[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.

[Assessment of motor and sensory pathways of the brain using diffusion-tensor tractography in children with cerebral palsy].

BACKGROUND: Diffusion tensor tractography--a new method of magnetic resonance imaging, that allows to visualize the pathways of the brain and to study their structural-functional state. OBJECTIVE: The authors investigated the changes in motor and sensory pathways of brain in children with cerebral palsy using routine magnetic resonance imaging and diffusion-tensor tractography. METHODS: The main group consisted of 26 patients with various forms of cerebral palsy and the comparison group was 25 people with normal psychomotor development (aged 2 to 6 years) and MR-picture of the brain. Magnetic resonance imaging was performed on the scanner with the induction of a magnetic field of 1,5 Tesla. Coefficients of fractional anisotropy and average diffusion coefficient estimated in regions of the brain containing the motor and sensory pathways: precentral gyrus, posterior limb of the internal capsule, thalamus, posterior thalamic radiation and corpus callosum. RESULTS: Statistically significant differences (p < 0.05) values of fractional anisotropy and average diffusion coefficient in patients with cerebral palsy in relation to the comparison group. All investigated regions, the coefficients of fractional anisotropy in children with cerebral palsy were significantly lower, and the average diffusion coefficient, respectively, higher. CONCLUSION: These changes indicate a lower degree of ordering of the white matter tracts associated with damage and subsequent development of gliosis of varying severity in children with cerebral palsy. It is shown that microstructural damage localized in both motor and sensory tracts that plays a leading role in the development of the clinical picture of cerebral palsy.

[The effectiveness of dynamic proprioceptive correction in patients with cerebral palsy with cognitive impairment].

One hundred and sixty-seven patients with cerebral palsy (CP), aged 11-16 years, with spastic diplegia (n=87) and hemiparetic forms (n=80), with subgroups of mental retardation (MR) or intellectual delay (ID) have been studied. Standard treatment and application of a method of dynamic proprioceptive correction (MDPC) in the complex rehabilitation with the use of a medical and loading Adeli suit were used. Cognitive deficit in patients was characterized by the relative integrity of short-term nonverbal memory and marked impairment of verbal memory, verbal and nonverbal intellect. CP patients with intellectual delay demonstrated the predominant impairment of verbal functions. CP patients with mental retardation have the deficiency of both verbal and non-verbal cognitive functions. An individual profile of brain functional asymmetry in patients with CP was more lateralized than in healthy peers that can represent a mechanism for irregular development of cognitive functions in CP. Implementing the MDPC into comprehensive rehabilitation promotes the improvement of postural regulation and cognitive functions in children with CP compared to traditional methods of treatment. This is accompanied by the changes in functioning of the associative brain areas and hemispheric interaction.

[Ontogenesis of neurocognitive development of children and adolescents].

The article represents the results of neurocognitive development study in progress. Clinical methods of investigation are supplemented with examination of children with Russian computer psychophysiological complex "Psichomat", which allows to examine a number of cognitive functions--perception, attention, memory, visual-motor coordination, processes of analysis and synthesis--in mathematical function expression: milliseconds and percentage of mistakes. A child's intrauterine and postnatal development is determined by various factors. Cognitive processes, which are ascending accordingly to a child's age, play significant role in social development. The standard charts of children psychoneurological development, worked out by the authors, must become key factors both for pediatricians of different subspecialities and for parents and psychologists, in order not to miss the beginning of some pathology condition--from development delay to retardation. During the analysis of cognitive status of a child, speech development, behavior and emotions should be assessed. The deficiency of cognitive functions causes difficulties in education and contact with a child, which in some cases leads to formation of syndromal pathological conditions and disease entities (from mild development delays to different stages of oligophrenia). It is necessary to educate pediatricians of various subspecialities and pediatric neurologists the methods of children examination in order to determine the "cognitive profile" according to the age, health condition, presence of somatic and/or psychoneurological diseases and influence of the drug therapy both on a child's organism and cognitive processes.

[Neurorehabilitation in pediatrics].

The main principles of long-term rehabilitation of children and adolescents with cerebral paralysis, related neurologic disorders, aftereffects of a neuroinfection, and some rare genetically determined diseases are the earliest possible initiation of remedial measures and the regular combined use of different forms of rehabilitative treatment. The proposed approach allowed to reduce severity of motor and speech disturbances and improve social and cognitive functions in 50.5% of the patients. Quality of life of the patients and their families also improved; healthy infants were born in 98 (19%) families.

