LECTURES 
Schizophrenia is a socially significant disorder with a high prevalence among young and middle-aged people. Movement disorders, or extrapyramidal syndrome, are potentially reversible antipsychotic-induced adverse effects (AEs) that stigmatize patients and worsen quality of life. Tardive dyskinesia (TD) is a neurological AE in the extrapyramidal system, which is accompanied by abnormal involuntary non-rhythmic choreiform or athetoid movements (hyperkinesis) that occur during the long-term use of antipsychotics. The reversible and persistent forms of TD are identified.
The article analyzes the prevalence and predictors of TD, as well as the issues of its diagnosis.
The paper considers the epidemiology and general etiological characteristics of cryptogenic stroke (CS). It discusses the concept of embolic stroke with an unknown source of embolism. It also characterizes the most significant causes of CS, such as paroxysmal atrial fibrillation, atrial cardiopathy, aortic atheroma, non-stenotic cerebral atherosclerotic plaques, and malignant neoplasms. The paper describes approaches to the diagnosis and secondary prevention of CS and proposes etiological and neuroimaging diagnostic algorithms for CI. Clinical cases are also presented.
Cognitive impairment (CI) is one of the leading causes of disability after stroke; CI is observed in more than half of patients and reaches a pronounced degree (of dementia) in every three to five patients. CI in poststroke patients is often caused not only by focal vascular lesions of the brain, but also by the presence of concomitant vascular and neurodegenerative diseases. The treatment and prevention of progressive CI are based on stroke prevention, non-drug and drug methods to improve cognitive functions. Blood pressure normalization during antihypertensive therapy is most effective in preventing the progression of CI in stroke patients. The use of Actovegin in patients with CI after stroke is discussed. The results of the author's own 5-year follow-up of 350 patients with stroke are presented.
ORIGINAL INVESTIGATIONS 
Alzheimer's disease (AD) is the leading cause of dementia in the population. Difficulties in diagnosing AD have served as an incentive for actively studying different current methods that increase the accuracy of diagnosis of the current neurodegenerative process in this disease. One of these areas is the post-processing of magnetic resonance imaging (MRI) data, by exactly calculating the volume of various anatomical formations, namely MRI morphometry.
Objective: to determine the possible relationship between the results of evaluating the higher brain functions and the reduction in the hippocampal volume calculated by MRI morphometry in AD patients with mild and moderate dementia and in healthy controls.
Patients and methods. Examinations were made in 41 AD patients aged 70.63±8.38 years with mild and moderate dementia and in healthy individuals. All study participants underwent neuropsychological testing that included the Mini-Mental State Examination (MMSE), the frontal lobe dysfunction battery (FLDB); immediate and delayed 12-word recall trials (12-word test); Benton's revised visual retention test; test of literal and categorical associations; clock drawing test; and series number test, Part A. MRI was performed on a Siemens Magnetom Skyra 3T MRI scanner. Statistical Parametric Mapping software was used to convert images and the volume of the hippocampus was estimated by FMRIB Software Library.
Results and discussion. A statistically significant decrease in hippocampal volumes was established in patients with AD compared with healthy individuals. No statistically significant differences in hippocampal volumes were found in patients with varying degrees of dementia. Patients with mild and moderate dementia differed in all indicators of neuropsychological tests, with exception for the 12-word test and Benton's test. There was a statistically significant correlation of the total volume of the hippocampi with the indicators of MMSE, FLDB, 12- word test, clock drawing test, and test of categorical associations.
Conclusion. Hippocampal MRI morphometry in combination with neuropsychological tests is an informative technique in the diagnosis of AD. There is a relationship between the degree of hippocampal atrophy and the neuropsychological characteristics of patients.
Objective: to assess the prognostic significance of cognitive impairment (CI) detected using the Mini-Mental State Examination (MMSE) scale in patients at high and very high cardiovascular risk (CVR).
Patients and methods. The investigation enrolled 111 men and women aged 40-75 years at high and very high CVR. High and very high CVR was established in 30 (27.0%) and 81 (73.0%), respectively. The median MMSE score in the examinees was 28.0 (27.0–28.0). The MMSE score was equal to ≥28 in 71 (63.9%) patients. Moderate CI (MCI) was found in 40 (36.1%) patients. The follow-up duration was 24.6 (14.4–34.5) months. The combined endpoint was taken to be death from cardiovascular causes, nonfatal myocardial infarction or unstable angina requiring hospitalization, nonfatal stroke, and coronary revascularization.
