[Pharmacogenomics of multiple sclerosis: association of immune response genes polymorphism with copaxone treatment efficacy].

Complex association analysis of copaxone (glatiramer acetate) immunotherapy efficacy with allelic polymorphism in the number of immune response genes, which encode interferone beta (IFNB1), transforming growth factor beta1 (TGFB1), interferone gamma (IFNG), tumor necrosis factor (TNF), interferon alpha/beta receptor 1 (IFNAR1), CC chemokine receptor 5 (CCR5), interleukin 7 receptor alpha subunit (IL7RA), cytotoxic T-lymphocyte antigen 4 (CTLA4) and HLA class II histocompatibility antigen beta chain (DRB1) was performed with APSampler algorithm for 285 multiple sclerosis patients of Russian ethnicity. The results show evidence for the contribution of polymorphic variants in CCRS, DRB1, IFNG, TGFB1, IFNAR1, IL7RA and, probably, TNF and CTLA4 genes to copaxone treatment response. Single alleles of CCR5 and DRB1 genes are reliably associated with treatment efficacy. Carriage of allelic variants of other above mentioned genes contribute with reliable effect to copaxone treatment response as part of bi- and three-allelic combinations only. Present investigation may support basis toward the future possibility of prognostic test realization, which can provide a personal choice of immunomodulatory treatment for a patient with multiple sclerosis.

[Experience of using interferon Β-1a biosimilans (cinnovex and genfaxon-44) in the Moscow Multiple Sclerosis Center]. / Opyt primeneniia bioanalogov Β-interferona-1a - sinnoveksa i genfaksona-44 v Moskovskom gorodskom tsentre rasseiannogo skleroza.

OBJECTIVE: To study the efficacy and tolerability of generics (interferon beta-1a biosimilans) cinnovex for intramascular introduction and genfaxon-44 for subcutaneous injections in multiple sclerosis (MS). MATERIAL AND METHODS: One hundred patients were treated with cinnovex and 104 patients were treated with genfaxon-44 during one year. Patient's status was assessed using clinical approach, psychometric scales and MRI. RESULTS AND CONCLUSION: The high percentage of withdrawal of treatment due to the lack of clinical effect and intolerance to the drugs was identified during the treatment. Positive effect with respect to stabilization of MS course was found only in patients who earlier did not receive disease-modifying drugs. Double-blind studies are needed to resolve the question of the adequacy of brand-name drugs and generics.

[Results of clinico-immunological testing of myelopid in chronic forms of multiple sclerosis]. / Rezul'taty kliniko-immunologicheskogo ispytaniia mielopida pri khronicheskikh formakh rasseiannogo skleroza.

Forty patients with a verified diagnosis of multiple sclerosis (MS), the majority of whom had the secondary progressive form of the disease, received a short-term treatment with myelopid (MP). After this 10 patients were given a long-term treatment with MP. The clinical trial was carried out by the double blind method using placebo. The patients' status was estimated by special evaluation scales (clinical), immunoassays (the content of T lymphocyte subpopulations, reaction of blast transformation of leukocytes to mitogens under different conditions of cultivation including that in the presence of 0.3 micrograms/ml MP, by assessment of the production and activity of interleukin-2), by the method of evoked potentials and NMR tomography. 60% of the patients manifested an improvement of the clinical status after the short-term MP treatment, which was accompanied by positive dynamics of evoked potentials and a decrease of the functional activity of the cells in the reaction of blast transformation of leukocytes. In such patients, MS ran a more favourable course during 0.5-1.5 years of observation. In 8 patients with the immunologic signs of the pathological process activation, the clinical status worsened after MP. The correlation and regression analyses allowed one to specify the clinico-immunologic indications and contraindications for MP administration. The clinico-immunologic changes noted were not recorded after placebo. In the patients receiving the long-term treatment, one could see a further decline of the functional activity of the cells in the reaction of blast transformation of leukocytes, a rise of the content of T suppressors/killers in the blood, a favourable clinical course of MS.(ABSTRACT TRUNCATED AT 250 WORDS)

[Study of cellular immunity and the opioid peptide system in patients with multiple sclerosis]. / Issledovanie kletochnogo immuniteta i sistemy opiatnykh peptidov u bol'nykh rassiannym sklerozom.

