Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova最新文献

The etiology and pathogenesis of schizophrenia remain poorly understood, but it has been established that the contribution of heredity to the development of the disease is about 80-85%. Over the past decade, significant progress has been made in the search for specific genetic variants associated with the development of schizophrenia. The review discusses the results of modern large-scale studies aimed at searching for genetic associations with schizophrenia: genome-wide association studies (GWAS) and the search for rare variants (mutations or copy number variations, CNV), including the use of whole exome sequencing. We synthesize data on currently known genes that are significantly associated with schizophrenia and discuss their biological functions in order to identify the main molecular pathways involved in the pathophysiology of schizophrenia.

Background: The purpose is to study the structure of clinical manifestations of mental disorders in the acute period of COVID-19 among patients, who were hospitalized with a new coronavirus infection and their relations with the severity of the immune response, to assess the efficacy and safety profile of the spectrum of used psychopharmacotherapy.

Material and methods: A study was conducted of patients, hospitalized to the department of infectious diseases and repurposed for COVID-19 clinical departments with a diagnosis of COVID-19 (compliance with the criteria for ICD-10: U07.1) from September 2020 to March 2021. Study design: single center opened retrospective cohort study. The main group is consisted of 72 patients, average age - 71 [56.0; 81.0] years, the part of women - 64.0%. The control group (n=2221) was formed from those hospitalized in the same period with a diagnosis of U07.1 without mental disorders during the hospitalization period, average age 62 [51.0; 72.0] years, the part of women - 48.7%. Mental disorders were diagnosed in accordance to ICD-10 criteria, the following peripheral markers of inflammation, that were evaluated: neutrophils, lymphocytes, platelets, ESR, C-reactive protein, interleukin; also coagulogram indicators: APTT, fibrinogen, prothrombin time, D-dimers.

Results: In the following range of mental disorders were identified: a depressive episode (ICD-10 F32) by 31 patients, by 22 - a disorder of adaptive reactions (ICD-10 F43.2), by 5 - delirium not caused by alcohol or other psychoactive substances (ICD-10 F05), by 14 - mild cognitive impairment caused by damage and disfunction of the brain or somatic diseases (ICD-10 F06.7). In comparison with the control group, these patients showed a statistically significant (p<0.001) increasing the level of inflammatory markers (CRP, IL-6) and changes in the coagulogram. and anxiolytic drugs were used most often. Regarding psychopharmacotherapy, drugs from the group of atypical antipsychotics - quetiapine was prescribed in 44% patients in average dose 62.5 mg per day, and Melatonin receptor type 1 and 2 agonist and antagonists of serotonin 5-HT2C receptors: agomelatine was prescribed in 11% patients in average dose 25 mg per gay.

Conclusion: The results of the study confirm the heterogeneity of the structure of mental disorders in the acute form of coronavirus infection, revealing the relations between the clinical picture and laboratory parameters of the immune response to systemic inflammation. Recommendations are given for the choice of psychopharmacotherapy, in conformity with the peculiarities of pharmacokinetics and interaction with somatotropic therapy.

Objective: To identify risk factors and predictors of the development of psychotic disorders in patients who used synthetic cathinones (SKat).

Material and methods: The study included 176 patients who used SKat, which was toxicologically confirmed. One hundred and eleven (63.1%) were male and 65 (36.9%) were female. The median age was 27 years (22-32 (Q1-Q3)). Patients were divided into main and control groups depending on the presence of a psychotic disorder. The main group (those who developed psychosis) consisted of 98 patients, the control groupincluded 78 participants. Clinical-psychopathological, parametric and statistical methods were performed to study predictors and risk factors for the development of psychotic disorders associated with the use of SKat.

Results: The study established factors influencing the incidence of psychosis. Older patients were more likely to develop psychosis (p=0.002). Patients who used SKat for more than 21 consecutive days developed psychoses more often (p=0.048). The use of α-pvp (α-pyrrolidinovalerophenone, alpha-pvp) more often led to the development of psychosis (p<0.001). Patients undergoing rehabilitation were less likely to experience the development of psychosis (p=0.009). The resulting regression model is statistically significant (p<0.001). Based on the value of the Nigelkirk coefficient of determination, the model explains 30.9% of the observed group variance. It has been established that the combination of the following factors increases the chances of developing psychosis: female gender, age, duration of daily use, the presence of signs of mental infantilism, fear of the dark in childhood. In turn, the experience of undergoing rehabilitation and any pathology of the mother's pregnancy reduces the risk of psychosis.

