BDNF, proBDNF and proBDNF/BDNF ratio with electroencephalographic abnormalities in children with attention deficit hyperactivity disorder: Possible relations to cognition and severity.

Attention deficit hyperactivity disorder (ADHD) with and without subclinical epileptogenic discharges (SED) have been suggested to negatively affect cognitive abilities of children with ADHD. The role of brain-derived neurotrophic factor (BDNF) and its precursor proBDNF in ADHD is in need of being investigated. The aims were to evaluate the levels of serum BDNF, proBDNF and the proBDNF/BDNF ratio in addition to the potential impacts of SED on the children's cognitive abilities and the severity of ADHD. The included participants with ADHD were 30 children with normal electroencephalogram (EEG) (G1) and 30 children with SED (G2), together with 30 healthy children (G3). The cognitive abilities and severity of the disorder were evaluated. The biochemical measures were determined by ELISA. The presence of coexisting SED and nocturnal enuresis has led to a deleterious effect on cognitive processes but not on the severity. The focal epileptogenic discharge was the most common among children in G2. The levels of BDNF in Groups 1 and 2 were less than those in G3. The higher proBDNF/BDNF ratio could be related to the low BDNF levels rather than high proBDNF levels. The findings of this study highlight the importance of investigating the presence of SED and nocturnal enuresis in children with ADHD. Targeting strengthening of cognitive abilities in children with coexisting ADHD and SED is advised. The role of proBDNF in the pathophysiology of ADHD needs further investigation.

Dyslexia with and without Irlen syndrome: A study of influence on abilities and brain-derived neurotrophic factor level.

The presence of comorbid Irlen syndrome (IS) in children with developmental dyslexia (DD) may have an impact on their reading and cognitive abilities. Furthermore, the brain-derived neurotrophic factor (BDNF) was reported to be expressed in brain areas involved in cognitive and visual processing. The aim of this study was to evaluate some cognitive abilities of a group of dyslexic children with IS and to measure and compare the plasma BDNF level to dyslexic children without IS and neurotypical (NT) children. The participants were 60 children with DD (30 in the DD + IS group; 30 in the DD group) and 30 NT children. The Irlen reading perceptual scale, the Stanford Binet intelligence scale, 4th ed, the dyslexia assessment test, and the Illinois test of psycholinguistic abilities were used. The BDNF level was measured using the enzyme-linked immunosorbent assay. One-minute writing and visual closure deficits were more prevalent, while phonemic segmentation deficits were less prevalent in the DD + IS group compared to the DD group. The BDNF level in the DD groups was lower than that in NT children (p < 0.001). Some reading and non-reading tasks were influenced by the presence of a coexisting IS. The reduced BDNF level could play a role in the deficits noticed in the abilities of children with DD.

Prevalence and risk factors of disabilities among Egyptian preschool children: a community-based population study.

BACKGROUND: Child disability has significant implications on their well-being and healthcare systems. AIM: This survey aimed to assess the magnitude of seven types of disability among Egyptian children aged 1 < 6 years and their socio-demographic, epidemiological, and perinatal predictors. METHODS: A national population-based cross-sectional household survey targeting 21,316 children from eight governorates was conducted. The screening questionnaire was derived from the WHO ten-question survey tool validated for identifying seven disability categories. RESULTS: The percentage of children with at least one disability was 8.1% as follows: speech/communication (4.4%), Mobility/physical (2.5%), Seizures (2.2%), Comprehension (1.7%), Intellectual impairment (1.4%), Visual (0.3%) and Hearing (0.2%). Age was not found to affect the odds of disability except for visual disability (significantly increased with age (AOR = 1.4, 95% CI:1.1-1.7). Male sex also increased the odds of all disabilities except visual, hearing, and seizures. Convulsions after birth significantly increased the odds of disability as follows: hearing (AOR = 8.1, 95% CI: 2.2-30.5), intellectual impairment (AOR = 4.2, 95% CI: 2.5-6.9), and mobility/physical (AOR = 3.4, 95% CI: 2.3-5.0). Preterm delivery and being kept in an incubator for more than two days after birth increased the odds for visual disability (AOR = 3.7, 95% CI: 1.1-12.1 & AOR = 3.7, 95% CI: 1.7-7.9 respectively). Cyanosis increased the odds of seizures (AOR = 4.7, 95% CI: 2.2-10.3). Low birth weight also increased the odds for all disability domains except for visual and hearing. Maternal health problems during pregnancy increased the odds for all types of disability except hearing and seizures. Higher paternal education decreased the odds for all disabilities by at least 30% except for vision and hearing. CONCLUSION: The study found a high prevalence of disability among Egyptian children aged 1-6 years. It identified a number of modifiable risk factors for disability. The practice of early screening for disability is encouraged to provide early interventions when needed.

