[Botulinum toxin type A (Incobotulinum toxin A) in spastic forms of cerebral palsy: a retrospective analysis of clinical experience]. / Botulinicheskii toksin tipa A (IncobotulinumtoxinA) pri spasticheskikh formakh detskogo tserebral'nogo paralicha: retrospektivnyi analiz klinicheskogo opyta.

OBJECTIVE: A retrospective analysis of the experience of using Incobotulinum toxin A injections for the treatment of spasticity in children with cerebral palsy (CP). MATERIAL AND METHODS: One hundred and eighty-five children with spastic forms of CP, including 114 boys (61,6%), were studied. The average age of the patients was 3,8±2,5 years; the average weight was 14,2±6,9. The patients received injections of Incobotulinum toxin A according to registered indications or recommendations of a consultation of specialists and voluntary informed consent of the patient's representative. At least 1 point decrease of muscle tone according to the modified Ashworth scale was used as a criterion of the antispastic effect of Incobotulinum toxin A. RESULTS: The total dose of Incobotulinum toxin A for the whole group of patients with CP was 154,5±67,7 U and 11,6±4,7 U per kg/body weight. The gracilis muscle (65,4% of cases, 95%CI 58,1-72,2) and the gastrocnemius muscle (49,4% of cases, 95%CI 41,8-56,6) were the most frequently injected targets in the lower extremities, and the pronator teres muscle (58,9% of cases, 95%CI 51,5-66,1) - in the upper extremities. Adverse events were observed in 13 patients (7,0%). They were mild in 9 patients and moderate in 4 patients. CONCLUSION: Our data confirmed the effectiveness and safety of Incobotulinum toxin A injections in spastic CP. The calculated average doses of Incobotulinum toxin A for target muscles and the frequency of different spasticity patterns could serve as a reference for the botulinum therapy planning.

[Changes of the spasticity patterns in children with cerebral palsy GMFCS III at the age of 2 to 12 years]. / Izmenenie patternov spastichnosti u detei s tserebral'nym paralichom s III urovnem dvigatel'nogo razvitiya po sisteme klassifikatsii bol'shikh motornykh funktsii (GMFCS III).

Spastic muscles in the pathological motor patterns may change at different ages that leads to the changes in anti-spastic treatment. OBJECTIVE: To study the specific patterns of spasticity in CP patients with level III according to the Gross Motor Function Classification System (GMFCS) in different age periods. MATERIAL AND METHODS: A retrospective analysis of injection protocols of Abobotulinum toxin A for 99 patients with bilateral spastic CP GMFCS III at the age of 2 to 12 years was performed. Spasticity patterns were evaluated according to the frequency of target muscle selection for the botulinum toxin A (Abobotulinum toxin A) injections. RESULTS: The equinus foot deformity (89.7%, 95%CI 72.8-97.2) and its combination with internal hip rotation (79.3%, 95% CI 61.3-90.5) and/or hip adduction (65.5%, 95% CI 47.3-80.2) were the main lower extremity spasticity pattern for the patients aged 2 to 4 years. Between 4 and 6 years, there was the decrease in injections to the gastrocnemius muscle (75%, 95% CI 52.8-89.2), and less to the m. gracilis (70%, 95% CI 47.9-85.7) and hip adductors (55% 95 CI 34.2-74.2). In the 6-12 year old patients, the predominant spasticity patterns were internal hip rotation (80%, 95% CI 66.8-88.9), adduction (54%, 95% CI 40.4-67.0) and knee flexion (66%, 95% CI 52.1-77.6). The leading upper extremity patterns at all observed ages were forearm pronation (70.7%, 95% CI 61.1-78.8) and elbow flexion (47.5%, 95% CI 37.9-57.2). The frequency of injections to these muscles slightly decreased in elder groups. CONCLUSIONS: CP GMFCS III patients demonstrate age-related changes of the spasticity patterns both in lower and upper extremities. These changes and typical spastic muscles should be taken into account during the rehabilitation and botulinum toxin treatment planning, as well as in the detection and prevention of the orthopaedic complications.

