Iranian Journal of Child Neurology (IJCN)
Volume:8 Issue: 4, Autumn 2014

Neurodegeneration with brain iron accumulation (NBIA) is a group of neurodegenerative disorder with deposition of iron in the brain (mainly Basal Ganglia) leading to a progressive Parkinsonism, spasticity, dystonia, retinal degeneration, optic atrophy often accompanied by psychiatric manifestations and cognitive decline. 8 of the 10 genetically defined NBIA types are inherited as autosomal recessive and the remaining two by autosomal dominant and X-linked dominant manner. Brain MRI findings are almost specific and show abnormal brain iron deposition in basal ganglia some other related anatomical locations. In some types of NBIA cerebellar atrophy is the major finding in MRI.

Epilepsy is one of the most common diseases in Iran contributing to an array of health problems. In light of this, the aim of the present study is to examine the prevalence of epilepsy in Iran through a systematic review and meta-analysis. A systematic search of several databases including PubMed, scientific information databases, Google, Google scholar, Elsevier and Scopus was conducted in June 2013. Observational studies were considered for inclusion if they were published in Iranian and examined epilepsy prevalence and/or related risk factors. Meta-analysis was conducted using a random effect model with the DerSimonian/Laird method. Heterogeneity was examined using the Breslow- Day test and inconsistency using the I2 statistic. A total of 45 studies were identified from the search strategy. Of these, nine published manuscripts with a total of 7,723 participants were included within the review. The pooled prevalence of epilepsy in Iran was estimated to be around 5% 95% confident interval (CI) 2 to 8). For each region the prevalence of epilepsy in central, northern and eastern Iran were 5% (95%CI 2 to 8), 1% (95%CI -1 to 3) and 4% (95 CI 3 to 11) respectively. The most common risk factors in order of prevalence were somatic diseases 39% (95%CI 15 to 62), convulsion 38% (95%CI 11 to 65), mental diseases 36% (95%CI 15 to 95) and hereditary development 26% (95%CI 9 to 42). A meta-regression model identified a declining trend in the prevalence of epilepsy within Iran for the last decade. Pooled analyses from the nine included publications in this review estimate the prevalence of epilepsy in Iran to be around 5%. Although this result is much higher than rates in other countries, a declining trend in prevalence over the past decade was also identified.

Migraines, a common health problem in children and adolescents, still do not have an FDA approved preventive treatment for patients under the age of 18 years. This study compares and contrasts the efficacy and safety of cinnarizine and topiramate in preventing pediatric migraines. In this randomized, double-blind clinical trial 44 migrainous (from 4–15 years of age) were equally allocated to receive cinnarizine or topiramate. The primary efficacy measure was monthly migraine frequency. Secondary efficacy measures were monthly migraine intensity and ≥ 50% responder rate. Efficacy measures were recorded at the baseline and at 4, 8, and 12 weeks of treatment. During the double-blind phase of the study, monthly migraine frequency and intensity were significantly decreased in both the cinnarizine and topiramate groups when compared to the baseline. However, at the end of the study, the cinnarizine group exhibits a significant decrease from the baseline in the mean monthly migraine intensity when compared to the topiramate group (4.7 vs. 3, respectively; 95% CI = -0.8 to -3.2). No significant difference between cinnarizine and topiramate was found for the prevention of pediatric migraines. Both treatments were well tolerated.

