[Assessment of the efficacy and safety of alemtuzumab in patients with highly active relapsing-remitting multiple sclerosis in Russian population]. / Otsenka effektivnosti i bezopasnosti alemtuzumaba u patsientov s vysokoaktivnym techeniem rasseyannogo skleroza v rossiiskoi populyatsii.

OBJECTIVE: To evaluate the severity and frequency of infusion reactions (IR) in patients with highly active relapsing-remitting multiple sclerosis (MS) In Russian population receiving alemtuzumab therapy. MATERIAL AND METHODS: In retrospective study, we analyzed data from 50 patients with highly active relapsing-remitting multiple sclerosis (MS) from six Regional MS Centers in the Russian Federation who received two courses of alemtuzumab between 2018 and 2022. RESULTS: Among all IRs, the most frequently reported were hives-like rashes, which were registered in 27 people, mostly of mild severity (70.6%). Headaches were the second most common IR, observed in 17 patients (34%). When comparing the group of patients who underwent music therapy (MT) with those who received alemtuzumab therapy without MT, no statistically significant difference was found in the frequency and severity of IRs. CONCLUSION: All patients experienced IRs of varying degrees of severity. A decrease in the score on the EDSS disability scale was noted. MT did not affect the occurrence or severity of IRs.

[Multiple sclerosis in the Republic of Bashkortostan: population-specific genetic predictors and the results of a 20-year clinical follow-up study]. / Rasseyannyi skleroz v Respublike Bashkortostan: populyatsionno-spetsificheskie geneticheskie prediktory i rezul'taty 20-letnego klinicheskogo nablyudeniya.

OBJECTIVE: Identification of a complex of genetic predictors of multiple sclerosis (MS) based on previously obtained results in genome-wide association studies of disease markers (GWAS markers) in a population of MS patients and healthy individuals of the Republic of Bashkortostan (Russian Federation) using polygenic detection. MATERIAL AND METHODS: The total study group consisted of 2048 people (641 patients with MS and 1407 healthy individuals) who permanently resided in the Republic of Bashkortostan and belonged to the Bashkir (n=325), Russian (n=772) or Tatar (n=951) nationalities. The analysis of association between MS and polymorphisms previously associated with the disease according to GWAS data was performed. Of the 641 MS patients, 247 were the subject of a 20-year prospective clinical follow-up. RESULTS: The C6orf10 rs3129934*T allele was most significantly associated with MS in Russians (OR=2.00, P=5.85·10-5) and Tatars (OR=2.38, P=8.61·10-7). An increased MS risk in Russians was also associated with the EOMES rs11129295*T (OR=1.56, P=0.007) and IL7R rs1494558*I (OR=1.61, P=0.003) alleles. Meta-analysis confirmed the association of the C6orf10 rs3129934*T, EOMES rs11129295*T and IL7R rs1494558*I alleles with MS in the total group, as well as revealed associations of the INAVA rs7522462*G, IL7R rs10624573*I, CD6 rs17824933*G, GPC5 rs9523762*A and GPR65 rs2119704*C alleles with the disease. Using polygenic analysis, we identified a complex predictor C6orf10 rs3129934*C + INAVA rs7522462*G + CD6 rs17824933*C with a pronounced protective effect against MS in the total group (OR=0.34, PFDR=2.65·10-7). CONCLUSION: We reproduced the association of eight polymorphisms (C6orf10 rs3129934, INAVA rs7522462, IL7R rs10624573, EOMES rs11129295, GPR65 rs2119704, GPC5 rs9523762, CD6 rs17824933 and CD58 rs2300747) with MS, previously identified in GWAS in European populations. Whole exome or genome sequencing may help to reveal the mechanisms underlying the pathogenesis of MS in populations of the Russian Federation.

[The analysis of association between multiple sclerosis and genetic markers identified in genome-wide association studies]. / Analiz assotsiatsii s rasseyannym sklerozom geneticheskikh markerov predraspolozhennosti, vyyavlennykh v rezul'tate polnogenomnykh issledovanii.

OBJECTIVE: Our aim was to analyse the association with multiple sclerosis of the genetic markers of autoimmune disorders identified in genome-wide association studies in ethnically homogenous groups of Russians and Tatars residing in the Republic of Bashkortostan. MATERIAL AND METHODS: We performed genotyping of the genetic variants rs2069762 in IL2 gene, rs759648 in PVT1 gene, rs1800682 in FAS gene and rs12708716 in CLEC16A gene in the study group consisting of 1724 people (547 patients with multiple sclerosis, 1177 representatives of the control group). We analysed the association of the studied genetic markers with multiple sclerosis using logistic regression under additive genetic model implemented in PLINK program with sex a covariate. RESULTS: In the group of Tatars, we detected an association of PVT1 rs759648*Callele with multiple sclerosis (OR=1.42, p=0,023). Meta-analysis of the study results in the two ethnic groups we confirmed the association of the PVT1 rs759648*C allele with the disease (random effects model and fixed effect model: OR=1.29, p=0,018). CONCLUSION: Our results provide an evidence of an association between multiple sclerosis and the PVT1 rs759648 allele in the populations of Russian and Tatars from the Republic of Bashkortostan. No association with any other studied polymorphic variant was found in the two ethnic groups.

