Neurology, Neuropsychiatry, Psychosomatics

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Vol 12, No 5 (2020)
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4-8 765

Drug-induced dystonia (DID) is a rarely diagnosed adverse reaction to a sufficiently large number of drugs. Acute DID (ADID) occurs soon after starting to take a drug or raising its dose, and switching from one antipsychotic medication to another, especially to its injectable dosage form. Tardive DID (TDID) develops a few months or years after starting drug intake or 3 months after stopping therapy. The diagnosis of TDID is based on the persistence of dystonic hyperkinesis for more than 1 month, the use of a dopamine receptor blocking agent, and the absence of other causes of its development. The risk factors for DID are male sex; young age (less than 30 years of age); a history of dystonic reactions; hypocalcemia, alcohol use while taking the drug. DID is most commonly related to therapy with antipsychotics, metoclopramide, antidepressants, and antiepileptic drugs. The short-term use of anticholinergic drugs (benzotropin, diphenhydramine) is effective in treating ADID. Anticholinergic drugs and atypical antipsychotics (clozapine, quetiapine), benzodiazepines, muscle relaxants (baclofen), and dopamine reuptake inhibitors (tetrabenazine) are used to treat TDID. To prevent DID, it is very important that a physician should be aware of that this unwanted adverse reaction may occur and that a drug with the lowest risk for DID should be chosen.


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Objective: to assess results from the Stroke Network created on the basis of the Infarction Network in the metropolis Moscow for endovascular treatment in patients with occlusion of the large cerebral artery (the internal carotid artery, the M1 and M2 segments of the middle cerebral artery, and the main artery).

Patients and methods. A total of 742 thromboextractions were performed in patients with ischemic stroke in Moscow Stroke Network hospitals in 2019. The final analysis included 729 patients aged 25 to 97 years (mean age, 71 years); of them there were 370 (50.8%) men and 359 (49.2%) women. The selection criteria for endovascular treatment for ischemic stroke were consistent with those set out in the 2015 American Heart Association/American Stroke Association (AHA/ASA) guidelines, which included a pre-stroke modified Rankin Scale (MRS) score of 0–1; ≥18 years of age; a National Institutes of Health Stroke Scale (NIHSS) score of ≥6; and an Alberta Stroke Programme Early CT score (ASPECTS) ≥6. The angiographic results were assessed using the Thrombolysis in Cerebral Infarction (TICI) scale. The clinical outcomes were measured with the NIHSS and the MRS.

Results and discussion. Successful recanalization (TICI 2b/3) was achieved in 547 (75%) patients. The predominant technique for thromboextraction was thromboaspiration that was used in 376 (51.6%) patients. Combined procedures (the co-use of an aspiration catheter and a stent retriever) were the second most commonly used – in 231 (31.7%) patients. By the end of the 20th day, good functional recovery (MSR 0–2 scores) was observed in 213 (29.2%) patients. The 20-day mortality rate was 31.8%.

Conclusion. The successfully functioning Infarction Network in Moscow was used to create the Stroke Network for treatment in patients with ischemic stroke and large cerebral artery occlusion, the clinical results of which are comparable to large European registry studies.

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The severity of neurological disorders in ischemic stroke (IS) in the presence of atrial fibrillation (AF) is known to be higher than that in patients with sinus rhythm. The impact of preventive antithrombotic therapy (ATT) on the clinical manifestations and outcomes of stroke remains a matter of debate.

Objective: to analyze the quality of preventive ATT and to clarify its relationship to the severity of IS in AF.

Patients and methods. The data from the registry of patients (n = 200; 96 (48%) men) (mean age, 71±9 years) with IS and AF were analyzed. Neurological deficit at admission was graded using the National Institutes of Health Stroke Scale (NIHSS). The presence and nature of prestroke antithrombotic therapy were studied.