Results and discussion. The events constituting the combined endpoint occurred in 40 (36.0%) patients. The Kaplan-Meier analysis showed that patients with MCI (24–27 MMSE scores) had a significantly lower >2-year survival rate. The Cox regression analysis established that MCI was associated with a 2.56-fold increase in the relative risk (RR) of the adverse cardiovascular events constituting the endpoint (95% CI, 1.22–5.33; p=0.013). The prognostic value of CI, in particular with respect to the development of cardiovascular events, was observed in various age groups of patients. MMSE is a simple screening test that should be used more widely, including for the identification of patients at increased CVR.
Conclusion. The presence of MCI is associated with the RR of adverse cardiovascular events.
Objective: to determine the prognostic value of the indicators of fluid and electrolyte balance in the acutest period of severe ischemic stroke (IS).
Patients and methods. A total of 150 patients with severe IS of various locations and pathogenetic subtypes were examined. The impact of plasma osmolarity or sodium levels on the course and prognosis of IS was studied on day 1 of the disease.
Results and discussion. It has been established that in patients with severe IS, the most common type of fluid and electrolyte imbalance is hyperosmolar hypernatremic syndrome that develops at the onset of severe IS, serves as a factor for poor outcome, and is accompanied by high mortality. The rate of fatal outcomes in hypoosmolar syndromes is higher than that in normal plasma osmolarity, but significantly lower than that in hyperosmolar syndromes. Cerebral salt wasting (CSW) is associated with a higher mortality rate than syndrome of inappropriate antidiuretic hormone secretion (SIADH), which confirms a worse prognostic value in hypovolemia than in normo- and hypervolemia. The development of diabetes insipidus at the onset of IS reflects the degree of brainstem structural destruction and, accordingly, is associated with the highest rate of fatal outcomes. The cardioembolic pathogenetic subtype of IS is characterized by a more severe course and a higher probable mortality rate in both hypoosmolar and normosmolar conditions.
Conclusion. Impaired fluid and electrolyte homeostasis is of significant prognostic value for the outcome of IS. In this case, the leading role is played by the hyperosmolar hypernatremic syndrome, in which the probability of a fatal outcome is highest and there is a need for continuous patient health monitoring and high-speed decision-making aimed to correct this condition. Therapeutic policy for diabetes insipidus depends on the duration of IS. The risk for fatal outcome in the cardioembolic pathogenetic subtype of IS is higher than that in atherothrombotic stroke, at any plasma osmolarity and sodium levels.
High-frequency repetitive transcranial magnetic stimulation (rTMS) is approved by the Food and Drug Administration (FDA) for the treatment of pharmacotherapy-resistant depressive disorders (DD). Individual target determination for stimulation can be one of the approaches that can increase the efficiency of the technique.
Objective: to compare of the effectiveness and tolerability of standard and personalized rTMS protocols.
Patients and methods. The investigation enrolled 30 patients with pharmacotherapy-resistant DD who were pseudo-randomized into two groups matched for age, gender, and episode severity. In the study group, the target was located at a point within the left dorsolateral prefrontal cortex (DLPFC) with maximum negative functional connectivity of the subgenual cingulate cortex. In the control group, the stimulation point was 5 cm anterior to the primary motor cortex (hand area). All the patients underwent 20 sessions of high-frequency rTMS DLPFC. For clinical evaluation, the investigators used the Beck Depression Inventory (BDI) and the 36-item Short Form Health Survey (SF-36) questionnaire before and after 10 and 20 rTMS sessions, respectively. Tolerability was assessed using the standardized questionnaires during and within 24 hours after each session.
Results and discussion. The study group showed a significant reduction in BDI scores and an increase in the SF-36 (“Mental Health” section) scores after both 10 and 20 rTMS sessions; the control group had those only after 20 sessions. The two groups exhibited no significant differences in the reduction of BDI scores before and after 10 and 20 sessions, respectively. The investigation can be considered to be pilot in searching for algorithms to enhance the efficiency of rTMS DLPFC in pharmacotherapy-resistant depression using the algorithm for personification of target selection. It demonstrated the more rapid onset of a clinical effect in the study group patients. No serious adverse events were reported. The patients had dizziness, headache, and contraction of the facial muscles during the session; headache and mood changes within 24 hours after it.
Conclusion. In both groups, rTMS was satisfactorily tolerated and effective; however, personalized target selection accelerated the onset of a clinical effect.