[Multilevel botulinum toxin treatment in severe spastic forms of cerebral palsy (GMFCS IV-V)]. / Mnogourovnevaya botulinoterapiya pri spasticheskikh formakh detskogo tserebral'nogo paralicha s tyazhelymi dvigatel'nymi narusheniyami (GMFCS IV­V).

OBJECTIVE: To evaluate the most typical target muscles and dosages for the first and repeated botulinum toxin A (BTA) injections in cerebral palsy (CP) patients with severe motor deficit - GMFCS IV-V. MATERIAL AND METHODS: A retrospective analysis of 677 protocols of the first and repeated Abobotulinumtoxin A (AboA) injections in 333 patients with CP GMFCS IV and V, aged 1 to 18 years, was carried out. RESULTS: Ninety-seven percent of patients received multilevel injections. In the lower extremities the most typical target muscles were: m.gracilis - 221 (66.4%) patients, hip adductors - 164 (49.2%), medial hamstring - 144 (43.2%). In the upper extremities the most typical muscles were: m.pronator teres - 237 (71.2%) patients, m.biceps brachii+m.brachialis - 197 (59.2%). The total dosages of AboA and dosages for every target muscle were calculated. Several patients required high dosages (more than 30 U/kg of AboA). Higher dosages per kg were used in younger children and for repeated injections. The age-related evolution of spastic patterns was described. Adverse events were observed in 36 cases (5.3% of all injections). CONCLUSION: The majority of patients with GMFCS IV-V required multilevel BTA injections in high dosages, especially in young age. Described selection of target muscles and dosages of AboA could be taken into account as a practical experience and reference for the BTA therapy in GMFCS IV-V patients.

[Efficacy and safety of botulinum toxin type A (IncobotulinumtoxinA) in the treatment of patients with cerebral palsy]. / Éffektivnost' i bezopasnost' primeneniia botulinicheskogo toksina tipa A (IncobotulinumtoxinA) pri lechenii patsientov s detskim tserebral'nym paralichom.

AIM: To assess the safety and clinical and neurophysiological efficacy of xeomin in children with spastic equinus and equinovarus foot deformity in cerebral palsy. MATERIAL AND METHODS: Sixty-four patients with spastic forms of cerebral palsy (levels I-IV on the GMFCS) were enrolled into this multi-center open-label comparative randomized trial. The patients were administered xeomin or botox once, each drug being administered to 32 patients. Efficacy was evaluated based on clinical characteristics (the modified Ashworth scale, goniometry) and electromyography data. The subjects were observed for 3 months (90±7 days) after injections. The incidence, severity and intensity of adverse events (AE) was also determined. RESULTS: Treatment with xeomin according to the suggested protocol has proven its high clinical efficacy. The efficacy was demonstrated by significant, stable and long-term decrease in the gastrocnemius muscle tone: in the xeomin group, the score on the modified Ashworth scale decreased from 2.6±0.49 points at baseline to 1.8±0.54 points (р<0.000001, paired t-test; р<0.000004, Wilcoxon test). In the botox group, this score decreased from 2.4±0.56 points to 1.6±0.45 points (р<0.000001, paired t-test; р<0.000002, Wilcoxon test). The increased range of ankle joint movements at passive and voluntary feet extension. In the xeomin group, the significant proportion of patients (45.1%) moved to the group of lower spasticity defined as less than two score points on the modified Ashworth scale. The clinical data fully matched the changes in electromyography parameters, which were characterized by the lower amplitude and area of the target muscle (lateral and medial gastrocnemius heads) M-responses. AE developed in three patients (9.4%) administered xeomin and in two patients (6.3%) administered botox. The AE recorded in the study are described in the recommendations on the use of xeomin and botox. In three cases (50.0%), AE intensity was determined as mild, in the remaining three cases (50.0%) as moderate. CONCLUSION: The results have shown the safety and efficacy of xeomin in the treatment of gastrocnemius spasticity in pediatric patients with cerebral palsy. These data are confirmed by the lack of significant differences in any clinical or electromyography parameters with the results in the reference group administered botox.

