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Neurology, Neuropsychiatry, Psychosomatics

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Vol 13, No 1S (2021): Спецвыпуск: рассеянный склероз
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https://doi.org/10.14412/2074-2711-2021-1S

LECTURES 

4-9 80
Abstract

A significant number of unique antigens expressed in the brain can activate an adaptive immune response, increasing the risk of autoimmune inflammation in the central nervous system (CNS). As a result, a complex protection system exists in the CNS to prevent autoimmune reactions. In addition to the blood-brain- and blood-cerebrospinal fluid-barriers, we discuss complex systems of antigen drainage and circulation of antigen-presenting cells in the CNS. Moreover, the interaction of the CNS with the peripheral immune system typically occurs in specific areas (choroid plexuses, perivascular spaces, and brain meninges), and resident cells of the innate immune system (macrophages, microglia, astrocytes) have limited opportunities for antigen presentation and do not migrate to regional lymph nodes. There are signs of activation of adaptive immunity against CNS antigens in normal conditions, which, however, do not lead to autoimmune diseases. The review covers the mechanisms of maintaining natural immune self-tolerance in the CNS and their failure in autoimmune CNS pathology.

ORIGINAL INVESTIGATIONS 

10-14 57
Abstract

Multiple sclerosis (MS) is a common autoimmune disease, which etiology includes a complex of genetic and environmental factors. Data suggests that their interaction can influence the age of the clinical manifestations and the course of the disease. Therefore, the study of risk factors of MS in regions with different ethnic compositions of the population and climatic and geographical characteristics is of considerable interest.

Objective: to study MS risk factors prevalence in the Republic of Kabardino-Balkaria (RKB).

Patients and methods. This case-control study of the representation of risk factors included a cohort of 112 MS patients living in two regions of the RKB (Nalchik and the Prokhladnensky district). The MS diagnosis was established with the McDonald criteria (2017). MS risk factors were assessed with a unified questionnaire. 112 respondents (matched by the main demographic characteristics and place of residence) were included in the control group.

Results and discussion. MS patients from the Prokhladnensky district were significantly more likely to contact harmful chemical compounds, had higher consumption of smoked meat products; and suffered from viral infections more often (all differences were significant, p<0.05). More patients with MS, regardless of their place of residence, had a history of scarlet fever than the controls (n=23; 19.5% and n=14; 13.4%, ratio indicator 0.43 (95% CI 0.32–1.01), p=0.041), and the maximum significance of this factor was found in patients who suffered from scarlet fever after the age of 15 years (n=7; 6.3% and n=1; 0.9%, ratio indicator 2.45 (95% CI 1.92–3.21), p=0.041). More patients with MS had a history of chickenpox (n=70; 62.5% and n=55; 41.1%; ratio indicator 0.78 (95% CI 0.65–0.94, p=0.032), the frequency of this factor was most significant in early (up to 7 years) disease onset. Regardless of the place of residence, patients with MS were more likely to suffer from tonsillitis and sinusitis in childhood (p=0.032).

Conclusion. In the RKB, as in other regions of the Russian Federation, the risk of MS, along with a genetic predisposition, is primarily determined by environmental factors, such as contact with potentially harmful chemicals, history of somatic diseases, characteristics of the ecological situation, etc. Therefore, MS risk is higher in people exposed to these factors before the age of 7 years and does not depend on the place of residence. 

15-20 66
Abstract

An expansion of the age range of multiple sclerosis (MS) manifestation has been reported recently. Considering the multifactorial etiology, high heterogeneity of the clinical symptoms, and the difficulties of early MS diagnosis in young people, the onset and course of this disease in students can be considered as one of the significant medical and social problems.

Objective: to analyze the clinical and epidemiological characteristics of MS in university and secondary specialized educational institutions students in the Republic of Bashkortostan (RB).

Patients and methods. This case-control study included 32 patients aged 15 to 24 years studying in universities and secondary schools of the RB. The clinical and epidemiological indicators analysis was carried out based on data from the register of MS patients in the RB. 32 sex-, age-, place of birth and residence-matching patients with MS, who were not students, were included in the control group.

Results and discussion. The median age of disease manifestation in students was 18 [16.5; 20] years, in the control group – 16 [14; 19] years (p=0.010). We found a lower «disease onset – diagnosis» in the students group of revealed a lower interval «disease onset – diagnosis» (0.5 [0; 1] years, p=0.006), and a shorter duration of MS compared to the control group ((2.8 [2; 4] years and 4 [2; 7] years, respectively, p=0.020). Students with MS predominantly had movement disorders: central paresis and cerebellar ataxia. Students also had a faster MS progression (0.4 [0.2; 0.6] EDSS scores per year, p=0.001), despite of the disease-modifying therapies.

