Role of Team Work in The Management Of Mitochondrial Disease In Children (Case Report)

Pls see PDF

Neurologic Manifestation of Organic Academia

Inborn errors of organic acid metabolism are relatively recently recognized diseases with a wide spectrum of clinical signs and symptoms: ranging from asymptomatic, normal appearing children to death during first few days of life.In my presentation I will try to explain some of the most common clinical presentation of these disorder with stress on neurologic findings. Organic acidemia usually have three clinical manifestations Severe neonatal form, Intermittent late-onset form and chronic progressive form. Recurrent coma, The main feature of these disorders is due to accumulation of toxic metabolites in Central Nervous system with direct effect on the function, while chronic accumulation of these materials may interfere with CNS development or cerebral metabolism leading to developmental delay.Severe neonatal formsFollowing a symptom free interval of a few days from birth, poor sucking and difficult feeding appears in the newborn, followed by unexplained and progressive coma. Seizures may appear during the course of the disease and EEG may show a burst-suppression pattern. During this stage most infants have axial hypotonia with peripheral dystonia, choreoathetosis, episodic opisthotonus and some repetitive bicycling and boxing movements.Associated biochemical abnormalities including metabolic acidosis, ketonuria and hyperammonemia also is usually present. The overall short-term prognosis with recent advances in medical care is improving. But later in life acute intercurrent episodes triggered by a stress often occur, which can be occasionally fatal.bulging fontanelle and cerebral edema may mimic CNS infection in these babies.Intermittent late-onset formsRecurrent attacks of coma or lethargy with ataxia can occur in childhood or even in adolescence or adulthood. These episodes may be frequent, though in between these the child is entirely normal. These attacks are precipitated by conditions that enhance protein catabolism (trauma, infection etc).Sometimes these episodes can lead to death or severe sequel. Seizure disorder is one of these sequels which is generalized in type with myoclonic seizure in infancy and childhood and later tonic-clonic and atypical absence seizures predominate.Also many of the survivors have acute or progressive extra pyramidal syndrome due to bilateral necrosis of basal ganglia.Chronic progressive formsNon specific Developmental delay, hypotonia, muscular weakness, microcephaly and seizures are rarely the only revealing signs in organic acidemia without any acute presentation.Seizures may become refractory to Anti Epileptic Drugs. In addition many asymptomatic or minimally symptomatic infants have been identified during tandem mass spectrometry newborn screening program. Cognitive deterioration associated with movement disorder such as dystonia or chorea may be caused by any form of organic aciduria

Approach to NPC Disease

How to Cite This Article: Tonekaboni SH. Approach to NPC Disease. Iran J Child Neurol. 2015 Autumn;9:4(Suppl.1): 7.Pls see Pdf

Juvenile Pompe

How to Cite this Article: Tonekaboni S.H. Juvenile Pompe. Iran J Child Neurol Autumn 2012; 6:4 (suppl. 1):10. pls see PDF