Results and discussion. Prestroke ATT was performed in 80 (40%) patients, of whom 36 (18%) took antiplatelet agents (APAs). Oral anticoagulants (OACs) were given to 44 patients. The international normalized ratio (INR) in the use of vitamin K antagonists (VKAs) averaged 1.26 [1.11; 1.64]. Neurological deficit was most obvious in the patients who had not previously received ATT (a NIHSS score of 8 [5; 12]). In comparison with them, the regular use of ATT, including APAs and OACs, was associated with the greater likelihood of less severe neurological deficit (a NIHSS of <8): odds ratio (OR), 2.121; 95% confidence interval (CI), 1.178–3.820. The greatest decrease in stroke severity was related to direct (OACs) (DOACs): OR, 2.727 (95% CI, 1.049–7.089), while there was no positive effect of VKAs (OR, 1.534; 95% CI, 0.538–4.377), which was associated with failure to achieve the INR target. Improvement was also related to the prescription of APAs (OR, 2.111; 95% CI, 0.981–4.539).

Conclusion. Preventive ATT for a significant proportion of AF patients does not meet the current recommendations. At the same time, ATT, especially that with DOACs, is associated with the lesser severity of IS.

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Children and adolescents are more likely than adults to experience adverse side effects when taking antipsychotics. Pharmacogenetic testing allows one to more accurately choose the initial dose of a drug. The genes of pharmacokinetic factors have been shown to be of high prognostic value for the safety of antipsychotics in adults.

Patients and methods. The study enrolled 36 adolescents (58.3% male) (mean age, 14.83±1.84 years). All the patients took an antipsychotic. The follow-up lasted 28 days. On 14 and 28 days of treatment, its efficiency and safety were evaluated using the Children's Global Assessment Scale (CGAS), the Positive and Negative Syndrome Scale (PANSS), the Udvalg for Kliniske Undersњgelser Side Effects Rating Scale (UKU-SERS), the Simpson-Angus Scale (SAS), and the Barnes Akathisia Rating Scale (BARS). The patients were genotyped for CYP3A4*22, CYP3A5*3, CYP2D6*4, *9, *10, ABCB1 1236C>T, 2677G>T/A, 3435C>T, DRD2 rs1800497, DRD4 rs1800955, and HTR2A rs6313.

Results and discussion. The decrease in the mean score of the PANSS subscale “Productive symptoms” was more pronounced in carriers of the DRD2 rs1800497 polymorphic variant (-6.5 [-10.25; -3.75] vs -3 [-6.5; -2 ] on 14 day (p=0.028) and (-11 [-13; -9.5] vs -5 [-9; -3.5] on 28 day (p=0.001) compared to baseline. The carriage of ABCB1 3435CT+TT was associated with worse tolerance to pharmacotherapy on 14 day (the total score of the UKU-SERS M, 8 [3; 11.75] vs M, 2 [1; 6]; p=0.034). The carriers of DRD2 rs1800497 reported a greater severity of antipsychotic-induced neurological disorders (UKU-SERS subscale score M, 1 [0; 2.25] vs M 0 [0; 1]; p=0.029).

Conclusion. The polymorphic variants DRD2 rs1800497 and ABCB1 3435C>T were established to be significantly associated with the efficacy and safety of antipsychotics in adolescents with an acute psychotic episode.

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Angioreconstructive interventions are generally known to be of prophylactic value for cerebrovascular diseases (CVD). At the same time, their prognosis in comorbid patients, particularly in those with type 2 diabetes (T2D), have been insufficiently covered.

Objective: to study the impact of T2D on cognitive functions after carotid angioplasty with stenting (CAS)

Patients and methods. CAS was performed in 99 patients with chronic CVD. Group 1 consisted of 51 patients (median age, 64.5 years) without carbohydrate metabolism disorders. Group 2 included 48 patients (median age, 64 years) with T2D. Over time, all the patients underwent clinical, neurological, and neuropsychological examinations, general clinical and biochemical blood tests, duplex scanning of the brachiocephalic arteries, and magnetic resonance imaging (MRI) of the brain. Blood flow in the middle cerebral artery was monitored to assess the embolic and hemodynamic situation during a CAS procedure.