Conclusion. MS manifestation and course in students receiving disease-modifying therapies indicate the need for close follow-up, adherence control, and psychological support in the educational process.

21-26 80
Abstract

To date, the features of clinical presentation, course, and the effectiveness of therapy for multiple sclerosis (MS) in the presence of persistent herpesvirus infection (PHVI) remain poorly understood.

Objective: to evaluate the features of clinical presentation and course of MS in patients with PHVI to optimize patient management.

Patients and methods. We examined 122 patients with a clinically definite diagnosis of MS according to McDonald criteria (2010) (82 women and 40 men, age: 18–50 years, mean age – 37.74±11.04 years). MS duration at the time of examination was from 6 months to 20 years (mean – 8.53±7.47 years), mean Expanded Disability Status Scale (EDSS) score – 2.91±1.67. 86% of patients had relapsing-remitting MS; 14% – secondary progressive MS. 98 (80%) patients received disease modifying therapies (DMTs). All patients underwent a comprehensive clinical and neurological examination, magnetic resonance imaging (MRI). 30 healthy donors (20 women and 10 men, age: 19–62 years, mean age: 39.1±12.1 years) were included in the control group. Serum levels of type-specific IgM and IgG antibodies to herpes simplex virus (HSV) 1, 2, 6, Varicella zoster virus (VVZ), Epstein–Barr virus (EBV), cytomegalovirus (CMV) were detected, in some patients – blood and cerebrospinal fluid (CSF) polymerase chain reaction, serum and CSF oligoclonal IgG.

Results and discussion. We identified two sub-groups of MS patients: with PHVI reactivation (main group, n=29) and without it (comparison group, n=93). There were a significantly higher VZV (72%) and EBV infection rate (100%) in MS patients compared to the control group (50% and 83%, respectively). Mixed herpesvirus infection prevailed over mono-infection in MS patients. In contrast to controls, the most common viral pattern in MS group was a combination of 4 herpes viruses: HSV 1, 2 + VZV + EBV + CMV (χ2=3.9; p<0.05). Patients in the main group had an unfavorable disease course: earlier MS onset, predominantly polysymptomatic onset, significantly higher relapse rate, faster disease progression, and higher EDSS and Functional Systems Scale (FSS) scores (p <0.05). MRI activity was also associated with EBV infection: new T1Gd+ and T2 foci were associated with an increase in VCA-IgM to EBV level. We also observed decreased DMTs effectiveness (χ2=4,6; p=0,033) and worse DMTs tolerability (χ2=5,3; p=0,022) in the main group.

Conclusion. MS patients with PHVI reactivation, have a more unfavorable course of the demyelinating process and, therefore, a greater degree of disability, compared with age-adjusted patients without a viral infection and the same disease duration.

27-30 93
Abstract

According to numerous studies, gut microbiota plays a significant role in multiple sclerosis (MS) development. However, data on changes in the gut microbiota in MS is often contradictory. The most common approach in gut microbiota research is the 16S ribosomal RNA sequencing of fecal microbiota. However, such data do not reflect the composition of the entire body microbiota. There is also a lack of data on microbiota markers in the cerebrospinal fluid (CSF) of patients with MS and predisposing conditions.

Objective: to assess the level of microbial markers in the CSF of patients with MS and radiologically isolated syndrome (RIS).

Patients and methods. We used gas chromatography-mass spectrometry (GC-MS) to evaluate microbial markers levels in eight patients with MS, five patients with RIS, and seven controls.

Results and discussion. We found an increase in microbial load in patients with MS, indicating a possible association of MS with polymicrobial infection. In particular, an increase in the content of Streptococcus markers was observed, as well as a tendency to a three-fold increase in the campesterol content (a marker of campesterol-producing microfungi) in the CSF of patients with MS, compared to the control group (diagnostic punctures, various diseases of the nervous system of a non-autoimmune or inflammatory nature, not acute states).

Conclusion. GC-MS of microbial markers can be used to assess the presence of microbial markers in the CSF. The CSF of patients with MS contains an increased amount of various microbial markers, which may indicate a possible association of MS with polymicrobial infection.

31-38 65
Abstract

Objective: to perform a genome-wide polygenic analysis of multiple sclerosis (MS) markers in the ethnic groups of Bashkirs, Russians, and Tatars living in the Republic of Bashkortostan (Russian Federation).

Patients and methods. Genotyping was performed using allele-specific polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism analysis of genes of the human leukocyte differentiation antigens CD6 (rs17824933), CD40 (rs6074022), CD58 (rs2300747), CD86 (rs9282641), transcription factors SOX8 (rs2744148) and ZBTB46 (rs6062314), beta-mannosidase MANBA (rs228614), C-type lectin domain CLEC16A (rs12708716), ribosomal protein S6 kinase B1 RPS6KB1 (rs180515), and long noncoding RNA gene PVT1 (rs759648) in 644 patients with MS and 1408 controls. Multilocus analysis of the disease associations with combinations of genotypes and alleles of the studied polymorphic loci was performed using the APSampler algorithm.

