Onset of Inattention and Hyperactivity in Children and Adolescents With Epilepsy 6 months After the Diagnosis.

OBJECTIVE: Complete or major symptoms of ADHD are often present in epilepsy. This study evaluated inattention and hyperactivity symptoms over the first 6 months in newly diagnosed pediatric epilepsy without comorbid ADHD. METHOD: Children and adolescents with newly diagnosed epilepsy were followed for 6 months after starting antiseizure medications. The Nisonger Child Behavior Rating Form (NCBRF), Adverse Event Profile (AEP), and the Revised Wechsler Intelligence Scale for Children were used. RESULTS: There was a marked increase in attention difficulties while a moderate increase in hyperactivity levels. AEP scores, changes in non-verbal aspects of intelligence, levels of hyperactivity at the follow-up, and attention at baseline were significant predictors for inattention. In contrast, only levels of hyperactivity at the baseline and inattention at the follow-up were significant predictors for hyperactivity. CONCLUSION: Significant inattention and hyperactivity levels originated 6 months after the diagnosis of epilepsy and starting antiseizure medication.

KCC2 rs2297201 Gene Polymorphism Might be a Predictive Genetic Marker of Febrile Seizures.

Introduction: Febrile seizures (FS) are the most common neurological disease in childhood. The etiology of FS is the subject of numerous studies including studies regarding genetic predisposition. Aim: The aim of the study was to analyze the association of TRPV1 rs222747 and KCC2 rs2297201 gene polymorphisms with the occurrence of FS. Materials and Methods: The study included 112 patients diagnosed with FS classified as simple febrile seizures (SFS) or complex febrile seizures (CFS). We analyzed selected polymorphisms of KCC2 and TRPV1 genes using the Real-time PCR method. Results: The CT and TT genotypes of the rs2297201 polymorphism of the KCC2 gene are significantly more common in the group of children with FS than the control group (p = .002) as well as the allele T of this polymorphism (p = .045). Additionally, genotypes CT and TT of the rs2297201 polymorphism of the KCC2 gene were more frequent in the group of children with CFS compared to the control group (p < .001). Different genotypes and alleles of the rs222747 TRPV1 gene polymorphism were not associated with the occurrence of febrile seizures or epilepsy, nor were associated with the occurrence of a particular type of febrile seizure (p = .252). Conclusion: These results indicate that the CT and TT genotypes, as well as the T allele of rs2297201 polymorphism of the KCC2 gene, could be a predisposing factor for the FS, as well as the occurrence of CFS.

Cognitive profile, psychopathological symptoms, and quality of life in newly diagnosed pediatric epilepsy: A six-month, naturalistic follow-up study.

Long-term studies indicated changes in aspects of cognition, psychopathology, and quality of life (QOL) in children and adolescents followed up after the diagnosis of epilepsy. However, evidence is limited regarding what happens during the first few months after epilepsy is diagnosed because at this phase is possible to adjust and/or change an AED regimen or add other treatment interventions, if needed. This is a naturalistic, six months follow-up study that evaluated changes in overall cognitive profiles, levels of psychopathological symptoms, and quality of life (QOL) in newly diagnosed, uncomplicated pediatric epilepsy. In total, 61 (35 [57.4%] males) children and adolescents aged 7-18 years were assessed at the time of diagnosis and the initiation of antiepileptic drug (AED) treatment and six months afterward. The Revised Wechsler Intelligence Scale for Children, the Revised Child Anxiety and Depression Scale (RCADS), Nisonger Child Behavior Rating Form for typically developing children and adolescents (NCBRF), KIDSCREEN-10 Quality of Life Measure, and Adverse Event Profile (AEP) were used. The RCADS and NCBRF scores significantly increased over time, while the KIDSCREEN-10 scores significantly decreased. The most significant increases were observed in scores measuring social phobia and depressive symptoms and inattentiveness. Verbal cognitive abilities and full-scale intelligence scores changed slightly, while more changes were found in aspects of non-verbal cognitive abilities. This study showed that six months after epilepsy diagnosis and AED initiation, there were marked increases in anxiety levels, depressive symptoms, and behavioral problems, with deteriorations in QOL, while cognitive changes were relatively minimal. Therefore, monitoring levels of psychopathological symptoms and QOL in newly diagnosed epilepsy is highly recommended.

The adjuvant aluminum fate - Metabolic tale based on the basics of chemistry and biochemistry.

