Azza A. Eltayeb

Cognitive function and event-related potentials in children with type 1 diabetes mellitus.

Type 1 diabetes mellitus is associated with cognitive changes, but the extent of cognition decline depends on age at onset, duration of diabetes, and occurrence of attacks of hypoglycemia or ketoacidosis. This study was designed to assess cognitive function in a group of children with type 1 diabetes mellitus. A total of 40 diabetic children were recruited from the pediatric department of Assiut University Hospital, Egypt. Forty healthy children matched for age, sex, and socioeconomic status were chosen as controls for comparison. Cognition was assessed using Stanford—Binet and event-related potentials tests. Compared to the control group, patients reported a significant reduction in intelligent quotient, comprehension, abstract visual reasoning, quantitative reasoning, bead memory, and total short memory testing for cognitive functions. Prolonged N1, P200, N2, and P300 latencies and reduced P300-N2 amplitude were reported. Significant negative correlations were identified in most studied cognitive functions and ketoacidosis or family history of diabetes mellitus.

A Randomized, Placebo-controlled Trial of Digestive Enzymes in Children with Autism Spectrum Disorders

Objective There is growing evidence for a gut-brain connection associated with autism spectrum disorders (ASDs). This suggests a potential benefit from introduced digestive enzymes for children with ASD. Methods We performed a double-blind, randomized clinical trial on 101 children with ASD (82 boys and 19 girls) aged from 3 to 9 years. ASD patients were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders 4th edition, text revision (DSM-IV-TR) diagnostic criteria. Structured interviews of at least one hour each both with the parents and the child were performed. Later on, another two hours-session was conducted applying the Childhood Autism Rating Scale (CARS). ASD patients were randomized to receive digestive enzymes or placebo. Results The ASD group receiving digestive enzyme therapy for 3 months had significant improvement in emotional response, general impression autistic score, general behavior and gastrointestinal symptoms. Our study demonstrated the usefulness of digestive enzyme in our population of ASD patients. Conclusion Digestive enzymes are inexpensive, readily available, have an excellent safety profile, and have mildly beneficial effects in ASD patients. Depending on the parameter measured in our study, we propose digestive enzymes for managing symptoms of ASD. Digestive enzyme therapy may be a possible option in treatment protocols for ASD in the future.

Tissue Factor Pathway Inhibitor and P-Selectin as Markers of Sepsis-Induced Non-overt Disseminated Intravascular Coagulopathy

Inflammation and coagulation occur concomitantly in sepsis. Thrombin activates platelet that leads to P-selectin translocation, which upregulate tissue factor (TF) generation. Tissue factor pathway inhibitor (TFPI) is an anticoagulant that modulates coagulation induced by TF. The term non-overt disseminated intravascular coagulation (DIC) refers to a state of affairs prevalent before the occurrence of overt DIC. It was suggested that an initiation of treatment in non-overt DIC has better outcome than overt DIC. This study investigated the role of TFPI level, P-selectin, and thrombin activation markers in non-overt and overt DIC induced by sepsis and its relationship to outcome and organ dysfunction as measured by the Sequential Organ Failure Assessment (SOFA) score. It included 176 patients with sepsis. They were admitted to the pediatric intensive care unit (ICU).They included 144 cases of non-overt DIC and 32 cases of overt DIC. There was a significant difference in hemostatic markers, platelet count, partial thromboplastin time (PTT), P-selectin, thrombin activation markers, TFPI, and DIC score between overt and non-overt DIC in both groups. It was noticed that P-selectin was positively correlated with DIC score, fibrinogen consumption, fibrinolysis (D-dimer), thrombin activation markers, and TFPI. Tissue factor pathway inhibitor was significantly correlated with fibrinolysis, DIC score, and prothrombin fragment 1+2. Sequential Organ Failure Assessment score was correlated with DIC score and other hemostatic markers in patients with overt DIC. To improve the outcome of patients with DIC, there is a need to establish more diagnostic criteria for non-overt-DIC. Plasma levels of TFPI and P-selectin may be helpful in this respect.

