[Associations of serum neuromarkers with clinical features of Parkinson's disease]. / Assotsiatsii syvorotochnykh neiromarkerov s klinicheskimi osobennostyami bolezni Parkinsona.

OBJECTIVE: To evaluate the clinical and laboratory correlation of biomarkers with anti- and pro-apoptotic activity with the severity of motor and non-motor symptoms depending on the progression rate of Parkinson's disease (PD). MATERIAL AND METHODS: A wide range of non-motor symptoms (emotional-affective, cognitive, psychotic and behavioral disorders, fatigue, sleep disorders and autonomic disorders) was evaluated using validated scales and a number of serum neuromarkers responsible for neuroplasticity and neuronal survival processes (BDNF, PDGF, cathepsin D) in 71 patients with PD (mean age 65 (55; 70) years, disease duration 7 (4; 9) years, age of onset 57 (49; 62) years). RESULTS: The concentration of biomarkers (BDNF, PDGF and cathepsin D) was the lowest in the group of patients with a rapid PD progression rate (p<0.001, p=0.001 and p=0.031, respectively), the severity of motor and most non-motor symptoms was higher (p=0.023 and p=0.001, respectively) compared to middle and slow progression rate. There were correlations between BDNF concentration and the severity of depression (r=-0.63, p<0.001), apathy (r=-0.48, p<0.001), impulsive behavioral disorders (r=0.500, p<0.001), level of cognitive functions (r=0.54, p<0.001), motor symptoms (r=-0.43, p<0.001); between PDGF level and the severity of motor manifestations of PD (r=-0.30, p=0.011), depression (r=-0.70, p<0.001), apathy (r=-0.460, p<0.001), the degree of severity of behavioral disorders (r=0.742, p<0.001). No significant correlations were observed between the level of cathepsin D and the severity of clinical manifestations of PD, which indicates the connection of cathepsin D with the general pathogenesis of PD. CONCLUSION: The possibility of using serum proteins of the neurotrophin subfamily and the protein associated with autophagy, cathepsin D, as biomarkers that determine the prognosis of PD, is considered.

[Long-term efficacy and safety of divozilimab during 2-year treatment of multiple sclerosis patients in randomized double-blind placebo-controlled clinical trial BCD-132-4/MIRANTIBUS]. / Effektivnost' i bezopasnost' dvukhletnei terapii divozilimabom u patsientov s rasseyannym sklerozom v ramkakh randomizirovannogo dvoinogo slepogo platsebo-kontroliruemogo klinicheskogo issledovaniya BCD-132-4/MIRANTIBUS.

OBJECTIVE: To evaluate the efficacy and safety of the anti-CD20 monoclonal antibody divozilimab (DIV) used as an intravenous infusion at a dose of 500 mg every 24 weeks during 100 weeks for the treatment of patients with multiple sclerosis (MS), including relapsing-remitting multiple sclerosis (RRMS) and secondary progressive MS (SPMS) with relapses. MATERIAL AND METHODS: The multicenter, randomized, double-blind and double-masked phase III clinical trial (CT) BCD-132-4/MIRANTIBUS (NCT05385744) included 338 adult patients with MS distributed in a 1:1 ratio into two groups: DIV 500 mg and teriflunomide (TRF) 14 mg. After screening, subjects were included in the main CT period, which consisted of two cycles of therapy over 48 weeks, then entered an additional period from weeks 49 to 100, which included three cycles of therapy. The efficacy was assessed based on the results of brain MRI and registration of data on relapses. RESULTS: 308 subjects completed 5 therapy cycles according to the study protocol. An analysis of the effectiveness of DIV therapy over 2 years showed a persistent suppression of MRI and clinical activity of the disease in comparison with TRF, which was confirmed by all the studied MRI indicators (including CUA; total number of gadolinium-enhancing (GdE) lesions on T1-weighted scans ; number of new or enlarged lesions on T2-weighted scans; lesions volume change on T2-weighted scans; change in the volume of hypointense lesions on T1-weighted scans). The use of DIV was associated with a statistically significant decrease in ARR compared to TRF (p=0.0001). The ARR in the DIV group was 0.057, in the TRF group - 0.164 with 95% confidential interval for the frequency ratio [0.202; 0.593]. The incidence of GdE lesions on T1-weighted scans in the DIV group was significantly lower than in the TRF group. The average number of such lesions was 0.0±0.08 and 1.0±4.46 in the DIV and TRF groups, respectively (p<0.0001). Progression of EDSS was detected in 18 (10.7%) and 36 (21.3%) patients in the DIV and TRF groups, respectively (p=0.0075). The proportion of patients with relapses was 11.2% (n=19) in the DIV group and 23.1% (n=39) in the TRF group (p=0.0039). In the subpopulation of patients with SPMS, no cases of increase in EDSS were detected, and not a single case of exacerbation was recorded over 2 years of using DIV. Also, DIV has shown a favorable safety profile. Among the adverse reactions (AR), infusion reactions and laboratory abnormalities, such as a decrease in the number of leukocytes, neutrophils, and lymphocytes, were most often recorded. Identified AR were expected, had mild to moderate severity, and resolved without any negative consequences. CONCLUSION: The results of the BCD-132-4/MIRANTIBUS CT indicate a high sustained efficacy and safety of long-term use of DIV in comparison with TRF during 2 years of therapy.

