[Results of a multicentre double-blind randomised placebo-controlled clinical trial evaluating the efficacy and safety of Mexidol in the treatment of Attention Deficit Hyperactivity Disorder in Children (MEGA)]. / Rezul'taty mnogotsentrovogo dvoinogo slepogo randomizirovannogo platsebo-kontroliruemogo klinicheskogo issledovaniya po otsenke effektivnosti i bezopasnosti preparata Meksidol v lechenii sindroma defitsita vnimaniya s giperaktivnost'yu u detei (MEGA).

OBJECTIVES: To evaluate the efficacy and safety of two dosing regimens of Mexidol film-coated tablets, 125 mg («RPC «PHARMASOFT¼ 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 «PHARMASOFT¼ 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.

[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.

[Intrathecal administration of drugs]. / Intratekal'noe vvedenie lekarstvennykh preparatov.

The article summarizes the introduction of drugs into the cerebrospinal fluid. Indications and contraindications for the administration of pharmaceuticals in the cerebrospinal fluid spaces are presented. Main groups of pharmacological agents used for endolumbar introduction and conditions under which they are used, as well as advantages and disadvantages of this treatment are considered. The authors describe a method of administration of antibiotics for bacterial and fungal infections of the central nervous system. The need to assess the intracranial pressure prior to cisternal puncture and exclude blocking of cerebrospinal fluid pathways is emphasized. Information about intrathecal administration of anticancer and cytostatic drugs in primary and metastatic brain lesions as well as data on the significant positive effect of oxygen-ozone mixture in the treatment of victims of traumatic brain injury in its acute period are presented. Of interest are the results of the study, which showed a statistically significant reduction in the severity of neurological deficit after the introduction of cerebrolysin in the lumbar space in the first days after the onset of cerebral infarction. Possible complications of the described method of drug delivery, measures taken against them and methods of preventionare described.

[Botulinum toxin type A (dysport) in the complex rehabilitation of children with spastic forms of cerebral palsy].

OBJECTIVE: To analyze the efficacy of repeated use of dysport in children with spastic forms of cerebral palsy (CP). MATERIAL AND METHODS: Forty-five children with CP (main group) received 8 consecutive injections of dysport in the complex treatment. A comparison group consisted of 41 children with CP who received the same complex treatment but without dysport. Disport was used intramuscular in mean dose 26±4 u/kg. RESULTS AND CONCLUSION: A significant decrease of the muscle tone was observed after each following injection of dysport. The muscle tone did not return to baseline 24 weeks after each following injection and significantly differed after the first 4 injections. After 8 repeated courses of botulinotherapy, a number of children needed the operative treatment, were significantly greater in the comparison group (71% vs 47%, p=0,041).

[Calcium homeostasis and nitric oxide processes in children with migraine].

Eighty-one children aged 6 to 17 years who had migraine were examined by clinical and biochemical studies. The activity of Ca2(+)-ATPase and the levels of total intracellular calcium of platelets and plasma nitrites were studied in the attack-free period. Children with migraine were fond to have elevated levels of stable nitric oxide metabolites (nitrites). The level of intracellular calcium was 2 times greater than that in healthy children of the same age, which was followed by compensatory Ca2(+)-ATPase activation. There was a relationship of the parameters of calcium homeostasis and the plasma level of nitrites to the clinical and pathogenetic manifestations of migraine.

Neurological aspects of the clinical features, pathophysiology, and corrections of impairments in attention deficit hyperactivity disorder.

The prevalence of attention deficit hyperactivity disorder (ADHD) in young schoolchildren in Nefteyugansk (Khanty-Mansiiskii Autonomous Region) was found to be 8%, with rates of 13% amongst boys and 3% amongst girls. Clinical investigation of a cohort of 122 children aged 6-11 years identified risk factors for the formation of ADHD as perinatal CNS injuries, inherited predisposition, and unfavorable social-psychological influences. Neuropsychological, neurophysiological (electroencephalography), and biochemical studies identified minor neurological abnormalities, some characteristic features of the motor and emotional spheres, and changes in higher mental functions. In addition, biochemical changes consisting of decreases in plasma and erythrocyte magnesium levels and decreases in Mg(2+)-ATPase activity were identified. Treatment with MAGNE-B(6) allowed correction of many of these changes.

[The significance of determination of the serum levels of nitrites for assessing severity of perinatal ischemia and predicting the nervous and mental development of a child].

The results of clinical and biochemical studies of 93 full-term neonatal infants with perinatal hypoxia-induced ischemic nervous system lesion are presented. Perinatal ischemia in the newborns has been found to cause an increase in the serum content of nitric oxide, more significant and stable in severe encephalopathy. The level of nitric oxide remained significantly elevated in the natural development of the disease in children with persistent neurological symptoms; its normalization was observed by the third month of life when the clinical syndromes regressed. The authors proposed to use the blood level of nitric oxide as a marker of acute cerebral ischemia and as an additional criterion for predicting the nervous and mental development of children with prior neonatal ischemia.

[Effect of MAGNE-B6 on the clinical and biochemical manifestations of the syndrome of attention deficit and hyperactivity in children].

