Assessment of Cognitive and Motor Development in 150 Children with Refractory Epilepsy

 ObjectiveNeuropsychological impairment is an important co-morbidity of chronic epilepsy. The aim of this study was to determine the state of the cognitive and motor development of patients with refractory epilepsy.Materials & Methods We studied 150 consecutive children with epilepsy who were referred to Mofid Children Hospital, a third level public referral University Hospital in Tehran, Iran, from October 2007 to October 2008. Refractory epilepsy was defined as therapeutic failure of three antiepileptic drugs which were used appropriately.Data regarding sex, age, age at which the first seizure occurred, microcphaly, muscle tonicity, EEG findings, kind of treatment for controlling seizures and cognitive and motor development delay were collected from medical records.Development delay was defined as delay in acquiring cognitive ability and motor skills for age according to the Denver Scale II.Results Of 150 patients 72% were younger than 2 years old and 56.7% were male. About 35.3% were microcephalic while 76% had normal muscular tonicity.Only 2.7% had normal EEGs. About 37.3% showed a good response to anticonvulsive drugs and became seizure free, 13.3% showed a relative response to anticonvulsants but 49.3% did not respond. In the present study, 68% had cognitive developmental delay and 60.7% suffering motor delay. There was a significant difference in response to treatment between patients with cognitive and motor development delay.Conclusion Cognitive developmental delay was more frequent in patients with refractory epilepsy, suggesting that early cognitive screening and introduvtion of rehabilitation programs are necessary for patients with refractory epilepsy.

Comparison of Serum Zinc Levels among Children with Simple Febrile Seizure and Control Group: A Systematic Review

How to Cite This Article: Nasehi MM, Sakhaei R, Moosazadeh M, Aliramzany M. Comparison of Serum Zinc Levels among Children with Simple Febrile Seizure and Control Group: A Systematic Review. Iran J Child Neurol. 2015 Winter;9(1):17-24 .AbstractObjectiveSeveral 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.ConclusionThe 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 contributingfactor for FS, a conclusion with a high consensus among different studies carriedout in different parts of the world. ReferencesHeydarian F, Ashrafzadeh F, Ghasemian A. Serum ZINC level in Patients with simple febrile seizure. Iran J Child Neurology 2010; 14(2):41-44.Mahyar A, Pahlavan AA, Varasteh-Nejad A. Serum zinc level in children with febrile seizure. Acta Medica Iranica 2008; 46(6): 477-80.Kunda GK, Rabin F, Nandi ER, Sheikh N, Akhter S. Etiology and Risk Factors of Febrile Seizure – An Update. Bangladesh J Child Health 2010; 34 (3):103-112.Abbaskhaniyan A, Shokrzadeh M, Rafati MR, Mashhadiakabr M, Arab A, Yazdani J. Survey and Relation of Serum Magnesium Level in Children with Seizure. J Mazand Univ Med Sci 2012; 2(90): 43-49.Abaskhanian A, Vahid Shahi K, Parvinnejad N. The Association between Iron Deficiency and the First Episode of Febrile Seizure. J Babol Univ Med Sci 2009; 11(3):32-36.Amiri M, Farzin L, Moassesi ME, Sajadi F. Serum Trace Element Levels in Febrile Convulsion. Biol Trace Elem Res 2010; 135:38–44.Fetveit A. Assessment of febrile seizures in children. Euro J Pedia 2008; 167:17-27.Sadeghzadeh M, Khoshnevis P, Mahboubi E. Iron Status and Febrile Seizure- A Case Control Study in Children Less Than 3 Years. Iran J Child Neurol 2012; 6(4):27-31.Salehiomran MR, Mahzari M. Zinc Status in Febrile Seizure: A Case-Control Study. Iran J Child Neurol. 