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

Plasma Pyridoxal 5´-Phosphate Level in Children with Intractable and Controlled Epilepsy

How to Cite This Article: Pirzadeh Z, Ghofrani M, Mollamohammadi M. Plasma Pyridoxal 5´-Phosphate Level in Children with Intractable and Controlled Epilepsy. Iran J Child Neurol. Spring 2017; 11(2):31-36. AbstractObjectiveIntractable epilepsy is a serious neurologic problem with different etiologies. Decreased levels of pyridoxal phosphate in cerebral spinal fluid of patients with intractable epilepsy due to pyridoxine dependency epilepsy are reported. The aim of this study was to compare plasma pyridoxal 5´-phosphate level in patients with intractable and controlled epilepsy.Materials & Methods This cross- sectional analytic study included 66 epileptic children, 33 patients with controlled and 33 patients with intractable epilepsy, after neonatal period up to 15 yr old of age. Thirty-three patients with intractable epilepsy (10- 162 months) and 33 patients with controlled epilepsy (14-173 months) were enrolled. The study was conducted in Pediatric Neurology Clinic of Mofid Children Hospital, Tehran, Iran from January 2010 to December 2010. Patients’ clinical manifestations, laboratory and neuroimaging findings were collected. Non-fasting plasma 5´- pyridoxal phosphate levels of these subjects were assessed by high-pressure liquid chromatography.Results Mean plasma 5´- pyridoxal phosphate level (PLP) in patients with controlled epilepsy was 76.78±37.24 (nmol/l) (15.5-232.4). In patients with intractable epilepsy, mean plasma 5´- pyridoxal phosphate was 98.67± 80.58 (25.5- 393) nmol/l. There was no statistically significant difference between plasma pyridoxal phosphate levels of these two groups (P═0.430).Conclusion Pyridoxine dependent epilepsy is under diagnosed because it is manifested by various types of seizures. Plasma pyridoxal phosphate levels did not differ in our patients with intractable or controlled epilepsy. If PDE is suspected on clinical basis, molecular investigation of ALDH7A1 mutations, as feasible test, until PDE biomarkers becomes available is recommended. References1.Cown LD. The epidemiology of the epilepsies in children. Ment Retard Dev Disabil Res Rev 2002;8(3):171-81.2.French JA. Refractory epilepsy: clinical overview. Epilepsia 2007;48 Suppl 1:3-7.3.Oliveira R, Pereira C, Rodrigues F, Alfaite C, Garcia P, Robalo C, et al. Pyridoxine-dependent epilepsy due to antiquitin deficiency: achieving a favourable outcome. Epileptic Disord 2013;15(4):400-6.4.Baxter P. Pyridoxine-dependent and pyridoxine-responsive seizures. Dev Med Child Neurol 2001; 43(6):416-20.5.Akhoondian J, Talebi S. High dose oral pyridoxine for treatment of pediatric recurrent intractable seizure. MJIRI 2004; 17(4):301-4.6.Ramachandrannair R, Parameswaran M. Prevalence of pyridoxine dependent seizures in south Indian children with early onset intractable epilepsy: A hospital based prospective study. Eur J Paediatr Neurol 2005;9(6):409- 13.7. Baxter P. Epidemiology of pyridoxine dependent and pyridoxine responsive seizures in UK. Arch Dis Child 1999;81(5):431-3.8. Yaghini O, Shahkarami MA, Shamsaii S. Neglected atypical pyridoxine dependent seizures. Iran J Pediatr 2010;20(4):498-501.9. Lumeng L, Lui A, Li TK. Plasma content of B6 vitamers and its relationship to hepatic rat B6 metabolism. J Clin Inves 1980;66(4):686-95.10. Clayton PT. B6-responsive disorders: a model of vitamin dependency. J Inherit Metab Dis 2006;29(2-3):317-26.11. Goyal M, Fequiere PR, McGrath TM, Hyland K. Seizures with decreased levels