Results and discussion. The baseline frequency of neurocognitive impairment was almost the same (75%) in both groups; however, the impairment was more obvious in patients with T2D. Re-examination in Group 1 patients immediately after intervention revealed slight positive cognitive changes, while the patients with T2D showed a decrease in the indicators of mental functions. The improved ability to abstract and increase the level of generalization of functions appeared in T2D patients only 2 months after intervention. Post-CAS MRI revealed ipsilateral acute ischemic foci (AIF) in the brain substance in 11 (22%) patients of Group 1 and in 24 (50%) with concomitant T2D. Comparison of neuroimaging data with cognitive function assessments for the entire group of the examinees established deterioration in the cognitive status in patients with new ischemic brain changes detected after intervention.

Conclusion. CVD concurrent with T2D usually contributes to deterioration in the cognitive status. Angioreconstructive interventions, in particular CAS, are frequently accompanied by the identification of AIF (including «silent» ones) that can cause a transient deterioration in cognitive functions. When planning angioreconstructive interventions in patients with T2D, the question arises of predicting such risks and possible neuroprotective methods.

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Depression is one of the most common non-motor manifestations of Parkinson's disease (PD), which largely determines both the severity of the course of the disease and the life expectancy of patients, as well as the compliance of patients to and the efficiency of antiparkinsonian therapy. In this connection, the search for a safe and effective antidepressant for patients with PD is of particular relevance.

Objective: to evaluate the efficacy and safety of vortioxetine in patients with PD complicated by mild to moderate depression.

Patients and methods. Examinations were made in 150 patients with PD in its early and advanced stages (Hoehn-Yahr stages: 1.0 to 3.0). All the patients were treated with vortioxetine at a dose of 15 or 20 mg/day for 8 months. The investigators used clinical and psychopathological rating scales, such as the Hospital Depression Scale (HADS-D), the Hospital Anxiety Scale (HADS-A), the Beck Depression Inventory (BDI), and the Montgomery-Asberg Depression Rating Scale (MADRS). The severity of PD motor manifestations was assessed according to the Unified PD Rating Scale (UPDRS) Part III.

Results and discussion. During the follow-up period corresponding to 12 weeks of vortioxetine use, all the patients showed a significant decrease in MARDS, HADS-A and HADS-D, and BDI scores for depression and anxiety (p < 0.001). Vortioxetine demonstrated an optimal balance between tolerability and clinical efficacy in correcting affective disorders in this patient group. In addition, analysis of the dynamics of motor disorders yielded data on the improvement of movement functions while correcting depression as lower UPDRS Part III total scores (p < 0.001).

Conclusion. The findings suggest that vortioxetine has a significant effect on depression and anxiety in patients with PD in its early and advanced stages, good tolerability, and a rapid-onset effect.

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Depression in Parkinson’s disease (PD) is one of the leading manifestations of the disease, which reduces quality of life in patients.

Objective: to compare the clinical features of depression at different stages of PD.

Patients and methods. Examinations were made in 162 PD patients aged 62.14±1.99 years without dementia (PD duration, 5.78±0.58 years; Stage, 2.5±0.6). The Unified PD Rating Scale (UPDRS), the Beck Depression Inventory (BDI), and the Spielberger Inventory, the 16-Item PD Fatigue Scale (PFS-16), and the Starkstein Apathy Scale were examined. Dopaminergic agents (DAAs) were prescribed when movement disorders were insufficiently corrected. Antidepressants were not used during the investigation. The follow-up period was 18 months.

Results and discussion. Depression was detected in 136 (84%) patients. Depression symptoms appeared in 16 (12%) patients within 1–8 years before the onset of motor symptoms (MS), in 37 (27%) in the first 2 years after the onset of MS, in 44 (32%) at Hoehn–Yahr stages 2–3 without motor fluctuations (MFs), and in 39 (29%) at the onset of MF. The most severity of depression was noted in cases of its development at the premotor stage and in the period of MF occurrence. During the follow-up, the manifestations of depression disappeared in 16% of the patients taking a DAA; these were relapsing-remitting in 9%, progressive in 11%, or remained stable in 64%. The patients with depression occurring at the premotor stage had a progressive course of depression and a low DAA efficacy: an increase in severity in 30% of cases despite therapy and a reversal in only 10% of cases (versus 25–45% of those at depression onset in the presence of MS). In cases of depression occurring in the first 2 years after MS onset, its reversal was observed in 45%; the group of patients with depression onset in the presence of MF showed a stable course with slight severity fluctuations in 77.8%.