Aluminum is inevitable component of many vaccines. The benefit of the vaccines is undeniable but effects of aluminum toxicity might be underestimated and neglected. In this review, we highlighted the mechanims of aluminum toxicity, which is still in debate. So far, all the papers that disscused the adverse aluminum effects pointed two mechanisms responsible for Al toxicity, direct Al toxicity and aluminum induced cell damage via the oxidative metabolism. According to our knowledge, which is based on basic principles of biochemistry and inorganic chemistry, we suggested that aluminum highly interferes with iron metabolism eventually resulting in iron-mediated cell damage. More importantly, in this paper, we offered easily feasible solutions, in order to avoid aluminum toxicity in the future. We suggest that as it once was, Calcium Phosphate again to be used as the adjuvant or better solution that the vaccine adjuvants should be based on zinc compounds or even better would be non-metal adjuvants, such as microcrystalline tyrosine and monosodium urate. Until an adequate adjuvant is provided, we suggest instant postponement of vaccination with vaccines which use aluminum as the adjuvant until the 12 months of age.

Hypersensitivity reactions to antiepileptic drugs in children.

BACKGROUND: Antiepileptic drugs (AEDs) can cause hypersensitivity reactions in children. These reactions are mainly cutaneous, self-limiting, and benign, but life-threatening severe cutaneous adverse reactions can occur. Infections can lead to skin eruptions and mimic drug hypersensitivity reactions, if a drug is taken at the same time. The aims of our study were to confirm or rule out the diagnosis of hypersensitivity reactions to AEDs in children and to detect an infection which mimics these reactions. METHODS: A prospective survey was conducted in a group of 100 children with histories of hypersensitivity reactions to AEDs by performing patch tests, delayed-reading intradermal test, and, in case of negative results, challenge test. In all children, a study was performed to detect infections by viruses or Mycoplasma pneumoniae. RESULTS: Maculopapular exanthema and delayed-appearing urticaria were the most reported hypersensitivity reactions to AEDs. Sixty-six (66%) of 100 children had confirmed hypersensitivity reactions to AEDs. Fifty-nine children had positive patch test. No children had positive challenge tests. The most common AEDs causing hypersensitivity reactions were carbamazepine (45.4%) and lamotrigine (43.6%). Thirty-two children had positive tests for viruses or M pneumoniae, and nine of them had also a positive allergy work-up. CONCLUSION: Considering that there are no specific tests to distinguish between a viral infection and hypersensitivity reactions to AEDs in the acute phase, a diagnostic work-up should be performed in all children with suspected hypersensitivity reactions to AEDs, as well as infectious agent study, to remove a false label of hypersensitivity.

Anthropogenetic Variability in the Group of Individuals with Febrile Seizures: Population-Genetic Study.

Febrile seizures (FS) are the most common neurological disorder in childhood and are a great stress for parents due to their dramatic clinical appearance. Using test for determination of homozygously recessive characteristics in humans (HRC test) we analyzed presence, distribution, and individual combination of 20 selected genetically controlled morphophysiological traits among FS patients (N=121) and control (N=121) to determine a possible deviation in the homozygosity level and genetic loads in the group of affected children and whether there is a predisposition to the occurrence of FS. The results of our study show a statistically significant difference in the mean values of the HRC tested ( x¯HRC/20 CN = 3.2 ± 0.2; x¯HRC/20 FS = 4.6 ± 0.2, t= 5.74 , p< 0.0001), as well as in the distribution and variability of two studied samples (VC=55,3%, VFS= 39,6%), which indicates a complex polygenic difference among the tested groups of subjects. The differences in the degree of genetic homozygosity and variability are also present between the genders (t Cf/FSf = 4.12; t Cm/FSm = 3.98; p <0.0001) (VCf=56.9%, VFSf= 39.3%; VCm=54.1%, VFSm=40.1%). Obtained results indicate the enlargement of recessively homozygous genetic loads in the group of children with FS which may represent some kind of predisposition for expressivity of this type of seizures.

Increased Serum Interleukin-10 but not Interleukin-4 Level in Children with Mycoplasma pneumoniae Pneumonia.