2013; 7(4):20-23.Shiva S, Barzegar M, Zokaie N, Shiva Sh. Dose Supplemental Zinc Prevents Recurrence of Febrile Seizures?. Iran J Child Neurol 2011; 5(4):11-14.Sadeghzadeh M, Khoshnevis Asl P, Mousavinasab N, Koosha A, Norouzi M. The Relation Between Serum Zinc Level and Febrile Seizures in Children Admitted to Zanjan Valie-Asr Hospital. ZUMS Journal 2011; 19 (74):17-24.Waruiru C, Appleton R. febrile seizures: an update. Archive Dis Child 2004; 89: 751-6.Moosazadeh M, Nekoei-moghadam M, Emrani Z, Amiresmaili M. Prevalence of unwanted pregnancy in Iran: A systematic review and meta-analysis. Int J Health Plann Mgmt, 2013; Published online in Wiley Online Library, DOI: 10.1002/hpm.2184. available at: http://onlinelibrary.wiley.com/journal/10.1002/%28ISSN%291099-1751/earlyview.Elm EV, Altman DG, Egger M, Pocock SJ, Gotzsche PC, Vandenbroucke P, et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Preventive medicine 2007; 45(4): 247-251.Shea BJ, Grimshaw JM, Wells GA, Boers M, Andersson N, Hamel C, et al. Development of AMSTAR: a measurement tool to assess the methodological quality of systematic reviews. BMC medical research methodology 2007; 7(1):10.Garty BZ, Olomucki R, Lerman-Sagie T, Nitzan M. Cerebrospinal fluid zinc concentration in febrile children’s. Arch Dis Child 1995; 73(4):338-41.Papierkowski A, Mroczkowska-Juchkiewics A, Pawlowska KA, Pasternak K. Magnesium and zinc levels in blood serum and cerebrospinal fluid in children with febrile convulsions. Pol Merkuriusz Le 1999; 6(33): 138-40.Burhanoglu M, Tutuncuoglu S, Coker C, Tekgul H, Ozgur T. Hypozincemia in febrile convulsion. Eur J Pediatr 1996; 155(6):498-501.Kumar L, Chaurasiya OS, Gupta AH. Prospective Study of Level of Serum Zinc In Patients of Febrile Seizures, Idiopathic Epilepsy, and CNS Infections. People’s Journal of Scientific Research 2011; 4(2):1-4.Palliana RR, Singh DK, Borade A. ZINC deficiency as a risk factor febrile seizure. Pediatrics 2008; 121(2):358-365.Ehsanipour F, Talebitaher M, Vahid Harandi N, Kani K. Serum Zinc Level in Children with Febrile Convulsion and its Comparison with that of Control Group. Iran J Pediatr 2009; 19)1):65-68.Kafadar I, Akıncı AB, Pekun F, Adal E. The Role of Serum Zinc Level in Febrile Convulsion Etiology. J Pediatr Inf 2012; 6: 90-93.Lee JH, Kim JH. Comparison of Serum Zinc Levels Measured by Inductively Coupled Plasma Mass Spectrometry in Preschool Children with Febrile and Afebrile Seizures. Ann Lab Med 2012; 32:190-193.Margaretha L, Masloman N. Correlation between serum zinc level and simple febrile seizure in children. Paediatr Indones 2010; 50(6): 326-330.Mollah MAH, Rakshit SC, Anwar KS, Arslan MI, Saha N, Ahmed S, et al. Zinc concentration in serum and cerebrospinal fluid simultaneously decrease in children with febrile seizure: Findings from a prospective study in Bangladesh. Acta Pædiatrica 2008; 97:1707–1711.Mollah MAH, Ranjan DP, Tarafdar SA, et al. Zinc in CSF of patients with febrile convulsion. Ind J Pediatr 2002; 69: 859-61.Modarresi MR, Shahkarami SMA, Yaghini O, Shahbi J, Mosaiiebi D, Mahmoodian T. The relationship between Zinc deficiency and Febrile Convulsion in Isfahan, Iran. Iran J Child Neurology 2011; 5(2):27-31.Tutuncuoglu S, Kutukculer N, Kepe L, Coker C, Berdeli A, Tekgul H. Proinflammatory cytokines, prostaglandins and zinc in febrile Convulsions. Pediatrics International 2001; 43: 235–239.Talebian A, Vakili Z, Talar SA, Kazemi