[Pharmacotherapy of attention deficit hyperactivity disorder in children: the results of a multicenter double-blind placebo-controlled study of hopantenic acid]. / Farmakoterapiia sindroma defitsita vnimaniia s giperaktivnost'iu u detei: rezul'taty mnogotsentrovogo dvoinogo slepogo platsebo-kontroliruemogo issledovaniia gopantenovoi kisloty.

AIM: To assess the efficacy and safety of hopantenic acid (pantogam) compared to placebo in the treatment of attention deficit hyperactivity disorder (ADHD) in children, aged from 6 to 12 years, during 4 month in the prospective multicenter comparative double-blind placebo-controlled study in parallel groups. MATERIAL AND METHODS: One hundred patients enrolled in the safety assessment population were stratified into two equal pantogam and placebo groups. Eighty-nine patients who completed the study in according to the protocol were included in the efficacy assessment group: 45 in the pantogam group and 44 in the placebo group. Pantogam was administered in tablets (250 mg) in the therapeutic dose 30 mg/kg of body mass, divided into 2 doses, during 4 month. Patient's state was assessed by the total score on ADHD-DSM-IV, CGI-S WFIRS-P and results of the Toulouse-Piéron test for sustained attention. RESULTS AND CONCLUSION: There was a trend towards an increase in the percentage of patients with positive changes (a decrease in the total ADHD-DSM-IV by ≥25%) in the end of the 3rd and 4th month in the pantogam group (treatment response was 66.7 and 68.9%, respectively) compared to the placebo group (treatment response was 52.3 and 61.4%, respectively). A significant decrease in disease severity assessed by the CGI-S was noted in the pantogam group compared to the placebo group. After 4 month of treatment with pantogam, the severity of functional disturbances was reduced by 4 out of 6 WFIRS-P domains: Family, School and learning, Child's self-concept and Risky activities. Pantogam improved the measures of sustained attention (accuracy and speed) in the Toulouse-Piéron test. The drug used in mean daily dose 30 mg/kg during 4 month had a favorable safety profile which did not differ from that of placebo.

[The First Russian Consensus on the Multilevel Abobotulinumtoxin A Injections in Spastic Forms of Cerebral Palsy]. / Pervyi Rossiiskii konsensus po primeneniyu mnogourovnevykh in''ektsii abobotulinumtoxin A pri lechenii spasticheskikh form detskogo tserebral'nogo paralicha.

Spasticity treatment is one of the key aspects of the contemporary cerebral palsy (CP) rehabilitation that influences on the effectiveness of other methods. The paper presents the first Russian document that unites the recommendations for the BTA treatment of CP and could be used as the guideline for the multilevel injections. The Russian consensus on the multilevel botulinum toxin A (BTA) treatment of spastic CP is based on the international data and the results of national studies. The authors describe typical CP spasticity patterns in the upper and lower extremities, give recommended intervals for the BTA (Abobotulinum toxin A) dosages for the whole injection procedure and for the separate muscles. The method of dosage calculation for functional segments is also described. Attention is paid to the frequency, optimal intervals between the repeated injections and the whole duration of BTA treatment. The authors discuss effectiveness and safety of BTA, factors that potentially influence the results of the injections, including ultrasound and electromyography control, and indications for the continuation and termination of treatment.

[Sanfilippo Syndrome].