of pyridoxal phosphate in cerebrospinal fluid. Pediatr Neurol 2013;48(3):227-31.12. Footitt EJ, Heales SJ, Mills PB, Allen GF, Oppenheim M, Clayton PT. Pyridoxal 5’-phosphate in cerebrospinal fluid; factors affecting concentration. J Inherit Metab Dis 2011; 34(2):529-38.13. Morris MS, Picciano MF, Jacques PF, Selhub J. Plasma pyridoxal 5’-phosphate in the US population: the National Health and Nutrition Examination Survey, 2003-2004.Am J Clin Nutr 2008;87(5):1446-54.14. Setiawan B, Giraud DW, Driskell JA. Vitamin B-6 inadequacy is prevalent in rural and urban Indonesian children. J Nutr 2000;130(3):553-8.15. Shin YS, Rasshofer R, Endres W. Pyridoxal-5’-phosphate concentration as marker for vitamin-B6-dependent seizures in the newborn. Lancet 1984;2(8407):870-1.16. Pérez B, Gutiérrez-Solana LG, Verdú A, Merinero B, Yuste-Checa P, Ruiz-Sala P, et al. Clinical, biochemical, and molecular studies in pyridoxine-dependent epilepsy. Antisense therapy as possible new therapeutic option. Epilepsia 2013;54(2):239-48.17. Gospe SM. Pyridoxine-dependent seizures: findings from recent studies pose new questions. Pediatr Neurol 2002;26(3):181-5.18. Plecko B, Hikel C, Korenke GC, Schmitt B, Baumgartner M, Baumeister F, et al. Pipecolic acid as a diagnostic marker of pyridoxine-dependent epilepsy. Neuropediatrics 2005;36(3):200-5.19. Albersen M, Groenendaal F, van der Ham M, de Koning TJ, Bosma M, Visser WF, et al. Vitamin B6 vitamer concentrations in cerebrospinal fluid differ between preterm and term newborn infants. Pediatrics 2012;130(1):e191-8.20. Ormazabal A, Oppenheim M, Serrano M, García-Cazorla A, Campistol J, Ribes A, et al. Pyridoxal 5’-phosphate values in cerebrospinal fluid: reference values and diagnosis of PNPO deficiency in paediatric patients. Mol Genet Metab 2008;94(2):173-7.21. Stockler S, Plecko B, Gospe SM Jr, Coulter-Mackie M, Connolly M, van Karnebeek C, Mercimek-Mahmutoglu S, Hartmann H, Scharer G, Struijs E, Tein I, Jakobs C, Clayton P, Van Hove JL. Pyridoxine dependent epilepsy and antiquitin deficiency: clinical and molecular characteristics and recommendations for diagnosis, treatment and follow-up.Mol Genet Metab. 2011 Sep- Oct;104(1-2):48-60. doi: 10.1016/j.ymgme.2011.05.014. Epub 2011 May 24.22. Steinberg SJ, Dodt G, Raymond GV, Braverman NE, Moser AB, Moser HW. Peroxisome biogenesis disorders. Biochim Biophys Acta 2006;1763(12):1733-48.23. Mills PB, Struys E, Jakobs C, Plecko B, Baxter P, Baumgartner M, et al. Mutations in antiquitin in individuals with pyridoxine-dependent seizures. Nat Med 2006;12(3):307-9.24. Struys EA, Nota B, Bakkali A, Al Shahwan S, Salomons GS, Tabarki B. Pyridoxine-dependent epilepsy with elevated urinary α-amino adipic semialdehyde in molybdenum cofactor deficiency. Pediatrics 2012; 130(6):e1716-9.25. Struys EA, Bok LA, Emal D, Houterman S, Willemsen MA, Jakobs C. The measurement of urinary Δ¹- piperideine-6-carboxylate, the alter ego of α-aminoadipic semialdehyde, in Antiquitin deficiency. J Inherit Metab Dis 2012;35(5):909-16.26. Nam SH, Kwon MJ, Lee J, Lee CG, Yu HJ, Ki CS, et al. Clinical and genetic analysis of three Korean children with pyridoxine-dependent epilepsy. Ann Clin Lab Sci 2012;42(1):65-72.27. Yang Z, Yang X, Wu Y, Wang J, Zhang Y, Xiong H, et al. Clinical diagnosis, treatment, and ALDH7A1 mutations in pyridoxine-dependent epilepsy in three Chinese infants. PLoS One 2014;9(3):e92803.28. Jung S, Tran NT, Gospe SM Jr, Hahn SH. Preliminary investigation of the use of newborn dried blood spots for screening pyridoxine-dependent epilepsy by LC-MS/MS. Mol Genet Metab 2013;110(3):237-40.

