Iranian Journal of Child Neurology (IJCN)
Volume:9 Issue: 1, Winter 2015

Neurometabolic disorders are an important group of diseases that mostly are presented in newborns and infants. Neurological manifestations are the prominent signs and symptoms in this group of diseases. Seizures are a common sign and are often refractory to antiepileptic drugs in untreated neurometabolic patients. The onset of symptoms for neurometabolic disorders appears after an interval of normal or near normal growth and development.Additionally, affected children may fare well until a catabolic crisis occurs. Patients with neurometabolic disorders during metabolic decompensation have severe clinical presentation, which include poor feeding, vomiting, lethargy, seizures, and loss of consciousness. This symptom is often fatal but severe neurological insult and regression in neurodevelopmental milestones can result as a prominent sign in patients who survived. Acute symptoms should be immediately treated regardless of the cause. A number of patients with neurometabolic disorders respond favorably and, in some instances, dramatically respond to treatment. Early detection and early intervention is invaluable in some patients to prevent catabolism and normal or near normal neurodevelopmental milestones. This paper discusses neurometabolic disorders, approaches to this group of diseases (from the view of a pediatric neurologist), clinical and neurological manifestations, neuroimaging and electroencephalography findings, early detection, and early treatment.

ObjectiveSeveral factors are involved in the etiology of febrile seizure (FS), among themis zinc (Zn), which has been discussed in various studies. The present systematic review compares Zn levels in children with FS and a control group.Materials & MethodsWe searched keywords of febrile seizure, febrile convulsion, children, childhood,fever, trace elements, risk factor, predisposing, zinc, Zn, and epilepsy in thefollowing databases: SCOPUS, PubMed, and Google Scholar. The quality ofresearch papers was assessed using a checklist. Data was extracted from primarystudies based on demographic variables and amounts of Zn in case and controlgroups.ResultsTwenty primary studies were entered in the present study. Of which, eighteenstudies, reported that Zn serum levels were significantly lower in the case group(patients with FS) than the control group. The present systematic review indicated that Zn is one factor for predicting FS. A low level of this element among children can be regarded as a contributing factor for FS, a conclusion with a high consensus among different studies carried out in different parts of the world.

Definitive diagnosis of the central nervous system (CNS) lesions is unknown prior to histopathological examination. To determine the method and the endpoint for surgery, intraoperative evaluation of the lesion helps the surgeon. In this study, the diagnostic accuracy and pitfalls of using frozen section (FS) of CNS lesions is determined. In this retrospective study, we analyzed the results of FS and permanent diagnoses of all CNS lesions by reviewing reports from 3 general hospitals between March 2001 and March 2011. 273 cases were reviewed and patients with an age range from 3 to 77 years of age were considered. 166 (60.4%) had complete concordance between FS and permanent section diagnosis, 83 (30.2%) had partial concordance, and 24 cases (9.5%) were discordant. Considering the concordant and partially concordant cases, the accuracy rate was 99.5%, sensitivity was 91.4%, specificity was 99.7%, and positive and negative predictive values were 88.4% and 99.8%, respectively. Our results show high sensitivity and specificity of FS diagnosis in the evaluation of CNS lesions. A Kappa agreement score of 0.88 shows high concordance for FS results with permanent section. Pathologist’s misinterpretation, small biopsy samples (not representative of the entire tumor), suboptimal slides, and inadequate information about tumor location and radiologic findings appear to be the major causes for these discrepancies indicated from our study.

Altered mental status is a common cause of intensive care unit admission in children. Differentiating structural causes of altered mental status from metabolic etiologies is of utmost importance in diagnostic approach and management of the patients. Among many biomarkers proposed to help stratifying patients with altered mental status, spinal fluid lactate dehydrogenase appears to be the most promising biomarker to predict cellular necrosis. In this cross sectional study we measured spinal fluid level of lactate dehydrogenase in children 2 months to 12 years of age admitted to a single center intensive care unit over one year. Spinal fluid level of lactate dehydrogenase in 40 pediatric cases of febrile seizure was also determined as the control group. The study group included 35 boys (58.3%) and 25 girls (41.7%). Their mean age was 2.7+/-3 years and their mean spinal fluid lactate dehydrogenase level was 613.8+/-190.4 units/liter. The control group included 24 boys (55.8%) and 19 girls (44.2%). Their mean age was 1.3+/-1.2 years and their mean spinal fluid lactate dehydrogenase level was 18.9+/-7.5 units/liter. The mean spinal fluid lactate dehydrogenase level in children with abnormal head CT scan was 246.3+/-351.5 units/liter compared to 164.5+/-705.7 in those with normal CT scan of the head (p=0.001). Spinal fluid lactate dehydrogenase level is useful in differentiating structural and metabolic causes of altered mental status in children.