Non-motor manifestations in focal muscular dystonia (FMD) have been little studied.
Objective: to analyze the characteristics of cognitive impairment (CI) and mental disorders (MDs) in FMD.
Patients and methods. Fifteen patients (7 men and 8 women) aged 25 to 80 years (mean age, 59.8±14.7 years) with FMD were examined. Cervical dystonia and blepharospasm were noted in 10 (66.7%) and 5 (33.3%) patients, respectively. A control group consisted of 15 healthy individuals (7 men and 8 women) (mean age, 58.2±14.9 years). Neurological and standardized psychiatric examinations and neuropsychological tests were performed; the Beck Depression Inventory and the Spielberger State-Trait Anxiety Inventory were used.
Results and discussion. Patients with FMD were found to have moderate CI as impaired control functions. Depression was diagnosed in 9 (60%) patients; it corresponded to the pattern of protracted psychogenically provoked conditions in most cases (n = 8). Six (40%) patients with FMD had anxiety and somatic disorders. The pathophysiology of non-motor manifestations of FMD is likely to depend on many factors, including the relationship between different clinical factors and basal ganglia dysfunction. The data on the association between emotional disorders and CI in FMD are contradictory. MDs can seem to be as an additional factor that aggravates the manifestations of dystonia.
Conclusion. In patients with FMD, moderate CI can be due to emotional disorders that aggravate the manifestations of the disease. The diagnosis and correction of emotional disorders are promising in the management of patients with FMD.
Objective: to study the association of the polymorphic genotypes of rs4680 in the catechol-O-methyl transferase (COMT) gene with vital exhaustion (VE) in a 45–64-year-old population.
Patients and methods. A representative sample of a 45–64-year-old population (781 men and 869 women) was surveyed within screening IV of the international Health, Alcohol and Psychological Factors in Eastern Europe (HAPIEE) program and the WHO MONICA-psychosocial program in 2003-2005. All the study participants filled out a VE scale of the WHO MONICA-psychosocial program. COMT Val158Met (rs4680) polymorphism was genotyped. Pearson' χ2 test was used to test the statistical significance of differences between these groups. The statistical significance level was taken to be p≤0.05 in all types of analysis.
Results and discussion. Heterozygous G/A polymorphism in the COMT gene was most common in both the general population (48.6%) and men (44.4%) and women (51.5%). In the general population, the A/A genotype was more common in individuals with a high VE (HVE) level; in women and men, it was detected in 13.3 and 30.8% of cases, respectively. The G/G genotype prevailed in individuals with moderate VE in both the general population (31.1%) and women (29.7%) and men (33.3%).
Conclusion. In the general population, the A/A genotype was found to be more common in individuals with HVE (18.6%), in women (13.3) and in men (30.8%).
In recent years, the genetics of juvenile myoclonic epilepsy (JME) has been actively studied; the association of JME with the carriage of polymorphic allelic variants of the BRD2 (EJM3 locus) and GJD2 (EJM2 locus) genes has been established.
Objective: to establish risk factors for JME in terms of a genetic predisposition; specifically, polymorphic allelic variants rs206787 and rs516535 in the BRD2 gene and rs3743123 in the GJD2 gene.
Patients and methods: Examinations were made in 79 patients with JME and in 150 healthy volunteers, who were Caucasian and resided in the Siberian Federal District (SFD) and underwent determination of the carriage of single nucleotide polymorphisms (SNPs) rs206787 and rs516535 in the BRD2 gene and rs3743123 in the GJD2 gene by real-time polymerase chain reaction.
Results and discussion. In 2003, American scientists from New York showed that the alleles associated with the development of JME with an autosomal recessive inheritance pattern might be located in the BRD2 gene. Patients with JME are assumed to have an autosomal dominant inheritance pattern of mutations in the BRD2 gene. British scientists revealed that different populations were found to have an association of SNP rs3918149 and no relationship of BRD2 rs206787 to the development of JME in Caucasians, as well as ascertained local linkage disequilibrium in the BRD2 gene. Our investigation has established complete linkage disequilibrium between the loci in patients with JME and in healthy individuals and no association of the carriage of SNPs rs206787 and rs516535 in the BRD2 gene with the development of JME in the patients residing in the SFD (p >0.05). German scientists studied the impact of SNP in the BRD2 gene on a predisposition to a photoparoxysmal response in patients with JME/genetic generalized epilepsy. Our investigation has indicated the association of the carriage of TT/TT haplotype for SNP rs206787 and rs516535 in the BRD2 gene with a photoparoxysmal response in patients with JME (odds ratio (OR), 3.6; 95% confidence interval (CI), 1.37–9.48; p=0.02). We have confirmed that in the studied sample, the carriage of the T allele in the GJD2 gene (rs3743123) in the homozygous form is associated with the development of JME in Caucasian patients residing in the SFD and is a risk factor for JME (OR, 2.66; 95% CI, 1.24–5.74; p=0.04). The clinically significant association of this SNP in the GJD2 gene with the development of JME had been also previously demonstrated in two independent studies conducted in the European populations in the UK and Germany. There is a rise in the proportion of homozygotes in JME patients versus the control group, suggesting that the 588T allele under consideration increases the risk for JME in the homozygous state in the autosomal recessive inheritance pattern.
