[MENTAL AND SPEECH DEVELOPMENT IN CHILDREN LIVING IN ECOLOGICALLY UNFAVOURABLE REGIONS OF GEORGIA].

The ecological condition of different cities and regions in Georgia is variable. The level of anthropogenic contamination with xenobiotics in most of them significantly exceed the normal level. In almost 25% of children residing in Tbilisi, Batumi and Kutaisi the level of xenobiotics varies 5.0-10.0 mkg/dL, 16% of children have higher than 10.0 mkg/dL. We have studied the profile of mental and speech development in children living in abovementioned cities according to the level of Pb in blood. On the basis of representative selection we have studied the level of Pb in the range of 5.0 mkg/dL and 10.0 mkg/dL for two groups of children with normal development: 65.5 months- (I study group) and 89.5 months (II-study group). Control group has no Pb in blood. The situation in family was also considered. Intellectual development was assessed by Wexler verbal and nonverbal subtests, neuropsychological methods by Luria-Kristensen and visual-motor and visual-spatial evidence by WBAVMA. According to results of children from group I living in ecologically unfavourable regions average evidence for mental and speech verbal awareness were within normal range and similar to controls. As for group II the difference from normal age range was not found. The development of awareness of false belief of second order for group-I was significantly delayed which could occur due to pitfalls in cognitive field. The redevelopment of structure of motivated behaviour in children from group-I was significantly restricted compared with group-II and controls.

[NEUROLOGICAL DISORDERS OF CHILDREN LIVING IN ECOLOGICALLY AFFECTED REGION OF GEORGIA].

Article discussed the clinical evidence of children with attention deficit hyperactivity disorder (ADHD) living in different regions with polluted air. We have revealed the correlation between severity of neurological impairment and level of Hg, Pb, Zn and Cu in blood of children of three different age group (2-5y, 6-9 y and 10-13y). According to our results we found correlation between living area and level of xenobiotics and essential microelements. Thus we have concluded that beyond the level of xenobiotics and essential microelements in child's blood their primary and secondary role in the development of neurological disorders in regions of various anthropogenic impact has to be considered.

[MODERN ISSUES OF KALCIPHEROL INFLUENCE ON CHILDREN AND ADULTS' HEALTH (REVIEW)].

The purpose of this review is study of literature for the development of biological effect of Kalcipherol (D vitamin group) on children population. Different factors seem, that D- vitamin deficiency disbalance elevated, children specifically negative effect, which have a major impact on health, growth and development of infants, children and adolescents. Vitamin D and calcium deficiencies are preventable global public health problems in pediatric medicine. The laboratory assessment of vitamin D (calcidiol-25(OH)D), epidemiological studies assessing the prevalence of vitamin D deficiency, are performed to analyze the relationships between neuropsychological function and mechanisms of toxic effects in the setting of vitamin D.

INFLAMMATION IN CHILDHOOD EPILEPSY SYNDROMES.

Epilepsy is one of the most common neurological disorder affecting up to 1% of the world population. It is a heterogeneous disorder and includes genetic, structural, metabolic causes, sometimes reason is unknown. In recent 20 years inflammation has been considered as a possible etiologic factor in angiogenesis and epileptogenesis in experimental models but there is still lack of evidence if inflammation could be seen in clinical cases of children with different forms of epilepsy. Epileptic encephalopathies are the group of epilepsies when seizure itself can cause severe cognitive and behavioral abnormalities. Besides seizures occurring in epileptic encephalopathies prone to be highly resistant to medication. Thus any etiological factor contributing to epileptogenesis could have high clinical relevance in modern epileptology. The aim of our research was to study the pro-inflammatory cytokines in different forms of epilepsy in children. We have assessed 56 children from 0-16 years of age. 20 were included in control group (Group 1), 20 children with resolved seizures were involved in study group (Group 2a) and 16 children with resistant seizures were identified as group 2b. The concentration of the following pro-inflammatory cytokines was assessed in blood serum: VCAM-1, CCL2, CCL3, CCL11 as well as a correlation between concentration and seizure repetition rate was also studied. All pro-inflammatory markers were within normal range in controls as well as in both study groups except CCL11. The concentration of CCL11 was elevated in group 2b. Thus we could hypothesize that inflammation could contribute to etiology of resistant epilepsies including epileptic encephalopathies. This evidence could serve as very significant information for pharmaceutical industry for future development of anti-inflammatory medicines as add on therapy with antiepileptic drugs for treatment of drug resistant epilepsies.