Conclusion: The results are consistent with other studies of substance-induced psychoses. The observed patterns demonstrate that this is a special group of disorders that requires the attention of specialists. The results allow us to outline the field for further study, and may also be useful in the development of therapeutic and preventive recommendations.

The review presents current data on the use of positron emission tomography and single-photon emission computed tomography in multiple sclerosis (MS) to assess the activity of the pathological process, including neuroinflammation, demyelination, activation of microglia, neurodegeneration and local blood flow disorders. These methodologies are a new approach for studying the mechanisms of action and evaluating the clinical effect of disease modifying therapy of MS, especially those capable of penetrating into brain tissue. Among them, the most attention is attracted by cladribine tablets acting on the mechanism of immune reconstitution therapy, most likely with the modulation of immune reactions directly in the brain tissue.

Bilateral vestibulopathy is a relatively widespread and at the same time rarely diagnosed cause of chronic postural instability. Numerous toxic factors, dysmetabolic, autoimmune and neurodegenerative processes can lead to this condition. The main clinical manifestations of bilateral vestibulopathy are balance disorders and visual disturbances (oscillopsia), which can significantly increase the risks of falls in such patients. In addition, cognitive and affective disorders, which also reduce the quality of life in patients with bilateral vestibulopathy, have been described and actively studied in recent years. The diagnosis of bilateral vestibulopathy is based on the results of a clinical neurovestibular study, including a dynamic visual acuity test and a Halmagyi test. A video head impulse test, a bithermal caloric test and a sinusoidal rotation test are used as instrumental methods confirming the dysfunction of the peripheral vestibular system. However, they are still not widespread in neurological practice. Treatment of bilateral vestibulopathy is reduced to vestibular rehabilitation. Encouraging results have been obtained in a number of studies using galvanic vestibular stimulation and the use of vestibular implants. In addition, cognitive rehabilitation methods are currently being developed, which presumably can also improve compensation for bilateral vestibular loss.

Objective: To find the optimal therapeutic dose of the anti-B cell mAb divozilimab (DIV) based on the efficacy and safety data of intravenous administration at a dose of 125 mg or 500 mg in patients with relapsing remitting multiple sclerosis (RRMS) compared to placebo (PBO) and teriflunomide (TRF). To study the efficacy and safety of DIV within 24 weeks of treatment.

Material and methods: A multicenter, randomized, double-blind and double-masked, placebo-controlled phase 2 clinical trial (CT) BCD-132-2 involved 271 adult patients with RRMS from 25 centres In Russia. Patients were randomly assigned (2:2:2:1) into 4 groups: TRF, DIV 125 mg, DIV 500 mg and PBO. After screening patients entered to the main period, which consisted of one cycle of therapy for 24 weeks. The primary endpoint was the total number of gadolinium-enhancing T1 lesions (Gd+) observed on brain MRI scans after 24 weeks (per scan - involves estimating the mean value of the score from all the MRI assessments performed for each participant in the study).

Results: 263 patients completed 24 weeks of treatment. Most of the patients in the DIV groups had no lesions on T1-weighted MRI after 24 weeks of treatment (94.44% on 125 mg and 93.06% on 500 mg). In the TRF and PBO groups the values were significantly lower: 68.06% and 56.36% respectively (both p<0.05). The proportions of relapse-free patients in the DIV groups were 93.06% and 97.22% (125 mg and 500 mg, respectively). As expected, DIV reduced the CD19+ B-cells. However, the repopulation rate of CD19+ B-cells in the 125 mg group was more pronounced (mainly due to the recovering pool of CD27-naive B-cells) compared to the 500 mg group. DIV showed a favorable safety profile at both doses.

Conclusion: Thus, the assessment of 24 weeks treatment demonstrated that DIV is a highly effective, safe and convenient option for the treatment of RRMS patients, both naive and previously treated with disease modifying therapy. A dose of 500 mg is recommended for further efficacy and safety evaluation during phase 3 CT.