Conclusion. The findings suggest that it is necessary to genotype Caucasian patients with JME, who reside in Siberia, for determination of the carriage of the TT/TT haplotype in terms of the investigated SNPs in the BRD2 gene (EJM 3 locus) and the carriage the T allele (rs3743123) in the GJD2 gene via a personalized approach to predicting the course of JME, as well as for identification of persons at risk for JME in the families having a history of this disease.
Levetiracetam (LEV) is an effective antiepileptic drug. Nevertheless, when the drug is used, its behavioral adverse drug reactions (ADRs), such as aggressivity, irritability, hyperexcitability, and anxiety, occur in almost 30% of cases. Recent studies show that personality traits can predispose to LEV-induced ARs.
Objective: to establish genetic risk factors for behavioral ADRs in epileptic patients taking LEV.
Patients and methods. Single nucleotide variants (SNVs) were chosen according to their importance for the development of impulsivity and aggressivity. At Stage 1, the dose-dependent effect of LEV, which was responsible for behavioral ADRs, was studied in 179 epileptic patients taking this drug, who were divided into four groups according to age and the presence of ADRs. Molecular genetic testing of SNVs DRD2 rs1800497 (DRD2/ANKK1 Taq1A), COMT rs4680, and DBH rs1611115 was done at Stage 2.
Results and discussion. The ADR and non-ADR groups showed no statistically significant differences in the daily dose of LEV in both children (696.1 and 500.0 mg/day, respectively; p=0.087) and adults (750.9 and 750.9 mg/day, respectively; p=0.13). The similar data were obtained for blood LEV concentrations in children (31.6 and 27.3 μg/ml, p=0.12) and in adults (23.1 and 17.6 μg/ml, respectively; p=0.12). There was a statistically significant association between the carriage of the heterozygous CT genotype of SNV rs1611115 and the rate of both behavioral (OR, 3.38; 95% CI, 1.25–9.14; p=0.042) and CNS ADRs in general (OR, 3.29; 95% CI, 1.29–8.44; p=0.036). Higher impulsivity values were recorded in the carriers of the CT + TT genotypes of SNV rs1800497 (p<0.05) and rs1611115 (p<0.01) compared with those of the CC genotype. No statistically significant intergroup differences were obtained for SNV COMP rs4680.
Conclusion. The dose-dependent effect of behavioral ADRs is absent in both pediatric and adult patients taking LEV. Increased impulsiveness in epileptic patients taking LEV is associated with the carriage of SNV rs1800497 and rs1611115. The LEV-induced behavioral ADRs are related to SNV DBH rs1611115 that can be considered as one of the potential genetic predictors for behavioral ADRs and impulsivity.
Objective: to investigate the features of the course and long-term outcome of catastrophic epilepsies.
Patients and methods. A total of 130 patients (62 (47.7%) men and 68 (52.3%) women) aged 21 to 78 years were examined. The follow-up was 1 year to 14 years. The inclusion criteria for the investigation were above 18 years of age; severe epilepsy with daily seizures considered as catastrophic epilepsy. The exclusion criteria were a history of nonepileptic seizures of any etiology, as well as noncompliance. The examination included history data collection; seizure diary analysis; clinical and neurological examination; routine EEG and/or EEG-video monitoring; brain magnetic resonance imaging; and laboratory tests.
Results and discussion. The onset of epilepsy immediately with catastrophic seizures was observed in 28 (21.5%) patients; this onset was most frequently seen in 18 of the 28 children. At the same time, catastrophic seizures did not appear immediately, but it took some time for them to occur after the onset of active epilepsy in 102 (78.5%) patients. Moreover, the onset of catastrophic seizures could not be associated with any external influences or errors in 58 (56.9%) of these patients taking the drugs. Transition to catastrophic epilepsy could occur both abruptly in 11 (10.8%) patients and gradually in 91 (89.2%). After treatment correction, 16.8% of patients achieved remission at the time of study completion; the frequency of seizures decreased by 50% or more in 27.1% of cases; the effect was absent in 56.1%.
