OBJECTIVES:To evaluate the efficacy and safety of two dosing regimens of Mexidol film-coated tablets, 125 mg («RPC «PHARMASOFT» LLC Russia), compared with placebo in children with attention deficit hyperactivity disorder (ADHD) aged 6 to 12 years.MATERIAL AND METHODS:A multicenter randomized, double-blind, placebo-controlled study in 3 parallel groups was conducted in 14 clinical centres of the Russian Federation to assess efficacy and safety of Mexidol film-coated tablets, 125 mg («RPC «PHARMASOFT» LLC Russia) in the treatment of attention deficit hyperactivity disorder (ADHD) in children 6-12 years old with different dosing regimens. The study involved 333 boys and girls aged 6 to 12 years with a confirmed diagnosis of ADHD established in accordance with ICD-10 and DSM-5 criteria. After screening (up to 14 days) the patients were randomised into 3 treatment groups in a 1:1:1: Mexidol 125 mg 2 times daily, Mexidol 125 mg daily+placebo and the placebo group. The duration of treatment in all groups was 42 days. 332 children completed the study. ADHD and comorbid disorders assessment scales were used.RESULTS:There were statistically significant changes in the sum of the total scores on the SNAP-IV inattention and hyperactivity/impulsivity subscales after 6 weeks of therapy in all three study groups (p<0.05). There were statistically significant differences between the Mexidol 125 mg and placebo groups and between the Mexidol 125 mg 2 times daily and placebo groups (for the PP population: p=0.000308 and p=0.000024, respectively; for the FAS population: p=0.000198 and p=0.000024, respectively), indicating that Mexidol therapy is superior to placebo. Statistically significant differences (p<0.05) were also obtained for most of the secondary efficacy criteria (average change in SNAP-IV inattention subscale score, average change in SNAP-IV hyperactivity/impulsivity subscale score, average change in SNAP-IV subscale score - Conners index, average change in ADHD-RS-IV score, change in CGI-ADHD-S scores, change in CGI-I score - the Clinical Global Impressions Scale - Improvement) when comparing Mexidol therapy with placebo. The results of statistical analysis of the incidence of adverse events, laboratory values, physical examination show no significant differences between the compared groups in the main safety parameters.CONCLUSIONS:The regimen of Mexidol, 125 mg film-coated tablets twice daily has been shown to be superior to the regimen of Mexidol, 125 mg film-coated tablets once daily and placebo. The safety profiles of the studied dosing regimens of Mexidol and placebo were comparable.

Modern data of frequency and structure of epilepsy in children with cerebral palsy were analyzed. Basic unfavorable prognostic factors of epilepsy development were formulated. Worsening prognosis of motor and cognitive development of children with cerebral palsy, epileptic seizures limit volume of their rehabilitation. Early prediction of epilepsy development risk in cerebral palsy children is extremely important link in the treatment choice procedure

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.

A randomized study on the efficacy and safety of the hopantenic acid preparation (pantocalcin) and its effect on cognitive functions in children with cerebral palsy (CCP) has been carried out. The positive effect of pantocalcin on the visual memory and attention concentration, activity and fatigability has been shown. At the same time, there was a decrease of anxiety in children and adolescents with CCP. No evidence for the effect of the drug on visual-motor skills has been found. The results of the study have demonstrated the high safety profile of pantocalcin when used in pediatric practice.

: Epilepsy is one of the most frequent and difficult for treatment co-morbid disease of cerebral palsy. In therapeutic aspect, the difficulty of the problem is defined by the necessity to combine the active restoration of motor disorders with a regime of antiepileptic treatment. It leads frequently to stopping the restoration process and aggravation of patient's motor disability. The diagnosis of epilepsy in the child with cerebral palsy should in no way discontinue the rehabilitation measures, albeit in case of the concomitant pathology a plan of rehabilitation scheme should be adjusted. The pharmacological control of epileptic seizures should be the first step of the new rehabilitation scheme. Epileptologists usually conduct the selection of multi-component antiepileptic treatment in patients with drug resistant epilepsy, however a neurologist of an outpatient clinics who follows up the patient in different stages of development and rehabilitation should play a key role. The authors suggest the general treatment tactics for children with cerebral palsy and epilepsy by the neurologist of the polyclinics.