[Serum neurofilament light chains in assessing the course of multiple sclerosis]. / Syvorotochnye legkie tsepi neirofilamentov v otsenke techeniya rasseyannogo skleroza.

OBJECTIVE: To study a role of serum neurofilament light chains (sNFL) in assessment of course and progression of multiple sclerosis (MS) in the population of patients with MS in the Tomsk region. MATERIAL AND METHODS: The study involved 93 patients with relapsing-remitting MS (RRMS) and secondary progressive MS (SPMS) (nRRMS=75, nSPMS=18). The study was carried out in a two-stage design: the first stage was a cross-sectional study for the entire sample; the second stage was a prospective observation with two visits for patients with relapse. sNFL concentration was determined by solid-phase ELISA. RESULTS: There was no statistically significant difference between RRMS and SPMS, and relapse and remission groups in terms of sNFL levels. Patients with a MS duration exceeding 14 years had higher rates of sNFL than those with a shorter duration (p=0.02). The subjects of the second study stage showed a decrease in sNFL from 2.05 (1.86; 2.19) pg/ml to 1.92 (1.87; 2.04) pg/ml (p=0.005), and slowdown in sNFL reduction correlated with the severity of cognitive impairment (k=0.52; p<0.05). CONCLUSION: Dynamic monitoring of sNFL allows the evaluation of the activity of the disease, as well as making an assumption about the compensatory possibilities of subsequent recovery.

[The relationship between the rs6265 polymorphism of the BDNF gene and the level of serum neurotrophic factor in patients with Parkinson's disease]. / Svyaz' polimorfizma rs6265 gena BDNF s urovnem syvorotochnogo neirotroficheskogo faktora u patsientov s bolezn'yu Parkinsona.

OBJECTIVE: To evaluate the clinical features and the level of serum brain-derived neurotrophic factor (BDNF) in groups of patients with Parkinson's disease (PD) differentiated by the genotypes of BDNF polymorphism (rs6265). MATERIAL AND METHODS: The level of serum BDNF in the biomarkers' multiplex panel of neurodegenerative diseases (HNDG3MAG-36K) was assessed in 134 PD patients. Allele discrimination was carried out by real-time PCR using TaqMan probes for the analysis of BDNF rs6265 polymorphism in groups of patients and controls (n=192) matched for sex, age and ethnicity. RESULTS: Comparing the distribution of rs6265 genotypes and alleles between groups of patients and controls no significant differences were found (p>0.05). Serum BDNF levels varied significantly by genotype (rs6265) among PD patients. Minimum mean serum BDNF level (320.1±164.6 pg/ml) was noted for individuals with the AA genotype, which significantly differs from the corresponding indicator among individuals with GA (2944.2±1590.6 pg/ml; p=0.0001) and GG genotypes (2949.4±1620.6 pg/ml; p=3.9×10-5). The concentration of BDNF significantly differed between patients with different forms of PD (p=0.0007) and increased as the stage of the disease progressed according to Hoehn and Yahr staging scale (p=1.0×10-6). CONCLUSION: The BDNF rs6265 polymorphism was not associated with the development of PD in the studied population. The variability of the mean serum BDNF level was established depending on the genotype of the BDNF polymorphism in PD patients and a number of clinical features.