Conclusion. Based on the findings, it can be concluded that in catastrophic epilepsy, the probability exists for spontaneous occurrence and remission of destructive seizures, frequently regardless of the therapy. The onset of the disease and that of catastrophic seizures can be spread in time. The efficiency of treatment remains low in patients with catastrophic epilepsies.
The complex interactions of the epileptic focus and the brain systemic response require an integrated approach to predicting the course of focal epilepsy.
Objective: to investigate the role of interictal neurophysiological parameters and neuroimaging data in predicting the course of epilepsy.
Patients and methods. Eighty-two patients with focal structural epilepsy and 82 healthy participants (a control group) were examined. Clinical, psychological, and social characteristics and the data of neuroimaging and comprehensive neurophysiological studies (electroencephalography (EEG), recording exogenous and cognitive evoked potentials, motor testing, and heart rate variability) were assessed.
Results and discussion. The investigators identified the prognostic factors of the unfavorable course of epilepsy: temporal lobe epilepsy, left temporal lobe lesion, nontraumatic intracerebral hemorrhages. They proposed algorithms for predicting the course of epilepsy based on neurophysiological and neuroimaging data. An analysis of physiological parameters in patients with the unfavorable course of epilepsy demonstrated the slowing of the background rhythm on the EEG, a decrease in the power of specific afferentation, and an increase in the decision-making time for the stimulus, as evidenced by the P300 potential, and insufficiency of the central mechanisms in providing a motor reaction. These patients also showed the enhanced activity of stress-implementing systems. Taking into account not only neurophysiological parameters, but also neuroimaging data could improve the prognostic capabilities of an artificial neural network that determines the type of a disease course.
Conclusion. The unfavorable course of focal epilepsy is associated with a number of clinical and physiological parameters; in this case, it is possible to identify the specific physiological pattern of this course of the disease. The integrated clinical and physiological approach and neuroimaging data make it possible to successfully predict the course of the disease through machine learning technology.
Objective: to make a clinical-scale assessment of remission in patients with recurrent depression.
Patients and methods. The clinical and functional characteristics of remission were investigated in 121 patients with recurrent depression. The investigators used the following tests: the Montgomery-Asberg Depression Rating Scale (MADRS), the Brief Assessment of Cognition in Affective Disorders (BAC-A), the WHO Disability Assessment Schedule 2.0 (WHODAS 2.0), and the 36-item Short Form Health Survey (SF-36) questionnaire. They systematized remission, by identifying its four types: asymptomatic, that with asthenic symptoms, that with anxiety symptoms, hypothymic.
Results and discussion. The criteria for complete remission with its average duration of 6 months were met in 58.6% of patients. Impaired social functioning was observed in all patients in remission. The predictors of incomplete remission were a family history; male gender; complex pattern of depression; and the presence of comorbid anxiety. The anxious variant of incomplete remission predominated, suggesting that it is advisable to choose anxiolytic antidepressants for maintenance therapy. New-generation antidepressant therapy is more frequently associated with complete remission. Whether therapy with different antidepressants might achieve functional remission was studied using agomelatine as an example.
Conclusion. When assessing the results of treatment for depression, it is necessary to take into account not only clinical changes, but also social functioning in patients and, as a target of therapy to identify positive affect as one of the psychological parameters of quality of life. When choosing an antidepressant for the maintenance therapy of recurrent depression, its positive efficacy on the social functioning of patients should be an important criterion.
Objective: to comparatively evaluate the clinical efficiency of cervicocranialgia therapy with dexketoprofen (flamadex) and tolperisone (calmyrex), as well as with their combination.
Patients and methods. The investigation enrolled 90 patients aged 30–60 years with cervicocranialgia, who were randomized into three equal groups. Group 1 included 7 men and 23 women who took dexketoprofen; Group 2 consisted of 13 men and 17 women who were prescribed dexketoprofen and tolperisone; Group 3 comprised 18 men and 12 women who used tolperisone. The three patient groups underwent assessment of the intensity of pain on a visual analogue scale and the degree of muscle tone on a 3-point scale and evaluation of the efficiency of therapy and the hemodynamic effect of the drugs in the common carotid and vertebral arteries.