Plasma Pyridoxal 5´-Phosphate Level in Children with Intractable and Controlled Epilepsy

Objective Intractable epilepsy is a serious neurologic problem with different etiologies. Decreased levels of pyridoxal phosphate in cerebral spinal fluid of patients with intractable epilepsy due to pyridoxine dependency epilepsy are reported. The aim of this study was to compare plasma pyridoxal 5´-phosphate level in patients with intractable and controlled epilepsy. Materials & Methods This cross- sectional analytic study included 66 epileptic children, 33 patients with controlled and 33 patients with intractable epilepsy, after neonatal period up to 15 yr old of age. Thirty-three patients with intractable epilepsy (10- 162 months) and 33 patients with controlled epilepsy (14-173 months) were enrolled. The study was conducted in Pediatric Neurology Clinic of Mofid Children Hospital, Tehran, Iran from January 2010 to December 2010. Patients’ clinical manifestations, laboratory and neuroimaging findings were collected. Non-fasting plasma 5´- pyridoxal phosphate levels of these subjects were assessed by high-pressure liquid chromatography. Results Mean plasma 5´- pyridoxal phosphate level (PLP) in patients with controlled epilepsy was 76.78±37.24 (nmol/l) (15.5-232.4). In patients with intractable epilepsy, mean plasma 5´- pyridoxal phosphate was 98.67± 80.58 (25.5- 393) nmol/l. There was no statistically significant difference between plasma pyridoxal phosphate levels of these two groups (P═0.430). Conclusion Pyridoxine dependent epilepsy is under diagnosed because it is manifested by various types of seizures. Plasma pyridoxal phosphate levels did not differ in our patients with intractable or controlled epilepsy. If PDE is suspected on clinical basis, molecular investigation of ALDH7A1 mutations, as feasible test, until PDE biomarkers becomes available is recommended. Keywords: Pyridoxine Dependent Epilepsy; Intractable Epilepsy; Plasma Pyridoxal Phosphate Level; Childre

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

Ataxia in Childhood: Epidemiological, Clinical and Neuroradiologic Features, and the Risk of Recurrence