Results and discussion. We determined the distribution of genotype and allele frequencies of the studied polymorphic loci in the ethnic groups of Bashkirs, Russians, and Tatars. We also observed disease associations with CD58 (rs2300747) and RPS6KB1 (rs180515) polymorphic loci in Russian men, CD86 (rs9282641) in Russian, PVT1 (rs759648) in Tatar women, CD40 (rs6074022) in Bashkir men, and identified 19 combinations of genotypes and/or alleles significantly associated with MS.

Conclusion. Based on the genome-wide polygenic analysis of MS markers, we identified ethno- and gender-specific combined markers of the disease susceptibility.

39-44 53
Abstract

Management of patients with secondary progressive multiple sclerosis (SPMS) remains one of the most challenging tasks of modern neurology. Patients with SPMS present with more severe neurological symptoms, increased hospitalization frequency, pronounced cognitive impairment in most of them, and a higher level of fatigue than patients with relapsing-remitting MS (RRMS). Another unfavorable course of MS is primary progressive MS (PPMS) when there is a steady increase in neurological disorders from the very beginning of the disease.

Objective: to compare medical and social characteristics and changes in quality of life (QoL) indexes in patients with PPMS and SPMS.

Patients and methods. In total, 437 patients with PPMS from 19 constituent entities of the Russian Federation and 500 patients with SPMS from 15 Russian Federation regions were interviewed using the original medical and social questionnaire. At the same time, we studied the QoL of patients with PPMS and SPMS using the specific MusiQoL questionnaire.

Results and discussion. Among the patients with PPMS, 54.3% were women and 45.7% – men. In patients with SPMS, women predominated (66.3% of women and 33.7% of men – the ratio was almost 2: 1). The degree of disability and the severity of the disease were higher in SPMS than in PPMS. The family continues to be the primary aid source in everyday life for patients with MS: 75–80% of patients who need such support receive it from their significant others. More patients with SPMS indicated a deterioration in their health status over the last year (70%, while among patients with PPMS – 55%). More patients with PPMS received outpatient care (82.1% compared to 64.7% in SPMS; p=0.01). Immobility and SPMS treatment problems were the main reasons for decreased outpatient care in patients with SPMS. Less than half of patients with SPMS (43.8%) and 62% of patients with PPMS received inpatient treatment. According to neurologists reports, there is a major problem in providing MS centers with effective drugs to treat both disease courses. When QoL was assessed, we found more profound changes in SPMS concerning both QoL's psychological and physical components. Only recently, a new drug, siponimod, has been approved for the treatment of SPMS. The lack of effective treatment formed the basis of negative attitudes towards the health care system in SPMS.

Conclusion. QoL changes reflect the patient's attitude to his condition. The introduction of new drugs for the pathogenetic treatment of SPMS (siponimod) will improve the QoL indicators in SPMS.

45-49 77
Abstract

Objective: to study the effectiveness of art therapy methods in the complex treatment of neuropsychological disorders and quality of life improvement in patients with relapsing-remitting and secondary-progressive multiple sclerosis (MS).

Patients and methods. A group of 42 patients (5 men and 37 women, mean age 32.9 years, mean EDSS severity 3.8 points) with MS underwent outpatient continuous active art therapy cycle. The mean group training cycle duration was six months. The comparison group included 15 age- and sex-adjusted individuals without neurological disorders. Tests on various drawing topics were carried out before and after a three-month therapy course. We used Hospital Anxiety and Depression Scale (HADS) to assess the severity of anxiety and depression and the SF-36 scale to evaluate the quality of life (QoL).

Results and discussion. Before the art therapy start, light blue, yellow, pink, blue, and green colors prevailed in the drawings. There was no predominance of any color depending on MS severity or course. The green color predominated in this test in the control group, and the light blue color was significantly less represented. The art therapy course did not lead to a significant change in the severity of MS according to the 

Expanded Disability Status Scale (EDSS). After the art therapy course, the color scheme of the drawings was mainly represented by red, light blue, green, yellow, and blue colors. In addition, a red-orange color appeared in the drawings, which was completely absent before the course. Positive trends were noted according to HADS: a decrease in anxiety by 23% and depression by 19%. The physical component of QoL assessed by the SF-36 scale did not change substantially, but the psychological component significantly improved by 11%.