Twenty-five patients with chronic progressing multiple sclerosis were examined for the content of beta-endorphin in blood serum, supernatants of activated lymphocytes and CSF by RIA. At the same time the parameters of cellular immunity were appraised. Different relations were discovered between cellular immunity and the content of beta-endorphin in biological fluids which may play a material part in the pathogenesis of multiple sclerosis.

[The first experience of the use the Russian Β-interferon-1b biosimilar (infibeta) in the daily practice of the Moscow Center of Multiple Sclerosis].

We summarized the 1-year experience of using the Russian Β-interferon-1b biosimilar (infibeta) in 123 patients including 65 patients with relapsing-remitting multiple sclerosis (RMS) and 58 patients with secondary progressive multiple sclerosis (SPMS). The significant decrease in the frequency of exacerbations per year was seen during the first year of treatment. We also noted the stabilization of the process of disability without the rise in EDSS scores in more than 50% of patients. Good tolerability comparable to that of the original drug was observed during the first year of treatment. There was no refusal from therapy with infibeta, which indicated sufficiently strong adherence to this type of treatment.

[Assessment of the size of the thalamus as a method for the evaluation of the activity of neurodegenerative process after the treatment with cerebrolisin in young patients with multiple sclerosis].

The aim of the study was to describe the atrophy of the thalamus in young patients with active relapsing multiple sclerosis (MS) treated with cerebrolysin. Eighteen MS patients (mean age 20.10±0.45 years) with disease onset in childhood or adolescence were studied. Neurological examination using the EDSS, neuropsychological testing and MRI were used. At baseline, MRI revealed the hypotrophy of the thalamus that was not correlated with the performance on neuropsychological tests. After treatment with cerebrolysin, there was the decrease in the level of atrophy that suggested the neuroprotective effect of this drug. This effect was more prominent in younger patients with the high frequency of previous relapses.

[The first results of a combined all-Russian study on clinical genetics of multiple sclerosis].

Multiple sclerosis is a classic multifactorial disease in which etiology interaction of external factors and structural features of a large number of genes plays an important role. Identifying risk factors for multiple sclerosis and creating an integrated model of pathogenesis are urgent tasks of neurology. Revealing true risk factors is possible only in studies with sufficient statistical power, so with a large amount of samples. We conducted the association study of CD40 gene's polymorphisms and multiple sclerosis among residents of the Russian Federation. The results demonstrated the need to combine data from different researchers in clinical studies to increase the power of the study.

[Efficacy and tolerability of long-term using of glatimer acetate (copaxone): a 10 year-study in the Moscow Municipal Multiple Sclerosis center].

Experience of 10-year administration of glatimer acetate (copaxone) in 74 patients with active remitting multiple sclerosis is summarized. The significant decrease in the frequency of exacerbations was seen over these ten years. Disease severity on the EDSS was stable and decreased only to the end of the 10-year period. The positive stable clinical dynamics did not depend on the disease severity at baseline. The drug was well-tolerated that allowed to control the course of multiple sclerosis: 64.8% of patients had no more than one exacerbation over 10 years and in 71.6% patients, the disease progression was absent or minimal (less than one score on EDSS). It has been concluded, that the long-term 10-year treatment with copaxone enables to control the development of disease in many patients.

[The comparative study of efficacy and tolerability of intramuscular introduction of beta-interferon-1a in adults and adolescents with remitting multiple sclerosis].

The experience of the treatment of patients with remitting multiple sclerosis (MS) with intramuscular introduction of beta-interferon-1a (avonex) is presented. Seventeen children and adolescents, aged from 11 to 18 years, and 55 adults, aged over 55 years, were treated for at least one-year period. Results revealed a significant reduction of exacerbations in both groups (from 1.35 to 0.06 in average in adolescents and from 0.86 to 0.17 in adults). The changes were accompanied by the stabilization of MS severity index: EDSS scores have decreased in 23.6% of adults and in 17.6% of adolescents. In both groups, good tolerability of the treatment was noted. There was a low probability of side-effects with the exception of increased frequency of a flu-like syndrome (47% cases) in patients younger than 18 years that demands special attention from children neurologists. The high efficacy and good tolerability and safety profile of beta-interferon-1a give grounds for administering this drug to children and adolescents with MS.

