The Effect of the Ketogenic Diet on the Growth and Biochemical Parameters of the Children with Resistant Epilepsy

ObjectiveThe aim of this study was to evaluate the effect of the ketogenic diet on the growth parameters of the children with resistant epilepsy.Materials & MethodsA total of 36 children with resistant epilepsy who were 2 to 7 year old were put on the ketogenic diet. Their growth and biochemical parameters were studied at the beginning of the study and after 3 months.ResultsWeight decreased in all patients. Serum levels of hemoglobin, calcium, and blood sugar decreased significantly but remained in the normal range. Creatinine did not change, but BUN showed a significant increase.ConclusionWe can lower the complications of ketogenic diets by using more unsaturated fat, more water, and more minerals.

Nonlinear dynamic analysis of a four-bar mechanism having revolute joint with clearance

In general, joints are assumed without clearance in the dynamic analysis of multi-body echanical systems. When joint clearance is considered, the mechanism obtains two uncontrollable degrees of freedom and hence the dynamic response considerably changes. The joints’ clearances are the main sources of vibrations and noise due to the impact of the coupling parts in the joints. Therefore, the system responses lead to chaotic and unpredictable behaviors instead of being periodic and regular. In this paper, nonlinear dynamic behavior of a four-bar linkage with clearance at the joint between the coupler and the rocker is studied. The system response is performed by using a nonlinear continuous contact force model proposed by Lankarani and Nikravesh [1] and the friction effect is considered by a modified Coulomb friction law [2]. By using the Poincaré portrait, it is proven that either strange attractors or chaos exist in the system response. Numerical simulations display both periodic and chaotic motions in the system behavior. Therefore, bifurcation analysis is carried out with a change in the size of the clearance corresponding to different values of crank rotational velocities. Fast Fourier Transformation is applied to analyze the frequency spectrum of the system response

Demographic and Clinical Findings in Pediatric Patients Affected by Organic Acidemia