Vitamin D status and viral response to therapy in hepatitis C infected children

AIM To study the frequency of vitamin D deficiency in patients with hepatitis C virus (HCV) infection and to evaluate the role of vitamin D supplementation in improving antiviral therapy. METHODS Sixty-six children aged from 7-14 years (mean ± SD, 11.17±2.293) diagnosed with HCV infection were matched to 28 healthy controls. Serum levels of 25 (OH) D3, calcium, phosphorus, alkaline phosphatase and plasma level of parathormone were measured. Quantitative PCR for HCV was performed Bone density was determined by dual energy X-ray absorptiometry. All cases received conventional therapy, and only 33 patients received vitamin D supplementation. RESULTS Children with HCV showed significantly increased levels of HCV RNA (P<0.001), parathormone (P<0.01) and decreased vitamin D levels (P<0.05) (33.3% deficient and 43.3% insufficient) compared with controls. Abnormal bone status (Z score -1.98±0.75) was found in ribs, L-spine, pelvis and total body. Cases treated with vitamin D showed significant higher early (P<0.04) and sustained (P<0.05) virological response. There was a high frequency of vitamin D deficiency among the Egyptian HCV children, with significant decrease in bone density. The vitamin D level should be assessed before the start of antiviral treatment with the correction of any detected deficiency. CONCLUSION Adding vitamin D to conventional Peg/RBV therapy significantly improved the virological response and helped to prevent the risk of emerging bone fragility.

Regulatory T cell subsets in children with systemic lupus erythematosus

The aim of this work was to quantify CD4+CD25+Foxp3+ T cells (Tregs) in Egyptian children with SLE and to correlate these findings with their disease activity scores and drug therapy. We enrolled 37 Egyptian children with active SLE. Disease activity was assessed by measuring serum levels of anti-dsDNA antibody and by the SLEDAI scores. Twenty healthy children were also enrolled as normal controls. The CD4+CD25+, CD4+CD25bright, and CD4+CD25dim cells in patients were significantly increased in comparison to controls. There was no significant difference in the Foxp3 gated on CD4+CD25bright and CD4+CD25dim, but there was a significant increase when gated on CD4+CD25− and whole CD4+ cells in patients than controls. There was no significant difference among patients with different degrees of activity on different lines of treatments and their outcomes as regards all studied values. There was no significant correlation between SLEDAI score and any of the studied parameters except for a significant negative correlation with gated lymphocytes. There is increased expression of Foxp3 in CD4+ T cells mostly CD25− in Egyptian children with active SLE under corticosteroid treatment regardless of disease activity.

Risk genes and autoantibodies in Egyptian children with type 1 diabetes – low frequency of autoantibodies in carriers of the HLA‐DRB1*04:05‐DQA1*03‐DQB1*02 risk haplotype

The study aimed to define the frequencies of type 1 diabetes‐associated gene polymorphisms and their associations with various diabetes‐associated autoantibodies in Egyptian children.

Activated and Memory T Lymphocytes in Children with Gaucher Disease

Gaucher disease (GD) is the most prevalent lysosomal storage disorder. Gaucher disease is associated with remarkable alterations in the immune system, and GD patients are more susceptible to infections and are at a higher risk of developing autoimmune disorders and malignancies. In a case–control study, we used three-color flow cytometric immunophenotyping for determination of the frequency of lymphocyte subpopulations and activated T lymphocytes among 18 children with GD1 under enzyme replacement therapy managed in Assiut University Hospitals. We found significant increases in the frequencies of total lymphocytes, CD19+, CD3+, CD4+, and CD8+ in children with GD1 when compared to healthy control. The frequencies of activated T lymphocytes (CD3+HLA-DR+), activated T-helper cells (CD4+HLA-DR+), and activated T-suppressor/cytotoxic cells (CD8+HLA-DR+) were significantly higher in GD1 as compared to healthy children. Our data show that the increased proportion of activated T lymphocytes in children with GD1 raises the issue of their possible involvement in the pathogenesis of the immune dysfunction seen in these patients. Our data suggested that the activated T lymphocytes could play a role in the clinical course of GD1. The relationship of these cells to immune disorders in GD1 children remains to be determined.

Socio-demographic, Clinical and Laboratory Predictors for the Diagnosis of Visceral Larva Migrans in Children - Upper Egypt

Visceral larva migrans (VLM) is a worldwide neglected disease, prevalent among children from socio-economically disadvantaged populations in temperate and tropical regions. Infections may go undiagnosed as the required diagnostic tests; serological, molecular and/or imaging examinations are expensive, which may not be affordable or available. We aimed to establish predictors useful in the diagnosis of VLM in children in Upper Egypt. A one year cross-sectional study was conducted at Assiut University Childrens Hospital and eighty-one children aged between 6 months to 13 years old (mean± SD 5.7 ± 3.2 years) were eligible to our inclusion criteria, 55.6% of Original Research Article Galal et al.; IJTDH, 19(2): 1-13, 2016; Article no.IJTDH.28780 2 them were males. Socio-demographic risk factors, clinical, laboratory and imaging tests were collected. ELISA (anti-T. canis IgG) results were positive in 60.5%. By using the bivariate analysis, a significant association was found between seropositive ELISA and younger age less than four years (p-value <0.0001), having underground water at their homes (p= 0.004), previous history of parasitic infection (p= 0.003) and positive liver ultrasonographic findings (p=0.001). In a multivariate logistic regression model with positive and negative ELISA results as a dependent factor, younger age (<4 years), history of parasitic infestation and positive liver ultrasonographic findings were found to be significant predictors, while no significant association with other factors was identified. Thus, clinicians should consider the positive liver ultrasonographic changes with the earlier history of parasitic infection in children under four years as predictors for VLM infection, according to which they should undergo ELISA or other tests to confirm their diagnosis.