The first demyelinating episode in the structure of multiple sclerosis is called clinically isolated syndrome, that is the clinical debut of the disease requiring an extensive differential diagnostic search and identification of long-term therapeutic tactics. It is well-known that experience of prescribing interferon β to adult patients at this earliest stage in the disease results in a substantially improved long-term disability prognosis. At the same time, promising techniques for an early launch of the biologic response modifier therapy have not yet found sufficient application in children and adolescents with multiple sclerosis.Key words: multiple sclerosis, clinically isolated syndrome, children, adolescents, interferon β. (Pediatric Pharmacology. – 2010; 7(3):91-94)

The first demyelinating episode in the structure of multiple sclerosis is called clinically isolated syndrome, that is the clinical debut of the disease requiring an extensive differential diagnostic search and identification of long-term therapeutic tactics. It is well-known that experience of prescribing interferon β to adult patients at this earliest stage in the disease results in a substantially improved long-term disability prognosis. At the same time, promising techniques for an early launch of the biologic response modifier therapy have not yet found sufficient application in children and adolescents with multiple sclerosis.

Disseminated sclerosis is chronic progressive disease of central nervous system, which is characterized by demyelination, degeneration of nerve fibers and polymorphous clinical symptoms. According to literature data, 2–10% of patients have onset of a disease in childhood and adolescence. Frequent clinical symptoms of disseminated sclerosis, especially in adolescents, are paroxysmal states and neuropsychological disorders. Drugs containing interferon beta which are used for immunomodulating treatment, can increase the rate of paroxysmal neuropsychological disorders in patients with disseminated sclerosis. Present study with participation of 78 adolescents analyzed frequency and spectrum of neuropsychological disorders and paroxysmal states in patients 12–17 years old and relation of revealed disorders with a treatment with interferon beta.Key words: adolescents, disseminated sclerosis, interferon beta, treatment, depression, paroxysmal states, anxiety, neuropsychological testing.(Voprosy sovremennoi pediatrii — Current Pediatrics. – 2010;9(4):34-39)

Рассеянный склероз — хроническое прогрессирующее заболевание центральной нервной системы, характеризую-щееся демиелинизацией, дегенерацией нервных волокон и полиморфной клинической картиной. По литературным данным, у 2–10% пациентов заболевание манифестирует в детском и подростковом возрасте. Частыми клиническими проявлениями рассеянного склероза, особенно у подростков, являются пароксизмальные состояния и нейропсихоло-гические нарушения. Препараты интерферонов бета, применяемые для иммуномодулирующего лечения при рассеян-ном склерозе, по данным литературы, также могут увеличивать частоту пароксизмальных расстройств и нейропсихо-логических нарушений у пациентов с рассеянным склерозом. Настоящее исследование, проведенное у 78 подростков с рассеянным склерозом, посвящено анализу частоты и спектра нейропсихологических нарушений и пароксизмаль-ных состояний у больных в возрасте 12–17 лет и связи выявленных отклонений с терапией интерферонами бета.Ключевые слова: подростки, рассеянный склероз, пароксизмальные состояния, интерферон бета, лечение, депрес-сия, тревожность.

Inflammatory demyelinating diseases in children and adolescents are sufficient problem of modern medicine. Its topicality is conditioned by as traditionally high prevalence of acute demyelinating conditions (acute disseminated encephalomyelitis) as increase of morbidity with chronic demyelinating forms of pathology (disseminated sclerosis) in children. The absence of clear diagnostic algorithm presents difficulties for the determination of tactics of treatment and prognosis on early stages of their development, e.g. at the time of maximal effectiveness of immunomodulatory medications. Besides, the list of medications for the prolonged immunomodulatory treatment of demyelinating diseases, registered in Russia, includes such drugs as interferon beta 1a for the subcutaneous injection, officially annotated for the use from 12-year old age.Key words: children, inflammatory demyelinating diseases, diagnostics, treatment.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2009;8(6):139-145)

Immunomodulatory drugs reduce relapse rate and disease progression In relapslng-remlttlng multiple sclerosis but extensive data are not available on the effectiveness and tolerablllty of these drugs In childhood or adolescence. Interferon beta tolerablllty biased by frequency and method of drug administration. Drug administration has great Impact on treatment compliance and adherence. That's why we discuss moreover Interferon beta la Intramuscular as perspective Immunomodulatlve medication In pediatric MS cohort.

Copper deficiency in adult rats was induced by addition of silver chloride to the feed. The concentrations of silver, copper, iron, and zinc and relative activity of genes for copper transporting proteins and copper enzymes were measured in the cortex, cerebellum, hippocampus, amygdala, pituitary gland, and hypothalamus. Silver was accumulated only in the hypothalamic—pituitary system. These changes were accompanied by a decrease in the concentration of copper and increase in the contents of iron and zinc. Activity of genes for copper transport enzymes (high-affinity copper transporter; and two copper transport ATPases, ATP7A and ATP7B) and copper enzymes that were formed in the intracellular secretory pathway did not decrease in the brain of rats with copper deficiency. Relative activity of genes for intracellular copper enzymes (Cu2+/Zn2+ superoxide dismutase and subunit IV of cytochrome c oxidase), concentration of immunoreactive polypeptides of superoxide dismutase, and enzymatic activity of superoxide dismutase remained unchanged under these conditions.