Glutamate receptor autoantibody concentrations in children with chronic post-traumatic headache.

We report here studies on the levels of autoantibodies (aAb) to AMPA glutamate receptors (GluR1 subunit) and NMDA glutamate receptors (NR2A subunit) in serum from 60 children aged 7-16 years with chronic posttraumatic headache (CPTHA) following mild craniocerebral trauma (CCT). The first group consisted of 48 children who had sustained cerebral concussion (CC), of which 34 had single-episode CC (subgroup 1a) and 14 had repeated CC (subgroup 1). The second group included 12 children with mild cerebral contusions (MCC). Serum glutamate receptor aAb levels were measured six months and one year after trauma. Increased aAb levels were expressed as percentages and were regarded as significant when increases were to 120% of the level seen in healthy children of the same age. The highest levels of aAb to NMDA receptors were seen in children with MCC (165 +/- 34%) and single CC (145 +/- 12.6%). Children with repeated CC had NMDA receptor aAb at normal levels (108 +/- 12.4%). Increases in NMDA receptor aAb were seen during the first year after trauma. Increases in AMPA receptor aAb were seen in children with repeated CC and MCC (150 +/- 16.8% and 167 +/- 31.3%). EEG studies showed that 18% of these children had nonspecific paroxysmal changes and 6% showed epileptiform activity. These results provide evidence that children with post-traumatic headache demonstrated hyperstimulation of glutamate receptors and overdevelopment of the autoimmune process. Increases in serum levels of aAb to NMDA glutamate receptors reflected hypoxic-ischemic brain lesions in children with CPTHA and dictate the need for these children to receive metabolic therapy.

[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.

[The use of beta-interferon-1b in children and adolescents with multiple sclerosis].

The use of beta-interferons for immunomodulating treatment of multiple sclerosis (MS) in children is rstudied. We present results of the prospective study of 22 children, aged 13-17 years, with MS treated with beta-interferon-1b (betaferon) during 2-15 (mean 10,72) months. High efficacy and good tolerability of beta-interferon-1b is demonstrated.

[Autoantibodies to glutamate receptors in children with chronic posttraumatic headache].

Autoantibodies (aAB) to AMPA (Glu R1 subunit) and NMDA (NR 2A subunit) glutamate receptors were studied in blood serum of 60 children, aged 7-16 years, with chronic posttraumatic headache after mild skull injury. All the children were divided into 2 groups: group 1 included 48 children with concussion of the brain, group 2--12 children with brain contusion. Group 1 was divided into 2 subgroups: subgroup 1a comprised 34 children with single concussion and subgroup 1b--14 children with repeated concussion. The aAB level was determined 6 months and 1 year after skull injury. The aAB concentration was expressed in percents to the control level being considered significant if the increase was higher than 120%. The increased NMDA aAB level was observed during the first year after skull injury. In the la subgroup, the NR2 aAB level in blood serum was 145 +/- 12,6%, in the 1b one--108 +/- 12,4%, in group 2--165 +/- 34%. The content of aAB to AMPA receptors was elevated only in children of lb subgroup and group 2 (150 +/- 16,8% and 167 +/- 31,3%, respectively). The EEG examination of this group revealed the nonspecific paroxysmal discharges in 18% of cases and epileptiform activity in 6% of children. The results obtained suggest that children with posttraumatic headache have elevated levels of aAB to glutamate receptors, hyperstimulation of which reflects hypoxic processes in the brain, and are in need of metabolic therapy.

[The psychoemotional condition of children in endoscopic examination].

Described in the paper is the instrumental examination of the psychoemotional condition of schoolchildren with esogastroenterologic pathology, who underwent, for the diagnostic purpose, esogastroduodenoscopy. It is demonstrated that the determination of the psychoemotional status in the course of dynamic follow-up optimizes the preparation of a child for endoscopy and smooths the anxiety during the procedure.

[Test computer systems in the diagnosis of cognitive disorders as observed in the syndrome of attention deficiency with hyperactivity in children].