Background: Mycoplasma pneumoniae (MP) is a common cause of community-acquired pneumonia in children, and it has been associated with wheezing. The aim of this study was to examine the serum level of interleukin (IL)-4 and IL-10 in children with Mycoplasma pneumoniae pneumonia (MPP) and to analyse them in relation to the presence of wheezing. Methods: The study included 166 children with radiologically confirmed pneumonia. MP infection was confirmed by enzyme-linked immunosorbent assay (ELISA) serum MP-IgM and MP-IgG test and throat swab MP DNA with real-time polymerase chain reaction. Serum levels of IL-4 and IL-10 were measured using ELISA. Results: There was no significant difference in serum level of IL-4 between children with MPP and those with non-MPP. Among children with MPP, we found similar level of IL-4 regardless of the personal and family history of allergy and asthma or the presence of wheezing. A significantly higher level of IL-10 was found in children with MPP than in children with non-MPP (32.92±18.582 vs. 27.01±14.100 pg/ml, p =0.022). Furthermore, wheezing children with MPP had a significantly higher level of IL-10 than children with MPP without wheezing (43.75±26.644 vs. 27.50±10.211 pg/ml, p=0.027). Conclusion: Our results show significantly increased serum level of IL-10 in children with MPP, which was significantly higher in children with wheezing. These findings may suggest a role of IL-10 in the pathogenesis of MPP and in the occurrence of wheezing during acute MP infection.

A 6-month follow-up of disability, quality of life, and depressive and anxiety symptoms in pediatric migraine with magnesium prophylaxis.

Magnesium is frequently used for pediatric migraine prophylaxis. The aim of this study was to evaluate to which extent the disability levels, quality of life (QOL), and anxiety and depressive symptoms change after 6-month magnesium prophylaxis in pediatric migraine. This is a follow-up study of 34 children aged 7-17 years with migraine treated with oral magnesium. Disability due to migraine was assessed by the Pediatric Migraine Disability Assessment tool (PedMIDAS), QOL was assessed by the KIDSCREEN-27, and anxiety and depressive symptoms were assessed by the Revised Child Anxiety and Depression Scale (RCADS). PedMIDAS scores significantly decreased from baseline to end-point (F(df, dferror) = 11.10 (1.63, 50.49), p<0.001), as well as anxiety (F(df, dferror) = 8.95 (1.64, 50.67), p = 0.001) and depressive symptoms (F(df, dferror) = 8.91 (1.59, 49.29), p = 0.001). Considering the KIDSCREEN-27, scores for physical and psychological well-being and social support domain significantly increased from baseline to end-point (p≤0.01). After 6 months of magnesium prophylaxis, disability due to migraine significantly decreased, whereas physical and psychosocial well-being improved. Children also reported fewer anxiety and depressive symptoms. More follow-up and randomized controlled clinical trials are needed to propose clinical recommendations for magnesium prophylaxis in pediatric migraine.

GSTA1, GSTM1, GSTP1 and GSTT1 polymorphisms in progressive myoclonus epilepsy: A Serbian case-control study.

PURPOSE: Oxidative stress is recognized as an important factor in progressive myoclonus epilepsy (PME). Genetic polymorphism of glutathione S-transferases (GSTs), which are involved in both protection from oxidative damage and detoxification, might alter the capacity for protecting tissues from exogenous and endogenous oxidants. We aimed to assess a possible association between GST polymorphism and PME, as well as, correlation between GST genotypes and oxidative phenotype in PME patients. METHODS: GSTA1, GSTM1, GSTP1 and GSTT1 genotypes were determined in 26 patients with PME and 66 controls. Byproducts of protein oxidative damage (thiol groups (P-SH) and nitrotyrosine), superoxide dismutase (SOD) and glutathione peroxidase (GPX) activities were determined. RESULTS: The frequency of GSTA1, GSTM1 and GSTP1 genotypes was not significantly different between PME patients and controls, while individuals with GSTT1-null genotype were at 5.44-fold higher risk of PME than carriers of GSTT1-active genotype. Moreover, significant risk of PME was obtained in carriers of both GSTT1-null and GSTM1-null genotypes. Carriers of combined GSTA1- active and GSTT1-null genotype were at highest, 7.55-fold increased risk of PME. Byproducts of protein damage did not reach statistical significance, while SOD and GPX activities were significantly higher in PME patients then in controls. When stratified according to GST genotype, P-SH groups were significantly lower only in patients with GSTT1-null genotype in comparison to carriers of active genotype. Only SOD activity was increased in GSTT1-null when compared to corresponding active genotype. CONCLUSIONS: GSTT1-null genotype might be associated with the increased risk and enhanced susceptibility to oxidative stress in PME patients.

A misdiagnosed myasthenia gravis with anti-muscle-specific tyrosine kinase antibodies with possible childhood onset.