Conclusion. Depression in PD is a heterogeneous affective disorder. There is a relatively favorable course of depression when the latter occurs in the first two years of MS onset. Along with DAA inefficacy, the more severity of depression is noted when the latter occurs in the premotor phase of PD and at the stage of MF.

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Addictive behavioral disorders are multifactorial diseases with clinical, neurophysiological, and genetic heterogeneity, a high comorbidity with other disorders, and a low curability. The etiopathogenetic mechanisms of non-chemical forms of addictive behavior have not been sufficiently studied, which makes it difficult to search for effective therapeutic procedures.

Objective: to study the psychological and genetic components of a non-chemical addictive disorder as the phenomenon of codependency.

Patients and methods. The investigation enrolled 256 women who were divided into three comparison groups: 1) those with the phenomenon of codependency, 2) phenotypically healthy women; 3) a population sample. Psychometric testing was carried out using the «Hand Test» by E. Wagner (adapted by A.I. Gerasimov and S.N. Enikolopov) and the clinical and genealogical characteristics of women with the phenomenon of codependency were studied. Results and discussion. There was a statistically significant predominance of the level of aggressiveness as autoaggression in the structure of the personality profile of women with the phenomenon of codependency (t=2.924–3.015; p=0.004–0.005). The clinical and genealogical characteristics of persons with addictive behavioral disorder as the phenomenon of codependency suggest that there is a statistically significantly high frequency of secondary alcoholism among first-degree and second-degree relatives or both and first-degree male relatives (p<0.001).

Conclusion. The phenomenon of codependency as a non-chemical addiction includes psychological and genetic components. Women with codependency had autoaggressive destructive behavior patterns and a family history of alcoholism. The identified psychogenic characteristics can be considered as a risk for an addictive disease and somatoform disorders.

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Objective: to identify the signs of neuropathic pain (NP) in patients with rheumatoid arthritis (RA) on the basis of the PainDETECT questionnaire and neurological examination.

Patients and methods. A total of 208 RA patients (39 men and 169 women; mean age, 47.7 years) with chronic pain syndrome were examined. The patients underwent rheumatological and neurological examinations; NP was diagnosed using the PainDETECT questionnaire; inflammation severity (DAS28 index), pain intensity (VAS), affective disorders (HADS), and quality of life (EQ-5D) were assessed.

Results and discussion. 172 (82.7%) patients had moderate and high disease activity according to the DAS28. The signs of possible and highly probable NP according to the PainDETECT questionnaire were detected in 29.8 and 26.9% of patients, respectively; they were significantly more likely to be detected in patients with more severe pain syndrome, clinically significant anxiety, and worse quality of life, but were unassociated with RA activity according to the DAS28. Somatosensory nervous system injury (polyneuropathy, tunnel syndromes, and cervical myelopathy) was found in 77.6% of patients with possible NP and in 80.4% with highly probable NP. In other patients, NP might be caused by central sensitization.

 Conclusion. In patients with a RA exacerbation, chronic pain syndrome is caused not only by an active inflammatory process in the joint area and adjacent tissues, but also by somatosensory nervous system injury and central sensitization.


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Anti-glutamic acid decarboxylase (GAD) antibody-associated ataxia is a rarely diagnosed but potentially curable disease associated with autoimmune damage to and death of Purkinje cells in the cerebellar cortex. In Russia, the authors have provided for the first time descriptions of three own observations of this disease, which had a number of clinical features, such as slow progression, mild ataxia, stroke-like episodes with stem symptoms, concomitant gluten sensitivity, onset of ataxia after hepatitis C with cerebellar hemiataxia and hemiatrophy. In the all patients, the diagnosis was verified based on the determination of high anti-GAD antibody titers in serum and cerebrospinal fluid. All the patients lacked intrathecal synthesis of oligoclonal antibodies; protein levels and cytosis were normal. Pulse therapy with methylprednisolone at a total dose of 3–5 g led to a slight reduction in ataxia in one case (a female patient with subacute onset of the disease); the treatment was ineffective in two other cases (patients with a primary chronic course). The paper analyzes the literature covering the pathogenesis and clinical presentations of this type of ataxia, and difficulties in its diagnosis and treatment.