SM, Mousavi GA. Assessment of the Relation between Serum Zinc & Magnesium Levels in Children with Febrile Convulsion. Iranian Journal of Pathology 2009; 4 (4), 157 – 160.Gunduz Z, Yavuz I, Koparal M, Kumandas S, Saraymen R. Serum and cerebrospinal fluid zinc level in children with febrile convulsion. Acta Paediatr Jpn 1996; 38(3): 237-41.Cho WJ, Son BH, Kim SW. Levels of Sodium and Zinc Concentration in Febrile Convulsion. J Korean Child Neurol Soc 1999; 7(2):214-219.Cho HS, Shin JH, Seo JY, Lee CA, Kim SH, Chae KY. The Levels of Zinc and Neuron-specific Enolase in Febrile Convulsion. Korean J Pediatr 2004; 47(10):1087-1092.Ganesh R, Janakiraman L, Meenakshi B. Serum zinc levels are low in children with simple febrile seizures compared with those in children with epileptic seizures and controls. Ann Trop Paediatr 2011; 31(4):345-9.Ganesh R, Janakiraman L. Serum zinc levels in children with simple febrile seizure. Clin Pediatr (Phila) 2008; 47(2):164-6.Okposio MM, Sadoh WE, Ofovwe GE, Onyiriuka AN. Serum zinc level in Nigerian children with febrile convulsion. Journal of Pediatric Neurology 2012; 10(3):187-191.Itoh M, Ebadi M. The selective inhibition of hippocampal glutamic acid decarboxylase in zinc induced epileptic seizures. Neurochem Res 1982; 7(10): 1287-98.Peters S, Koh J, Choi W. Zinc selectively blocks the action of N-methyl-D-aspartate on cortical neurons. Science 1987; 236 (4801): 589-93

Neuroimaging Findings of the High-risk Neonates and Infants Referred to Mofid Children’s Hospital

Abstract Objectives Neuroimaging in high-risk neonates and infants is done to help child neurologists predict the future neurodevelopmental outcome of these children. In this study, we assessed high-risk neonates and infants admitted to the NICU or neonatal wards of Mofid children’s Hospital, especially regarding clinical development and brain imaging Materials & Methods This cross-sectional study was conducted on 170 patients admitted to the neonatal and NICU ward of Mofid children’s Hospital.Considering the inclusion criteria, 112 patients were included in this project. Brain ultrasonography was performed on almost all of these babies by a single radiologist. Some patients underwent a brain CT scan, and brain MRI without contrast was done on the others. These images were interpreted and compared by a single pediatric neuroradiologist blinded to clinical data. All of these babies were followed up until 18 months of age. Results In this study, 57.1% of the patients were male and 42.9% were female. Of 44 patients who obtained Electroencephalogram (EEG) during the hospitalization period with probable seizure, 25 (56.8%) had normal EEGs. Of 89 babies who were examined by ultrasound, 19 (21.3%) had abnormal findings; ventriculomegaly and then germinal matrix hemorrhage (GMH) were the most common abnormalities.Also, 27 cases (71.1%) of 38 patients undergoing a CT scan had abnormal findings. The most common findings were a hypodense area in the white matter and ventriculomegaly. Of 41 patients who underwent MRI between 1 and 27 months, 34 cases (82.9%) had an abnormal MRI. The most common findings were periventricular hyperintensities in 17 cases (41.5%), mildly delayed myelination in 15 cases (36.6%), and severe brain atrophy or thinning of corpus callosum or white matter volume loss in seven cases (17.1%). During the follow-up period, which was 18.55 ± 6.56 months, 79 (70.5%) of the children had normal development and 33 (29.5%) were suffering from a global neurodevelopmental delay. More precisely, 49 (43.7%) and 35 (31.2%) patients had motor development delay and delayed verbal development, respectively. The abnormal findings of brain imaging in the ultrasound, CT scan, and MRI were all significantly associated with an adverse neurodevelopmental outcome (P <0.001, P = 0.02, and P <0.001, respectively). ConclusionIn this study, we showed that at any time before six months or afterone year of age, the result of brain MRI was a strong predictor of thepatient’s outcome