National screening for developmental delays and their determinants among Egyptian school age children: A step towards implementing life skills programs.

AIM: This study aimed to estimate the national prevalence of developmental delays (DDs) and their determinants among Egyptian children aged 6 to 12 years. Such estimation is a prerequisite step toward the application of Life Skill Education (LSE) programs that will potentiate children's future capabilities. METHODS: Vineland Adaptive Behavior Scales" was used as a reliable and diagnostic test for DDs screening during this national cross sectional study. Gross motor (GM), fine motor (FM), daily living skills, communication, and socialization skills were assessed. The multivariate logistic regression analysis was used to identify factors associated with DDs. The Adjusted Odds Ratio (AOR) with a 95% Confidence Interval was estimated to indicate the strength of association. A p-value of <0.05 was used to declare statistical significance. RESULTS: Out of the 20324 surveyed school-aged children, 7.4% were found to have at least one delay. Communication deficits were the most common (6.4%) followed by delay in daily living skills (2.0%). The final model of logistic regression had a good fit for seven variables out of the sociodemographic, epidemiological characteristics, maternal and perinatal problems that were associated with a higher likelihood of at least one DD: Children suffering from any convulsions (AOR = 4.32; 95% CI: 3.18-5.88), male gender (AOR = 1.86; 95% CI: 1.65-2.09), birth weight less than 2.5 kg (AOR = 1.77; 95% CI: 1.40-2.24), history of maternal health problem during pregnancy (AOR = 1.64; 95% CI:1.34-2.01), children staying in an incubator for more than two days (AOR = 1.57, 95% CI: 1.29-1.91), having less educated fathers (AOR = 1.55, 95% CI: 1.24-1.95) and belonging to the middle social class (AOR = 1.40, 95% CI: 1.24-1.58). CONCLUSION: The identified types and determinants for each DD are allowing for the implementation of tailored programs for school children's life skills promotion for achieving the most sustainable effects on children's biological and psychological health and well-being.

National screening for Egyptian children aged 1 year up to 12 years at high risk of Autism and its determinants: a step for determining what ASD surveillance needs.

This study aimed to provide a national estimate of the prevalence of the high risk of autism spectrum disorder (ASD) and their determinants. A national screening survey was conducted for 41,640 Egyptian children aged 1 to 12 years in two phases. Tools used were Vineland's Adaptive Behavior Scales, Modified Checklist for Autism in Toddlers, Gilliam Autism Rating scale, and Denver II Developmental screening test. The overall prevalence of children at high risk of ASD was 3.3% (95% CI:3.1%-3.5%). Children living without mothers in homes, suffered from convulsions (AOR = 3.67; 95%CI:2.8-4.8), a history of cyanosis after birth (AOR = 1.87; 95% CI:1.35-2.59) or history of LBW babies (AOR = 1.53; 95% CI:1.23-1.89) carried higher odds of being at high risk of ASD.

Diagnostic value of molecular approach in screening for fragile X premutation cases.

BACKGROUND: Fragile X syndrome (FXS) is the most common form of inherited intellectual disability, caused by CGG-repeats expansion (> 200 repeats). Premutation alleles (PM) (55-200 CGG repeats) are associated with tremor ataxia syndrome (FXTAS), fragile X-associated primary ovarian insufficiency (FXPOI), and autistic problems. AIM: To screen the frequency of premutation carriers using molecular diagnostic assays, in a cohort of Egyptian males with suspected clinical features of (FXS) checking for the presence of premutation alleles. METHODS: The current study comprised 192 Egyptian male children, 92 participants presented with intellectual disability, delayed language development, autistic-like features, behavioral difficulties, anxiety, seizures, and depression compared to 100 healthy males. All cases were subjected to clinical and neuroimaging assessments, when indicated as well as molecular analysis using methylation-specific PCR (MS-PCR) and quantitative real-time PCR (qRT-PCR). RESULTS: Thirty-four premutation carriers out of 92 Egyptian males (37%) of CGG repeats (55 to 200) were illustrated with elevated FMR1 mRNA expression level (p-value < 0.001). Additionally, 2 intermediate (IM) cases (0.03%) (45-55 CGG repeats) showed poor increase in expression level (p-value = 0.02838) plus 6 full mutation (FM) patients (0.07%) with (> 200 CGG repeats) (p-value < 0.001) resulted in FMR1 gene silence. CONCLUSION: Molecular diagnostic assay including (MS-PCR) and (qRT-PCR) proved to be a sensitive and rapid screening tool for the detection of premutation cases. Furthermore, the presence of positive correlation between FMR1 mRNA expression levels with CGG repeats in premutation cases could serve as a potential diagnostic marker. Application of these diagnostic tools on larger number clinically suspected cases is recommended.