Neurodegeneration with Brain Iron Accumulation: An Overview

How to Cite This Article: Tonekaboni SH, Mollamohammadi M. Neurodegeneration with Brain Iron Accumulation: An Overview. Iran J Child Neurol. 2014 Autumn;8(4): 1-8.AbstractObjectiveNeurodegeneration 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 anatomicallocations. In some types of NBIA cerebellar atrophy is the major finding in MRI.ReferencesShevel M. Racial hygiene, activeeuthanasia, and Julius Hallervorden. Neurology 1992;42:2214-2219.HayflickSJ. Neurodegeneration with brain Iron accumulation: from genes to pathogenesis.Semin Pediatr Neurol 2006;13:182-185.Zhou B, Westawy SK, Levinson B, et al. A novel pantothenate kinase gene(PANK2) is defective in Hallervorden-Spatzsyndrome. Nat Genet 2001;28:345- 349.www.ncbi.nlm.nihgov/NBK111Y/university of Washington, seattle. Allison Gregory and Susan Hayflick.Paisan-Ruiz C, Li A, Schneider SA, et al. Widesread Levy body and tau accumulation in childhood and adult onset dystonia-parkinsonism cases with PLA2G6 mutations. Neurobiol Aging 2012;33:814-823.Dick KJ, Eckhardt M, Paison-Ruiz C, et al. Mutation of FA2H underlies a complicated form of hereditary spastic paraplegia(SPG 35). Hum Mutat 31: E1251-E1260.Edvardson S, Hama H, Shaag A, et al. Mutation in the fatty acid 2-Hydroxylase gene are associated with leukodystrophy with spastic paraparesis and dystonia. Am I Hum Genet 2008;83:647-648.Schneider SA, Aggarwal A, Bhatt m, et al. Severe tongue protrusion dystonia: clinical syndromes and possible treatment. Neurology 2006;67: 940-943.Egan RA, Weleber RG, Hogarth P. et al. Neuroopthamologic and electroreinographic finding in pantothenate kinase associated neurodegeneration. Am J ophtalmol 2005;140:167-274.Kruer MC, Boddaert N. Adiadnostic Algorithm. Semin Pediatrn Neurol  2012;19: 67-74.Dezfouli MA, Alavi A, Rohani M, Rezvani M, Nekuie T, Klotzle B, Tonekaboni SH, Shahidi GA, Elahi E. PANK2 and C19orf12 mutations are common causes of neurodegeneration with brain iron accumulation. Mov Disord 2013 Feb;28(2):228-32. doi: 10.1002/mds.25271.Epub 2012 Nov 19.Hartig MB, Hortnagel K, Garavaglia B, et al. Genotype and phenotypic spectrum of PANK2 mutations in patients with neurodegeneration with brain iron accumulation Ann Neurol 2006;59: 248-256.Kotzbauer PT, Truax AC, Trojanowsli JQ, et al. Altered neuronal mitochondrial coenzyme A synthesis in neurodegeneration with brain iron accumulation cause by abnormal processing of mutant pantothenase Kinase2. J Neurosci 2005;25:689-698.Poli M, Deosas M, Lusciete S, et al. Pantothenate Kinase2 silencing causes cell growth reduction and iron  deregulation Neurobiol Dis 2010;39: 204-210.Wakabayashi K, Fukushima T, Koide R, et al. Juvenile-nset generalized neuroaxonal dystrophy with  diffuse neurofibrillary and Lewy body pathology. ActaNeuropathonal 2000;99: 331-336.Galvin JE, Giasson B, Hurting HI, et al. Neurodegeneration with brain iron accumulation, type1 is characterized by alpha, beta and gamma-synuclein neuropathology, Am T Pathol 2000;157: 361-368.Li A, Paudel R, Johnson R, et al. Pantothenate Kinaseassocated neurodegeneration is not a  synucleinopathyneuropathol Appl Neurobiol(in press).Gregory A, Polster BJ, Hayflick SJ: Clinical and genetic delineation of neurodegeneration with brain iron accumulation. J Med Genet 2009;46:73-80.Gregory A, Westaway SK, Holm IE, et al. Neurodegeneration associated with genetic defects in phospholipase A2. Neurology 2008;71:1402-1409.Harting MB, Lsao A, Haa KT, et al. Absence of an orphan mitochondrial protein, c19orf12 with brain iron accumulation, Am J Hum Genet 2011;89: 543-550.Najim al-Din AS, Wriekat A, Mubaidin A, et al. Pallidopyramidal degeneration, supraneuclearupgaze paresis and dementia: Kufor- Rakeb syndrome. Acta Neurol Scand 2011;89: 347-352.Tobias B Hoak, Penelope Hogarth, Micheal C Kruer et al. Am J Hum Genet 2012 Dec 7; 91 (6): 1144-49.Chummery PF, Crompton DE, Bircholl D, et al. Clinical features and matural history of Neuroferritinopathy caused by the FTL1 gene mutation. Brain 2007;130:110-119.Mc Neil A, Bircholl D, Hayflich SJ, et al. T2 and FSE MRI distinguishes L subtypes of NBIA, Neurology 2008;70: 1614- 1619. McNeil A , Pandolfo M, Kuhn J,et al.The Neurological presentation of ceruloplasmin gene  mutations. Eur Neurol 2008;60:200-205.Dusi S, Valletta L, Hoach TB, et al. Exone sequencing reveals mutations in Co A synthtas as a cause of neurodegeneration with brain iron accumulation: Am J Hum Genetic Jan2, 2014. Aras M Alazim, Amir Alsaif, Abdulaziz Al-Semari, et al. mutation in C2 orf 37, cause hypogonadism, diabetes Melitus, Mental retardation and extrapyramidal syndrome: Am J Hum Genetic. 2008 Dec 12; 83(6): 684-691