INTRODUCTION: Childhood onset myasthenia gravis associated with anti-muscle-specific tyrosine kinase antibodies is very rare and atypical in presentation. CASE REPORT: As a baby, the pre- sented patient was choking and sleeping with open eyes. She had weak cry and breathing difficulties. In childhood, there were fre- quent falls and fluctuating swallowing difficulties. At the age of 19 she was misdiagnosed with Miller Fisher syndrome due to the presence of diplopia, ataxia and hyporeflexia with spontaneous recovery. Repetitive nerve stimulation test was normal. Four years later, after several relapses, there was significant decrement on facial muscles. Neostigmine test was negative, provoking muscle fasciculations. Serum anti-muscle-specific tyrosine kinase antibodies were positive. With cyclosporine therapy she achieved the minimal manifestations status. CONCLUSION: The presented case confirms that childhood onset myasthenia gravis associated with anti-muscle-specific tyrosine kinase antibodies is often with atypical presentation and spontaneous remissions, so it could be easily misdiagnosed.

The Diagnosis of Prediabetes in Adolescents.

BACKGROUND: Prediabetes is characterized by isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT), and combined IFG/IGT. This study aimed to establish the prevalence of prediabetes and examine possible contributory factors in a cohort of obese adolescents. METHODS: In this prospective study, we recruited 85 obese patients from the Obesity Clinic at the University Children's Hospital and 17 normal weight controls. All patients were of Caucasian origin, 60 males/42 females, aged 7.4-18.3 years, with at least Tanner 2 stage of puberty. RESULTS: Depending on criteria we used, insulin resistance was confirmed in 62-100% of obese patients, predominantly in the group with BMI SDS > 3. oGTT revealed isolated impaired fasting glucose (IFG) in 13.9%, impaired glucose tolerance (IGT) in 20.8% and combined IFG and IGT only in 2.8% of the obese patients. Patients in the prediabetes group were older (14±2.4 vs 12.8±2.5 p=0.04) and had higher glucose levels (p<0.001) during the whole oGTT compared to normal glucose tolerance (NGT) group. There was no difference between groups in respect to family history, BMI, lipids and fasting insulin. Insulinogenic index, WBISI and HOMA%B were significantly lower in the prediabetes group compared to the NGT group (p=0.07, 0.01 and 0.04 respectively). HbA1c level was measured in 58% of patients and was significantly higher in the prediabetes group (5.4±0.3 vs 5.7±0.4, p=0.002). CONCLUSION: Prediabetes occurrence was fairly high in our obese adolescents. Further studies should establish what would be the most appropriate screening test to diagnose these patients at risk for type 2 diabetes and initiate treatment without delay.

Mycoplasma pneumoniae as a causative agent of community-acquired pneumonia in children: clinical features and laboratory diagnosis.

BACKGROUND: Mycoplasma pneumoniae is a common cause of community-acquired pneumonia (CAP) in children. The aim of this study was to assess the prevalence of Mycoplasma pneumoniae infection in children with CAP and find clinical, radiological and laboratory features helpful to diagnose Mycoplasma pneumoniae pneumonia. Furthermore, we evaluated the value of serology, real-time PCR (RT-PCR) and culture for the accurate diagnosis of Mycoplasma pneumoniae pneumonia. METHODS: The study included 166 children aged between 1 and 15 years with radiologically confirmed pneumonia. Throat swab specimens were cultured and assessed by RT-PCR for the presence of Mycoplasma pneumoniae. Mycoplasma pneumoniae-specific IgM and IgG antibodies were determined using ELISA in paired sera. RESULTS: Mycoplasma pneumoniae pneumonia was diagnosed in 14.5% CAP cases. Cough (p=0.029), headache (p=0.001) and wheezing (p=0.036) were more frequent in children with Mycoplasma pneumoniae pneumonia compared to children with pneumonia caused by other pathogens. Logistic regression analysis showed that headache (odds ratio [OR] =36.077, p=0.001) and wheezing (OR=5.681, p=0.003) were significantly associated with MP pneumonia. Neither radiological findings, nor common laboratory parameters distinguished Mycoplasma pneumoniae infection in children with CAP. Using IgG serology in paired sera as the gold standard, we found that sensitivity of IgM serology, RT-PCR and culture was equal (81.82%), while specificity values were 100%, 98.6% and 100% respectively. We observed that combination of IgM detection in acute-phase serum and RT-PCR was positive for 91.7% of cases with Mycoplasma pneumoniae infection. CONCLUSIONS: There are no characteristic radiological findings, or routine laboratory tests that would distinguish CAP caused by Mycoplasma pneumoniae from other CAP. It was found that clinical features such as headache and wheezing are indicative for Mycoplasma pneumoniae infection. Furthermore, it was found that during the acute phase of disease, detection of IgM antibodies in combination with RT-PCR allows for precise and reliable diagnosis of Mycoplasma pneumoniae infections in children.