Sodium Channel Gene Mutations in Children with GEFS+ and Dravet Syndrome: A Cross Sectional Study

 How to Cite This Article: Tonekaboni SH, Ebrahimi A, Bakhshandeh Bali MK, Houshmand M, Moghaddasi M, Taghdiri MM, Nasehi MM. Sodium Channel Gene Mutations in Children with GEFS+ and Dravet Syndrome: A Cross Sectional Study. Iran J Child Neurol. 2013 Winter; 7 (1):25-29. Objective Dravet syndrome or severe myoclonic epilepsy of infancy (SMEI) is a baleful epileptic encephalopathy that begins in the first year of life. This syndrome specified by febrile seizures followed by intractable epilepsy, disturbed psychomotor development, and ataxia. Clinical similarities between Dravet syndrome and generalized epilepsy with febrile seizure plus (GEFS+) includes occurrence of febrile seizures and joint molecular genetic etiology. Shared features of these two diseases support the idea that these two disorders represent a severity spectrum of the same illness. Nowadays, more than 60 heterozygous pattern SCN1A mutations, which many are de novo mutations, have been detected in Dravet syndrome. Materials & Methods From May 2008 to August 2012, 35 patients who referred to Pediatric Neurology Clinic of Mofid Children Hospital in Tehran were enrolled in this study. Entrance criterion of this study was having equal or more than four criteria for Dravet syndrome. We compared clinical features and genetic findings of the patients diagnosed as Dravet syndrome or GEFS+. Results 35 patients (15 girls and 20 boys) underwent genetic testing. Mean age of them was 7.7 years (a range of 13 months to 15 years). Three criteria that were best evident in SCN1A mutation positive patients are as follows: Normal development before the onset of seizures, onset of seizure before age of one year, and psychomotor retardation after onset of seizures. Our genetic testing showed that 1 of 3 (33.3%) patients with clinical Dravet syndrome and 3 of 20 (15%) patients that diagnosed as GEFS+, had SCN1A mutation. Conclusion In this study, normal development before seizure onset, seizures beginning before age of one year and psychomotor retardation after age of two years are the most significant criteria in SCN1A mutation positive patients.References Dravet C, Bureau M, Oguni H, Fukuyama Y, Cokar O.Severe myoclonic epilepsy in infancy (Dravet syndrome). In: Roger J, Bureau M, Dravet C, Genton P, Tassinari CA, Wolf P, eds. Epileptic Syndromes in Infancy, Childhood and Adolescence, 4th  ed. London: John Libbey Eurotext Publishers; 2005. p. 89-113.Dalla Bernardina B, Colamaria V, Capovilla G, Bondavalli S. Nosological classification of epilepsies in the first three years years of life. Prog Clin Biol Res 1983;124:165-83.Commission on Classification and Terminology of the International League against Epilepsy. Proposal for revised classification of epilepsies and epileptic syndromes. Epilepsia 1989;30:389-99.Scheffer IE, Zhang. YH, Jansen FE, Dibbens L. Dravet syndrome or genetic (generalized) epilepsy with febrile seizures plus? Brain Dev 2009;31(5):394-400.Singh R, Andermann