[Autonomic dysfunction in patients with multiple sclerosis]. / Vegetativnaia disfunktsiia u patsientov s rasseiannym sklerozom.

AIM: To optimize the early diagnosis of the autonomic dysfunction in patients with MS. MATERIAL AND METHODS: The main group consisted of 46 patients: 15 men and 31 women with MS (McDonald, 2005), the average age was 33.35±9.9 years, the average score of the Expanded disability scale (EDSS) was 2.8±1.17 points. The control group consisted of 24 healthy subjects matched by age and sex with the main group. A study of the autonomic nervous system was carried out using the Scheme for detection of signs of autonomic disorders (A.M. Vein, 1998) and analysis of heart rate variability (HRV) at rest and after active orthostatic test (AOT). RESULTS: Autonomic dysfunction was found in 73% of the patients. The overall score of the Scheme was significantly higher in MS patients (31.32±9.43 points) compared to the comparison group (2.36±4.39 points, p<0.05). According to HRV, the contribution of brainstem autonomic centers in the regulation of stress-response during AOP was significantly reduced (p<0.05) and was characterized by the lack of activation of the sympathetic division of the ANS. In patients with MS, cerebral influences were dominating on HRV baseline records, evaluated by the domination of the VLF component in the spectrum. During AOP, VLF was almost leveled in both groups, and the VLF changes in patients before and after the AOP reached statistical significance (p<0.05). CONCLUSION: The use of the Scheme is preferable in outpatient clinics to screen the large numbers of patients with MS, and then selected patients could be referred to the instrumental methods of investigation.

[Experience of using genfaxon for treating patients with relapsing-remitting multiple sclerosis in the Russian Federation].

UNLABELLED: Multiple sclerosis (MS) is a chronic autoimmune demyelinating disorder of the central nervous system. Nowadays some disease-modifying drugs (DMD) in the Russian Federation (RF) are biosimilars. Their full spectrum of tolerability and efficacy is to be determined. Here we present results of two retrospective-prospective studies on efficacy and safety of a biosimilar interferon beta-1a (genfaxon) in treatment of MS in the RF. AIMS: determination of safety and efficacy profile of genfaxon in a routine neurological practice in the RF. MATERIALS AND METHODS: Trials were performed in 18 MS centers in the RF. A total of 649 patients aged from 18 to 68 years with the EDSS score no more than 6.0 were treated with genfaxon for 12 months. The first group was comprised of 'naïve' patients without previous history of DMD administration. There were patients in the second group which have already received some of DMD. Statistical analysis was performed with the help of significance criteria (χ-square), t-criteria of Student for analysis of independent samplings. RESULTS: There were no serious adverse events during the period of the study. "Naïve" patients had significantly lower number of adverse events, than patients with previous history of DMD usage. Efficacy results were comparable with results published for the Rebif. CONCLUSIONS: Data, received from the studies show equal efficacy and tolerability of genfaxon compared with original DMD Rebif.

[Cancer diseases in patients with multiple sclerosis in the Bashkortostan Republic]. / Onkologicheskaia patologiia u bol'nykh rasseiannym sklerozom v Respublike Bashkortostan.

A database on patients with multiple sclerosis (MS) of the Republican center of multiple sclerosis (Ufa city) is analyzed. The database includes 1436 patients. For the period 2005-2012, 4 female patients with cancer, including 2 patients with thyroid gland cancer, 1 patient with rectum tumor and 1 patient with breast cancer, were identified. Clinical features of MS in these cases were studied. In two patients, cancer developed during the treatment with Β-interferon-1b. A possible association of cancer with MS and multiple sclerosis disease modifying drugs is discussed.

[Multiple sclerosis in the Bashkortostan Republic and the Rostov region: a comparative epidemiologic study]. / Rasseiannyi skleroz v Respublike Bashkortostan i Rostovskoi oblasti: sravnitel'naia épidemiologicheskaia kharakteristika.

Epidemiological characteistics of multiple sclerosis (MS) in the Bashkortostan Republic (BR) and the Rostov region have been compared. Prevalence and incidence of MS were higher in BR (38.0 and 2.92 per 100 000) compared to the Rostov region (29.8 and 0.73 per 100 000). This finding may be explained by geographic and ethnic differences. The comparative analysis suggests that both environmental and genetic factors contribute to the etiology of MS.