How to Cite This Article: Najafi R, Hashemipour M, Mostofizadeh N, Ghazavi MR, Nasiri J, Shahsanai A, Famori F, Najafi F, Moafi M. Demographic and Clinical Findings in Pediatric Patients Affected by Organic Acidemia. Iran J Child Neurol. Spring 2016; 10(2): 74-81.AbstractObjectiveMetabolic disorders, which involve many different organs, can be ascribed to enzyme deficiency or dysfunction and manifest with a wide range of clinical symptoms. This study evaluated some of the demographic and clinical findings in pediatric patients affected by organic acidemia.Materials & MethodsThis cross-sectional study was part of a larger study conducted in patients with metabolic disorders during a period of 7 years from 2007 to 2014 in Isfahan Province, Iran. Our study covered a wide range of cases from newborn infants (one-week old) to adolescents (children up to the age of 17 years). This study evaluated patients’ demographic information, history of disease, developmental and educational status, clinical and general conditions. Phone and in-person interviews were used to gather information.ResultsOut of 5100 patients screened in this study, 392 patients were affected by one of the different metabolic disorders and 167 individuals were diagnosed as organic acidemia. Propionic acidemia/methyl malonic acidemia (PA/MMA) was the most prevalent form of this metabolic disorder. The frequency of consanguinity was 84.7% in the group of patients. The mortality rate was 18.8% in patients with organic academia.ConclusionEach of the metabolic diseases, as a separate entity, is rare; nevertheless, in aggregate they have a somewhat high overall prevalence. These diseases result in mental and developmental disorders in the absence of quick diagnosis and initiation of treatment. Furthermore, more mutations should be identified in societies affected by consanguinity. Further research should also be conducted to determine worthwhile and more-efficient screening methods as well as longterm neurological prognosis. References:Champion MP.An approach to the diagnosis of inherited metabolic disease. Arch Dis Child EducPract Ed 2010; 95:40.D.L. Marsden,Inborn Errors of Metabolism: Classification and Biochemical AspectsEncyclopedia of Human Nutrition (Third Edition), 2013, Pages 1-10Huang X, Yang L Dr, Tong F Dr, Yang R Dr, Zhao Z Prof. Screening for inborn errors of metabolism in high-risk children: a 3-year pilot study in Zhejiang Province, China. BMC Pediatr. Feb 24 2012;12(1):18Waisbren SE. Expanded newborn screening: information and resources for the family physician. Am Fam Physician. Apr 1 2008;77(7):987-94.Kliegman RM, Behrman RE, Genson HB, Stanton BF .,An Approach to Inborn Errors of Metabolism, : Nelson textbook of pediatric19th ed, Philadelphia:Saunders;2011, Chapter 78 ;309-16.Ayelet Erez, Oleg A. Shchelochkov, Sharon E. Plon, Fernando Scaglia, and Brendan Lee The American Journal of Human Genetics April 8, 2011,88; 402–421Disorders of energy metabolism1-Nyhan WL, Ozand PT. Atlas of Metabolic Diseases, 1st ed, Chapman and Hall Medical, London 1998.Fowler B. Genetic defects of folate and cobalamin metabolism. Eur J Pediatr 1998; 157 Suppl 2:S60.Hoffmann GF, Zschocke J. Glutaric aciduria type I: from clinical, biochemical and molecular diversity to successful therapy. J Inherit Metab Dis 1999; 22:381.Hoffmann GF, Gibson KM, Trefz FK, et al. Neurological manifestations of organic acid disorders. Eur J Pediatr 1994; 153:S94.Wappner RS. Biochemical diagnosis of genetic diseases. Pediatr Ann 1993; 22:282.Weiner DL. Metabolic emergencies. In: Textbook of pediatric emergency medicine, 5th ed, Fleisher GR, Ludwig S, Henretig FM (Eds), Lippincott, Williams and Wilkins, Philadelphia 2006. p.1193.Lindor NM, Karnes PS. Initial assessment of infants and children with suspected inborn errors of metabolism. Mayo Clin Proc 1995; 70:987.Kamboj M. Clinical approach to the diagnoses of inborn errors of metabolism. Pediatr Clin North Am 2008; 55:1113.J. Golbahar, E.A. Al-Jishi, D.D. Altayab, E. Carreon, M. Bakhiet, H. Alkhayyat .Selective newborn screening of inborn error of amino acids, organic acids and fatty acids metabolism in the Kingdom of Bahrain ;Molecular Genetics and Metabolism, Volume 110, Issues 1–2, September–October 2013, Pages 98-101.Carlo Dionisi-Vici , Cristiano Rizzo, Alberto B. Burlina, , Ubaldo Caruso, Gaetano Sabetta , Graziella Uziel, Damiano Abeni, ,Inborn errors of metabolism in the Italian pediatric population: A national retrospective survey , the Italian Metabolic Network Contributing Investigators:J Pediatr 2002;140:321-7.Moacir Wajner a,b , Daniella de Moura Coelho a, Rafaela Ingrassia a, Anderson Büker de Oliveira a, Estela Natacha Brandt Busanello a, Kimiyo Raymond c, etal :Selective screening for organic acidemias by urine organic acid GC–MS analysis in Brazil: Fifteen-year experience:Clinica Chimica Acta 400 (2009) 77–81.It-Koon Tan, FRCPath, Bani Gajra, Maria SF Lim, Study of Inherited Metabolic Disorders in Singapore – 13 Years Experience :Ann Acad Med Singapore 2006;35:804-13.Moammar H, Cheriyan G, Mathew R, Al-Sannaa N. Incidence and patterns of inborn errors of metabolism in the Eastern Province of Saudi Arabia, 1983-2008. Ann Saudi Med. 2010; 30:271-7.Nagaraja D, Mamatha SN, De T, Christopher R. Screening for inborn errors of metabolism using automated electrospray tandem mass spectrometry: study in high-risk Indian population. Clinical biochemistry. 2010; 43(6):581-8.Hendriekje Eggink, Anouk Kuiper, Kathryn J Peall, Maria Fiorella Contarino, Annet M Bosch, Bart Post, Deborah A Siva, Marina AJ Tijssen and Tom J de Koning :Rare inborn errors of metabolism with movement disorders: a case study to evaluate the impact upon quality of life and adaptive functioning Eggink et al. Orphanet Journal of Rare Diseases 2014, 9:177.Han LS, Qiu J, Ye WJ, Gao XL, Wang Y, Gu XF: Selective screening for inborn errors of metabolism on clinical patients using tandem mass spectrometry in China: a four-year report. J Inherit Metab Dis 2007, 30:507-514.Xinwen Huang, Lili Yang, Fan Tong, Rulai Yang and Zhengyan Zhao: Screening for inborn errors of metabolism in high-risk children: a 3-year pilot study in Zhejiang Province, China:Huang et al. BMC Pediatrics 2012, 12:18.Tarun Choudhuri and Sivajee Sengupta .Inborn Error of Metabolism –An Indian Perspective،Int J Hum Genet, 6(1): 89-91 (2006).Elsobky E, Elsayed SM. Extended metabolic screen in sick neonates and children. Egypt J Med Hum Genet. 2004; 5: 1-7.Satwani H, Raza J, Hanai J, Nomachi S. Prevalence of selected disorders of inborn errors of metabolism in suspected cases at a Tertiary Care Hospital in Karachi. JPMA. 2009; 59:815-9.Narges Pishva, Alie Mirzaee, Zohre Karamizade, Shahnaz Pourarian, Fariba Hemmati, Mostajab Razvi, Forough Saki.Selective Screening of High-risk Iranian Patients for the Detection of Inborn Error of Metabolism 14 Iranian Journal of Neonatology 2014; 5(4).A. García-Cazorla, N.I. Wolf, M. Serrano, U. Moog, B. Pérez-Dueñas, P. Póo, M. Pineda, J. Campistol, G.F. Hoffmann, Mental retardation and inborn errors of metabolism, J. Inherit. Metab. Dis. 32 (2009) 597–608.Sitke A, Ulrich D, Peter H, Johannes K, Manfred S, Hartmut S. NMR-Based Screening for Inborn Errors of Metabolism: Initial Results from a Study on Turkish Neonate. JIMD Reports DOI 10.1007/8904_2014_326.Waleed H A, Magdy HB, Mohammed SM, Ibrahim H. Risk factors and birth prevalence of birth defects and inborn errors of metabolism in Al Ahsa, Saudi Arabia. Pan Afr Med J 2011; 8:14.Karimzadeh P, Jafari N, Jabbehdari S, Taghdiri MM, Nemati H, Saket S, Alaee MR, Ghofrani M, Tonakebni SH. Methylmalonic Acidemia: Diagnosis and Neuroimaging Findings of This Neurometabolic Disorder (An Iranian Pediatric Case Series). Iran J Child Neurol 2013 7(3): 63- 66. Ibarra GI, Fernández LC, Reyes GD, Belmont M L, Guillén LS, Monroy SS et al. Inborn Errors of Intermediary Metabolism in Critically Ill Mexican Newborns. J Inborn Errors Metabol Screening 2014:1–7.Hanna AO. Patterns of inborn errors of metabolism: A 12-year single-center hospital-based study in Libya. Qatar Med J 2013 (2):57-65.Tu W, He J, Dai F, Wang X, Li Y. Impact of inborn errors of metabolism on admission in a neonatal intensive care unit--a prospective cohort study. Indian J Pediatr 2012 Apr;79(4):494-500