[Betahistine in the treatment of vestibular and coordination disturbances in multiple sclerosis].

We present the results of the efficacy trial of betahistine (Vestibo) based on the complex clinical/instrumental examination (stabilometric, vestibulometric) in 40 patients with multiple sclerosis of different severity of vestibular and coordination dysfunction. We demonstrated the clinical efficacy and safety of using this drug as one of the areas of symptomatic therapy in treatment vestibular and coordination disturbances in multiple sclerosis.

[Possibilities of treatment of multiple sclerosis exacerbations without corticosteroids: a role of metabolic and antioxidant therapy].

A multicenter randomized post-registration control-comparative trial included 94 patients with relapsing-remitting and secondary-progressive multiple sclerosis (MS) in the acute phase. Patients were stratified into 2 groups: patients of group 1 (n=53) received cytoflavin and basic treatment (trental and group B vitamins) and patients of group 2 (n=41) received only basic treatment. Based on the results of the 5-day treatment, each of these groups was stratified into 2 subgroups: patients of subgroup 1A (n=22) who demonstrated a positive effect continued to receive cytoflavin and basic treatment; subgroup 1B (n=31) received corticosteroids (metipred) as an add-on in the pulse- treatment regime; group 2A (n=14) continued to receive basic treatment due to the positive effect; group 2B (n=27) received corticosteroids as an add-on in the pulse-treatment regime. The treatment including cytoflavin, trental, group B vitamins and corticosteroids, was well-tolerated. The positive effect was due to the decrease in the need for corticosteroids: 41.5% of patients treated with cytoflavin and only 34% of patients receiving basic treatment did not need corticosteroids. The significant reduction of neurologic symptoms assessed with the EDSS was seen in patients treated with cytoflavin compared to the group which did not receive this drug. The clinical effect was observed in all patients. There was a decrease in lipid peroxidation levels and in the content of antibodies to basic myelin protein and the improvement of cognitive function.

[The use of rebif in the Moscow Municipal Multiple Sclerosis Center].

We summarized the 3-year experience of using beta-interferon 1a (44 mcg, subcutaneously) in the form of the preparation rebif in 141 patients including 120 patients with active remitting multiple sclerosis (RMS) and 21 patients with secondary progressive MS (SPMS). All patients were examined every three months. The significant decrease in the frequency of exacerbations per year was seen already during the first year of treatment. EDSS scores remained stable in 47.37% of all RMS cases and in 57.14% of all SPMS cases during the first year. A one point and more increase of EDSS was found only in 5.26% patients during three years of treatment. The drug was well tolerated during the long period, adverse effects were found in 16.31%, with a flu-like syndrome in the first place. Only 1.42% of patients refused treatment. All other patients were highly motivated and adherent to treatment.

[Instrumental methods of the rehabilitation of motor disorders in patients with multiple sclerosis].

Motor and coordination disorders are the most prominent clinical presentations of multiple sclerosis. Currently, good results were achieved in the pathogenetic treatment of the disease. However methods of treatment of motor and coordination disorders are not widely used. The positive experience in the treatment of motor disorders using the apparatus Moto-med is presented. The use of this treatment led to positive changes in the state of motor functions, i.e. the decrease of neurologic deficit and improvement of quality of life, of patients.

[Data of MRI and neuropsychological tests predict the course of typical remitting multiple sclerosis during five years].

A complex study of 50 patients with active typical remitting multiple sclerosis (MS) was carried out. Neuropsychological testing using Wechsler and Stroop tests and MRI of the brain with the morphometric analysis of focal and diffusive changes were used in the study. Patients were stratified into two subgroups by the changes in the performance of neuropsychological tests. The disease course was assessed during five years. In all cases, the natural course of the disease, i.e. when patients did not receive disease modifying drugs, was analyzed. The transition to secondary progressive MS and the marked increase in MS severity on the EDSS were found in the subgroup of patients who demonstrated changes in the neuropsychological test performance. The strongest correlation was observed between EDSS scores and the diffusive atrophy of the brain white matter on MRI. The data of neuropsychological testing and some brain MRI parameters may be recommended as a predictive test in remitting MS.