[THE CALCIUM-PHOSPHORIC METABOLISM AND DEVELOPMENT OF BONE ORGANIC MATRIX AT CHILDREN AND ADOLESCENTS ON D-AVITAMIN BACKGROUND (REVIEW)].

The purpose of the review is to study the literature data on the manifestation of D-deficient rickets in children of various age groups. It is shown that the rapid growth of the musculoskeletal system requires timely intake of both macronutrients and vitamin D, its biologically active metabolites. The role of the relationship between the intestines, liver, kidneys and bone tissue in regulating the necessary level of phosphorus-calcium salts in bone tissue, the synthesis of its organic matrix is shown. Modern data on the content of phosphorus, calcium and d vitamin in women's milk during various periods of lactation are presented. It is shown that the prevention of their deficiency should begin already in the antenatal period of the child's development. The article presents prevalence of vitamin D deficiency in children of puberty and pre-puberty age, The hypo Vitamin D status in children with complicated forms orthopedic pathology is descid. The level of vitamin D and calcium-phospharic metabolism are presented summarizing the literature data. Vitamin D availability and vitamin D insufficiency in pediatric clinical practice is analysed, showing high prevalence of vitamin D difficiency in children in the first part of life. Analyses of results demonstrated differences of vitamin D serum concentration in length of age and food additives. Its manifestation, with confusing and wildly differing guidance being change the structure and volume of each components. Vitamin D, calcium-phosphoric deficiencies and osteomalacia are global public health problems in infants, children and adolescents.

[MODERN INSUES OF ESSENTIAL TRACE ELEMENTS LEVEL INFLUENCE ON CHILDREN AND ADULTH HEALTH (REVIEW)].

Systematic review article reported that essential trace elements, mainly microelements Copper and Zinc (deficiency and high values concentration disbalance in blood) play significant roles in neurodevelopmental processes and are associated not only with inattention and hyperactivity, impulsivity symptoms among children and adolescents in the most critical active growth and development periods (between 3 and 16 years old). In the same time previous studies have proposed that clinical symptoms are significant associated their levels and positively correlated with cognitive symptomatology as trace bioactive substances. Their functional connectivity is different and is one of the serious problems for clinical pediatric.

[MODERN ISSUES OF D-VITAMIN SIGNIFICANCE IN DEVELOPMENT OF FULERUM-MOVE DEVICES OF INFANTS, CHILDREN AND ADOLESCENTS ( REVIEW)].

The purpose of this review is the study of literature for the current data on the metabolism of vitamin D and its role in development of bone tissue in children. The role of the main marker enabling assessing 25(OH)D concentration in the body the reference values has been analyzed. Summarizing the literature data, we may say that vitamin D and calcium deficiencies are common worldwide, causing nutritional rickets and osteomalacia, which have a mayor impact on health of infants, children and adolescents.

[MODERN ASPECTS OF THE EFFECT OF XENOBIO-TICS ON CHILDREN AND ADOLESCENTS (REVIEW)].