[Efficacy and safety of antiCD20 monoclonal antibody divozilimab during 48-week treatment of multiple sclerosis patients in randomized double-blind placebo-controlled clinical trial BCD-132-4/MIRANTIBUS]. / Effektivnost' i bezopasnost' 48 nedel'nogo primeneniya monoklonal'nogo antitela protiv CD20 divozilimaba u patsientov s rasseyannym sklerozom: rezul'taty randomizirovannogo dvoinogo slepogo platsebo-kontroliruemogo klinicheskogo issledovaniya BCD-132-4/MIRANTIBUS.

OBJECTIVE: To evaluate the efficacy and safety of the anti-CD20 monoclonal antibody divozilimab (DIV) used as an intravenous infusion at a dose of 500 mg for the treatment of patients with relapsing-remitting multiple sclerosis (RRMS) in comparison with the teriflunomide (TRF). The study of the efficacy and safety of the use of the drug DIV was carried out for 48 weeks of therapy. MATERIAL AND METHODS: The multicenter, randomized, double-blind and double-masked phase III clinical trial (CT) BCD-132-4/MIRANTIBUS included 338 adult patients with RRMS distributed in a 1:1 ratio into two groups: DIV 500 mg and TRF 14 mg. After screening, subjects were included in the main CT period, which consisted of two cycles of therapy over 48 weeks. The primary end point was «Mean annualized relapse rate 48 weeks after the last patient is randomized in the study¼. RESULTS: 321 subjects completed 48 weeks of therapy according to the study protocol. The analysis of the of efficacy data for the primary endpoint successively proved the hypothesis of superiority of the test drug DIV at a dose of 500 mg over the reference drug TRF. A rapid suppression of acute disease activity according to the brain MRI and clinical manifestations of the disease was shown after the first infusion of DIV in patients with RRMS. Thus, after 48 weeks of therapy in patients treated with DIV, there were no T1 gadolinium-enhancing lesions, while in the TRF group such lesions were observed in 20.7% (35/169) of subjects. Evaluation of the CUA per scan showed that the mean values for the estimated period were statistically significantly lower in the DIV drug group compared to the TRF group: the ratio of the adjusted per scan rates (DIV/TRF) was 0.125 [95% CI: 0.089; 0.177]. Over the 48 weeks of therapy, the proportion of subjects with relapses was 9.5% (n=16/169) in the DIV group and 19.5% (33/169) in the TRF group (p=0.0086). DIV has shown a favorable safety profile. Among the adverse reactions (AR), infusion reactions and deviations of laboratory data, such as a decrease in the number of leukocytes, neutrophils, and lymphocytes, were most often recorded. Identified AR were expected, had mild to moderate severity, and resolved without any negative consequences. CONCLUSION: The results of the clinical study indicate the high efficacy and safety of DIV in comparison with TRF.

[Clinical factors and response to therapy with disease-modifying drugs for multiple sclerosis: the experience of the Tomsk region]. / Klinicheskie faktory i otvet na terapiyu preparatami, izmenyayushchimi techenie rasseyannogo skleroza: opyt Tomskoi oblasti.