CNS Involvement by Novel Influenza Virus Type A (H1n1), the First Report from Iran

ObjectiveThis is the first report of CNS involvement by the new influenza virus (influenza A [H1N1]) in Iran. The patient was a 10-year-old boy with chief complaints of fever, malaise, and cranial nerve involvement, resulting in respiratory muscle paralysis and intubation. This shows that the new influenza virus, as well as the seasonal flu, can cause neurologic complications; however, the severity of the signs and symptoms is less and the disease may resolve without complications in the case of seasonal flu. Therefore, in each patient with neurologic involvement and typical influenza signs & symptoms or a flu-like syndrome, diagnostic tests for H1N1 flu virus should be considered, especially during epidemics, and treatment with oseltamivir should be started.

Proton MR Spectroscopy in The Diagnostic Evaluation of Suspected Mitochondrial Disease in Iran

Pls see PDF

Pregabalin in childhood epilepsy: a clinical trial study

How to Cite This Article: Mollamohammadi M, Tonekaboni SH, Pirzadeh Z, Vahedian M . Pregabalin in Childhood Epilepsy: A Clinical TrialIran J Child Neurol. 2014 Autumn;8(4): 62-65.AbstractObjectiveThe 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.Material & MethodsForty 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.ResultsAfter 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).ConclusionWe recommend Pregabalin as an add-on therapy for refractory seizures (except for myoclonic seizures) for children.ReferencesKwan P., Brodie MJ. Early identification of refractory epilepsy. N Engl J Med 2000;342(5):314-9.Mikati MA. Seizures in childhood. In: Kliegmann RM, Behrman RE, Jenson HB, Stanton BF, editors. Nelson Textbook of Pediatrics. 19th ed. Philadelphia, Pa:Saunders Elsevier. 2011.P.2013-2039.Camfield PR, Camfield CS. Pediatric Epilepsy. In: Swaiman KF, editors. Swaiman`s pediatric neurology: Principles and Practice.7th ed. Edinburgh: Elsevier Saunders; 2012.P 703-710.Piña-Garza EJ. Fenichel’s clinical pediatric neurology. Altered States of Consciousness. 7th ed. Elsevier Saunder. 2013.P.47-75.Austin JK, Smith S, Risinger MW, McNehs AM. Childhood epilepsy and asthma comparison of quality of life. Epilepsia 1994:35(3):608-15.Farvwell JR, Dodrill CB, Batzel LW. Neuropsychological abilities of children with epilepsy. Epilepsia 1985;26(5):395-400.Kotagal P, Rothner AD, Erenberg G, Cruse RP, Wyllie E. Complex partial seizures of childhood onset. Arch Neurol 1987:44(11):1177-80.Miller R, Frame B, Corrigan B, Burger P, Backbrader H, Garofalo EA, et al. Exposure- response analysis of pregabalin add- on treatment of patients with refractory partial seizures. Clin Pharmacol Ther 2003;73(6):491-505.Fink K, Dooley DJ, Meder WP, Suman-Chauhan N, Duffy S, Clusmann H, et al. Inhibition of neuronal ca(2+) influx by gabapentin and pregabalin in the human neocortex. Neuropharmacology 2002;42(2):229-36.Topol A. Pregabalin for epilepsy. New medicines profile 2004 November; (04/12):1-3.Arroyo S, Anhut H, Kugler AR, Lee CM, Knapp LE, Garofalo EA, et al. Pregabalin add-on treatment: a randomized, double-blind, placebo-controlled, doseresponse study in adults with partial seizures. Epilepsia 2004; 45(1):2-7.Beydoun A, Uthman BM, Kugler AR, Greiner MJ, Knapp LE, Garoflo EA. Safely and efficacy of two pregabalin regimens for add-on treatment of partial epilepsy. Neurology 2005;64(3):475-80.French JA, Kugler AR, Robbins JL, Knapp LE, Garoflo EA. Dose-response trial of pregabalin adjunctive therapy in patients with partial seizures. Neurology 2003;60(10):1631-7.Carreno M, Maestro I, Molins A, Donaire A, Falip M, Becerra JL, et al. Pregabalin as add-on therapy for refractory seizures in every day clinical practice. Seizure 2007;16(8):709-12.Jan MM, Zuberi SA, Alsaihati BA. Pregabalin: Preliminary experience in intractable childhood epilepsy. Pediatr Neurol 2008;40(5):347-50.Chisanga E, Manford M. Pregabalin drug information. NHS foundation trust. March 2013.Gil-Nagel A. Zaccara G. Baldinetti F. Leon T. Add-on treatment with pregabalin for partial seizures with or without generalization: pooled data analysis of four randomized placebo-controlled trials. Seizure 2009;18(3):184-92