Mitotic crossover--an evolutionary rudiment which promotes carcinogenesis of colorectal carcinoma.

Mitotic crossover is a natural mechanism that is a main source of the genetic variability of primitive organisms. In complex organisms such as mammals, it represents an evolutionary rudiment which persisted as one of the numerous DNA repair mechanisms, and results in the production of homozygous allele combinations in all heterozygous genes located on the chromosome arm distal to the crossover. This event is familiar as loss of heterozygosity, which is one of the key mechanisms responsible for the development and progression of almost all cancers. We propose the hypothesis in which mitotic crossover is a principal source of the increased loss of heterozygosity that leads to the initiation and progression of colorectal carcinoma. The hypothesis could be tested by in vitro inhibition of Rad51 protein, orthotopic grafting of human colon cancer tissue into the gut of mice, and treatment with potential inhibitors. After these procedures, the frequency of mitotic crossover would be estimated. The development of selective inhibitors of mitotic crossover could stop further carcinogenesis of colorectal carcinoma, as well as many other neoplastic events. Loss of heterozygosity is an event responsible for carcinogenesis, its reduction by selective inhibitors of mitotic crossover could have a positive effect on cancer chemoprevention, as well as on growth reduction and a cessation in the progression of earlier developed tumors.

Association between pet-keeping and asthma in school children.

BACKGROUND: The role of pet exposure in childhood asthma and allergy is still controversial. The aim of this study was to investigate the association between pet-keeping during different periods of childhood and asthma and sensitization in school children. METHODS: One hundred and forty-nine children aged between 7 and 14 years were enrolled in this study. Seventy-four children had current physician-diagnosed asthma, while 75 children did not have asthma. Pet-keeping was investigated by questionnaire. Allergic sensitization to pet allergen was assessed on skin prick tests and specific serum IgE concentration. Logistic regression analysis was performed, taking into account potential confounders. RESULTS: Early, past and current pet-keeping was not significantly associated with asthma. Neither owning a cat nor dog during childhood was associated with asthma. Early pet-keeping, however, was significantly associated with sensitization to pet allergens (adjusted odds ratio [aOR], 24.11; 95% confidence interval [CI]: 3.28-177.27). Further analysis showed that only early cat-keeping was significantly associated with sensitization to cat allergen (aOR, 51.59; 95%CI: 2.28-1167.07). Keeping a cat or a dog after the first year of life was not associated with sensitization to those allergens. CONCLUSIONS: Keeping a cat or a dog does not increase risk for asthma. Keeping a cat in the first year of life, however, increases risk of sensitization to cat allergen. Considering that this is a relatively small study, larger, prospective, birth cohort studies are required in Serbia to accurately assess the relationship between pet-keeping, asthma and sensitization.

Early presentation of neuromyelitis optica.

Neuromyelitis optica is a rare autoimmune demyelinating disease of the central nervous system in childhood. Its relapsing form is usually reported in adults. We report a 3-year-old girl with relapsing, IgG seropositive neuromyelitis optica. Initially she presented with optic neuritis, followed by three relapses with deterioration of optic neuritis and developing transverse myelitis. With each relapse, the treatment was less effective. Four years after the onset of the disease, the patient was blind, had paraplegia associated with urinary and bowel incontinence and short stature.

Inhaled nitric oxide therapy for acute respiratory distress syndrome in children.

The aim of this study was to evaluate the effects of inhaled nitric oxide (iNO) therapy on oxygenation and mortality in children with acute respiratory distress syndrome (ARDS). Thirty-three children with ARDS and an arterial SatO2 <88% despite mechanical ventilation were analyzed. Patients in the iNO group were prospectively enrolled and treated with conventional therapy plus iNO. The control group consisted of retrospectively analyzed patients treated only with conventional therapy. A significant increase in PaO2/FiO2 ratio (25.6%) and decrease in oxygenation index (19.5%) was observed after 4 h of iNO treatment, when compared to baseline values. A positive response to iNO was detected in 69% of patients, and there was no difference between pulmonary and extrapulmonary ARDS. There was no difference in mortality and duration of mechanical ventilation between iNO and control group.