VEGF gene polymorphism interactions with dietary trace elements intake in determining the risk of metabolic syndrome

There is a complex interaction between genetic, metabolic, and environmental factors in determining the risk of Metabolic Syndrome (MetS). The aim of this study was to investigate the interaction between the dietary intake of iron, copper, zinc, manganese, selenium and iodine (assessed by 24 recall) with vascular endothelial growth factor variants (rs6921438, rs4416670, rs6993770, and rs10738760), on the risk of metabolic syndrome. Two hundred and forty eight individuals with MetS and 100 individuals without MetS recruited. Dietary intake and the daily average of energy and nutrients intake were obtained by questionnaire and quantified using Diet Plan 6 software. DNA was extracted from EDTA anticoagulated whole blood. The SNPs were assessed using using a Sequenom iPLEX Gold assay. Data analysis was undertaken using the Student’s t-test, χ2 test and logistic regression using SPSS 11.5 software. There was a significant interaction between low dietary iron intake with rs6993770 (β= 0.10, p<0.05), and a low dietary zinc and a high manganese intake with rs6921438 in relation to the presence of metabolic syndrome (β= -0.17, p<0.05, β= -0.30, p<0.05, respectively). Our data showed the association of rs6993770 with iron intake and rs6921438 with zinc and manganese intake, indicating further investigating in a larger population to evaluate their values