Early diagnosis and treatment of congenital hypothyroidism (CH) and the prevention of developmental retardation is the main goal of public health national screening programs. This study compares the cognitive ability of children with CH diagnosed by neonatal screening with a healthy control group (2007) in Yazd, Iran. In a case-controlled study, the intelligent quotient (IQ) of 40 five-year-old children with early treated CH and good compliance were evaluated by the Wechsler preschool and primary scale of intelligent test and compared to 40 healthy age and gender matched children as controls. 22 boys (55%) and 18 girls (45%) in both groups were evaluated. In children with CH, 19 (47.5%) and 21 (52.5%) persons had transient and permanent hypothyroidism, respectively.Range of TSH and T4 level at the onset of diagnosis were 11.41–81 mu/l and 1.50–14.20 μg/dl, respectively.The intelligence levels of all children with CH were within the average or normal range and IQs ranged from 91–108.Children with CH had lower full-scale IQs (107.25 ± 2. 9 versus 110.50 ± 2.66, p=0.001), verbal IQ (106.95 ± 3.5 versus 109.90 ± 3.44, P-value=0.001) and performance IQ (106.3 ± 3.68 versus 108.87 ± 3.70) than the control group.However, no statistically significant differences were observed for mean IQ scores in permanent and transient CH. Children with CH who had early treatment and good compliance had normal cognitive abilities, but may have a decreased IQ relative to the healthy control group.

Many patients with late-diagnosed phenylketonuria (PKU) suffer from severe behavior problems. This study compares the effects of buspirone and risperidone on reducing behavior disorders in these patients. In this crossover clinical trial study, patients with severe behavior disorders after medical examination were randomly divided into two groups of two 8-week crossover treatments with risperidone or buspirone. Patient behavioral disorders before and after treatment by each drug was rated by parents on the Nisonger Child Behavior Rating Form (NCBRF), and after treatment by each drug, were assessed by a physician through clinical global impression (CGI). Thirteen patients were able to complete the therapy period with these two medications.The most common psychiatric diagnoses were intellectual disability accompanied by pervasive developmental disorder NOS, and intellectual disability accompanied by autistic disorder. Risperidone was significantly effective in reducing the NCBRF subscales of hyperactivity disruptive/ stereotypic, and conduct problems. Treatment by buspirone only significantly decreased the severity of hyperactivity, but other behavior aspects showed no significant differences. Assessment of the severity of behavior disorder after treatment by risperidone and buspirone showed significant differences in reducing hyperactivity and masochistic/stereotype. Although buspirone is effective in controlling hyperactivity in patients with PKU, it has no preference over risperidone. Therefore, it is recommended as an alternative to risperidone.

The first line-screening test for mucopolysaccharidosis is based on measurement of urinary glycosaminoglycans. The most reliable test for measurement of urine glycosaminoglycans is the 1,9-dimethyleneblue colorimetric assay. Biological markers are affected by ethnical factors, for this reason, the World Health Organization recommends that the diagnostic test characteristics should be used to determine results for different populations. This study determines the diagnostic value of 1,9-dimethyleneblue tests for diagnosis of mucopolysaccharidosis type I patients in Iran. In addition to routine urine analysis, the qualitative and quantitative measurements of urine glucosaminoglycans were performed with the Berry spot test and 1,9-dimethyleneblue assay. Diagnostic values of the tests were determined using the ROC curve. Urine total glycosaminoglycans were significantly higher in male subjects than in female subjects. Glycosaminoglycan concentration was markedly decreased in specimens with elevated white blood cell and epithelial cells count. Using a cut-off level of 10.37 mg/g creatinine, sensitivity, and specificity were 100% and 97.22%, respectively, for a 1,9-dimethyleneblue colorimetric assay. Urine glycosaminoglycans concentration significantly differs in our studied population. In addition to determine diagnostic validity of the 1,9-dimethyleneblue test, our results demonstrate the usefulness of measuring glycosaminoglycans for early screening of mucopolysaccharidosis type I Iran.