Sanfilippo syndrome (mucopolysaccharidosis type III) is a lysosomal disorder caused by a defect in the catabolism of heparan sulfate. Mucopolysaccharidosis type III is the most common type of all mucopolysaccharidoses. The pathogenic basis of the disease consists of the storage of undegraded substrate in the central nervous system. Progressive cognitive decline resulting in dementia and behavioural abnormalities are the main clinical characteristics of Sanfilippo syndrome. Mucopolysaccharidosis type III may be misdiagnosed as otherforms of developmental delay, attention deficit/hyperactivity disorder and autistic spectrum disorders because of lack of somatic symptoms, presence of mild and atypical forms of the disease. Patients with Sanfilippo syndrome may have comparatively low urinary glycosaminoglycans levels resulting in false negative urinary assay. Definitive diagnosis is made by enzyme assay on leucocytes and cultured fibroblasts. There is currently no effective treatment of mucopolysaccharidosis type III, though ongoing researches of gene, substrate reduction and intrathecal enzyme replacement therapies expect getting curative method to alter devasting damage of central nervous system in near future.

[Selection of a dose of the botulinum toxin A in spastic forms of cerebral palsy]. / Vybor dozy preparata botulinicheskogo toksina tipa A pri lechenii spasticheskikh form detskogo tserebral'nogo paralicha.

AIM: To analyze the efficacy and safety of dose ranges of abobotulinum toxin A (BTA) for multilevel injections into upper and lower extremity muscles in children with spastic forms of cerebral palsy (CP). MATERIAL AND METHODS: We analyzed retrospectively multilevel BTA injections for 216 patients, aged from 2 to 17 years. Children received 1-6 repeated injections and complex physiotherapy. Patients were classified according to the GMFCS. Treatment results were evaluated with the modified Ashworth and Tardieu scales. RESULTS: Multilevel BTA injections were indicated for the most (89/8%) of the patients with spastic forms of CP, and in most of them the total dosage exceeded 30 U/kg. In the bilateral forms of CP, the total dosage (U and U/kg) was higher compared to the unilateral forms. Doses for each muscle in U/kg were similar in all CP forms. The total doses of BTA and the intervals between the repeated injections were stable for each patient. CONCLUSION: The dose ranges suggested for CP are effective and safe for the reduction of spasticity in several functional segments of upper and lower extremities in one treatment session.

[Evaluation of physical development in children with classical phenylketonuria].

Classical phenylketonuria (PKU) is hereditary disease, which is based on the disturbance of phenylalanine conversion to tyrosine. The basic treatment of PKU is low phenylalanine diet. Prolonged restriction of natural protein may have a negative impact to PKU patient growth and physical development. The objective was to evaluate the physical development of patients with classical PKU at birth and on the diet based on the products with different chemical composition without phenylalanine. 257 PKU patients have been examined with the computer program "WHO Anthroplus 2009". All patient were born at term. Z-score of body weight, height and body mass index (BMI) to age has been retrospectively estimated. Patients were divided into 2 groups: group 1--101 children born in 1980-1993 were fed by unadapted specialty products based on protein hydrolyzate with restricted phenylalanine, and group 2--156 children born in 1995-2012 were fed by contemporary amino acid mixtures without phenylalanine. All newborn PKU patients had the middle for age Z-score of weight and BMI, 21% of neonates had high Z-score growth. Before the diet therapy BMI Z-score was normal in 84.1% patients in group 1 and 87.2% patients of group 2. After 6 mo of treatment with low phenylalanine diet the number of patient with normal BMI Z-score was 71.3% in group 1 against 95.6% in group 2. Thus, using of modern amino acid mixtures without phenylalanine, enriched with essential nutrients can promote the normal physical development of PKU patients.

[Open, non-comparative phase III clinical study to evaluate the efficacy and safety of sapropterin in patients with phenylketonuria and hyperphenylalaninemia].