Prothrombotic risk factors and antithrombotic therapy in children with ischemic stroke

Objective: Congenital and acquired prothrombotic disorders have been highlighted in a recent series of cerebrovascular stroke (CVS), with a controversial role in pathogenesis. The aim is to study some prothrombotic risk factors [activated protein C (APC) resistance, von Willebrand factor (vWF), anticardiolpin (ACL) antibodies and plasma homocysteine] in children with ischemic stroke, and to evaluate the role of aspirin and low molecular weight heparin (LMWH) in its management in relation to outcome. Methods: A total of 37 cases aged from 1 month to 15 years ( mean ± standard deviation 26.2 ± 35.7 months), diagnosed as ischemic stroke (>24 hours) were recruited. Complete blood count, prothrombin time and concentration, partial thromboplastin time, serum electrolytes, random blood sugar, C-reactive protein, electrocardiogram and echocardiography were done. Levels of APC resistance, vWF, ACL antibodies [immunoglobulin G (IgG) and immunoglobulin M (IgM)] and plasma homocysteine were estimated. A total of 25 cases received aspirin 3–5 mg /kg/d and 12 patients received LMWH as initial dose at 75 international units (IU)/kg subcutaneously (SC) then 10–25 IU/kg/day for 15 days in a nonrandomized fashion. Results: The levels of APC resistance, vWF, ACL antibodies (IgG and IgM) and plasma homocysteine were significantly higher in stroke cases than in controls. There was no significant difference between cases treated with aspirin and those with LMWH in all prothrombotic factors. Significant positive correlations were found between vWF and ACL antibodies (IgG and IgM) levels before treatment. Significant decrease in cognitive function was detected between cases treated with LMWH and those treated with aspirin. Conclusion: Ischemic CVS in children is multifactorial. Thrombophilia testing should be performed in any child with CVS. Early use of aspirin improves the prognosis and has less effect on cognitive function.

Brain function in children with untreated epilepsy: Relationship to biomarkers of brain damage

Many studies have reported cognitive and behavioral abnormalities with recurrent seizures in adults. Similar evidence from the pediatric population is scarce and controversial. We aimed to investigate the effect of recurrent seizures on the developing brain. Included were 42 children with epilepsy (mean age 14.1±1.72 yr) and 30 healthy children for comparison. Patients had recurrent untreated epilepsy (generalized or focal). Negative attitudes and misconceptions about epilepsy are common in developing countries, often resulting in neglect of medical services and treatment. Epilepsy is greatly misunderstood by the public, and is attributed to spiri- tual causes such as the devil or mistaken as odd behavior or daydreaming. Another misconception is that medications will harm the child. Intelligence quotient (IQ) and cognition were examined using Wechsler Intelligence Scale for Children and Stanford Binet Subsets Test version 4 (SBST4). Serum levels of neuron-specific enolase (NSE) and S100s proteins, sensitive markers of neuronal and glial cell damage were measured. Compared to controls, patients had lower mean score of full scale IQ on the Wechsler Intelli- gence Scale for Children (P = 0.045), particularly performance IQ scores (P <0.01), and comprehension, pattern analysis, quantita- tion, bead memory and memory for sentences of SBST4 (P = 0.045; P =0 .013,P = 0.007, P = 0.002; P = 0.035), but not for NSE or S100s. Severe epileptogenic (EEG) records were observed in children with lower IQ. Serum concentrations of NSE and S100s were lower in children with higher seizure frequency but did not reach significance compared to controls. Significant correlation was observed between full scale IQ and duration of illness (r = �0.430, P = 0.035), number of seizures (r = �0.580, P = 0.005) and sever- ity of electroencephalography changes (r = �0.450, P = 0.052), but not with S100s or NSE levels. Lower intelligence and poor cog- nitive performance were common with recurrent childhood epilepsy. Functional brain abnormalities without structural brain injury may likely be the cause. It seems that serum levels of NSE and S100s are not sensitive markers for structural or minimal brain damage in children with untreated epilepsy. Thus, early recognition and optimal seizure control is necessary to prevent the subse- quent damaging effects on the brain due to prolonged and recurrent seizures and subclinical epileptiform activity. Looking for addi- tional, more specific markers of brain injury is necessary, elevated serum levels of NSE and S100s were not detected.