OBJECTIVE: To investigate a disease-modifying drugs (DMD) response in multiple sclerosis (MS) in the Tomsk region population and detect clinical factors associated with the treatment response. MATERIAL AND METHODS: A 5-year prospective clinical study included 363 MS patients of the Tomsk region taking DMDs of the «first-line¼ and «second-line treatments¼. The response to DMDs therapy and the impact of MS clinical characteristics on response to treatment were assessed. RESULTS: Clinical factors associated with resistance to DMD are male gender, partial reduce of the MS onset symptoms, short period of the first remission, severe neurological impairment, high relapse rate and disease progression rate. CONCLUSION: Clinical features of MS are crucial factors associated with DMD response and should be used to prescribe DMD. This factor assessment can improve efficacy of the personalized MS treatment.

[BDNF gene RS6265 polymorphism in patients with multiple sclerosis of Tomsk region]. / Polimorfizm RS6265 gena BDNF v populyatsii bol'nykh rasseyannym sklerozom Tomskoi oblasti.

OBJECTIVE: To study the effect of the RS6265 polymorphism of BDNF gene on the risk of development, main clinical characteristics and DMT response in MS patients in Tomsk region. MATERIAL AND METHODS: The study group included 321 patients, the control group consisted of 266 healthy volunteers. Deoxyribonucleic acid (DNA) was isolated from venous blood using the standard phenol-chloroform method. Genotyping was carried out by real-time polymerase chain reaction (PCR) using competing TaqMan probes complementary to the polymorphic nucleotide sequence. RESULTS: Carriage of the C allele and CC genotype of the RS6265 polymorphism of the BDNF gene was found to be a factor determining a more favorable MS course. CONCLUSION: Carriers of the indicated genotype had a low rate of MS progression, a lower frequency of relapses and a less pronounced degree of disability with a comparable MS duration, and significantly more often demonstrated a more optimal response to first and second line of DMT.

[Efficacy and safety of divozilimab during 24-week treatment of multiple sclerosis patients in randomized double-blind placebo-controlled clinical trial BCD-132-2]. / Effektivnost' i bezopasnost' 24 nedel' primeneniya divozilimaba sredi patsientov s rasseyannym sklerozom v ramkakh randomizirovannogo dvoinogo slepogo platsebo-kontroliruemogo klinicheskogo issledovaniya BCD-132-2.

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.

[Results of the implementation of measures aimed at improving medical care for patients with vascular diseases in the Tomsk region]. / Itogi realizatsii meropriyatii, napravlennykh na sovershenstvovanie meditsinskoi pomoshchi bol'nym s sosudistymi zabolevaniyami na territorii Tomskoi oblasti.

OBJECTIVE: To study the dynamics of population indicators: the total number of deaths from diseases of the circulatory system, coronary heart disease, cerebrovascular diseases and strokes, hospitalization profile for strokes, their structure and mortality in the Tomsk region for several years in comparison with these indicators for the Russian Federation and the Siberian Federal District. MATERIAL AND METHODS: A retrospective study was conducted using acute cerebrovascular accidents monitoring data and data of the Territorial body of state statistics of the Tomsk region in comparison with the literature data. The indicators of all causes of death, from circulatory diseases, coronary heart disease, cerebrovascular diseases and stroke in the territory of the Tomsk region, profile of hospitalization, structure of acute cerebrovascular accidents were analyzed for several years. Particular attention was paid to case fatality rate, one of the key indicators of the effectiveness of the system of care for patients with stroke. RESULTS: Typical for many regions of the Russian Federation predominance of chronic forms in the structure of mortality from circulatory diseases, the absence of significant differences in the structure of strokes, as well as the features of the Tomsk region in the form of high levels of hospitalization profile and hospital case fatality rate, were revealed. The dependence of hospital mortality on logistics is shown, on the basis of which assumptions are made about the possible causes of high fatality rates in the region: excessive centralization of the system of vascular centers and the absence of really working mechanisms for timely reevacuation from them. CONCLUSION: To bring chronic circulatory diseases structure in line with international standards, it is necessary to regulate the rules for formulating and coding diagnoses. In order to reduce hospital fatality rates in the Tomsk region, it is necessary to carry out organizational measures: opening a primary vascular department in the area of responsibility of the regional stroke center, as well as strengthening rehabilitation and palliative services for the timely reevacuation of patients from vascular centers.