The literature review presents data on the effect of organic and inorganic compounds, the so-called "main" xenobiotics (lead, mercury) on children and adolescents. It is noted that the effect of each heavy metal is different. Therefore, only their total assessment (blood, urine, saliva, hair, biological tissues) makes it possible to determine the level of toxic effects on the child and confirm the clinical decision. "Carrying mercury", in the absence of clinical signs of intoxication, does not always correlate with chronic poisoning. Ranking of clinical syndromes with the level of heavy metals in the body of children, monitoring of cause-and-effect relationships, detection of the prevalence of neurological changes becomes a priority in clinical Pediatrics. At the moment, the effects of heavy metals on the health of children and adolescents are a universal medical category. It forms the strategy of clinical pediatrics and pediatric neurology and a subject of interest for ecologists, toxicologists and sociologists.

CORRELATION BETWEEN PERINATAL RISK FACTORS AND NEURODEVELOPMENTAL OUTCOMES IN CHILDREN AT 24 MONTHS OF AGE.

The purpose of this research was to investigate the developmental follow-up of children of 24 months age, exposed to separate and combination impact of perinatal risk factors, compared with not exposed cases, within the prospective cohort study. Between January 2017 and January 2018, was conducted final stage of research, where were participated the medical centers in Tbilisi (capital of Republic of Georgia) and Mtskheta, Dusheti (districts of Georgia). Within postnatal follow-up, the children from whole population were assessed at 24 month of age by family doctors using the Denver Developmental Screening Test (Denver II). The association between the risk factors and neurodevelopmental outcomes was analyzed by Chi-square test of independence. Statistical analysis of these data was performed using the SPSS version 12.0.1 (SPSS Inc., Chicago, IL). A P value of less than 0.01 was considered as significant. Prevalence of abnormal development in whole population was revealed 2.9% or 30 cases at age of 24 month. Statistical analysis showed that an abnormal developmental outcomes were more frequent when researched risk factors, such as maternal age <17>35YY (OR-22.17, CI 95% - 8.91 to 55.15), pathologies of pregnancy (OR-13.79 CI 95% - 6.19 to30.71) and/or delivery (OR -7.74 CI 95% - 3.69 to 16.26), birth before 37 weeks of gestation (OR-29.30 CI 95% - 13.29 to 64.61), were exposed as well, as correlation of these risk factors with neurodevelopmental adverse outcomes was significant (p<0.0001). Neonatal pathologies, such as gestation age, neonatal sepsis with complication and combination with other risk factors and CNS malformation, combined with some perinatal risk factors were correlated strongly with adverse neurological disorders (p<0.0001) at age of 24 month. There was less significant correlation between Hypoxic-ischemic encephalopathy I-II stage of severity, as well as intracranial hemorrhage of I-II stages and neurodevelopmental outcomes (p<0.05). The most significant single risk factor for abnormal neurodevelopmental outcome was gestation age, maternal age and pathologies of pregnancy. High frequency of neurodevelopmental adverse outcomes were correlated with combined impact of risk factors and neonatal disorders, especially neonatal sepsis with complication and CNS malformation.

EPIDEMIOLOGICAL FEATURES OF THE PERINATAL RISK FACTORS AND NEONATAL OUTCOMES IN GEORGIA - PILOT STUDY.

The purpose of this work was to identify and evaluate the epidemiological features, like the point prevalence of the perinatal risk factors and related to them pathological conditions revealing at the neonatal period. The descriptive population based prospective pilot study of children population of age 0-2 years was con-ducted in the City Tbilisi (in clinical centers "Medcapital", "family center N3" and "Valeo"), also in medical centers of districts of Mtsketa and Dusheti in period January 2015- January 2017. Summary was surveyed 1018 newborns during two years. According to research objectives newborns were di-vided into the three groups: I - 715 (70.2%) low risk group newborns with normal development, not influenced by risk factors, II - 215 (21.1%) risk group newborns with normal development, influenced by risk factors and III - 88 (8.7%) high risk group newborns with some neonatal pathology. Epidemiological evaluations, such as point prevalence and risk ratio (RR) for each risk factor and neonatal outcome, were conducted. At the neonatal period the point prevalence of perinatal risk factors in whole population (1018 newborns) were: mother age (<17 >35) - 175 (17.2%) cases, pathologies of pregnancy - 164 (16.1%) and pathologies of delivery -128 (12.6%) cases. RRs of neonatal outcomes associated with these factors were rated as 15.4/5.7/3.8. A total of 88 (8.6%) newborns were placed in III High risk group. In this population the most frequent pathologies were: preterm birth in 74 cases (7.26%), hypoxic-ischemic encephalopathy in 29 (2.84%) cases, low Apgar scores (<7 at 5 minutes) in 26 (2.6%) cases, neonatal sepsis in 16 (1.6%) cases, CNS malformation in 7 (0.7%) cases, intracranial hemorrhage in 6 (0.6%) cases. 13 newborns (1.28%) from III group were treated at department of emergency therapy. Newborns from II group, despite the impact of perinatal risk factors on them, were born healthy and evaluated as normal. Results of investigation show, that the point preva-lence of maternal age, pregnancy and delivery pathologies as well as neonatal outcomes are determined as risks of pathological conditions and outcomes of newborns.