Multiple Sclerosis (MS) is a common disease of the central nervous system. The interaction between inflammatory and neurodegenerative processes typically results in irregular neurological disturbances followed by progressive disability. Mitochondrial dysfunction has been implicated in neurodegenerative disorders. The DNA polymerase-gamma (POLG) gene, which encodes the catalytic subunit of enzyme responsible for directing mtDNA replication, contains a poly glutamine tract (poly-Q) in the N-terminal, encoded by a CAG sequence in exon 2. We analyzed the POLG trinucleotide repeats in 40 Iranian patients with MS (27 females and 13 males with an age range of 18–55); and 47 healthy age, gender, and ethnic matched controls were chosen by PCR-SSCP analysis. Our results indicated that the most common allele in patients had 10 consecutive CAG repeats (10Q). Other alleles of 11and 12 trinucleotide repeats were detected. We did not find any difference between the CAG repeat length distribution in controls and MS patients. No correlation was observed in the POLG gene CAG repeat with pathogenesis of MS, but it looks that other point mutations in POLG gene may have an important role in the disease’s pathogenesis and produced more significant results.

Duchene and Becker Muscular Dystrophy (DMD/ BMD) are x-linked disorders that both are the result of heterogeneous mutations in the dystrophin gene. The frequency and distribution of dystrophin gene deletions in DMD/ BMD patients show different patterns among different populations. This study investigates the deletion rate, type, and distribution of this gene in the Azeri Turk population of North West Iran. In this study, 110 patients with DMD/ BMD were studied for intragenic deletions in 24 exons and promoter regions of dystrophin genes by using multiplex PCR. Deletions were detected in 63 (57.3%) patients, and around 83% localized in the mid-distal hotspot of the gene (on exons 44–52), 21 cases (33.3 %) with singleexon deletions, and 42 cases (66.6%) with multi-exonic deletions. The most frequent deleted exons were exon 50 (15 %) and exon 49 (14%). No deletion was detected in exon 3. This study suggests that the frequency and pattern of dystrophin gene deletions in DMD/ BMD in the Azeri Turk population of North West Iran occur in the same pattern when compared with other ethnic groups.

ADHD children have anomalous and negative behavior especially in emotionally related fields when compared to other. Evidence indicates that attention has an impact on emotional processing. The present study evaluates the effect of emotional processing on the sustained attention of children with ADHD type C. Sixty participants form two equal groups (each with 30 children) of normal and ADHD children) and each subject met the required selected criterion as either a normal or an ADHD child. Both groups were aged from 6–11-years-old. All pictures were chosen from the International Affective Picture System (IAPS) and presented paired emotional and neutral scenes in the following categories: pleasant-neutral; pleasant-unpleasant; unpleasant-neutral; and neutral–neutral. Sustained attention was evaluated based on the number and duration of total fixation and was compared between the groups with MANOVA analysis. The duration of sustained attention on pleasant in the pleasant-unpleasant pair was significant. Bias in duration of sustained attention on pleasant scenes in pleasant-neutral pairs is significantly different between the groups. Such significant differences might be indicative of ADHD children deficiencies in emotional processing. It seems that the highly deep effect of emotionally unpleasant scenes to gain the focus of ADHD children’s attention is responsible for impulsiveness and abnormal processing of emotional stimuli.

Neonatal seizures are the most common neurological symptoms and often signal an underlying serious neurologic condition. This study determines the frequency of neonatal seizure, predisposing factors, and brain computed tomography (CT) scan findings. In a descriptive cross-sectional study, we evaluated all neonates with seizures who had been hospitalized in Besat hospital from 2007–2012. All data were gathered with questionnaires and used to compare with statistical tests by SPSS (ver 16). 141 (4.08%) neonates (M:F; 1:2.2) were diagnosed with neonatal seizures. From the total number of 3,452 neonatal hospitalization, 78% of neonates with seizures were less than 10 days old and 60.3% of infants were born from natural vaginal delivery. As the most common cause, hypoxic-ischemic encephalopathy in this study was associated with 31.3% (n=44) of neonatal seizures and with the highest mortality rate (n=6). Among admitted neonates with seizures, the overall mortality rate was 12.8% (18 cases). A total of 33.3% of patients (47 cases) had abnormal CT scan reports and 24.8% (35 cases) of patients were not evaluated with a CT scan. Hypoxic-ischemic encephalopathy (47%) and local ischemic changes (25.5%) were the most common findings in the CT scans of neonates with seizures. There was a significant correlation between neonatal seizures and delivery circumstances (p-value < 0.05). Therefore, with improvement of obstetric and delivery circumstances, early detection of predisposing factors and other rare conditions, and rapid effective treatment of these contributing factors, the rate of neonatal seizure in this period can be reduced.