How to Cite This Article: Javadzadeh M, Hassanvand Amouzadeh M, Sadat Esmail Nejad Sh, Abasi E, Alipour A, Mollamohammadi M. Ataxia in Childhood:Epidemiological, Clinical and Neuroradiologic Features, and the Risk of Recurrence. Iran J Child Neurol.Summer 2017; 11(3):1-6.AbstractObjectiveThis study was conducted on the demographic data, clinical characteristics, electroencephalography, neuroradiological findings, and their impact on the recurrence of ataxia. Materials & MethodsA 3-yr retrospective review of 49 children with ataxia in Mofid Children Hospital, Tehran, Iran was conducted from Apr 2013 to Apr 2016.The demographic, clinical and paraclinical data were recorded in pre-preparedquestionnaires. The patients were also classified in two groups of with or without recurrence and the results were compared. The diagnostic etiologies in our patients were classified as brain tumor, drug ingestion, encephalitis, postinfectious immune-mediated disorders, pseudoataxia, trauma, congenital malformations of the central nervous system and hereditary ataxias. ResultsForty-nine children with ataxia were enrolled. The mean age of the patients with a recurrence of ataxia was more than those without a recurrence.Neurodevelopmental delay in patients with recurrence was more frequent than those without a recurrence. Abnormal findings in the neuroimaging were seen more in the patients with recurrence than those without recurrence. The most common cause of ataxia in patients with recurrence was hereditary ataxia and in patients without recurrence was a viral post infectious disorder. ConclusionAfter a mean follow-up period of 16.36 months (range: 2-37 months), 9 cases (18.4%) showed recurrence. Older age, abnormal neuroimaging, and neurodevelopmental delay should be considered as the risk factors of recurrence of ataxia in children. References1.Piña-Garza JE. Ataxia. In: Piña-Garza JE, editor. Fenichel’s clinical pediatric neurology. 7th ed. Philadelphia: Elsevier Saunders;2013.p.215-35.2.Konczak J, Timmann D. The effect of damage to the cerebellum on sensorimotor and cognitive function in children and adolescents. Neurosci Biohav Rev 2007; 31: 1101-1113.3.Jafar-Nejad P, Maricich SM, Zoghbi HU. The Cerebellum and the Hereditary Ataxias. In: Swaiman KF, Ashwal S, Ferriero DM, Schor NF, editors. Swaiman’s Pediatric Neurology. 5th ed. Philadelphia: Elsevier Saunders;2012.p.939-64.4.Mink JW. Movement Disorders. In: Kliegman RM, Stanton BF, St Geme JW, Schor NF, editors. Nelson Textbook of Pediatrics. 20th ed. Philadelphia: Elsevier;2016.p.2882-96.5.Musselman KE, Stoyanov CT, Marasigan R, Jenkins ME, Konczak J, Morton SM, et al. Prevalence of ataxia in children: a systematic review. Neurology 2014; 82(1):80-9.6.Martínez-González MJ, Martínez-González S, García-Ribes A, Mintegi-Raso S, Benito-Fernández J, Prats-Viñas JM. Acute onset ataxia in infancy: its aetiology, treatment and follow-up. Rev Neurol 2006; 42(6):321-4.7.Benini R, Ben Amor IM, Shevell MI.Clinical clues to differentiating inherited and noninherited etiologies of childhood ataxias. J Pediatr 2012; 160(1):152-7.8.Karimzadeh P, Ghofrani M. A Survey on 100 Children with Acute Ataxia in Mofid Children Hospital Tehran, Iran. Iran RJ 2003; 4(1):7-13.(Full Text in Persian)9.Farghaly WM, El-Tallawy HN, Shehata GA, Rageh TA, Hakeem NA, Abo-Elfetoh NM. Population-based study of acquired cerebellar ataxia in Al-Kharga district, New Valley, Egypt. Neuropsychiatr Dis Treat 2011; 7:183.10.Ryan MM, Engle EC. Acute ataxia in childhood. J Child Neurol 2003; 18(5):309-16.11.Nafissi S, Maghdouri A, Sikaroodi H, Hosseini SS. Epidemiology of Cerebellar Ataxia on the Etiological Basis: A Cross Sectional Study. Acta Medica Iranica 2009; 47(6):465-8.12.Esscher E, Flodmark O, Hagberg G, Hagberg B. Non-progressive ataxia: origins, brain pathology and impairments in 78 swedish children. Dev Med Child Neurol 1996; 38(4):285-96.13.Salman MS, Lee EJ, Tjahjadi A, Chodirker BN. The epidemiology of intermittent and chronic ataxia in children in Manitoba, Canada. Dev Med Child Neurol 2013; 55(4):341-7.14.Weiss S, Carter S. Course and prognosis of acute cerebellar ataxia in children. Neurology 1959; 9:711– 721.15.Teoh HL, Mohammad SS, Britton PN, Kandula T, Lorentzos MS, Booy R, et al. Clinical Characteristics and Functional Motor Outcomes of Enterovirus 71 Neurological Disease in Children. JAMA Neurol 2016; 73(3):300-7.16.Connolly AM, Dodson WE, Prensky AL, Rust RS. Course and outcome of acute cerebellar ataxia. Ann Neurol 1994; 35(6):673-9.   