ASSESSMENT OF NEURODEVELOPMENTAL OUTCOMES IN INFANTS 6-12 MONTHS OF AGE ACCORDING TO IMPACT OF PERINATAL RISK FACTORS.

The purpose of this research was to investigate the developmental follow-up of infants (at age of 6 month and 12 month), exposed to separate and combination impact of perinatal risk factors, compared with not exposed cases, within the prospective cohort study. Between January 2015 and January 2017, in this research we prospectively enrolled 1018 live-born infants from the medical reports of the participating clinics in Tbilisi (capital of Republic of Georgia) and Mtskheta, Dusheti (districts of Georgia). Within postnatal follow-up, the children from whole population were assessed at 6 and 12 months of age by family doctors using the Denver Developmental Screening Test (Denver II). The association between the risk factors and neurodevelopmental outcomes was analyzed by Chi-square test of independence. Statistical analysis of these data was performed using the SPSS version 12. (SPSS Inc., Chicago, IL). A P value of less than 0.05 was considered as significant. Prevalence of abnormal development in whole population was revealed 9.0% or 92 cases at age of 6 month and 36 cases or 3.5% at age of 12 month. Point prevalence of farther neurodevelopmental adversities for healthy born children not influenced by studied risk factors was 0.1% and for infants with impact of the risk factors - 1.5%; on the other hand, prevalence of observed abnormal development in infant's population who had neonatal pathologies was 2.3% if risk factors were not exposed and 21.6% under influence of risk factors. Statistical analysis showed that an abnormal developmental outcomes were more frequent when researched risk factors were exposed (OR-23.18, CI 95% - 11.83 to 45.41 - at age of 6 month; OR - 26.12, CI 95% - 7.95 to 85.85 - at age of 12 month) as well, as correlation of these risk factors with neurodevelopmental adverse outcomes was significant (p<0.001). Significant correlations were identified for separate risk factors, such as maternal age (<17Y>35Y), pathologies of pregnancy and delivery as well as gestation age (<37 weeks). Coexistence of revealed risk factors increased probability of adverse neurological outcomes in infants at age of 6 month as well as at age of 12 month. There was a statistically important association between infant's 1-year neurological outcomes and these perinatal risk factors.

[REASONS AND CONSEQUENCES OF SOMATOFORM DISORDERS IN CHILDREN AND ADOLESCENTS].

The aim of our study was to find the reason of various forms of somatoform disorders (phobias, behavioral disorders, insomnia, tics, stuttering, enuresis, encopresis) in children and adolescents of various social status for diagnosis and treatment. We have examined 202 patients who referred to our clinic from 2012-2016. The age range was 2-18 years. After examination we have concluded the following recommendations: - to implement neuropsychological rehabilitation in order to stimulate mental development; - to work with speech therapist to improvement the speech; - to work individually with psychotherapist to improve the behavior; - to train the parent to manage the behavior at home; - to give the personal card containing information about exercises, games and puzzles to stimulate the development and in some cases to give individual educational program; - to give separate information to parents and in some cases to teachers of kindergartens and schools.