The clinical and genetic spectrum of autosomal-recessive TOR1A-related disorders.

In the field of rare diseases, progress in molecular diagnostics led to the recognition that variants linked to autosomal-dominant neurodegenerative diseases of later onset can, in the context of biallelic inheritance, cause devastating neurodevelopmental disorders and infantile or childhood-onset neurodegeneration. TOR1A-associated arthrogryposis multiplex congenita 5 (AMC5) is a rare neurodevelopmental disorder arising from biallelic variants in TOR1A, a gene that in the heterozygous state is associated to torsion dystonia-1 (DYT1 or DYT-TOR1A), an early-onset dystonia with reduced penetrance. While 15 individuals with TOR1A-AMC5 have been reported (less than 10 in detail), a systematic investigation of the full disease-associated spectrum has not been conducted. Here, we assess the clinical, radiological and molecular characteristics of 57 individuals from 40 families with biallelic variants in TOR1A. Median age at last follow-up was 3 years (0-24 years). Most individuals presented with severe congenital flexion contractures (95%) and variable developmental delay (79%). Motor symptoms were reported in 79% and included lower limb spasticity and pyramidal signs, as well as gait disturbances. Facial dysmorphism was an integral part of the phenotype, with key features being a broad/full nasal tip, narrowing of the forehead and full cheeks. Analysis of disease-associated manifestations delineated a phenotypic spectrum ranging from normal cognition and mild gait disturbance to congenital arthrogryposis, global developmental delay, intellectual disability, absent speech and inability to walk. In a subset, the presentation was consistent with fetal akinesia deformation sequence with severe intrauterine abnormalities. Survival was 71% with higher mortality in males. Death occurred at a median age of 1.2 months (1 week - 9 years) due to respiratory failure, cardiac arrest, or sepsis. Analysis of brain MRI studies identified non-specific neuroimaging features, including a hypoplastic corpus callosum (72%), foci of signal abnormality in the subcortical and periventricular white matter (55%), diffuse white matter volume loss (45%), mega cisterna magna (36%) and arachnoid cysts (27%). The molecular spectrum included 22 distinct variants, defining a mutational hotspot in the C-terminal domain of the Torsin-1A protein. Genotype-phenotype analysis revealed an association of missense variants in the 3-helix bundle domain to an attenuated phenotype, while missense variants near the Walker A/B motif as well as biallelic truncating variants were linked to early death. In summary, this systematic cross-sectional analysis of a large cohort of individuals with biallelic TOR1A variants across a wide age-range delineates the clinical and genetic spectrum of TOR1A-related autosomal-recessive disease and highlights potential predictors for disease severity and survival

Visual Perception in Children with a History of Hypoglycemia due to Hyperinsulinism

ObjectivesHyperinsulinism refers to improper insulin secretion in the presence of low plasma glucose, causing severe and persistent hypoglycemia in infants and children. The brain’s occipital lobe, which includes the visual and plays an essential role in visual perception is specifically sensitive to hypoglycemia-induced damage. The present study aims to investigate the visual perception in children suffering from hyperinsulinism and to compare it with the control group.Materials &amp; MethodsThis cross-sectional control study, conducted in 2020 in Isfahan, Iran, involved 20 children aged 4-13 years with hyperinsulinism and 20 healthy children of the same age and gender for comparison. In both groups, the measuring instrument was the Test of Visual Perceptual Skills (non-motor) Third Edition ResultsThe mean visual perceptual quotient in the case and control groups was 80.50±26.74 and 116.50±7.56 (p-value&lt;0.001), respectively. The results overall indicated that children suffering from hyperinsulinism were weaker than healthy children in all areas of visual perception.ConclusionBased on the obtained results, it is recommended that children  suffering from hyperinsulinism be screened regarding visual perceptual disorders since this screening may be helpful in initiatingdifferent rehabilitation programs among these patients.