Risk Factors and Prognosis of Epilepsy in Children with Hemiparetic Cerebral Palsy

ObjectiveEpilepsy is reported in 15-90% of the children with Cerebral Palsy (CP) but its clinical course is not well defined.We conducted a retrospective study on children with hemiparetic CP who were referred to Pediatric Neurology Department of Mofid Hospital. The aim of our study was to evaluate the risk factors and prognosis of epilepsy in children with hemiparetic CP.Materials & MethodsWe evaluated 64 children with hemiparetic CP who were referred to Pediatric Neurology Department of Mofid Hospital between 2006 and 2008.According to our protocol, patients were divided into two groups: 34 children in the case group (hemiparetic patients with epilepsy) and 30 children in the control group (hemiparetic patients without epilepsy).ResultsPrenatal, perinatal and postnatal events, maternal age at the time of delivery, socioeconomic status of the family, familial history of epilepsy, neuroimaging findings, side of the hemiparesia and age at diagnosis of hemiparesis were not considered as risk factors for epilepsy in hemiparetic children, but microcephaly, severity of hemiparetic CP and mental retardation were significantly associated with an increased risk of epilepsy in children with hemiparetic CP.ConclusionOur study showed that microcephaly, severity of hemiparesis and mental retardation were risk factors for developing epilepsy in children with hemiparetic CP; furthermore, they had negative effects on rehabilitation outcome in these patients.

A Novel Mutation of GDAP1 Associated with Charcot-Marie-Tooth Disease in An Iranian Family

As a result of higher distributed consanguinity in the Mediterranean region and the Middle East, autosomal-recessive forms of Charcot-Marie-Tooth (ARCMT) are more common in these areas. CMT disease caused by mutations in the ganglioside-induced differentiation-associated protein 1 (GDAP1) gene is a severe autosomal recessive neuropathy resulting in either demyelinating CMT4A neuropathy or axonal neuropathy with vocal cord paresis. The patient was an 8-year-old boy with AR inheritance that showed some delayed achievement of motor milestones, including walking, also bilateral foot drop, wasting of distal muscles in the legs, pes cavus and marked weakness of the foot dorsiflexors. He had no hoarseness or vocal cord paralysis. Total genomic DNA was extracted from whole peripheral blood of the patient and his family by using standard procedures. PCR- sequencing method were used to analysis the whole coding regions of the GDAP1 gene. A novel homozygote insertion of T nucleotide in codon 34 was detected (c.100_101insT) that probably led to an early stop codon. This mutation may be associated with a common haplotype, suggesting a common ancestor that needs further investigation in the Iranian population