserve concept that is most widely used in the context of dementia is often employed to explain the mechanisms, by which the functional systems of the brain resist neuropathological changes. The mechanisms that ensure cognitive reserve function in the health and disease of the brain are to activate its neuronal connections. Therefore, individuals with more efficient neuronal connections and an ability to form alternative neural networks and, accordingly, to create cognitive strategies in response to increased cognitive load are characterized by greater cognitive reserve. The modern concept of cognitive reserve opens up prospects for explaining the causes and mechanisms of development of CI and also justifies the possibilities of using alternative strategies for their correction.

Cognitive impairment (CI) is a nonclassical manifestation of primary hyperparathyroidism associated with impaired calcium and phosphorus metabolism. The pathophysiological mechanisms of cognitive dysfunction in this endocrine disease have not been fully elucidated. Nonetheless, studies have demonstrated neuropsychological improvements and better quality of life in patients who have achieved normocalcemia with reduced parathyroid hormone levels after surgical treatment for hyperparathyroidism. Further large-scale controlled studies are needed to determine the possibility of using neuropsychiatric complications as indications for parathyroidectomy.

Age-related diseases are becoming an important public health problem due to the rise in the number of elderly and senile people around the world. In this age group, the prevalence of cognitive impairment (CI) no dementia and dementia is great, which determines a significant deterioration in quality of life. Orthostatic hypotension (OH) that is also often detectable at elderly and senile ages is one of the possible risk factors for CI and dementia. The paper reviews publications a relationship between OH and risk for CI/dementia in patients from older age group. Although the results of studies are contradictory, a number of studies and meta-analysis indicate a relationship between OH and CI/dementia in elderly and senile patients. Timely diagnosis of OH will be able not only to identify groups at risk for CI and/or dementia, but also to implement preventive measures in time to reduce this risk.

The pathogenesis of sarcopenia is complex and associated with impaired muscle protein synthesis, enhanced myocyte apoptosis, increased systemic inflammation, etc. The authors have carried out a systems analysis of 31 992 articles on sarcopenia, which are presented in the biomedical database PubMed, to clarify a set of comorbid interactions of sarcopenia with osteoarthritis, osteoporosis, and other diseases and to justify the use of chondroitin sulfate (CS) and glucosamine sulfate (GS) in these patients. The molecular mechanisms of action of CS and GS on the pathophysiology of sarcopenia have been formulated. By interacting with CD44 receptor, the CS/GS molecules inactivate the proinflammatory factor NF-kB, the activity of which is enhanced in muscle atrophy. In addition, CS/GS provides building material for the regeneration of connective tissue around the myocytes. Thus, the highly purified drugs CS /GS should be used to slow sarcopenia progression.

Functional movement disorders (FMDs) are a complex medical problem requiring a set of different diagnostic and treatment approaches: neurological, psychiatric, psychotherapeutic, and neurophysiological. With the advent of positive criteria for the diagnosis of FMDs, the latter are no longer just a diagnosis of exclusion, which is difficult for clinical interpretation. The review considers positive clinical and instrumental diagnostic criteria and presents the neurophysiological characteristics of functional tremor and functional myoclonus, which allow one to suspect this diagnosis. Their timely recognition is extremely important, as this permits patients to reduce the cost of unnecessary examinations and ineffective drugs and increases the chances for successful treatment, since the best prognosis is noted with the shortest duration of the disease.

Depression is the most common form of mental illness in patients with cardiovascular diseases (CVD). Depression and CVD can worsen the clinical and dynamic characteristics of each other. The timely detection and adequate psychopharmacotherapy of depressive states in patients with CVD are of great clinical, therapeutic, and prognostic importance. Anti-antidepressant therapy promotes a more pronounced somatic stabilizing effect in patients with CVD. Adverse events to the use of antidepressants in patients with CVD may be associated with their negative effect on the hepatic cytochrome CYP450 isoenzymes involved in the metabolism of various drugs. The authors' own data of clinical psychopharmacotherapeutic studies and the results of meta-analyses indicate the high efficiency and good tolerability of agomelatine, an antidepressant with an innovative mechanism of action, in a wide range of patients