THE CAUSES AND SYMPTOMS OF SOMATOFORM DISORDERS IN CHILDREN (REVIEW).

The causes of somatoform disorders in children and adolescents and clinical description of various syndromes like hypochondric impairment, non epileptic paroxysmal disorders, chronic fatigue syndrome, trauma and headache are presented in this review. The modern epidemiological evidences of mentioned conditions are also considered which indicate on progressive increase of these diseases for recent 20 years. We have also discussed the standardized methods of prevention, differential diagnosis and treatment of somatoform diseases.

[MITOCHONDRIAL DYSFUNCTION: MODERN ASPECTS OF THERAPY (REVIEW)].

Mitochondrial diseases are considered as one of the major problems of modern interdisciplinary neonatology and pediatrics. Mitochondrial pathology can be revealed as refractory myoclonic or multifocal seizures, craniofacial dysostosis, dysmetabolic manifestations and respiratory disorders. Central nervous system (CNS), muscles, heart, liver and kidneys is involved in this pathological process. An important criterion for diagnosis of mitochondrial dysfunction is increases in blood lactate and pyruvate levels; the absolute criterion - molecular genetic diagnostic studies of mitochondrial DNA. Polymorphism of clinical symptoms complicates the process of early diagnostics, the lack clear recommendations complicates therapy. Modern aspects of treatment of mitochondrial dysfunction in various neurological syndromes are based primarily in improving the efficiency of the processes of oxidative phosphorylation at the system level. Dietary carbohydrate restriction, and medication (Coenzyme Q10, Idebenonum, Cofactors, drugs which reduce lactic acidosis- Dimephosphon, Dichloroacetate, Antioxidants, Anticonvulsants and Antidiabetic agents, vitamins C, E, K, hemotransfusions) is prescribed. Such complex approach allows us to achieve a reduction in lactate-acidosis, and improve the condition of patients in 70% of cases.

[The role of lactate acidosis in the development and treatment of various neurologic syndromes in children and adolescents].

The aim of the study was to detect the role of lactate acidosis, also to find the share of mitochondrial insufficiency in development of various neurologic syndromes in children and adolescents. The detection of cellular energetic metabolism and acid based imbalance is also important for finding the specific method of management. We have studied 200 patients with various degree of neurodevelopment delay with epilepsy and epileptic syndromes, headache, vertigo, early strokes, floppy infant syndrome, atrophy of ophthalmic nerve, cataracta, neurosensory deafness, systemic myopathy, cerebral palsy. In 27% of cases with various ages we have detected lactate acidosis and increase level of pyruvate. Mitochondrial insufficiency was seen in 8% of cases which gives us opportunity to find the specific method of treatment in this group of patients. Each patient with neurological symptoms requires correction of parameters of energetic and oxidative metabolism.

Management of burning mouth syndrome taking into consideration various etiologic factors.

The aim of the research was to detect the stomatologic, endocrine and psycho-neurologic status in patients with burning mouth syndrome, elaborate different diagnostic criteria and effective therapy for the patients with burning mouth syndrome. 92 patients with burning mouth syndrome were studied. Patients ranged in age from 28 to 72 years. The conducted studies gave the possibility to make conclusions, the most important of which are: burning mouth syndrome (BMS) is not only stomatologic problem; this psychosomatic syndrome belongs to gerontologic disease and tendency of its "rejuvenation" was revealed as well (in the current study --2 women (28 and 32 year old, and 38 year old man); degree of revelation of the symptoms of depression, anxiety, obsession and somatization is closely related with duration of the diseases. These symptoms are progressing together with aging and reach the peak at 60-70 years old. Individual scheme of therapy was developed on the background of clinico-paraclinical study.

Changes in cognitive evoked potentials during non pharmacological treatment in children with attention deficit/hyperactivity disorder.