BACKGROUND: Phenylketonuria (PKU) is an autosomal recessive inherited disease associated with impaired metabolism of the amino acids phenylalanine (Phe) and tyrosine. The main criterion for diagnosis of PKU is high blood Phe level determined during neonatal screening. In case where PKU patient is responsive to tetrahydrobiopterin treatment, sapropterin restores the impaired activity of the enzyme phenylalanine hydroxylase, resulting in the stimulation of normal Phe metabolism and thereby enhancing patient tolerance to natural products. AIM: The present open, non-comparative clinical study was initiated to assess the degree and frequency of response after 8-day sapropterin administration and assess the safety of 6-week sapropterin treatment in patients with PKU and hyperphenylalaninemia. PATIENTS AND METHODS: The study enrolled 90 patients with PKU. The criterion of response to 8-day sapropterin therapy was the reduction of Phe blood levels ≥ 30% compared with the baseline value. RESULTS: Positive response to treatment was observed in 30 (33.3%) patients (95% CI 23.7-44.1). The mean percentage change in Phe blood levels after the 8-day response test period compared to Phe levels prior to dosing was 14.1 ± 28.4% in the overall subject population (95% CI 8.2-20.1) and 44.3 ± 15.1% in the subpopulation of patients with a positive response (95% CI 38.6-49.9). During the study, adverse events were reported in 24 (26.7%) patients in the overall population in 16 (53.3%) patients in the subpopulation who had a response. CONCLUSION: The study results confirmed the efficacy and safety of sapropterin therapy in patients with PKU, which is consistent with international clinical trials data.

[Assessment of the life quality in children with phenylketonuria].

BACKGROUND: Phenylketonuria (PKU) - the most common inherited disorder of amino acid metabolism, identified in Russia by neonatal screening. The results of dietary treatment demonstrate a positive effect. However, the quality of PKU patients life remains unknown. OBJECTIVE: The aim of the study was to assess the quality of PKU children life in comparison with their healthy peers, also depending on the treatment onset and the patient's age. METHODS: The study involved 64 pairs - PKU child and one of his parents. It was used the common questionnaire survey Pediatric Quality of Life Inventory (PedsQLtm4. 0, Varni et al., USA, 2001) and the program SPSS v. 14.0 (US) for statistical processing of the results. RESULTS: The statistically significant (p <0.001) differences between PKU patients and healthy children in the physical, emotional, social and role functioning were found. The most pronounced differences were observed in the social (70 points vs 90 respectively) and role (57.5 vs 80 respectively) functioning. Maximum significant correlation (p <0.001) was installed between the social functioning of PKU patients and timing of the dietary treatment. Also the statistically significant interaction (p <0.05) was found between the role functioning, patient's age and treatment onset. The assessment points of social and role functioning were higher (p <0.05) in the PKU patients subgroup with early treatment initiation. CONCLUSION: These results confirmed the need of early diagnostics of PKU and initiation of dietary treatment, as well as the organization of timely psychological support for parents of sick children.

[Clinical experience of the repeated multilevel injections of the botulinum toxin type A (abobotulinum toxin A) in the spastic forms of cerebral palsy].

OBJECTIVE: Our aim was to analyze the dosages of Abobotulinum toxin A used for each muscle in the clinically effective and safe repeated multilevel injections in CP children, and the intervals between injections. METHODS: Retrospective analysis of 229 injection sessions into 359 muscles of the upper and 361 muscles of the lower extremities in 133 children (2-18 years) with spastic CP. Analysis included only patients who were injected for the first time and demonstrated decrease of spasticity in injected muscles according to modified Ashworth and/or Tardieu scales without significant side effects 2-4 weeks after injections. Motor deficit according to GMFCS was: GMFCS I--16(12%) children, GMFCS II--26 (19.6%), GMFCS III--43 (32.3%), GMFCS IV--30 (22.6%), GMFCS V--18 (13.5%). Repeated injections (up to 5 sessions) were done in 59 children. Maximum follow-up perion was 22 months. 40 patients (30.1%) had one-sided injections, 93 (69.9%)--two-sided, 125 (94%)--multilevel injections. RESULTS: We presented minimal and maximal dosages, interquartile ranges for each injected muscle, also "off-label" and our proposition of per-segment calculation of dosages in multilevel injections in CR. We also demonstrated the stability of intervals between repeated injections and dosages per kg in a patient. These results are compared with the official Russian and international recommendations of BTX-A treatment for children. CONCLUSION: We presented our experience of BTX-A dosages calculation for the spastic CP treatment which could be used as a recommendation and guide for the multilevel injections treatment according to the aims of rehabilitation, spasticity level, muscle size and motor deficit of a concrete patient.