Results and discussion. In all the groups, their treatment reversed neck pain, headache, and dizziness, normalized muscle tone, and improved hemodynamics in the carotid and vertebral arteries. The effect was more pronounced in patients receiving combination treatment (Group 2). The therapy showed a high safety and a good tolerability.
Conclusion. Dexketoprofen and tolperisone have been demonstrated to be effective and safe in treating cervicocranialgia.
Objective: to evaluate the effect of piribedil on cognitive functions in elderly patients with chronic cerebrovascular disease (CCVD) and cognitive impairment (CI).
Patients and methods. A total of 67 patients aged 60-75 years with CCVD and CI were examined. A control group included 32 patients who had received basic therapy with antihypertensive and, if indicated, lipid-lowering and antithrombotic drugs. A study group consisted of 35 patients who additionally took piribedil 50 mg after evening meals for 3 months. Neuropsychological examination was made before and after a treatment cycle.
Results and discussion. After 3 months, only the piribedil group showed a significant neuropsychological improvement (p<0.05-0.001). There were statistically significant differences in the measures of short-term (5.9±0.5 and 4.27±0.5 words; p<0.05) and long-term (6.4±0.8 and 4.16±0.5 words; p<0.05) memories, correction task (38.4±0.8 and 49.1±0.1 errors; p<0.001), attentiveness (421.0±0.9 and 406.0±0.6 sec; p<0.001), and work efficiency (16.3±0.9 and 12.3±1.2 sec; p<0.05). The investigation revealed that the drug had a good tolerability, neither adverse events nor drug-drug interactions.
Conclusion. When used in CCVD and CI, piribedil 50 mg once daily for 3 months is able to improve cognitive functions in elderly patients, which indicates that it is feasible to use the drug in combined therapy with essential (antihypertensive, lipid-lowering, antithrombotic) medicines.
REVIEWS 
The review considers works devoted to convolutional neural networks as a main method for digital image processing, as well as to the diagnosis of neurological diseases based on computer-aided analysis of magnetic resonance imaging and electroencephalography. It describes approaches to building computer-aided diagnostic systems and gives examples of these systems in neurology. The virtual reality technology used to rehabilitate patients with imbalance, posttraumatic disorders, and consequences of stroke is presented. Digitalization is stated to be one of the priority areas for medicine development.
Metamorphopsia is distortion of the visual perception of environmental objects (shape, sizes, orientation, color, and/or motion parameters), but without affecting their essential characteristics. It can be observed in the clinical picture of a number of diseases, interfering with daily activities and restricting the behavior of patients due to fear of its sudden occurrence. However, the importance of metamorphopsia is underestimated in practice, which is associated with both patients' tendency to be reticent about it and with physicians' unawareness about this condition. The review presents the classification of visual distortions, the clinical characteristics of peripheral (in eye structural pathology) and central (in brain damage) metamorphopsia. The most detailed discussion focuses on palinopsia. The Pulfrich phenomenon and the visual snow symptom are briefly described. The review considers metamorphopsia concurrent with illusions in the Alice-in-Wonderland syndrome. It characterizes the neurophysiological mechanisms of distorted vision and the pathology in which the latter can occur. There is evidence that it is important to timely detect metamorphopsia.
This paper presents the definition, epidemiology, etiological factors, and approaches to classifying infertility and describes the relationship between mental health and infertility in women. The problem of idiopathic infertility is analyzed from both obstetric/gynecological and psychiatric positions. The psychological factors influencing the reproductive function of a woman are disclosed. Mental health disorders potentiating infertility are considered. Attention is paid to that mental disorders are insufficiently and untimely diagnosed in women with reproductive disorders, that certain forms of psychopathology are masked by functional gynecological disorders, and that obstetricians/gynecologists have no specialized ideas of women's mental health, which may lead to unsuccessful infertility therapy.
Patients with multiple sclerosis (MS) are at high risk for transition to secondary progressive MS (SPMS). To date, there has not been a sufficiently effective therapy for SPMS. Siponimod is a selective sphingosine-1-phosphate types 1 and 5 receptor modulator that has been shown to be more effective than placebo in slowing the progression of disability in patients with SPMS in the international phase III (EXPAND) clinical trial. This review analyzes data on the pathophysiology of MS progression, the features of the mechanism of action of siponimod, the efficiency and safety of its use, including those by the results of the EXPAND study. The latter studied the efficacy of siponimod by the time to 3-month confirmed disability progression (3M-CDP) and also assessed other clinical and radiological parameters. The analysis included data on 1,651 patients with SPMS from 31 countries. In the patients who received siponimod, the risk of 3M-CDP decreased by an average of 21% compared with those who took placebo. The administration of siponimod positively affected the speed of cognitive processes. Mild adverse events associated with liver failure, hypertension, and upper respiratory tract infections were more common in the siponimod group. Siponimod did not pose a higher risk for developing malignant neoplasms. The drug reduces the risk of disability progression in patients with SPMS and has a favorable safety profile.