Inflammatory demyelinating diseases in children and adolescents are sufficient problem of modern medicine. Its topicality is conditioned by as traditionally high prevalence of acute demyelinating conditions (acute disseminated encephalomyelitis) as increase of morbidity with chronic demyelinating forms of pathology (disseminated sclerosis) in children. The absence of clear diagnostic algorithm presents difficulties for the determination of tactics of treatment and prognosis on early stages of their development, e.g. at the time of maximal effectiveness of immunomodulatory medications. Besides, the list of medications for the prolonged immunomodulatory treatment of demyelinating diseases, registered in Russia, includes such drugs as interferon beta 1a for the subcutaneous injection, officially annotated for the use from 12-year old age.

This article presents results of a trial, studying quality of life of adolescents with multiple sclerosis. Obtained data show, that adolescents had decreased quality of life, including physical and psychosocial functioning. Decreasing of total rate of quality of life was concerned with, first of all, disorders in school and physical functioning, and emotional constituent was intact. It was shown, that pathogenetic treatment with interferon beta-1a (Rebif) did not significantly decreased psycho-emotional constituent of quality of life. On the contrary, patient in remission had increase of rates of psycho-social health on the basis of insignificant decrease of physical and emotional indices, ant that caused increase of summary rate of quality of life

Fibrillogenesis was induced in rats by injection of a fragment of neurotoxic protein, β-amyloid protein precursor, into the cerebral ventricle. Copper, iron, and zinc concentrations and relative activities of genes of copper-transporting protein and extracellular and intracellular cuproenzymes were evaluated in different brain compartments of these animals. Copper and zinc concentrations decreased significantly in different compartments of the brain of rats with experimental fibrillogenesis, while iron content did not change. According to the data of RT-PCR analysis, activities of genes of copper-transporting protein and extracellular coenzyme decreased. The expression of intracellular cuproenzyme genes and the content of SOD1 protein did not change, SOD1 activity in the cytosol decreased, and active SOD1 was detected in the mitochondrial intermembrane space. The relationship between fibrillogenesis and copper metabolism is discussed.

This article presents results of a trial, studying quality of life of adolescents with multiple sclerosis. Obtained data show, that adolescents had decreased quality of life, including physical and psychosocial functioning. Decreasing of total rate of quality of life was concerned with, first of all, disorders in school and physical functioning, and emotional constituent was intact. It was shown, that pathogenetic treatment with interferon beta1? (Rebif) did not significantly decreased psycho-emotional constituent of quality of life. On the contrary, patient in remission had increase of rates of psycho-social health on the basis of insignificant decrease of physical and emotional indices, ant that caused increase of summary rate of quality of life.Key words: adolescents, multiple sclerosis, quality of life.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2009;8(2):99-103)

Immunomodulatory drugs reduce relapse rate and disease progression in relapsing-remitting multiple sclerosis but extensive data are not available on the effectiveness and tolerability of these drugs in childhood or adolescence. Interferon beta tolerability biased by frequency and method of drug administration. Drug administration has great impact on treatment compliance and adherence. That’s why we discuss moreover interferon beta 1a intramuscular as perspective immunomodulative medication in pediatric MS cohort.Key words: immunomodulatory drugs, interferon beta, multiple sclerosis, compliance, adherence, adolescence, childhood.

This article presents results of a trial, studying quality of life of adolescents with multiple sclerosis. Obtained data show, that adolescentshad decreased quality of life, including physical and psychosocial functioning. Decreasing of total rate of quality of life was concerned with,first of all, disorders in school and physical functioning, and emotional constituent was intact. It was shown, that pathogenetic treatmentwith interferon beta1a (Rebif) did not significantly decreased psychoemotional constituent of quality of life. On the contrary, patient inremission had increase of rates of psychosocial health on the basis of insignificant decrease of physical and emotional indices, ant thatcaused increase of summary rate of quality of life.Key words:adolescents, multiple sclerosis, quality of life.

Tissue-specific regulation of the expression of ceruloplasmin (Cp) gene, which encodes major copper-containing extracellular glycoprotein was investigated. A decrease of the Cp concentration associated with copper amounts in milk during the first 3 days of lactation was used as phenotypic index for evaluating the Cp enzyme activity in the mammary gland. Computer analysis of mammalian Cp gene promoter region has revealed conserved sequences of cis-elements, which potentially were capable of regulating the enzyme activity. It has been shown that changes in the nucleotide sequence of specific transcriptional factor binding sites located at 5′-end of Cp gene were associated with disturbance of the regular downregulation of Cp gene activity during lactation.