[Case of combination of Beckwith-Wiedemann syndrome with West syndrome].

Beckwith-Wiedemann syndrome (BWS) is etiologically connected with genetic/epigenetic growth dysregulation. The supposed localization of this disorder is a short arm of chromosome 11 (11p 15.5). Its prevalence is 1:13 per 700 newborns. West syndrome is an age-dependent epileptic syndrome related to a group of infantile epileptic encephalopathies and characterized by a triad of basic symptoms: series of infantile spasms, psychomotor retardation and severe paroxysmal EEG changes. The incidence of West syndrome is estimated at 1 case per 2,000-4,000 newborns. The article describes a rare clinical case: a combination of BWS with one of the types of infantile epileptic encephalopathies--West syndrome. A detailed analysis of the West syndrome progression in a female patient with BWS is given, the tactics of antiepileptic therapy is analyzed, and its complexity in terms of metabolic disorders caused by the presence of a genetic syndrome in a patient is shown. The results of a long catamnesis are described. The figures are the fragments of native electroencephalograms at the eruptive phase of West syndrome and against the background of a long-term remission. When describing the clinical case in detail, the authors actively discuss the obtained information and available literature data. The article also presents practical guidelines for the early detection of metabolic disorders in patients with infantile epileptic encephalopathies. In addition to anti-epileptic drugs, the authors propose to include a mandatory metabolic correction in the therapy complex for these patients.

[Differential diagnosis of multiple sclerosis with pediatric onset: the experience of the Moscow Division for treatment of children and adolescents with multiple sclerosis].

The diagnosis of multiple sclerosis in children and adolescence should be differentiated from a group of rare white matter diseases, with fuzzy diagnostic criteria. Some of these conditions require modern diagnostic techniques and wide knowledge of the doctor. The Moscow Division for treatment of children and adolescents with multiple sclerosis is a specialized advisory structure, which has specialists with experience in the differential diagnosis of multiple sclerosis with pediatric onset. The emphasis on the clinical aspects in differential diagnosis of early onset multiple sclerosis can reduce the time for the diagnosis and help to avoid diagnostic mistakes.

[An electromyographic study on the development of optimal tactics of botulinum toxin type A injections in children with spastic forms of cerebral palsy].

We studied 67 children, aged 2-9 years, with cerebral palsy including 56 children with a spastic form. An electromyographic method was used for the development of optimal tactics of botulinum toxin type A injections in different clinical presentations of spasticity. The best clinical results were obtained in children with the following changes on EMG: 1) the tonic muscle activity in resting state was minimal (<10 microvolts) and had local or regional distribution; 2) the pathological synkinetic activity during voluntary movements was minimal (synergetic activity coefficient for shin muscles was less than 0.45); 3) the disturbance of interactions between synergistic and antagonistic muscles was moderate (reciprocity coefficient was not less than 0.4); 4) EMG amplitude in voluntary muscle contraction should not be less than 150 microvolts. This approach to the treatment allowed to reach higher levels on The Gross Motor Function Classification System in part of children.

[The use of topiramate in the treatment of focal epilepsy in children].