Management of patients with back pain is an interdisciplinary problem requiring a package of diagnostic and differential measures. Despite the elaboration of algorithms for the differential diagnosis and therapy of back pain, a number of questions remain difficult to interpret, which can lead to diagnostic errors. This review considers the main causes of back pain and the principles of their diagnosis and treatment. It gives data from studies of therapy for nonspecific back pain with nonsteroidal anti-inflammatory drugs and muscle relaxants, aceclofenac and tolperisone in particular.
The cause of persistent postural-perceptual dizziness (PPPD) is considered to be chronic dysfunction of the regulatory system for maintaining equilibrium in general and that of the vestibular system in particular, which causes a persistent sensation of dizziness and/or unsteadiness. The pathogenetic mechanisms of PPPD are associated with impaired adaptation to an acute vertigo or unsteadiness episode due to various causes (vestibular, lipothymic, or emotional).
Patients severely experience PPPD, which often leads to avoidant behavior and even disability. The timely diagnosis of this disorder and the use of right treatment, including vestibular rehabilitation, antidepressants, and cognitive behavioral therapy, are of great importance. Currently developed new treatments for PPPD are highly therapeutically effective. Among the medicines, Ginkgo biloba extract has been shown to be effective in improving vestibular compensation.
Epidemiological data show that Alzheimer's disease (AD) is the most common cause of acquired cognitive impairment (CI). At the same time, according to statistics, vascular CI and vascular dementia predominate in Russia, which is mainly due to imperfect diagnosis, when any pathological condition associated with cerebral dysfunction in a patient with vascular risk factors is interpreted as dyscirculatory encephalopathy or chronic brain ischemia. However, this can be asthenoneurotic syndrome, migraine, vestibular dysfunction, and a number of neurodegenerative diseases, the most common condition of which is certainly AD. What is more, the treatment of age-related diseases, with the exception of acute vascular disease, is receiving manifestly inadequate attention. All this leads to the lack of a unified methodology for the management of these patients, to the impossibility to have adequate primary medical care, to the low detection rate of CI, to the prescription of drugs without appropriate indications, and to the denial of psychological correction methods. The review highlights the challenges facing the management of patients with AD and the possible ways of their solution.
Chronic nonspecific lower back pain (LBP) is one of the most common causes of adult disability. The chronic course of back pain is often supported by the patient's unhealthy lifestyle and the use of ineffective treatments. The combination of cognitive behavioral therapy, therapeutic exercises, gradually increased physical activity, and rational pharmacotherapy are effective in most cases of chronic non-specific LBP. In this disease, nonsteroidal anti-inflammatory drugs (NSAIDs) are the first-choice drugs that should be prescribed in a short cycle. The choice of NSAIDs is determined by the presence of concurrent diseases in the patient and by the risk of developing adverse events. The paper discusses the efficacy and safety of meloxicam in non-specific NSAIDs.
CLINICAL OBSERVATIONS 
The paper describes a clinical case of the rare status epilepticus syndrome FIRES (febrile infection responsive encephalopathy) + NORSE (new-onset refractory status epilepticus). The difficulty of diagnosing this condition is due to the fact that it occurs extremely rarely and the laboratory and instrumental findings are nonspecific. The disease is characterized by acute onset, fever, and subsequent development of status epilepticus, cognitive impairment, and pharmacotherapy-resistant epilepsy. The paper describes a 19-year-old male patient who was observed to have a favorable course of FIRES + NORSE syndrome without pharmacotherapy-resistant epilepsy, motor deficiency, and with the preservation of self-care skills.
The paper presents experience with antithrombotic therapy in a critically ill patient with acute coronary syndrome and transient ischemic attack. It characterizes problems in triple antithrombotic therapy in a very ill patient with comorbidity. The paper demonstrates an incremental approach to choosing therapy according to the clinical picture of disease, an assessment of risk factors for ischemic and hemorrhagic complications over time, which is very important in the routine practice of a physician. It also shows how, based on existing recommendations, the optimal anticoagulant is chosen as part of triple and double antithrombotic therapy in terms of its potential risks and possible complications.