E, Whitehouse WP, Harvey AS, Keene DL, Seni MH, et al. severe myoclonic epilepsy of infancy: extended spectrum of GEFS+? Epilepsia 2001;42(7):837-44.Scheffer IE, Harkin LA, Dibbens LM, Mulley JC, Berkovic SF. Neonatal epilepsy syndromes and generalized epilepsy with febrile seizures plus (GEFS+). Epilepsia 2005;46 Suppl 10:41-7.Harkin LA, McMahon JM, Iona X, Dibbens L, Pelekanos JT, Zuberi SM, et al. The spectrum of SCN1A-related infantile enceptic encephalopathies. Brain 2007;130(Pt 3):843-52.Sun H, Zhang Y, Liang J, Liu X, Ma X, Qin, et al. Seven novel SCN1A mutations in Chinese patients with severe myoclonic epilepsy of infancy. Epilepsia 2008;49:1104-7.Miller SA, Dykes DD, polesky HF. A simple salting out procedure  for  extracting  DNA from  human  cucleated Nucleated cells. Nucleic Acids Res 1988;16(3):2115.Marini C, Scheffer IE, Nabbout R, Mei D, Cox K, Dibbens LM, et al. SCN1A duplications and deletions detected in dravet syndrome: implications for molecular diagnosis. Epilepsia 2009; 50(7):1670-8.Striano P, Mancardi MM, Biancheri R, Madia F, Gennaro E, Paravidino R, et al. Brain MRI findings in severe myoclonic epilepsy in infancy and genotype- correlations. Epilepsia 2007;48(6):1092-6.Wang JW, Kurahashi H, Ishii A, Kojima T, Ohfu M, Inoue T, et al. Micro chromosomal deletions involving SCN1A and adjacent genes in severe myoclonic epilepsy in infancy. Epilepsia 2008;49(9):1528-34.Lossin C. A catalog  of  SCN1A variants.  Brain  Dev 2009;31:114-30.Fountain-Capal JK, Holland KD, Gilbert DL, Hallinan BE When should clinicians order genetic testing for Dravet syndrome? Pediatr Neurol 2011;45(5): 319-23. Hattori J, Ouchida M, Ono J, Miyake S, Maniwa S, Mimaki  N,  et  al. A screening  test  for  the  prediction of Dravet syndrome before one year of age. Epilepsia 2008;49(4):626–33.Nabbout R, Gennaro E, Dalla Bernardina B, Dulac O, Madia F, Bertini E, et al. spectrum of SCN1A mutations severe myoclonic epilepsy of infancy. Neurology 2003;60(12):1961-7.Ohmori I, Ouchida M, Ohtsuka, Y oka E, Shimizu K. Significant correlation  of  The  SCN1A mutations  and severe myoclonic epilepsy in infancy. Biochem Biophys Res Commun 2002;295:17-23.Cales. L, Del-favero J, Ceulemans B, Lagae L, Van Broeckhoven C, De jonghe P. De novo mutations in the sodium- chnnel gene SCN1A cause severe myoclonic epilepsy of infancy. Am J Hum Genet 2001; 68(8):1327-32.Brunklaus A, Ellis R, Reavey E, Forbes GH, Zuberi SM.Prognostic, clinical and demographic features in SCN1A mutation-positive Dravet syndrome. Brain 2012;135(Pt 8):2329-36.Engel J Jr; International League Against Epilepsy (ILAE).A proposed diagnostic scheme for people with epileptic seizures  and  with  epilepsy:  report  of  the  ILAE Task force  on  Classifications  and  Terminology.  Epilepsia 2001;42(6):796-803.Fujiwara T, Sugawara T, Mazaki-Miyazaki E, Takahashi Y, Fukushima K, Watanabe M, et al. Mutations of sodium channel alpha subunit type 1 (SCN1A) in intractable childhood epilepsies with frequent generalized tonic- clonic seizures. Brain 2003;126:(Pt 3):531-46.Claes L, Ceulemans B, Audenaert D, Smets K, Löfgren A, Del-Favero J. De novo SCN1A mutations are a major cause of severe myoclonic epilepsy of infancy. Hum Mutat 2003;21(6):615-21.Lakhan R, Kumari R, Misra UK, Kalita J, Pradhan S, Mittal B. Differential role of sodium channels SCN1A and SCN2A gene polymorphisms with epilepsy and multiple drug resistance in the north Indian population. Br J Clin Pharmacol 2009;68(2):214-20

Clinical and Epidemiological Aspects of Multiple Sclerosis in Children