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The paper reviews clinical trials evaluating the efficacy of N-methyl-D-aspartate (NMDA) receptor antagonists used to treat various neurological diseases: neurodegenerative dementias, vascular cognitive disorders, including post-stroke cognitive impairment. It discusses the possibility of treating cognitive disorders with NMDA receptor antagonists in Parkinson's disease, traumatic brain injury, and some other diseases, as well as the potential possibilities of using drugs of this pharmacotherapeutic group in childhood. The paper describes a clinical case illustrating the use of akatinol memantine in a child with a delay in speech and mental development in the presence of fetal alcohol syndrome. The possibilities of using akatinol memantine in the treatment of childhood cognitive impairments are sure to be of particular interest; however, in view of the small amount of data, this aspect requires further clinical trials.


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At the present stage of development of medicine and society, there is no doubt that early detection and treatment of nervous system diseases accompanied by impaired cognitive functions is one of the main tasks of clinical neurology. The prevalence of cognitive impairment (CI) is so high that today we can say that it exceeds the particular "epidemic" threshold, when the problem causes not only medical, but also a serious socioeconomic burden. Currently, studies of the problem of CI have shifted focus to the non-dementia stages of diseases. In recent years, it has become possible to make early nosological diagnosis of CI even before the development of dementia, which is associated with the development and introduction of in vivo laboratory and neuroimaging markers of Alzheimer's, neurodegenerative, and vascular processes. The paper discusses the existing classification and diagnostic criteria for non-dementia stages of CI. It proposes a new category, such as the initial signs of cognitive impairment, and presents diagnostic criteria. The author considers the importance of an integrated approach to diagnosing CI with the aim of early identification of the nosological entity of the syndrome. He presents a critical review of existing approaches to preventing and treating the non-dementia stages of CI.

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The paper presents the current etiopathogenetic classification of chronic cerebrovascular diseases (CVD) and discusses the role of hypertension, cerebral amyloid angiopathy, and genetically determined syndromes in the development of this pathological condition. It gives recommendations for the neuroradiological diagnosis of chronic CVD in accordance with the international standards. The paper discusses the clinical manifestations of chronic CVD, primarily vascular cognitive impairment. It discusses international guidelines for the examination and treatment of patients with chronic CVD, as well as the rules for stroke prevention in this patient cohort. The possibilities of pathogenetically based therapy in decreasing the severity of vascular cognitive impairment in the presence of chronic CVD are also highlighted.

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Hypertension is a widespread disease related to modifiable vascular risk factors for stroke and chronic cerebrovascular diseases. The pathogenetic basis of brain damage in hypertension is cerebral microangiopathy that leads to vascular cognitive impairment (CI), instability, and falls. Microcirculatory changes in the presence of hypertension at the initial stages of cerebrovascular disease occur without visible clinical manifestations of brain damage. Pathogenetically justified treatment used at an early stage of the disease makes it possible to achieve good results in the prevention of vascular brain damage. An important aspect of selecting effective therapy is the competent diagnosis of the causes of dizziness and instability, which can be caused not only by brain damage, but also by peripheral vestibular system diseases. Early diagnosis of vascular CI, selection of adequate therapy, and prevention of their further progression are of great importance. The studies performed have shown the high efficacy of vinpocetine (Cavinton®) that has a multifactorial mechanism of action in the treatment and prevention of CI, dizziness, and instability caused by cerebrovascular disease.