The instrumental methods of evaluation of the cognitive ability of child by means of test computer systems open up real opportunities for the objective and thorough examination of main processes of the cognitive ability. An objective quantitation of the cognitive sphere makes it possible to prognosticate the intellectual development of child and to use such methods not only in the diagnosis and prevention but also in the correction of cognitive disorders.

[Multiple sclerosis in children and adolescents: history and current experience of immunomodulating treatment]. / Rasseiannyi skleroz u detei i podrostkov: istoriia izucheniia problemy i sovremennyi opyt immunomoduliruiushchego lecheniia.

An agreement accepted worldwide for treatment of multiple sclerosis (MS) in adult patients has not been achieved so far for children and adolescents, mostly due to the insufficient information on the features of MS with early age-at-onset. New methods of immunomodifying treatment and the conception of early MS treatment have changed the attitude to prognosis of MS with early onset. In such cases, a course of the disease is less aggressive and characterized by more intensive remyelination as well as brain plasticity and less neurological deficit that may predict highest efficacy of the disease modifying treatment timely started in these patients. Such drugs, as beta-interferons, glatiramer acetate and high-dosage intravenous immunoglobulines G, which are able to decrease MS relapse frequency and disability progression in adult patients, are poorly studied in children and adolescents. Preliminary positive results of international and Russian investigations on the efficacy and tolerability of immunomodulating therapy of MS with early age-at-onset require further investigations in this field.

Five patients with a recently described novel leukoencephalopathy with brainstem and spinal cord involvement and elevated lactate.

Recently, a novel leukoencephalopathy syndrome was described in eight patients with a distinct pattern of MRI abnormalities. Here we describe the clinical, laboratory, and MRI findings in five new, unrelated patients. The clinical picture was homogeneous with onset in childhood, a slowly progressive course, variable mental deficits, signs of pyramidal and cerebellar dysfunction and sometimes dorsal column dysfunction. In two patients, a minor head trauma was followed by neurological deterioration and fever. No underlying metabolic defect was found. In two patients serum lactate was elevated, but no evidence of a mitochondrial defect was found. MRI showed variably extensive, diffuse, or spotty cerebral white matter abnormalities and a selective involvement of particular brainstem tracts. The tracts involved included the pyramidal tracts, sensory tracts, superior and inferior cerebellar peduncles, and intraparenchymal trajectories of the trigeminal nerve. In four patients spinal MRI was performed and revealed involvement of tracts over the entire length depicted. Single voxel proton MRS in three patients revealed increased lactate within the abnormal white matter. The uniform and highly characteristic MRI findings, in combination with the similarities in clinical and MRS findings, provide evidence for a distinct nosological entity.

[Three cases of non-differentiated leukodystrophy with involvement of cerebral hemisphere's white matter and cerebellum and specific lesions of cerebral pathways. Neuroimaging and clinico-biochemical characteristics]. / Tri sluchaia nedifferentsirovannoi leikodistrofii s porazheniem glubinnogo belogo veshchestva bol'shikh polusharii, mozzhechka i spetsifichnym porazheniem provodiashchikh putei. Neirorentgenologicheskie i kliniko-biokhimicheskie kharakteristiki.

We presented three cases of the non-differentiated White Matter's disease. There are clinical resemblance and the similar MRI patterns including MR spectroscopy in all patients. They are outpatients: girl (K), 7 years old, boy (N), 13 yrs and young men (N), 24 yrs without any family relationship, and were investigated in Burdenko Neurosurgical Institute, in 2002 year. The cerebral MRI examinations all of that patients have shown extensive abnormalities in the hemispheric's white matter of cerebrum and cerebellum. Meanwhile there are some specific lesions of the brain stem's tracts (the posterior limb of the internal capsule, the splenium of the corpus callosum, the medial lemniscus and the mesencephalic trigeminal tracts). Step by step progression of suffer ness with unknown time of beginning, mild mnestic reduction and hemyparesis and moderate cerebellar disorder without loss of sensitivity were characteristic for all patients. The results of the biochemical markers for leucodistrophy testing are negative. A proton spectrum of the abnormal white matter showed elevated lactate in one case (girl, 7 yrs). In our opinion clinical diagnosis in all three cases is the new pathology that some body named as "WMDL" (White matter disease with lactate). It should be differentiated with adrenoleucodistrophy, Refsum disease and NARP syndrome (neuropathy, ataxia, pigmentive retinitis).