The Clinical Features and Diagnosis of Canavan’s Disease: A Case Series of Iranian Patients

How to Cite This Article: Karimzadeh P, Jafari N, Nejad Biglari H, Rahimian E, Ahmadabadi F, Nemati H, Nasehi MM, Ghofrani M, Mollamohammadi M. The Clinical Features and Diagnosis of Canavan’s Disease: A Case Series of Iranian Patients. Iran J Child Neurol. 2014 Autumn;8(3): 66-71.AbstractObjectiveCanavan’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.Material & Methods45 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.ResultsVisual 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).ConclusionWe 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. ReferencesAdornato BT, O’Brien JS, Lampert PW, Roe TF, Neustein HB. Cerebral spongy degeneration of infancy. A biochemical and ultrastructural study of affected twins. Neurology 1972;22(2):202-10.Banker BQ, Robertson JT, Victor M. Spongy Degeneration of the Central Nervous System in Infancy. Neurology 1964; 14:981-1001.Chou SM, Waisman HA. Spongy Degeneration of the Central Nervous System: Case of Homocystinuria. Arch Pathol 1965; 79:357-63.Divry P, Vianey-Liaud C, Gay C, Macabeo V, Rapin F, Echenne B. N-acetylaspartic aciduria: report of three new cases in children with a neurological syndrome associating macrocephaly and leukodystrophy. J Inherit Metab Dis 1988; 11(3):307-8.Feigenbaum A, Moore R, Clarke J, Hewson S, Chitayat D, Ray PN, et al. Canavan disease: carrier-frequency determination in the Ashkenazi Jewish population and development of a novel molecular diagnostic assay. Am J Med Genet A 2004;124a(2):142-7.Hagenfeldt L, Bollgren I, Venizelos N. N-acetylaspartic aciduria due to aspartoacylase deficiency--a new aetiology of childhood leukodystrophy. J Inherit Metab Dis 1987; 10(2):135-41.Ishiyama G, Lopez I, Baloh RW, Ishiyama A. Canavan’s leukodystrophy is associated with defects in cochlear neurodevelopment and deafness. Neurology 2003; 60(10):1702-4.Janson CG, Kolodny EH, Zeng BJ, Raghavan S, Pastores G, Torres P, et al. Mild-onset presentation of Canavan’s disease associated with novel G212A point mutation in aspartoacylase gene. Ann Neurol 2006; 59(2):428-31.Kaul R, Gao GP, Aloya M, Balamurugan K, Petrosky A, Michals K, et al. Canavan disease: mutations among Jewish and non-Jewish patients. 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Prediction of response to treatment in children with epilepsy

Objective: Predicting the response to treatment in patients treated  with anti-epilepsy drugs are always a major challenge. This study was conducted to predict the response to treatment in patients with epilepsy.Material and Methods: This analytical questionnaire-based study was conducted in 2014 among patients with epilepsy admitted to Mofid Children's Hospital. The inclusion criteria were children 2 months to 12 years of age with epilepsy and patients who experienced fever and seizure attacks at least once were excluded from the study. After the initial recording of patient information, patients were followed up for 6 months and the response to their treatment was recorded. The response to good treatment was defined as the absence of maximum seizure with two drugs during follow up.Result: This study was conducted among 128 children with seizure. 72 patients (56.3%) were boys. The age of the first seizure was under 2 years old in 90 patients (70.3%). History of febrile convulsion, family history of seizure and history of asphyxia was found in 16 patients (12.5%), 41 patients (32%), 27 (21.1%), respectively.  IQ was decreased in 79 patients (61.7%). Seizure etiology was idiopathic in 90 patients (70.3%), and the number of seizures was 1 - 2 in 36 patients (28.1%). 57 patients (44.5%) had cerebral lesion according to CT scan or MRI, and EEG was normal in 21 patients (16.4%) and abnormal in 101 patients (78.9%). In 6-month follow-up, 40 patients (31.3%) responded well to the treatment and 88 patients (68.8%) responded poorly to the treatment. The results of multivariate analysis demonstrated that history of asphyxia (OR = 6.82), neonatal jaundice (OR = 2.81) and abnormal EEG (OR = 0.19) were effective factors in response to treatment.Conclusion: Results of univariate and multivariate analysis indicated that abnormal EEG is an effective factor in treatment response in the children studied