[Mild encephalopathy with a reversible splenial lesion in a child]. / Sindrom umerennoi entsefalopatii s obratimym porazheniem valika mozolistogo tela u rebenka.

Mild encephalopathy with a reversible splenial lesion (MERS) is a clinical and radiological syndrome that can be caused by infectious and non-infectious factors. The most common neurological symptoms are impaired consciousness, impaired speech, convulsions, muscle weakness, ophthalmoplegia, facial paralysis, and headache. A case of a 5-year-old child with a leading clinical symptom of bilateral transient blindness and radiological characteristics of MERS syndrome is presented.

[The role of alleles with an intermediate number of trinucleotide repeats in Parkinson's disease and other neurodegenerative disorders]. / Rol' allelei s promezhutochnym kolichestvom trinukleotidnykh povtorov pri bolezni Parkinsona i drugikh neirodegenerativnykh zabolevaniyakh.

Genetic factors underlie the pathological processes that cause the manifestation of a wide range of neurodegenerative diseases. The pathological expansion of unstable trinucleotide repeats is known to lead monogenic neurological diseases such as Huntington's disease, Kennedy's disease, spinocerebellar ataxia, and others. However, the latest data suggests individuals with intermediate allele (IA) repeat length have a risk of developing common neurological phenotype, for example, Parkinson's disease, Alzheimer's disease. In this study, we review the current knowledge on intermediate alleles of HTT gene for pathogenesis and clinical features of neurodegenerative diseases, with the focus on Parkinson's disease. Early diagnosis of neurodegenerative disease and genetic counselling of the family can be improved via the implementation of specific management strategies of IA carriers by team of highly experienced professionals in the fields of neurology and genetics.

[Prognostic markers of multiple sclerosis]. / Prognosticheskie markery rasseyannogo skleroza.

Multiple sclerosis (MS) is a chronic autoimmune disease with a high degree of heterogeneity due to course and prognosis. More than half of MS patients do not discuss their long-term prognosis with the doctor. At the same time, most patients consider the importance of personalized prognosis for decisions in family planning, career, and medical interventions. Clinical markers are used to determine the prognosis in routine clinical practice. However, it is nominally divided into positive and negative factors. It allows making a general conclusion about the MS prognosis. Neuroimaging and biological markers are used mostly for research purposes. But also they are already actively used in clinical trials for endpoint`s investigation. The review describes studies investigating prognostic clinical, neuroimaging, and biological markers.

[Assessment of the levels of neuron-specific enolase and BDNF at the stages of rehabilitation in the acute and early recovery periods of ischemic stroke]. / Otsenka urovnei neironspetsificheskoi enolazy i mozgovogo neirotroficheskogo faktora na etapakh reabilitatsii v ostrom i rannem vosstanovitel'nom periodakh ishemicheskogo insul'ta.