[Smoking as a risk factor of development and progression of multiple sclerosis (a review and experimental data)].

Epidemiological data on smoking influence on the development and course of multiple sclerosis (MS) are presented. The relative risk (RR) of MS for smokers was calculated as 1.3-1.8 in various cohort studies. Smoking was positively correlated with MS progression. The RR of the transition of remitting-relapsing MS to secondary progressive MS was in the range of 2.5-3.6. The RR of the transition to clinically isolated syndrome authentic MS was 1.8. Results of the MRI study of 239 MS patients (102 smokers and 137 non-smokers) revealed the higher level of disability on EDSS, higher rate of disease progression and lesser cases with remitting course in the group of smokers. The primary progressive MS course was more often observed in the group of smoking patients. The more favorable prognosis in terms of sensitivity and visual symptoms of disease onset were found in nonsmokers.Forms with a late onset prevailed in smokers.

[Polymorphism of the prion protein PRNP gene and risk of multiple sclerosis development in ethnic Russians from Bashkortostan].

M129V polymorphism of prion protein gene PRNP has been studied in patients with multiple sclerosis (MS) and healthy ethnic Russians from Bashkortostan using allele-specific PCR. The genotype frequency distribution of the examined polymorphism in Russians from Bashkortostan was similar to that in European populations. MM, MV, and VV genotype frequencies in control group and in the MS patients were 50.24%, 42.58%, 7.18% and 43.33%, 45.83%, 10.84%, respectively. It was shown that in the group of MS patients with onset of the disease at the age of 21 and older, the frequency of the VV genotype was higher than in the control group (14.3% versus 6.18%, respectively, P = 0.041). We suggest that the VV genotype is associated with higher risk factor of MS development in the patients aged 21 years and older.

[Analysis of the association of allelic variants of apolypoprotein E and interleukin 1 beta genes with multiple sclerosis in ethnic Tatars].

Multiple sclerosis (MS) is a multifactorial disease of the central nervous system. The apolipoprotein E (APOE) and interleukin 1 beta (IL1B) genes are considered to be candidate genes of MS. The aim of the study was to examine the hypothesis of the importance of APOE and IL1B gene polymorphisms in MS development in ethnic Tatars. DNA samples isolated by phenol-chloroform extraction from peripheral blood of 383 ethnic Tatars (120 MS patients and 263 healthy donors) were studied. 112C/R and 158R/C APOE gene polymorphisms as well as -511T/C IL1B gene polymorphism were analyzed by polymerase chain reaction (PCR) followed by PCR product digestion by endonuclease. Odds ratio (OR) values were used for evaluation of the relative risk of alleles and(or) genotype combinations. It has been shown that APOE*2/*3 genotype is associated with low risk of the disease development (OR = 0.20) in women. A combined effect of APOE and IL1B allelic variants has been discovered indicating the increased risk of the disease development in the carriers of APOE*4 and IL1B*T/*T alleles (OR = 4.76).

[Polymorphism of APOE gene and risk of development of the multiple sclerosis at ethnic Russians].

The multiple sclerosis is a complex disease of the central nervous system with the pronounced hereditary predisposition. The purpose of our research consisted in acknowledgement of the assumption on importance of apolipoprotein E gene (APOE) polymorphism in exon 4 in development of the multiple sclerosis in ethnic Russians. Research was lead on the samples independently collected in Moscow (106 patients and 189 persons of control group), Sverdlovsk area (54 and 109, accordingly) and republic Bashkortostan (119 and 285, accordingly). 2059C/T and 2197C/T polymorphisms of APOE gene, which determine aminoacid substitutions C112R and R158C in apolipoprotein E, were determined by polymerase chain reaction with the following restriction analysis of amplicons. There was not detected statistically significant distinctions on genotypes frequencies and alleles frequencies between control group and group of patients with multiple sclerosis. APOE*4 allele is not assosiated with risk of development of the multiple sclerosis at ethnic Russians.

[Multiple sclerosis in ethnic groups of Bashkortostan Republic].

Clinical presentations and course of multiple sclerosis (MS) have been studied in ethnic groups of Bashkortostan Republic. An analysis of 4 groups of patients, 234 Tartars, 80 Bashkirs, 22 Chuvashes and 237 Russians, revealed that the prevalence of MS was the least in the Bashkirs--3 times less than in Tartars (chi2 = 7.84; p < 0.05) and 2 times less than in Russians (chi2 = 2.95; p < 0.05). In all the groups, the disease more often developed in women. Mean age at disease onset in women was less in Tartars and Chuvashes and by 1 year more in Bashkirs. In debut, polysymptomatic beginning and movement disorders prevailed in patients with different ethnic origin. The higher prevalence of MS in Tartars, Russians and Chuvashes as compared to Bashkirs is probably caused by historically developed isolation of populations in the territory of the republic and by the features of marriage traditions.