The article reports on the rarest case of Guillain-Barré syndrome in the form of acute motor-sensory polyneuropathy in a female patient with tuberculous meningitis, disseminated pulmonary tuberculosis, and tuberculous pleurisy. In the neurological status at the exit from the coma, the patient was diagnosed with tetraplegia, bulbar syndrome, and respiratory disorders. Further, within a week, pronounced muscle atrophy appeared. Active etiotropic, pathogenetic therapy, including plasmapheresis, gave a dramatic effect with a significant improvement in the condition and a gradual regression of neurological disorders. The differential diagnosis was carried out primarily with critical illness polyneuropathy. The authors emphasize the rarity of the presented case: to date, such a combination of pathologies has never been described in the literature.

Objective: Evaluation of the bioequivalence of the tested Relonova, tablets, 10 mg and Maxalt, tablets, 10 mg drugs on an empty stomach in healthy volunteers.

Material and methods: The pharmacokinetic analysis population included 40 volunteers, the safety analysis population included 40 volunteers. The average age of randomized volunteers (men - 20, women - 20) was 29.3±8.9 years, height 1.71±0.09 m, body weight 70.86±11.66 kg, mean BMI 24.18±2.81 kg/m². The method used high performance liquid chromatography with tandem mass spectrometric detection. Statistical analysis of the obtained data was performed based on the assumption of a log-normal distribution of the parameters AUC0-72 and Cmax.

Results: The ratio of geometric means for the key pharmacokinetic parameters (AUC0-t, AUC0-inf and Cmax) of rizatriptan is close to 90%, CI is within the acceptable range for bioequivalent drugs (80-125%). The intrasubject variability (CVintra) for rizatriptan was 23.74% (Cmax), 10.94% (AUC0-t). The average profiles of the pharmacokinetic curves of rizatriptan when taking the test and reference drugs have similar shapes. Relonova and reference Maxalt are bioequivalent.

Conclusion: The results of the study make it possible to recommend Relonova for further clinical study and wide practical application.

Objective: To identify and study variants of the clinical course of the acute period of ischemic stroke (IS) in young and middle-aged patients, to establish their dependence on the presence of the main risk factors for cardiovascular diseases.

Material and methods: The study included 145 patients (111 men and 34 women) with IS in its acute period, including 22 young (15.2%) and 123 middle-aged people (84.8%). The main risk factors of cardiovascular diseases were analyzed. Five variants of the clinical course of the acute period of IS were identified: regredient, regredient with residual mild focal neurological symptoms, stable, slowly progressive, and rapidly progressive. The regredient course and the regredient course with residual mild focal neurological symptoms are attributed to the favorable course of the acute period of IS; stable, progressive, and rapidly progressive predicted unfavorable course.

Results: Regredient course was observed in 43 (29.7%) patients; regredient with residual mild focal neurological symptoms in 78 (53.8%) patients; stable course was established in 4 (2.8%) patients; slow progressive course in 15 (10.3%) patients and fast progressive course in 5 (3.4%) patients. The following risk factors significantly contributed to the favorable course: less pronounced motor, sensory and speech disorders at the time of admission of the patient to the hospital and at the end of the acute period of IS, timely hospitalization in the neurological department for the treatment of patients with acute disorders of cerebral circulation within the «therapeutic» window, intravenous thrombolytic therapy, mild severity of IS on the NIHSS, a lesion of the vertebral-basilar brain basin, absence of overweight and ischemic heart disease in the patient's anamnesis (p<0.05).

Conclusion: Determining the clinical course of the acute period of IS in young and middle-aged patients will make it possible to predict the rehabilitation potential of a particular patient and increase the effectiveness of individual neurorehabilitation measures at the stages of early and late rehabilitation treatment.

Objective: Systematization and generalization of data from domestic and foreign literature on alternative methods of treatment of sleep disorders in epilepsy.

Material and methods: The search for data from domestic and foreign literary sources was carried out in the electronic databases Medline (PubMed), Scopus, Web of Science, eLibrary, CyberLeninka, Google Scholar.

Results: The data of modern randomized trials, meta-analyzes on the effectiveness of various non-traditional methods as a method of choice for epilepsy with comorbid sleep disorders have been analyzed.

Conclusions: Complementary (alternative) treatments have many advantages over the classical pharmacotherapy of sleep disorders in epilepsy, in the form of non-invasiveness, low incidence of side-effects, ease of use, and lack of a dose-dependent effect. Of course, the targets of most of the above methods are not focused and not very specific, and the sample size is too small to obtain impartial and meaningful clinical conclusions, but this once again emphasizes the urgent need for large-scale clinical trials, which is necessary to develop evidence-based treatments for comorbid sleep disorders in epilepsy.