Topiramate was used in the treatment of 66 children, aged 2--16 years (mean age 7.0±4.6 years), including 19 patients with idiopathic form of focal epilepsy (IFE), 21 patients with cryptogenic forms (CFE) and 26 patients with symptomatic forms (SFE). The drug was administered in capsules in dose from 3 to 7 mg/kg/day. Thirty-three patients were on monotherapy, 26 patients received the drug in the combination with one antiepileptic (AED) drug and 7 patients received topiramate in the combination with 2 AEDs. The efficacy of topiramate in focal epilepsy was demonstrated in 65% of patients, including high efficacy in 15% and complete reduction of seizures in 12%. No effect was seen in 27% of patients. The results revealed the high efficacy of topiramate in all subgroups of patients. The significantly higher efficacy was noted in patients with IFE and CFE forms compared to those with SFE form. The tolerability was satisfactory in all subgroups. Side-effects observed in 5 patients were eliminated by increasing the duration of dose titration.

[Hereditary thrombophilia in children: current views of etiology and pathogenesis].

This review is focused on the role of genetic factors in etiology and pathogenesis of thrombophilia in adults and children. Their knowledge permits to elucidate the main causes of this pathology and choose adequate measures for its prevention.

Family Analysis of Linkage and Association of HLA-DRB1, CTLA4, TGFB1, IL4, CCR5, RANTES, MMP9 and TIMP1 Gene Polymorphisms with Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system (CNS). Proteins of the immune system, as well as proteins that are involved in the infiltration of activated immune cells in the CNS, play an important role in the pathogenesis of MS. We investigated the association and linkage with MS of the following immune-system genes polymorphisms: HLA-DRB1,CTLA4,TGFB1,IL4,CCR5 andRANTES, as well as of the matrix metalloproteinase 9 (MMP9) and tissue inhibitor of metalloproteinase  1 (TIMP1) genes polymorphisms. For this purpose we used the transmission disequilibrium test (TDT). The group investigated was comprised of 100 nuclear families of Russian ethnicity, each consisting of an affected offspring and his nonaffected parents. It was found that HLA-DRB1*15alleleandMMP9*-1562C allele were transmitted from healthy heterozygous parents to affected children more frequently than alternative alleles (p  =  0.02 andp  =  0.04, respectively). Another family-based method, AFBAC (affected family-based control), showed MS association with HLA-DRB1*15, but not with theMMP9*-1562C allele.

[Analysis of linkage and association of alleles of proinflammatory cytokines genes IL-6, IFNg and TNF with multiple sclerosis using transmission disequilibrium test (TDT)].

Proinflammatory cytokines Interleukin-6 (IL-6), Interferon-gamma (IFNg) and Tumor necrosis factor (TNF) are known as participants of inflammation and play an important role in pathogenesis of multiple sclerosis (MS). Based on literature data about influence of SNPs G(-308)A of TNF gene, A(+874)T of IFNG gene and G(-174)C of IL-6 gene on production of these cytokines, we investigated association of these polymorphic sites with MS. Linkage and association of alleles of these genes with MS was analyzed by transmission disequilibrium test (TDT). In investigated group of 104 nuclear families of Russian ethnicity it was found that TNF* (-308)A allele transmitted from healthy heterozygous parents to affected children more frequently (p = 0.01). Linkage/association of IFNG and IL-6 alleles with MS was not revealed. Thus, data obtained indicate the participation of TNF gene in MS susceptibility in Russians.

[Effective treatment of multiple sclerosis with rebif-22 mcg in children and adolescences: results of a long-term study].

Management from an early age and availability of new treatment options have changed the outcome of paediatric patients with multiple sclerosis (MS). Currently available for treatment of MS in adults, such drugs as interferons beta and copolymer-1 are not widely used in paediatric neurological practice. The present long-term study of the effect of interferon beta la (rebif-22 mcg) included 20 children with MS from Moscow population. The data of this open-label study were compared with our previously reported data from the prospective population-based study of 67 ethnically-matched children with MS. The results revealed early formation of stable neurological deficit at late-onset treatment, high therapeutic efficacy when the drug was timely used and good tolerability of the treatment. So, it is necessary to use immunomodulating therapy with these drugs in children and adolescents as early as possible.