MAGNE-B6 was used for the therapy of a group of 31 children aged from 6 to 12 with attention deficiency and hyperactivity syndrome. The control group included 20 children with similar manifestations of the same pathology, which received a polyvitamin complex. The efficacy of therapy was assessed in the 30th day with the aid of a complex clinical-neuropsychological and biochemical investigations. It was established that the administration of MAGNE-B6 led to improvements in the behavior, decreased the level of anxiety and aggression, improved both large- and small-scale mobility, decreased the level of synkinesis, increased the characteristics of attention, corrected the magnesium homeostasis, and favored normalization of the blood electrolytes. Reliable differences (p < 0.01 or 0.001) between the test and control groups in the degree of expression of the indicated disorders were observed.

[Neurological aspect of clinical symptoms, pathophysiology and correction in attention deficit hyperactivity disorder].

We studied prevalence of attention deficit hyperactivity disorder (ADHD) in senior schoolchildren of Nefteyugansk (Khanty-Mansysky autonomic region) it was 8% (13% among boys and 3% among girls). Clinical examination of 122 children, aged 6-11 years, revealed that risk factors for ADHD were perinatal CNS injures, familial predisposition, unfavorable social and psychological influences. Neuropsychological, neurophysiologic (electroencephalography) and biochemical study showed mild neurological disturbances, some peculiarities of motor and emotional spheres and higher mental functions. Moreover, there were such biochemical alterations as a decrease of magnesium level in the plasma and erythrocytes and a reduction of Mg(2+)-ATPase activity. The use of MAGNE-B6 allowed us to correct many of the disturbances.

[Diagnostic value of examination of the magnesium homeostasis in children with attention deficit syndrome with hyperactivity].

We followed, within the present case study, 51 children, aged 6 to 11, with attention deficit hyperactive syndrome (ADHS); special biochemical tests were made. The magnesium level was found to be moderately decreased in plasma and erythrocytes and the Mg2+ -ATPase activity was reduced in ADHS children. No essential changes of calcium or sodium homeostasis were detected in cells. The MAGNE-B6 drug, when used in the complex therapy of ADHS, normalizes the magnesium homeostasis, it enhances the large and small motility, attention, psychic stability and EEG parameters, and it reduces anxiety. The method of determination of magnesium in erythrocytes and in blood plasma can be used to detect the deficit of the microelement in patients and to monitor the efficiency of therapy.

[Membrane destabilizing processes in perinatal nervous system disorders in children]. / Sostoianie membranodestabiliziruiushchikh protsessov pri perinatal'nom porazhenii nervnoi sistemy u detei.

A complex prospective clinical and biochemical study was carried out in 252 children with perinatal encephalopathy during the 1st year of their life. The lipid peroxidation process, antioxidant system, lysosomal enzymes, phospholipid compound of thrombocyte membranes were studied. The lipid peroxidation process and lysosomal enzymes activation as well as a decrease of antioxidant defense level have been found. Membrane destabilization processes in the children with perinatal encephalopathy correlated with a character of hypoxic influence (acute, chronic, combined), a degree of severity and clinical manifestations of the pathology, and disease stage. Clinical and biochemical efficacy of antioxidant mexidol (0.1-0.2 ml/kg of the body weight intravenously for 10 days) and inhibitor of lysosomal enzymes contrical (1000 U/kg intravenously for 3-5 days) in the infants with perinatal CNS damages is claimed.

[Membrane and immunological aspects of perinatal nervous system disorders in newborns]. / Membrannye i immunologicheskie aspekty perinatal'nogo porazheniia nervnoi sistemy u novorozhdennykh detei.

Results of clinical, biochemical, and immunological studies in 157 full-term newborns with perinatal hypoxic damage to the nervous system are analyzed. Activation of lipid peroxidation processes in platelet membranes (increased levels of dienic conjugates and Schiff bases), activation of endogenous phospholipases and lysosomal enzymes (cathepsin D and acid phosphatase) were revealed. Free-radical and enzymatic aggression led to stabilization of the lipid bilayer, which manifested by increase of enzymatic lysoforms and decrease in the total phospholipid content of membranes. Study of lymphocyte subpopulations by means of monoclonal antibodies and measurements of immunoglobulin concentrations showed that perinatal hypoxia impaired the formation of immune status. Acute hypoxia promoted the formation of transitory "stress immunodeficiency", while chronic hypoxia induced more stubborn immune disorders.

[Effect of mexidol on clinical and biochemical parameters of perinatal hypoxia in newborn children]. / Vliianie meksidola na kliniko-biokhimicheskie proiavleniia perinatal'noi gipoksii u novorozhdennykh detei.

A complex prospective clinical and biochemical study was carried out in a group of 252 children with perinatal encephalopathy in dynamics during the 1st year of their life. The state of the lipid peroxidation (LPO) process, antioxidant system, and the phospholipid content of thrombocyte membranes were studied. Activation of the LPO process and a decrease in the antioxidant resistance level were observed. The efficacy of the antioxidant drug mexidol in infants was investigated for intravenous drug administration in a daily dose of 0.1-0.2 ml/kg over a 10-day period. The results confirmed good efficacy of the antioxidant therapy with mexidol in children with perinatal CNS disturbances.