Kynurenine and oxidative stress in children having learning disorder with and without attention deficit hyperactivity disorder: possible role and involvement.

BACKGROUND: The etiological and pathophysiological factors of learning disorder (LD) and attention deficit hyperactivity disorder (ADHD) are currently not well understood. These disorders disrupt some cognitive abilities. Identifying biomarkers for these disorders is a cornerstone to their proper management. Kynurenine (KYN) and oxidative stress markers have been reported to influence some cognitive abilities. Therefore, the aim was to measure the level of KYN and some oxidative stress indicators in children with LD with and without ADHD and to investigate their correlations with the abilities of children with LD. METHODS: The study included 154 participants who were divided into 3 groups: one for children who have LD (N = 69); another for children with LD and ADHD (N = 31); and a group for neurotypical (NT) children (N = 54). IQ testing, reading, writing, and other ability performance evaluation was performed for children with LD. Measuring plasma levels of KYN, malondialdehyde, glutathione peroxidase, and superoxide dismutase by enzyme-linked immunosorbent assay was performed for all participants. RESULTS: Some IQ measures and learning skills differed between the first two groups. The biochemical measures differed between children with LD (with and without ADHD) and NT children (p < 0.001). However, the biochemical measures did not show a significant statistical difference between the first two groups. KYN and glutathione peroxidase levels were correlated with one-minute writing and at-risk quotient, respectively (p = 0.03;0.04). KYN and malondialdehyde showed the highest sensitivity and specificity values. CONCLUSION: These biochemical measures could be involved or have a role in the abilities' performance of children with specific learning disorder.

Cognitive Function and Heat Shock Protein 70 in Children With Temporal Lobe Epilepsy.

We conducted the present study to examine cognitive function and serum heat shock protein 70 levels among children with temporal lobe epilepsy. The Stanford-Binet Intelligence Test was carried out to examine cognitive function in 30 children with temporal lobe epilepsy and 30 controls. Serum heat shock protein 70 levels were determined with an enzyme-linked immunosorbent assay. The epilepsy group had significantly lower cognitive function testing scores and significantly higher serum heat shock protein 70 levels than the control group; there were significant negative correlations between serum heat shock protein 70 levels and short-term memory and composite scores. Children with uncontrolled seizures had significantly lower verbal reasoning scores and significantly higher serum heat shock protein 70 levels than children with controlled seizures. Children with temporal lobe epilepsy have cognitive dysfunction and elevated levels of serum heat shock protein 70, which may be considered a stress biomarker.

Molecular mechanisms underlying fibrosis and elastin destruction in childhood interstitial lung diseases.

OBJECTIVE: This study aimed to evaluate fibrosis and elastin destruction in childhood interstitial lung disease (chILD) patients. METHODS: Sixty patients and twenty healthy children were recruited. On admission, evaluation of chILD severity was made using Fan chILD score. Participants provided urine and blood samples. Plasma levels of transforming growth factor (TGF)-ß1, connective tissue growth factor (CCN2), soluble factor related apoptosis (sFas) and long non-coding RNAs and urinary levels of desmosine/urinary creatinine (UDes/UCr) were measured. RESULTS: In patients, clinical findings were crackles (100.00%), tachypnea (65.00%), cardiomegaly (45.00%), digital clubbing (43.30%), cough (33.00%), cyanosis (26.70%), hepatomegaly (28.30%) and wheezes (23.30%). Categorizing of the patients with Fan chILD clinical score revealed that most patients 33.30% scored (3, symptomatic with abnormal saturation/cyanosis during exercise) then 28.30% scored (5, symptomatic with clinical and echocardiographic features of pulmonary hypertension), 18.30% scored (2, symptomatic with normal room air saturations), 15.00% scored (1, asymptomatic) and 5.00% scored (4, symptomatic with abnormal room air saturation/cyanosis at rest). TGF-ß1, CCN2, sFas, lncrRNA-2700086A05Rik relative gene expression and UDes/UCr levels were higher in patients than controls (P=0.002, P=0.001, P=0.001, P=0.001, P=0.001, respectively). In patients, significant positive correlations were found between TGF-ß1 and CCN2, sFas, UDes/UCr; between CCN2 and both sFas and UDes/UCr; between UDes/UCr and sFas. Morbidity and mortality rates were 46.70% and 10.00%, respectively. CONCLUSION: Markers of fibrosis (TGF-ß1, sFas, CCN2) and elastin destruction (UDes/UCr) were increased in chILD especially in patients with long disease duration. So blockage of their pathways signals may offer novel therapeutic targets.