Peripheral nervous system (PNS) damage is one of the most common complications of diabetes mellitus. There may be different PNS damage types that differ in clinical symptoms and pathogenesis. A clinical case of diabetic cervicobrachial radiculoplexopathy is presented for the first time in Russia. The paper discusses the clinical features of this type versus diabetic lumbosacral radiculoplexopathy, instrumental diagnosis of diabetic radiculoplexopathies, pathogenetic mechanisms of the disease, and treatment approaches. It shows the efficacy of alpha-lipoic acid supplementation in a patient with diabetic radiculoplexopathy.
PHARMACOTHERAPY 
More than 10 multiple sclerosis-modifying drugs (MSMDs) are widely used now. Novel MSMDs should be investigated in strict accordance with the evidence-based medicine principles governing clinical trials (of both original drugs and their analogues) that prove the high efficiency, safety, and tolerability of new drugs versus the already existing ones. Russia has gained extensive experience in conducting such studies using the well-known drugs as a comparison group. The efficiency and safety of new therapy should be evaluated according to the international criteria on the basis of a sufficient number of patients during a long-term follow-up. When combining the drugs, their efficiency and the risk of adverse effects can vary. The published results of a small study of the combined drug Leucovir (Belarus) do not meet these requirements, and the possibility of using this drug to treat multiple sclerosis can be discussed only after adequate phases II and III clinical trials.
RECOMMENDATIONS FROM EXPERT MEETING 
The meeting of experts discussed the clinical and pathophysiological features of secondary progressive multiple sclerosis (MS) (SPMS), clinical trials, and promising treatments for the progressive MS stage, as well as proposals contributing to the improvement of the current state of the problem of SPMS. In particular, the definition of and criteria for SPMS are formulated; the earliest period, when its confirmed progression can be recorded, is stated to be 3 months. The exacerbation-unaffected disability progression confirmed 6 months later may be considered to be more convincing. The introduction of tools for the early assessment of disability progression into routine practice will be able to identify the signs of progression at an earlier stage in order to timely change treatment policy. It is also noted that therapeutic possibilities in establishing secondary progression, especially in the absence of exacerbations, but in maintaining progression, are still insufficient. Certain hopes for slowing the progression in patients with SPMS are associated with the advent of siponimod, a new molecular class of S1P receptor modulators. The confirmed efficiency of siponimod in a large population of patients with SPMS allows the latter to be recommended for its treatment with both persistent disease activity (SPMS with exacerbations) and disability progression without exacerbations (SPMS without exacerbations).
Articles 
Objective: to discuss the feasibility of identifying the causes of chronic nonspecific LBP and in the case of detection of damage to the facet joint (FJ) or sacroiliac joint (SIJ), use of nonsteroidal anti-inflammatory drugs (NSAIDs), and injection of anesthetics and glucocorticoids into the region of the FJ or SIJ.
Patients and methods. A total of 121 female patients aged 22 to 59 years with chronic nonspecific LBP were followed up. A FJ lesion was found in 53 (43.8%) patients. The patients were informed of a favorable disease prognosis, had motor activity recommendations, and were also prescribed NSAIDs and muscle relaxants. Twenty-eight (23%) patients achieved a clinically significant analgesic effect within 2 weeks; the remaining 93 (77%) patients received combination therapy with anesthetics injected into the region of the FJ and SIJ.
Results and discussion. The basis for successful personified therapy in these patients is shown to be adequate diagnosis by identifying of the prevailing sources of pain impulses (triggers), and by using minimally invasive diagnostic methods, such as local injection of a local anesthetic solution into the suspected pain trigger. The high efficiency of combination therapy for chronic nonspecific LBP, which included anesthetics injected into the region of the FJ and SIJ, and is largely associated with rapid pain elimination, which is of great psychological importance. The central mechanisms of action of NSAIDs, etoricoxib in particular, are discussed.
Conclusion. Thus, elucidation of the causes of chronic nonspecific LBP in a patient makes it possible to recommend personalized therapy aimed at eliminating not only the symptoms, but also the underlying cause of the disease. The use of etoricoxib for FJ lesion, which shows the highest analgesic efficacy in patients with osteoarthritis is pathogenetically justified and should be combined with nondrug treatments.
ISSN 2310-1342 (Online)