Finite Element Analysis of Static and Dynamic Pull-In Instability of a Fixed-Fixed Micro Beam Considering Damping Effects

In this paper the static and dynamic pull-in phenomenon of a fixed-fixed micro beam, considering the effects of residual stress, axial stress, damping coefficient, and Fringing field effects have statically and dynamically been analyzed. The nonlinear electromechanical coupled integro- differential equation governing the problem has been derived using variational principle and solved using a computer code based on Finite element method. The problem has been solved for various values of damping coefficients, residual and axial stresses, and various initial gaps between the micro beam and the substrate. The results showed that by increase in damping coefficient the dynamic pull-in voltage is also increased but this increase is continued up to a definite value of damping coefficient more than which, the dynamic pull-in voltage is constant and equal to the static one. The pull-in time is also determined for various damping coefficients and has been shown that with increasing the damping coefficient the pull-in time is increased

Efficacy of lacosamide add-on therapy on Refractory Focal Epilepsies in children and adolescents: An open-label clinical trial

Objective: Epilepsy is a chronic neurological disorder that affects 0.5%–1% of children. 30%–40% of patients are resistant to current anti-epileptic drugs. Lacosamide (LCM) appeared to be effective, safe, and well tolerated in children and adolescents. This study was aimed to evaluate whether LCM could be an effective add-on therapy in children with refractory focal epilepsies. Methods: This study was conducted from April 2020 to April 2021 in Imam Hossein Children Hospital, Isfahan, Iran. We included 44 children aged 6 months to 16 years with refractory focal epilepsy (based on International League Against Epilepsy criteria). LCM was given in divided doses of 2 mg/kg/day, increasing by 2 mg/kg every week. The first follow-up visit was 6 weeks later, when all patients had reached the therapeutic dose. Findings: The average age of the patients was 89.9 months. 72.5% of children had focal motor seizures. Evaluation of percent change in seizure frequency and duration before and after treatment showed a 53.22% reduction in seizure frequency and 43.72% reduction in seizure duration after treatment. Our study group tolerated LCM well, with few side effects. Headache, dizziness, and nausea were common side effects. In line with other studies, none of the suspected risk factors could predict response to LCM treatment. Conclusion: LCM appears to be an effective, safe, and well-tolerated medication in children with uncontrolled drug-resistant focal epilepsy

Magnetic Resonance Imaging Findings in Epileptic Children and Its Relation to Clinical and Demographic Findings

Epilepsy is an important disease with a cumulative incidence of 3% all over the life and more than half of them are started from childhood. In this study we surveyed magnetic resonance imaging (MRI) findings in epileptic children and its relation with clinical and demographic findings in order to find better diagnostic and treatment modalities for these children in the future. In this cross sectional study, we investigated consecutively all 1 to 15-year-old epileptic children who referred to the pediatric neurology outpatient clinic from 2004 to 2010. Two hundred children were enrolled for investigation. There were 85 (42.5%) girls and 115 (57.7%) boys, aged 1 to 15-year-old (7.7±4). 196 (98%) of the children had abnormal electroencephalography (EEG). Abnormal MRI was seen in 57 (28.5%) patients and consisted of brain atrophy (10%), increasing white matter signal intensity in T2-weighted images (8%), benign cysts (5%), brain tumors (4%) and vascular abnormalities (1.5%). Abnormal MRI findings had significant relation with abnormal EEG, age, positive family history for epilepsy, dysmorphic appearance, and abnormal physical exam. Considering 98% EEG abnormalities in these epileptic children, benign nature of MRI findings in most of our cases, the high price of MRI and the small minority of patients who benefit from active intervention as a result of MRI, we suggest to use EEG for confirmation of epilepsy and perform MRI for patient with abnormal physical exams, focal neurologic deficits or focal EEG abnormalities