BACKGROUND: The issue of the diagnostic significance and clinical value of neuron-specific enolase (NSE) and brain-derived neurotropic factor (BDNF) in the acute period of stroke remains controversial. Therefore, it is advisable to study the correlation of biomarkers with the clinical characteristics of stroke in the time period of early recovery. OBJECTIVE: To monitor NSE and BDNF levels in peripheral blood, to analyze the clinical and laboratory correlations in patients with ischemic stroke at the stages of medical rehabilitation in the early recovery period. MATERIAL AND METHODS: Forty-nine patients with ischemic stroke in the middle cerebral artery were examined. The observation period is 90 days. Observation Points are Day 1; Day 14; Day 45; Day 90. The National Institute of Health Stroke Scale (NIHSS), the Fugle-Meyer Scale (FMA), the Modified Rankin Scale (mRS) were administered. NSE was determined in blood serum by enzyme-linked immunosorbent assay, BDNF was analyzed on a multiplex analyzer. RESULTS AND CONCLUSION: NSEDay1 in patients was significantly higher than in the comparison group (pDay1-comparison group<0.001) with a trend to a maximum decrease on the 90th day of stroke (pDay1-90<0.001). BDNFDay1 turned out to be lower than in the comparison group (pDay1-comparison group=0.006) and significantly increased by the 14th day of the stroke (pDay1-14<0.001; pDay14-comparison group=0.637). A negative correlation was found between a decrease in NSEDay14 and an increase in BDNFDay14 (r= -0.349; p=0.05). A positive correlation was found between an increase in BDNFDay14 and a decrease in mRS scores Day90 (r=0.499, p=0.035). Outcomes in patients in group 1 (after stages I and II of rehabilitation) on the assessment scales were significantly better than in patients discharged after stage I for outpatient monitoring - group 2 (p<0.05). In group 1, BDNFDay90 did not differ from BDNFDay14 (pDay14-90-Group1=0.17), and in group 2 it was significantly lower by the end of the early recovery period (pDay14-90-Group2=0.002).

[Brain-derived neurotrophic factor in multiple sclerosis]. / Mozgovoi neirotroficheskii faktor pri rasseiannom skleroze.

The review presents data on brain-derived neurotrophic factor (BDNF), its structure and functions, the effect on the pathogenesis of experimental autoimmune encephalomyelitis and multiple sclerosis (MS). The correlation of BDNF level with clinical manifestations of MS and the changes of its level during disease-modifying therapy is considered.

[An effect of complex therapy on cognitive impairment in patients with chronic cerebral ischemia]. / Vliianie kompleksnoi terapii na kognitivnye narusheniia u patsientov s khronicheskoi ishemiei golovnogo mozga.

AIM: To study the efficacy of complex therapy in the correction of cognitive impairment in patients with chronic cerebral ischemia. MATERIAL AND METHODS: One hundred patients with chronic cerebral ischemia were examined. All of them received standard neurometabolic therapy. In the main group, patients were additionally treated with soft techniques of manual therapy. Cognitive status was assessed using the frontal assessment battery, the clock drawing test, MMSE, the Global Deterioration Scale and a sequencing test. RESULTS AND CONCLUSION: Patients with chronic cerebral ischemia demonstrated a significant impairment of cognitive functions. Patients who received comprehensive (drug and non-drug) treatment showed a more significant improvement in cognitive status than those receiving only neurometabolic therapy.

[Evaluation of serum neurofilament light chains levels for diagnosis, treatment monitoring and prognosis in multiple sclerosis]. / Primenenie otsenki urovnia syvorotochnykh legkikh tsepei neirofilamentov v diagnostike, monitoringe lecheniia i prognoze pri rasseiannom skleroze.

Pathophysiological processes in multiple sclerosis frequently not diagnosed by clinicians become available for analysis only on the basis of paraclinical data (biomarkers). Nowadays neurofilament light chain can be defined as a promising biomarker for multiple sclerosis (MS). Neurofilaments are a structural part of normal neuronal processes consisting of light, intermediate and heavy chains. However, a damage of neurons such as neurodegeneration or axonal damage causes the escape of neurofilaments into extracellular space. Cutting-edge highly sensitive methods make it possible to detect neurofilament light chains not only in the cerebrospinal fluid but also in the blood serum thus opening the opportunities to utilize them in routine diagnosis in clinical practice. This review comprises existing data on the possible opportunities for research of serum neurofilament light chains in terms of exacerbations, effectiveness of basic therapy, assessment of individual disability, the atrophy of central nervous system structures. Also, there is some information on comparison of two methods: routine MRI of the brain with the contrast agents and detection of serum neurofilament light chains.

[Parkinson's disease and glutamate excitotoxicity]. / Bolezn' Parkinsona i glutamatnaia éksaitotoksichnost'.