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Idiopathic cervical dystonia (CD) is a movement disorder that is characterized by sustained or intermittent muscle contractions causing often repetitive movements, fixed postures, or both. This is the most common form of focal dystonia. The lack of highly effective rehabilitation in CD can substantially increase the number of disabled people and/or lead to a significant decrease in the working capacity of young patients. Despite the high social significance of the problem, there are currently insufficient studies of the use of medical and physical rehabilitation methods for CD. Taking into account the complexity, multicomponent pattern, and clinical diversity of CD manifestations, these patients require multidisciplinary treatment and rehabilitation approaches to achieve maximum results. This review discusses rehabilitation strategies and methods in CD, which are based on the modern understanding of the etiology and pathogenesis of the disease. As a supplement to botulinum toxin therapy, a multimodal physiotherapy program, kinesio taping, and special and general strengthening physical exercises are considered, which can assist in correcting the posture, reducing the severity of pain in patients with CD, improving daily activity, and increasing the intervals between botulinum toxin injections and lowering the dose of the drug administered.

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The paper provides a definition of sexual and reproductive health and infertility and also reflects modern ideas about ways to overcome infertility using assisted reproductive technologies, such as in vitro fertilization (IVF) and surrogacy. It shows the specificity of the impact of an IVF procedure on the mental health of a potential mother. The features of the neonatal health status, as well as neuropsychiatric disorders in babies born using the IVF procedure are described. The authors present two types of surrogacy (traditional and gestational ones) and the features of their use in different countries according to governmental legislative regulation, socioeconomic and religious factors, and cultural traditions in society. They unveil the features of a psychological relationship between the mother (surrogate and presumed one) and the fetus. The consequences of surrogacy for a surrogate mother, genetic parents, and a child himself/herself are noted to be little studied. It is shown that the development of assisted reproductive technologies (IVF and surrogacy), on the one hand, helps fight infertility and, on the other hand, entails a number of problems (moral and ethical, legal, cultural and religious, socioeconomic, and neuropsychiatric ones) that need to be solved in order to prevent psychological, neurological, and mental abnormalities in all the participants (a surrogate mother, an unborn child, and potential parents) in the assisted reproductive process:

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Biological ageing is a process that changes living systems over time, causing impairments in their structure and function. Studying the individual biomarkers of ageing is regarded as the most plausible current theory of age-related inflammatory processes (inflammageing). According to this theory, slightly pronounced chronic aseptic inflammation develops during ageing, which is the basis for the pathogenesis of age-related syndromes and diseases. A key role in implementing different cellular interactions and in regulating the type of an inflammatory response is assigned to the cytokine status (nuclear factor kappa-B (NF-κB), tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1) and IL-6) in an elderly patient with age-related diseases, such as osteoarthritis (OA) and diabetes mellitus (DM), developed in the altered background. Anti-inflammatory drugs include chondroitin sulfate (CS) that, in addition to directly affecting the severity of pain syndrome in OA, also has a modulating effect on the level of systemic inflammation. Pharmaceutical CS plays an important role in tissue remodeling, cell proliferation, migration, and differentiation, apoptosis, activation and deactivation of chemokines and cytokines, by increasing the synthesis of hyaluronic acid and proteoglycans, by suppressing the synthesis of prostaglandin E2 (PGE2), IL-1, and IL-6 and the expression of cytokines and NF-κB. CS belongs to anti-aging drugs.

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Back pain significantly affects quality of life in patients. Therapy for acute and chronic nonspecific back pain (NBS) includes non-drug and drug treatments. The non-drug treatment includes educational conversations with a patient, recommendations to maintain an active lifestyle, therapeutic exercises, behavioral and cognitive-behavioral therapy, and mindfulness. Manual therapy and injections of anesthetics into the area of tender joints may be prescribed. Nonsteroidal anti-inflammatory drugs (NSAIDs) are used for drug treatment of acute and chronic NBS. Antidepressants may be prescribed for chronic pain and depression symptoms. B vitamins (thiamine, pyridoxine, and cyanocobalamin) can be considered as adjuvant analgesics in NBS. The results of animal experimental studies have shown that B vitamins at high doses have analgesic and anti-inflammatory effects. Clinical studies, a systematic review, and a meta-analysis published in 2020 demonstrated the safety and advantages of combination therapy with NSAIDs and B vitamins over NSAID monotherapy in the treatment of acute NBS and exacerbations of chronic NBS. The addition of B vitamins to NSAIDs can reduce the duration of treatment by 2 times. By reducing the duration of pharmacotherapy, the risk of adverse reactions to NSAIDs decreases and the patient returns to daily activities more quickly. It is advisable to conduct further, larger studies of combined pharmacotherapy for NBS.