[Omaron in the complex treatment of patients with multiple sclerosis].

We studied efficacy and tolerability of the combined drug omaron (25 mg of cinnarizine and 400 mg of piracetam in one tablet) in patients with multiple sclerosis. The dosage of the drug was 1 tablet 3 times a day during 12 weeks in 33 patients (mean age 35.3±4.2 years) of the index group. A comparison group consisted of 27 patients matched for demographic and clinical characteristics who did not receive nootropics during the study. None of patients included in the study received disease modifying drugs. The significant (p<0.05) decrease in the severity of chronic fatigue syndrome (by 28.6% compared to baseline), improvement (p<0.05) of cognitive functions (increase of MMSE scores by 9.4%) were found in the index group compared to the comparison one. The statistically significant changes in the severity of disability assessed by EDSS were not observed. Omaron was well-tolerated with no serious adverse-effects.

[The use of sirdalud MR in patients with multiple sclerosis].

The study included 54 patients with multiple sclerosis, aged from 23 to 53 years (mean age 37.7 +/- 8.5 years). To reduce muscle tension, 34 patients of the main group received tizanidine with the modified release of active substance (sirdalud MR) in dosage one capsule (6 mg) per day. Twenty-two patients of the comparison group received a standard form of tizanidine--sirdalud in tablets (2 mg) 3 times daily. Patients were examined at baseline, 1, 2 and 4 weeks of the treatment and 2 weeks after the end of the trial. The use of different forms of sirdalud had no effect on disability (the EDSS) scores in patients. Spasticity scores (the Ashworth scale) were decreased during the treatment with different forms of sirdalud but sirdalud MR had more stable effect which remained for 2 weeks after the end of treatment (p < 0.05). Significant differences were observed between tolerability of two forms: side-effects (sleepiness, asthenia) were more frequents in patients treated with the standard form of sirdalud (p < 0.05), the rate of their reduction was significantly higher in the sirdalud MR group (p < 0.05).

[Use of multichannel programmed electrostimulation for the rehabilitation of patients with multiple sclerosis].

Ninety-eight patients with definite multiple sclerosis (MS) have been examined. An effect of functional multichannel programmed electrostimulation (FMPES) on the restoration of balance and biomechanics of walking of patients with different types of MS and severity of neurological deficit was estimated. The effectiveness was measured with stabilometric analysis. The method was efficient in patients with mild and moderate degree of neurological deficit severity. Recommendations on the use of FMPES for patients with different disease severity are formulated.

[Dynamic stabilometry as a monitoring of movement and coordination disorders in the rehabilitation of patients with multiple sclerosis].

Disorders of movement and coordination are the most frequent and debilitating symptoms of multiple sclerosis. It has been shown that distinct changes of balance support are typical of the disease. This report includes an analysis of preliminary positive results of the use of stabilometry and biological feedback for the correction of balance in multiple sclerosis. A test "balance" has been used at baseline of the stabilometric study. After the rehabilitation, the positive changes of balance maintenance were seen in patients with low disability (EDSS<3,5). This test may be used as a measure of rehabilitation effectiveness. The results of the study may provide further determination of the approaches to the development of rehabilitation stabilometric algorithms.

[Adherence to long-term therapy with disease modifying drugs].

Adherence to long-term therapy is a necessary condition of successful long-term treatment of the such chronic disabling disease as multiple sclerosis (MS). We studied factors associated with the rejection of treatment with disease modifying drugs (DMD) in 153 patients of the Moscow multiple sclerosis center who received or rejected the DMD treatment by their own choice. The groups were compared by neurological, socio-demographic and neuropsychological characteristics. The EDSS, HADS and the original socio-demographic questionnaire have been administered. Patients receiving glatimer acetate rejected the treatment less often compared to those receiving other DMD. The withdrawal of any DMD in the anamnesis predicted the future rejection of treatment. The first four months was the most risky period with respect to the rejection. Lack of family support, absence of work and age were independent factors associated with the rejection of DMD. Marked anxiety, lack of cooperation and lack of compliance were associated with the patient's rejection of treatment. No significant correlations of the treatment rejection, duration and type of MS course with depression were found.