Prediction of response to treatment in children with epilepsy

Abstract Objective: This study was conducted to predict the response to treatment in patients treated with anti-epilepsy drugs. Material and Methods: This analytical questionnaire-based study was conducted in 2014 among 128 patients with epilepsy admitted to Mofid Children's Hospital, Tehran, Iran. The inclusion criteria were children 2 months to 12 yr of age with epilepsy and patients who experienced fever and seizure attacks at least once were excluded from the study. Patients were followed up for 6 months and the response to their treatment was recorded. The good response to treatment was defined as the absence of seizure with two drugs during follow up. Results: Seventy-two patients (56.3%) were boys. The age of the first seizure was under 2 yr old in 90 patients (70.3%). History of febrile convulsion, family history of epilepsy and history of asphyxia was found in 16 (12.5%), 41 (32%), and 27 (21.1%) patients, respectively. Seizure etiology was idiopathic in 90 patients (70.3%), and the number of seizures was 1-2 in 36 patients (28.1%). Overall, 57 patients (44.5%) had cerebral lesion according to CT scan or MRI, and EEG was abnormal in 101 patients (78.9%). In 6-month follow-up, 40 patients (31.3%) responded well to the treatment and 88 patients (68.8%) responded poorly to the treatment. History of asphyxia (OR = 6.82), neonatal jaundice (OR = 2.81) and abnormal EEG (OR = 0.19) were effective factors in response to treatment. Conclusion: Abnormal EEG is an effective factor in treatment response in the children studied. Key Words: Pediatric, Anti-seizure drug, Response to treatment, Children, Epileps

Co-transplantation of Human Embryonic Stem Cell-derived Neural Progenitors and Schwann Cells in a Rat Spinal Cord Contusion Injury Model Elicits a Distinct Neurogenesis and Functional Recovery

Co-transplantation of neural progenitors (NPs) with Schwann cells (SCs) might be a way to overcome low rate of neuronal differentiation of NPs following transplantation in spinal cord injury (SCI) and the improvement of locomotor recovery. In this study, we initially generated NPs from human embryonic stem cells (hESCs) and investigated their potential for neuronal differentiation and functional recovery when co-cultured with SCs in vitro and co-transplanted in a rat acute model of contused SCI. Co-cultivation results revealed that the presence of SCs provided a consistent status for hESC-NPs and recharged their neural differentiation toward a predominantly neuronal fate. Following transplantation, a significant functional recovery was observed in all engrafted groups (NPs, SCs, NPs+SCs) relative to the vehicle and control groups. We also observed that animals receiving co-transplants established a better state as assessed with the BBB functional test. Immunohistofluorescence evaluation five weeks after transplantation showed invigorated neuronal differentiation and limited proliferation in the co-transplanted group when compared to the individual hESC-NPs grafted group. These findings have demonstrated that the co-transplantation of SCs with hESC-NPs could offer a synergistic effect, promoting neuronal differentiation and functional recovery

The individual-cell-based cryo-chip for the cryopreservation, manipulation and observation of spatially identifiable cells. I: Methodology

<p>Abstract</p> <p>Background</p> <p>Cryopreservation is the only widely applicable method of storing vital cells for nearly unlimited periods of time. Successful cryopreservation is essential for reproductive medicine, stem cell research, cord blood storage and related biomedical areas. The methods currently used to retrieve a specific cell or a group of individual cells with specific biological properties after cryopreservation are quite complicated and inefficient.</p> <p>Results</p> <p>The present study suggests a new approach in cryopreservation, utilizing the Individual Cell-based Cryo-Chip (i3C). The i3C is made of materials having appropriate durability for cryopreservation conditions. The core of this approach is an array of picowells, each picowell designed to maintain an individual cell during the severe conditions of the freezing - thawing cycle and accompanying treatments. More than 97% of cells were found to retain their position in the picowells throughout the entire freezing - thawing cycle and medium exchange. Thus the comparison between pre-freezing and post-thawing data can be achieved at an individual cell resolution. The intactness of cells undergoing slow freezing and thawing, while residing in the i3C, was found to be similar to that obtained with micro-vials. However, in a fast freezing protocol, the i3C was found to be far superior.</p> <p>Conclusions</p> <p>The results of the present study offer new opportunities for cryopreservation. Using the present methodology, the cryopreservation of individual identifiable cells, and their observation and retrieval, at an individual cell resolution become possible for the first time. This approach facilitates the correlation between cell characteristics before and after the freezing - thawing cycle. Thus, it is expected to significantly enhance current cryopreservation procedures for successful regenerative and reproductive medicine.</p