AIM: To measure the concentration of glutamate in the serum of patients with Parkinson's disease (PD) and determine its association with clinical variants of disease course. MATERIAL AND METHODS: One hundred and ten patients with PD and 90 healthy people were examined. Glutamate concentration in the blood serum was determined with a spectrophotometric method. RESULTS AND CONCLUSION: Patients with Parkinson's disease had significantly higher levels of serum glutamate compared with healthy subjects (p<0,0001). Patients with a tremor-dominant subtype had significantly higher levels of serum glutamate compared to those in patients with akinetic-rigid and mixed subtypes. The results obtained allow us to expand our understanding of the pathogenesis of this disease. Changes in the concentration of glutamate may reflect neurodegenerative process in PD.

[A rare variant in the sortilin-related receptor 1 gene is associated with declined cognitive functions in the elderly]. / Redkii variant v gene sortilinpodobnogo retseptora 1: sviaz' s pokazateliami kognitivnykh funktsii u pozhilykh.

AIM: To estimate the association of rs11218343 in the sortilin-related receptor 1 (SORL1) gene with cognitive performance in the elderly and with Alzheimer's disease (AD) in the Russian population. MATERIAL AND METHODS: A sample included 586 elderly people (mean age 70.9±5.7 years) without AD diagnosis and 100 patients with late-onset AD (mean age 72.1±7.8 years) from the Tomsk population. SORL1 rs11218343 was genotyped using PCR and MALDI-TOF mass spectrometry. Cognitive performance in the sample of elderly without AD was assessed by Montreal Cognitive Assessment (MoCA) test. RESULTS: Allele frequencies of the SORL1 polymorphism were not significantly different between the elderly without AD and AD patients. However mean MoCA score in the carriers of the rare allele (19.00±6.61) was significantly lower than in homozygotes for the common variant (22.25±3.89) (F=4.97; p=0.026). CONCLUSION: The rare variant in SORL1 gene previously associated with AD in genome-wide association studies and meta-analyses was associated with lower total МоСА scores in the random sample of elderly people that suggests declined cognitive functions in the carriers of this variant in elderly.

[Parkinson's disease and glutamatergic system]. / Bolezn' Parkinsona i glutamatergicheskaia sistema.

Clinical variants of Parkinson's disease (PD) are not restricted to motor symptoms but include a wide spectrum of different non-motor symptoms: cognitive, psychotic, autonomic and sensory. These non-motor symptoms often occur long before classical motor features. Associated pathologic changes can now be identified at earliest stages using neuroimaging, pathomorphological and genetic studies. Therefore, PD is currently considered as a multifactorial, heterogenic systemic disease associated with involvement of multiple neurotransmitter systems. This leads to understanding that not only dopaminergic but also other neurotransmitter systems, including glutamatergic system, are involved in the pathogenesis of PD. This article aimed at investigating a role of glutamatergic system in the initiation of neurodegenerative process. The role of glutamate as a neurotransmitter and a neurotoxin in the pathogenesis of PD and progression of its clinical manifestations is discussed. The authors suggest that research into glutamate excitotoxicity in PD patients might allow the improvement of treatment tactics and correction of pathogenetic therapy.

[Efficacy, safety and tolerability of glatiramer acetate injections in dose 40 mg/ml in patients with relapsing-remitting multiple sclerosis]. / Éffektivnost', bezopasnost' i perenosimost' glatiramera atsetata 40 mg/ml u patsientov s retsidiviruiushche-remittiruiushchim rasseiannym sklerozom.

The article presents the results of an international study on the efficacy and safety of glatiramer acetate (GA) (40 mg/ml administered 3 times a week) compared with placebo in patients with relapsing-remitting multiple sclerosis (RRMS). This study was conducted in 142 sites in 17 countries including Russia. In total, the study included 1404 patients with RRMS including 166 patients from Russia. Glatiramer acetate (40 mg/ml 3 times a week) demonstrated the high efficacy, safety and tolerability profile. In conclusion, glatiramer acetate GA in dose 40 mg/ml should be considered as a more convenient regimen for RRMS patients which can improve patients' adherence to treatment and as a result, its efficacy.