Neonates are at greater risk for sepsis and meningitis than other ages and in spite of rapid diagnoses of pathogens and treatments, they still contribute to complications and mortality. This study determines risk factors, causes, and neurologic complications of neonatal meningitis in ospitalized neonates. In this descriptive, cross sectional study, we evaluated 415 neonates with sepsis and meningitis admitted to the neonatal intensive care unit at our center between 2008 and 2012. The data that was recorded was age, sex, birth weight, prenatal risk factors, clinical features, blood and cerebrospinal fluid analysis, and brain sonographic findings and outcomes. Twenty patients had meningitis. Eleven cases (55%) were male. The mean age was 8. 41 days and mean birth weight was 2891.5±766 grams. Poor feeding, seizures, and tachypnea were detected in 12 (60%), 11 (55%), and 6 (30%) patients, respectively. Prenatal risk factors were prolonged rupture of membranes, maternal vaginitis, asymptomatic bacteriuria, prematurity, low birth weights, and asphyxia. Four patients had positive cerebrospinal fluid cultures with klebsiella pneumoniae 2 50%), Enterococcus spp. 1 (25%), and Group B streptococcus 1 (25%) cases, respectively. Two cases had positive blood cultures with klebsiella pneumoniae. Neurologic complications were brain edema, subdural effusion, and brain abscesses with hydrocephaly. One neonate (5%) died. Our study provides some information about risk factors, pathogens, and neurologic complications for neonatal meningitis. Prenatal assessments help to diagnose and reduce risk factors of this hazardous disease.

Febrile seizures (FS) are the most common type of childhood seizures, affecting 2–5% of children. As the seizure may be the sole presentation of bacterial meningitis in febrile infants, it is mandatory to exclude underlying meningitis in children presenting with fever and seizure. To determine the frequency of meningitis in children with FS and related risk factors, the present study was conducted at Ali-Asghar Children’s Hospital. The records of children aged from 1-month–6 years of age with fever and seizure admitted to the hospital from October 2000–2010 were studied. The charts of patients who had undergone a lumbar puncture were studied and cases of meningitis were selected. The related data was collected and analyzed with SPSS version 16. A total of 681 patients with FS were known from which 422 (62%) lumbar punctures (LP) were done. Meningitis (bacterial or aseptic) was identified in 19 cases (4.5%, 95% CI 2.9–6.9 by Wilson- Score internal) and bacterial meningitis in 7 (1.65%, 95% CI 0.8–3.3). None of the patients with bacterial meningitis had meningeal irritation signs. Complex FS, first attack of FS, and impaired consciousness were more common in patients with meningitis when compared to non- meningitis patients. Meningitis is more common in patients less than 18 months presenting with FS; however, complex features of seizures, first attack of FS, or impaired consciousness seem significant risk factors for meningitis in these children and an LP should be considered in this situation.

Febrile convulsions (FC) are the most frequent seizure disorder in children.Some studies have detected serum electrolyte disturbances in patients with FC.This study determines serum electrolytes, renal function tests, and frequency of urinary tract infection in hospitalized children with FC. In this descriptive, cross sectional study, we evaluated 291 children with FC admitted to the Neurology ward of Ali-Asghar Children’s Hospital from 2008–2013. Data was recorded on age, sex, type (simple, complex), and recurrence of seizures, family history of FC and epilepsy, serum electrolytes, renal function tests, and urinary tract infections. A total of 291 patients with diagnosis of FC were admitted to our center. Of these 291 patients, 181 (62.2%) were male. The mean age was 24.4 ± 14.6 months.There were simple, complex, and recurrent FCs in 215 (73.9%), 76 (26.1%) and 61 (21%) of patients, respectively. Urinary tract infections (UTI) were found in 13 (4.5%) patients, more present in females (p-value = 0.03) and under 12 months of age (p-value = 0.003). Hyponatremia, hypocalcemia, and hypokalemia was detected in 32 (11%), 16 (5.5%), and 4 (1.4%) of cases, respectively. Twentyfour (8.2%) patients had a glomerular filtration rate less than 60 ml/min/1.73m2.There were no abnormalities in serum magnesium, BUN, and creatinine levels. During FCs, mild changes may occur in renal function but a serum electrolyte evaluation is not necessary unless patients are dehydrated. In children with FC, urinary tract infections should be ruled out.