[Multiple sclerosis with early onset: pathogenesis, clinical characteristics, possibilities in the treatment of its pathogenesis]. / Rannee nachalo rasseiannogo skleroza -- osobennosti patogeneza, kliniki i vozmozhnost' patogeneticheskoi terapii.

Early onset multiple sclerosis (MS) has some peculiarities in the disease course. 56 patients with definite MS with the onset at the age under 15 years were included in this clinical, immunogenetical and neurophisiological study. The analyses of the relations between different clinical characteristics of MS in children has shown, that patients with onset under 10 years, had rare relapses, but more progressive development of disability in contrast to the patients with MS onset at the age of 11-15 years. Duration of the first remission was associated with the time to sustained disability in children with MS. The number and volume of MRI T2-positive lesions in the white matter of the brain was associated with the age of onset, duration of the disease and with the number of relapses. In several cases the phenomena of clinical-MRI dissociation was observed. Generic HLA-DRB1 genomic typing was performed in all the patients. High frequency of DR2(15) genotype in MS-affected children in comparison with the group of healthy controls was more expressed as compared with MS-affected adults. The comparison of frequencies of DRB1 alleles in transmitted, i.e. appeared in the affected child haplotypes and in non-transmitted haplotypes confirmed results of the case-control study showing the very significant association of MS with DR2 alleles and extremely significant--with its DR15 subtype in children. The data of transmission/disequilibrium test (TDT) analysis provide strong evidence for linkage of DR15 alleles and susceptibility to sporadic MS in patients with disease onset before 15 years. The positive experience of management (beta-interferon-1a) was shown in MS-affected children in three cases.

Association and linkage of juvenile MS with HLA-DR2(15) in Russians.

The aim of this study was to determine the role of the HLA-DRB1 gene [6p21] in susceptibility to juvenile MS (JMS) (age at onset < or =15 years) of children of Russian descent. Association of DR2(15) with JMS has been found by the comparison of patients with JMS with both unrelated and affected family-based healthy controls. The linkage of DR2(15) with JMS was shown by transmission disequilibrium test. There were no significant differences in the frequencies of DRB1 alleles and genotypes between 56 patients with JMS and 234 patients with MS with age at onset > or =16 years.

Autoantibodies to nerve growth factor in disorders of mental development in infants.

Studies were performed using 80 children aged 1-3 years with lesions to mental development. Patients were divided into three groups according to the severity and structure of lesions of mental development: those most strongly characterized by delayed speech development (group 1), those with delayed mental development due to organic CNS lesions (group 2), and those with abnormal mental development and high levels of psychopathological symptoms (group 3). There were significant increases (p < 0.001) in blood levels of autoantibodies to nerve growth factor (NGF) in children in each of these groups as compared with a control group (0.75 +/- 0.24 OD units). The levels of anti-NGF autoantibodies increased from group 1 to group 3 (0.95 +/- 0.24 OD units in group 1, 1.13 +/- 0.27 OD units in group 2. and 1.24 +/- 0.4 OD units in group 3). These correlations suggest that the level of anti-NGF autoantibodies can, taken in conjunction with a number of other parameters, be regarded as a potential molecular marker demonstrating abnormal development of the nervous system.

[Medical engineering computer technologies of testing cognitive functions in children]. / Mediko-inzhenernye komp'iuternye tekhnologii testirovaniia poznavatel'nykh funktsii u detei.

Studies of higher mental functions in children are shown to present great difficulties in many parameters. Analysis has provided a number of requirements for medical devices and complexes and principles of their construction. Based on these data, the authors have developed and put computer test systems into practice, their advantages being shown. The studies of cognitive functions in children by using computer test systems are dealt with.

[Computer-assisted screening of the cognitive sphere in school children]. / Komp'iuterizatsiia skrininga poznavatel'noi sfery shkol'nikov.

The cognitive sphere was studied in schoolchildren with good study progress by using computer test systems. This provided age-dependent standards of major cognitive functions: perception, attention, memory, psychomotor activity, and thinking that determine the quality of cognitive activity. Comparatively, this may objectify age-specific prognosis of schoolchildren and specify causes of learning difficulties in children.