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Transdermal nonsteroidal anti-inflammatory drugs (NSAIDs) are actively used for mild and moderate pain syndrome, muscle contusions and sprains, sports injuries, and the widest range of musculoskeletal diseases. The transdermal administration of NSAIDs aims to create sufficiently high drug concentrations in the lesion focus, provided that the side effects associated with its systemic action are maximally reduced.

Objective: to comparatively simulate the effects of transdermal NSAIDs.

Material and methods. Chemoreactome profiling of six NSAIDs (meloxicam, diclofenac, ibuprofen, ketoprofen, nimesulide, and dexketoprofen) was performed. The pharmacological capabilities of molecules were analyzed within the framework of a chemoreactome methodology, by comparing the chemical structure of the studied molecule with those of millions of other molecules, the pharmacological properties of which had already been studied in experimental and clinical studies. Training the artificial intelligence algorithms based on the big data available in in the databases PubChem/PHARMGKB, HMDB, STRING, and others was done with multi-level training quality control in the cross validation framework according to the combinatorial theory of solvability and the theory of feature value classification.

Results and discussion. Meloxicam versus other NSAIDs accumulates primarily in the muscles and skin and, to a much lesser extent, in heart tissues, lymphocytes, gonads, and cartilage. This drug showed the greatest dose-dependent decongestant effect in the model of edema induced by croton oil. Analysis of the systemic effects of NSAIDs indicated that meloxicam might affect the metabolism of vitamins A, D, PP, and B6 to a lesser extent than other NSAIDs.

Conclusion. The chemoreactomе analysis has demonstrated that meloxicam as a gel causing minimal side effects can be used effectively and long.

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Postgenomic pharmacology deals with the desirable and undesirable effects of drugs in relation to the genome, transcriptome, proteome, and reactome. The transcriptomic activity of ethylmethylhydroxypyridine succinate (EMHPS) has not been previously characterized.

Objective: to investigate the dose-dependent effects of EMHPS on the transcription of 12,700 annotated human genes in the neural progenitor cells (NPC.TAK cell line).

Material and methods. The paper presents the results of chemotranscriptome analysis of the EMHPS molecule from the point of view of its impact on transcription of the human genome in the NPC.TAK line cells during 24-hour incubation of cells with EMHPS.

Results and discussion. The significant dose-dependent effects of EMHPS on transcription (on average, ≥10% transcription changes for each 1 μmol/L of EMHPS) were evaluated for 2,400 of the 12,700 annotated human genes. EMHPS reduced the transcription of groups of the genes that were involved in cell division (n = 226), those in gene expression processes (n = 122), and those in protein synthesis, degradation, and secretion (n = 123). EMHPS increased the transcription of the genes encoding proteins involved in neurotransmission (n = 103) and those in exerting neuroprotective and neurotrophic effects (n = 49).

Conclusion. The efficacy of EMHPS may be related to its effect on the transcription of the genes that are involved in neurotransmission and in the showing of neuroprotective and neurotrophic effects.


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The need for optimal treatment of the active forms of multiple sclerosis (MS), especially highly active MS (HAMS), poses a number of difficult problems for specialists, including not only the choice of a highly effective disease-modifying drug for MS (DMDMS), but also conditions for the timely and safe switching from other DMDMS. A group of expert neurologists from various clinics in Russia presents a consensus on the practical aspects of switching patients with HAMS from other DMDMS to cladribine tablets, which has been registered in Russia in March 2020. The paper discusses indications for changing therapy and gives indications, contraindications, and conditions for initiating cladribine therapy. It details the procedure and results of the expert consensus, on the basis of which the recommendations have been developed to switch to cladribine tablets from each of the DMDMS registered in Russia for the treatment of MS.

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ISSN 2074-2711 (Print)
ISSN 2310-1342 (Online)