The prevalence of active epilepsy is about 0.5–1%, and approximately 70% of patients are cured with first anti-epileptic drugs and the remaining patients need multiple drugs. Pregabalin as an add-on therapy has a postive effect on refractory seizures in adults. To the best of our knowledge, there is no research with this drug in childhood epilepsy. We use pregabalin in children with refractory seizures as an add-on therapy. The objective of this study is to evaluate the effects of pregabalin in the reduction of seizures for refractory epilepsy. Forty patients with refractory seizures who were referred to Mofid Children’s Hospital and Hazrat Masoumeh Hospital were selected. A questionnaire based on patient record forms, demographic data (age, gender,…), type of seizure, clinical signs, EEG record, imaging report, drugs that had been used, drugs currently being used, and the number of seizures before and after Pregabalin treatment was completed. We checked the number of seizures after one and four months. After one month, 26.8% of patients had more than a 50% reduction in seizures and 14.6% of these patients were seizure-free; 12.2% had a 25–50% reduction; and approximately 61% had less than a 25% reduction or no change in seizures.After the fourth month, 34.1% of patients had more than a 50% reduction in seizures and 24.4% of these patients were seizure-free. Additionally, 65.9% of patients had less than 50% reduction in seizures (9.8% between 25–50% and 56.1% less than 25% or without improvement). We recommend Pregabalin as an add-on therapy for refractory seizures (except for myoclonic seizures) for children.

Canavan’s disease is a lethal illness caused by a single gene mutation that is inherited as an autosomal recessive pattern. It has many different clinical features especially in the non-Ashkenazi Jewish population. 45 patients were referred to the Pediatric Neurology Department of Mofid Children’s Hospital in Tehran-Iran from 2010–2014 with a chief complaint of neuro developmental delays, seizures, and neuroimaging findings of leukodystrophy were included in this study. Magnetic Resonance Spectrometry (MRS) and neuro metabolic assessment from a referral laboratory in Germany confirmed that 17 patients had Canavan’s disease. Visual impairment, seizure, hypotonia, neuro developmental arrest, and macrocephaly were the most consistent findings in the patients in this study. Assessments of neuro developmental status revealed that 13 (76%) patients had neuro developmental delays and 4 (24%) patients had normal neuro development until 18 months of age and then their neuro developmental milestones regressed. In this study, 100% of cases had macrocephalia and 76% of these patients had visual impairment. A history of seizures was positive in 8 (47%) patients and began around 3 months of age with the most common type of seizure was tonic spasm. EEGs were abnormal in all epileptic patients. In ten of the infantile group, we did not detect elevated level of N-acetylaspartic acid (NAA) in serum and urine. However, the MRS showed typical findings for Canavan’s disease (peaks of N-acetylaspartic acid). We suggest using MRS to detect N-acetylaspartic acid as an acceptable method for the diagnosis of Canavan’s disease in infants even with normal serum and urine N-acetylaspartic acid levels.

Griscelli syndrome (GS) is a rare autosomal recessive immune deficiency disorder that presents with pigmentary dilution of the skin and hair, recurrent skin and pulmonary infections, neurologic problems, hypogammaglobulinemia, and variable cellular immunodeficiency. Three mutations have been described in different phenotypes of the disease. In most of cases, GS leads to death in the first decade of life. In this article, we report a one-year-old child with type 2 GS who suffers from pigmentation disorder and hypogammaglobulinemia.

Bart’s syndrome is defined as congenital localized absence of skin, and associated with epidermolysis bullosa. A newborn with Bart’s syndrome is reported because it is a very rare condition, especially when associated with corpus callosum agenesis and concomitant choanal atresia. Clinically it is characterized by raw beefy areas of denuded skin mainly on hands and feet.We report a rare case of a term female newborn born to non-consanguineous parents who presented with congenital absence of skin in, face, trunk and extremities. To the best of our knowledge, this is the first report presenting a case of Bart’s syndrome associated with corpus callosum agenesis.