ADHD children have anomalous and negative behavior especially in emotionally related fields when compared to other. Evidence indicates that attention has an impact on emotional processing. The present study evaluates the effect of emotional processing on the sustained attention of children with ADHD type C. Sixty participants form two equal groups (each with 30 children) of normal and ADHD children) and each subject met the required selected criterion as either a normal or an ADHD child. Both groups were aged from 6–11-years-old. All pictures were chosen from the International Affective Picture System (IAPS) and presented paired emotional and neutral scenes in the following categories: pleasant-neutral; pleasant-unpleasant; unpleasant-neutral; and neutral–neutral. Sustained attention was evaluated based on the number and duration of total fixation and was compared between the groups with MANOVA analysis. The duration of sustained attention on pleasant in the pleasant-unpleasant pair was significant. Bias in duration of sustained attention on pleasant scenes in pleasant-neutral pairs is significantly different between the groups. Such significant differences might be indicative of ADHD children deficiencies in emotional processing. It seems that the highly deep effect of emotionally unpleasant scenes to gain the focus of ADHD children’s attention is responsible for impulsiveness and abnormal processing of emotional stimuli.

Headaches are common neurologic problems for children and adolescents. They are divided into two types: primary and secondary. Primary headaches include migraines and tension-type as well as comprise the majority of headaches. We detect the causes of headaches and their associations with demographic variables among children and adolescents. This cross-sectional study was performed on 5–15 year-old children with headaches from March 2010 to April 2012 who presented at a pediatric neurology clinic in Kashan, Iran. Diagnosis of headaches was done in accordance with the International Classification of Headache Disorders. Data regarding the type of headache, age, gender, pain severity, aura, family history, and sleep disorder were collected. One hundred fourteen children (44 male and 70 female) with headaches were enrolled in the study. The types of headaches were comprised as follows: 67 cases of migraines, 38 cases of tension-type headaches, 2 cases of cluster headaches, and 7 cases of secondary headaches. Pulsating headaches, family history of headaches, insomnia, and pain severity had higher prevalence in migrainous patients. Physicians should extend their information gathering about primary and secondary headaches. Sleep disturbances and a family history of headaches were the most important factors associated with migraine headaches.

Cerebral palsy (CP) is the most common cause of chronic disability that restricts participation in daily life for children. Thereby, it is comprised of quality of life. Quality of life (QOL) measures have been a vital part of health outcome appraisals for individuals with CP and to obtain empirical evidence for the effectiveness of a range of interventions. The CP QOL-Child is a conditionspecific QOL questionnaire designed for children with CP to assess well-being rather than ill-being. Forward and backward translations of the CP QOL-Child were performed for: (1) the primary caregiver form (for parents of children with CP aged 4–12 years); and (2) the child self-report form (for children with cerebral palsy aged 9–12 years). Psychometric properties assessment included reliability, internal consistency, and item discrimination, construct validity with Gross Motor Function Classification System (GMFCS) and Manual Ability Classification System (MACS) was done. SPSS was used to analyze the results of this study. sample of 200 primary caregivers forchildren with CP (mean = 7.7 years) and 40 children (mean = 10.2 years) completed. Internal consistency ranged from 0.61–0.87 for the primary caregivers form, and 0.64–0.86 for the child self-report form. Reliability ranged from 0.47–0.84. Item discrimination analysis revealed that a majority of the items (80%) have high discriminating power. Confirmatory factor analysis demonstrated a distinguishable domain structure as in the original English version. Moderate associations were found between lower QOL and more severe motor disability(GMFCS; r =. 18–.32; p <. 05 and MACS; r=. 13 -. 40; p <. 05). The highest correlation between the primary caregiver and child forms on QOL was in the domain of functioning and consistent with the English version. Content validity, item discriminant validity, internal consistency, and test-retest reliability of the Persian version of the CP QOL- Child were all acceptable. Further study of concurrent validity of this version is needed.