UNLABELLED: Attention deficit/hyperactivity disorder (ADHD) is one of the most widely spread condition of school aged children affecting 5% of children of this age. The unified consensus of the precise diagnosis of this condition is still absent. This fact encourages the researchers to seek the alternative neurometric tools which will help the clinicians in diagnosis making process of ADHD. The neurophysiologic approaches especially event-related potentials (ERPs) are mostly important from this point of view. The later response of ERPs (P3) reflects the most important parts of executive functioning frequently affected in ADHD children - the process of mental effortfullness to select the appropriate behavior and decision making. Besides the diagnosis the treatment of ADHD is also the point of concern of neurologists and neurophyschologists. In recent years EEG biofeedback ( Neurofeedback-NF) have become the alternative treatment as in some cases pharmacological drugs are non effective. The positive impact of NF was based on improvement detected by various questionnaires which are less valid but its effectiveness on ERPs parameters is still unknown. Thus we aimed to study the changes of ERPs after NF therapy. METHODS: We have studied 93 children with ADHD of combined subtype (ADHDcom) without any kind of pharmacological treatment. Age range 9-12 years. The children were divided into two subgroups: The first ADHDcom-1 (48 children) were children where NF treatment was carried out and the second subgroup of ADHDcom-2 (45 children) were non treated children. RESULTS: We have observed statistically significant improvement of parameters of later response like P3 in ADHD-1 compared with ADHD-2 whereas NF was non effective for earlier component like N1. CONCLUSIONS: NF can positively affect on the P3 parameters which is very important in ADHD children as P3 reflects the speed of information processing as well as selection of appropriate action and decision making which are frequently affected in ADHD children.

Quantitative electroencephalography coherence and dipole source index during various cognitive tasks in children with attention deficit hyperactivity disorder.

Attention deficit hyperactivity disorder (ADHD) is one of the most important disorder of childhood and adolescence. Debates about diagnostic approaches requiring for the precise assessment of ADHD remains actual till nowadays. The role of neurophysiological methods for this purpose is controversial. Thus the aim of our study was to observe QEEG changes by means of the most modern software analysis systems- coherence and brainwave activity dipole source localization. We have assessed 39 children- 18 of them from control group (Age range 9-12 years). QEEG was registered during Raven test and adding of one digit numbers. The results were analyzed by means of coherence measures and brainwave bilateral synchronous activity dipole source generator localization detection system (BrainLoc. 6). As a result we observed high coherence measures for ADHD compared to controls. As for dipole source generator we have detected higher dipole equivalent index in control group compared with ADHD children. Thus according to our results it is obvious that QEEG can serve as a valid neurometric tool in the diagnosis of Attention deficit hyperactivity disorder.

Quantative EEG during baseline and various cognitive tasks in children with attention deficit/hyperactivity disorder.

It is known that attention deficit/hyperactivity disorder is a widely spread condition in school aged childhood population. Making of precise diagnosis is a serious problem of modern pediatric neurology. In spite of large amount of guidelines and questionnaires the unified consensus of diagnosis is still absent. Thus it is important to search additional diagnostic criteria which can help physicians to confirm ADHD. For this purposes we have used quantative EEG (QEEG) parameters. There are numerous papers regarding QEEG changes of ADHD children during baseline (resting with closed eyes, resting with opened eyes, photic stimulation, hyperventilation).But information concerning QEEG evidences during cognitive tasks is insufficient. For this purposes we have used QEEG during Raven test, reading and calculation in children with ADHD and control group. QEEG was carried out according to standard 10-20 electrode placement rule from the following derivations: F3, F4, C3, C4, P3, P4, O1, O2. We have observed that in controls fulfilling of Raven test is more difficult than reading. Thus they are eulectic but in ADHD children reading is more difficult than Raven test. Thus they are dyslexic. By means of alpha and delta bands analysis it became apparent that alpha band is inversely proportional to mental effort and delta band is directly proportional to mental activity.