Conclusion. The predominance of light blue color observed in MS is associated with damage to the nervous and musculoskeletal systems, and blue color – with psychological problems and depression. However, after a course of art therapy for MS, red, red-orange, yellow, and green colors representation increased significantly, which indicates an increase in positive attitude, a decrease in the level of depression, and an improvement in QoL.

50-56 85
Abstract

The problem of an adequate choice of a treatment method in multiple sclerosis (MS) remains one of the most urgent in modern neurology. The number of patients and the cost of drugs are increasing, leading to an increased MS societal burden. However, treatment costs can be reduced due to the introduction of generic drugs, including domestic ones, which price is significantly lower.

Objective: to assess the attitude of Russian patients to the reproduced disease modifying therapies (DMTs) and features influencing an attitude to the replacement from the original to the reproduced drug.

Patients and methods. We interviewed 300 patients from six regions of the Russian Federation, receiving interferon beta-1a 44 μg, interferon beta-1b, glatiramer acetate, and teriflunomide, who had an experience of switching from an original drug to a domestic biosimilar drug or generic not earlier than 2009.

Results and discussion. The majority of patients (63%) do not notice any changes due to drug replacement from the original to the generic one, some (28%) experience a deterioration in their well-being, and others (7%) experience an improvement in their condition. Young patients (up to 30 years) are relatively less likely to notice a deterioration in well-being after drug replacement. The clinical deterioration after drug replacement is much more often experienced by the patients whose drug was replaced in a pharmacy (74% of cases) and not by the attending clinician (only 54% of cases of deterioration). The majority (87%) of patients with relapsing-remitting MS (RRMS) did not interrupt the treatment after replacement; 13% of respondents reported that they had stopped taking the drug. Among them, there were much more patients whose drug was replaced in a pharmacy, and not due to clinician recommendation (more than 80% of such cases). Adverse reactions to a new drug are another reason for drug withdrawal (20% of all withdrawals). Patients receiving interferon beta-1b have a higher negative attitude towards domestic DMTs: 52% of the respondents gave negative feedback (compared to 20–35% in other groups). Relatively higher loyalty to Russian DMTs was observed in patients receiving interferon beta-1a (20% of negative feedback, which is noticeably lower than in other groups) and teriflunomide (a relatively higher proportion of positive feedback to Russian drugs – 25% compared to 11–16% in other groups). The majority (76%) of the respondents noted that they are interested in learning more about the development and registration of new Russian drugs.

Conclusion. The majority of RRMS patients do not tend to have a negative attitude towards Russian DMTs. Consequently, the proportion of ratings in favor of Russian DMTs exceeds the weight of ratings against them. The key priority in the formation of loyalty to Russian DMTs should be changing the perception of adverse reactions. This will significantly increase the adherence to therapy and the quality of the provided treatment.

CLINICAL OBSERVATONS 

57-61 84
Abstract

The presence of a single demyelinating focus with signs of the blood-brain barrier (BBB) disruption, revealed during magnetic resonance imaging (MRI), in the absence of clinical symptoms, is most often an accidental finding and requires careful follow-up and anamnesis clarification for diagnosis. Such a focus can be a sign of multiple sclerosis onset, be a symptom of acute disseminated encephalomyelitis, inflammatory demyelinating pseudotumor, brain tumor, encephalitis, etc. Difficulties of differential diagnosis in a radiologically isolated syndrome are reflected in the presented clinical case of a 26-year-old woman who had recovered from COVID-19, in whom an MRI revealed a large single focus in the left frontal lobe with signs of active process.

REVIEWS 

62-68 75
Abstract

Endothelial dysfunction is a universal pathological mechanism underlying or contributing to the development/progression of many diseases, including cerebrovascular disease and multiple sclerosis. Von Willebrand factor is a multimeric glycoprotein synthesized by endothelial cells and megakaryocytes that participates in a range of physiological and pathological processes, including primary hemostasis and coagulation. It also regulates secretion and transport of a variety of molecules, exerts a proinflammatory effect, modulates angiogenesis and smooth muscle mitotic activity, influences atherogenesis. In this review, we discuss the synthesis, secretion, and regulation of the von Willebrand factor within the context of endothelial dysfunction and other common mechanisms that play a significant role in brain tissue damage in cerebrovascular diseases and multiple sclerosis.

69-72 82
Abstract

The spread of the COVID-19 pandemic posed a serious challenge for scientific and clinical medical institutions in terms of research for new multiple sclerosis (MS) treatments. In this review we discuss the associations between coronavirus infection and MS and provide data on the features of MS pathogenetic therapy during a pandemic. We also analyze the ethical aspects of clinical trials, the problems faced by researchers and patients, especially when using immunosuppressive therapy for MS. We provide examples of violations during research caused by the influence of a pandemic, as well as ways of solving them. Improving ethical standards is an essential component of ensuring the safety of MS and other immune-mediated diseases treatment.



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