Wharton’s jelly (WJ) is the gelatinous connective tissue from the umbilical cord. It is composed of mesenchymal stem cells, collagen fibers, and proteoglycans. The stem cells in WJ have properties that are interesting for research. For example, they are simple to harvest by noninvasive methods, provide large numbers of cells without risk to the donor, the stem cell population may be expanded in vitro, cryogenically stored, thawed, genetically manipulated, and differentiated in vitro. In our study, we investigated the effect of human cerebrospinal fluid (CSF) on neural differentiation of human WJ stem cells. The cells in passage 2 were induced into neural differentiation with different concentrations of human cerebrospinal fluid. Differentiation along with neural lineage was documented by expression of three neural markers: Nestin, Microtubule-Associated Protein 2 (MAP2), and Glial Fibrillary Astrocytic Protein (GFAP) for 21 days. The expression of the identified genes was confirmed by Reverse Transcriptase PCR (RT-PCR). Treatment with 100 and 200μg/ml CSF resulted in the expression of GFAP and glial cells marker on days 14 and 21. The expression of neural-specific genes following CSF treatment was dose-dependent and time-dependent. Treatment of the cells with a twofold concentration of CSF, led to the expression of MAP2 on day 14 of induction. No expression of GFAP was detected before day 14 or MAP2 before day 21, which shows the importance of the treatment period. In the present study, expression analysis for the known neural markers: Nestin, GFAP, and MAP2 using RT-PCR were performed. The data demonstrated that CSF could play a role as a strong inducer. RT-PCR showed that cerebrospinal fluid promotes the expression of Nestin, MAP2, and GFAP mRNA in a dose-dependent manner, especially at a concentration of 200 μl/ml. In summary, CSF induces neurogenesis of WJ stem cells that encourages tissue engineering applications with these cells for treatments of neurodegenerative defects and traumatic brain injury.

Homocystinuria is a neurometabolic diseases characterized by symptoms include Neurodevelopmental delay, lens dislocation, long limbs and thrombosis. The patients who were diagnosed as homocystinuria marfaniod habits, seizure in the Neurology Department of Mofid Children’s Hospital in Tehran, Iran between 2004 and 2014 were included in our study. The disorder was confirmed by clinical andneuroimaging findings along withneurometabolic and genetic assessment fromreference laboratory in Germany. We assessed age, gender, past medical history, developmental status, clinical manifestations, and neuroimaging findings of 20 patients with homocystinuria. A total of 75% of patients were offspring from consanguineous marriages. A total of 95% of patients had a history of developmental delay and 40% had developmental regression. A total of 75% had seizures from these 45% showed refractory seizures. Seizures among 13 patients werecontrolled with suitable homocystinuria treatment. The patients with homocystinuriawere followed for approximately 10 years and the follow-ups showed that the patients with an early diagnosis and treatment had more favorable clinical responses for growth index, controlled refractory seizures, neurodevelopmental status, and neuroimaging findings. Neuroimaging findings include brain atrophy and/or white matter involvement. According to the results of this study, we suggest that early assessment and detectionplayan important role in the prevention of disease progression and clinical signs. Homocystinuria in patients with a positive family history, developmental delays, or regression, refractory, or recurrent seizures should take precedence over other causes.

Autism is a disorder of unknown etiology. There are few FDA approved medications for treating autism. Co-occurring autism and epilepsy is common, and glutamate antagonists improve some symptoms of autism. Ceftriaxone, a beta-lactam antibiotic, increases the expression of the glutamate transporter 1 which decreases extracellular glutamate levels. It is hypothesized that modulating astrocyte glutamate transporter expression by ceftriaxone or cefixime might improve some symptoms of autism. This case report of a child with autism and epilepsy suggests a decrease in seizures after taking cefixime

Deficiency of hypoxanthine-guanine phosphoribosyltransferase (HGPRT) is a rare inborn error of purine metabolism and is characterized by uric acid overproduction along with a variety of neurological manifestations that depend on a degree of the enzymatic deficiency. Inheritance of HPRT deficiency is X-linked recessive; thus, males are generally more affected and heterozygous females are carriers (usually asymptomatic). Human HPRT is encoded by a single structural gene on the long arm of the X chromosome at Xq26. More than 300 mutations in the HPRT1 gene have been detected. Diagnosis can be based on clinical and biochemical findings as well as enzymatic and molecular testing. Molecular diagnosis is the best way as it allows for faster and more accurate carrier and prenatal diagnosis. In this report, a new small duplication in the HPRT1 gene was found by sequencing, which has yet to be reported.

Many neurologic manifestations of Epstein-Barr virus (EBV) infection have been documented, including encephalitis, aseptic meningitis, transverse myelitis, and Guillain-Barre syndrome. These manifestations can occur alone or coincidentally with the clinical picture of infectious mononucleosis. EBV encephalitis is rare and is indicated as a wide range of clinical manifestations. We report a 10-yearold girl presented with fever, gait disturbance, and bizarre behavior for one week. The results of the physical examination were unremarkable. The diagnosis of EBV encephalitis was made by changes in titers of EBV specific antibodies and MRI findings. A cranial MRI demonstrated abnormal high signal intensities in the basal ganglia and the striatal body, especially in the putamen and caudate nucleus. EBV infection should be considered when lesions are localized to the basal ganglia.