How to Cite This Article: Nasehi MM, Sahraian MA, Naser Moghaddasi A, Ghofrani M, Ashtari F, Taghdiri MM, Tonekaboni SH, Karimzadeh P, Afshari M, Moosazadeh M. Clinical and Epidemiological Aspects of Multiple Sclerosis in Children. Iran J Child Neurol. Spring 2017; 11(2):37-43.AbstractObjectiveOverall, 2%-5% of patients with multiple sclerosis (MS) experienced the first episode of disease before the age 18 years old. Since the age of onset among children is not similar to that in general population, clinicians often fail to early diagnose the disease. This study aimed to determine the epidemiological and clinical patterns of MS among Iranian children.Materials & Methods In this cross-sectional study carried out in Iran in 2014-2015, information was collected using a checklist with approved reliability and validity. Method sampling was consensus. Data were analyzed using frequency, mean and standard deviation indices by means of SPSS ver. 20 software.Results Totally, 177 MS children were investigated. 75.7% of them were female. Mean (SD), minimum and maximum age of subjects were 15.9 (2), 7 and 18 yr, respectively. The most reported symptoms were sensory (28.2%), motor (29.4%), diplopia (20.3%) and visual (32.8%). Primary MRI results showed 91.5% and 53.1% periventricular and spinal cord lesions, respectively.Conclusion MS is significantly more common among women. The most common age of onset is during the second decades. Sensory and motor problems are the most symptoms, while, periventricular and spinal cord lesions are the most MRI results. References 1. Ascherio A, Munger K. Epidemiology of multiple sclerosis: from risk factors to prevention. Semin Neurol 2008; 28(1): 17-28.2. Abedidni M, Habibi Saravi R, Zarvani A, Farahmand M. Epidemiologic study of multiple sclerosis in Mazandaran,Iran, 2007. J Mazandaran Univ Med Sci 2008; 18(66): 82-6.3. Taghdiri MM, Gofrani M, Barzegar M, Moayyedi A, Tonekaboni H. The survey of 20 cases of multiple sclerosis in children in mofid hospital of Tehran. J Rehabil, 2001; 4(6-7):61-67.4. Benito-Leon J, Martinez P. Health-related quality of life in multiple sclerosis. Neurologia 2003; 18: 207-10.5. Nedjat S, Montazeri A, Mohammad K, Majdzadeh R, Nabavi N, Nedjat F, et al . Quality of Life in Multiple Sclerosis Compared to the Healthy Population in Tehran. Iran J Epidemiol 2006; 2 (3 and 4) :19-24.6. Marrie RA. Environmental risk factors in multiple sclerosis aetiology. Lancet Neurol 2004; 3(12):709-18.7. Milo R, Kahana E. Multiple sclerosis:geoepidemiology, genetics and the environment. Autoimmun Rev 2010; 9(5): A387-A394.8. Banwell B, Ghezzi A, Bar-Or A, Mikaeloff Y. Multiple sclerosis in children: clinical diagnosis, therapeutic strategies, and future directions. The Lancet Neurol, 2007;6(10):887-902.9. Ebers GC. Environmental factors and multiple sclerosis. The Lancet Neurol, 2008;7(3):268-277.10. Noseworthy JH, Lucchinetti C, Rodriguez M, Weinshenker BG. Multiple Sclerosis. N Engl J Med 2000; 343(13):938-52.11. Rudick RA, Cohen JA, Weinstock-Guttman B, Kinkel RP, Ransohoff RM. Management of multiple sclerosis. N Engl J Med 1997: 337(22): 1604-11.12. Greer JM, McCombe PA. Role of gender in multiple sclerosis: clinical effects and potential molecular mechanisms. J Neuroimmunol 2011;234(1-2): 7-18.13. Boiko A, Vorobeychik G, Paty D, Devonshire V, Sadovnick D. Early onset multiple sclerosis A longitudinal study. Neurology 2002; 59(7):1006-1010.14. . Ashtari F, Shaygannejad V, Heidari F, Akbari M. Prevalence of Familial Multiple Sclerosis in Isfahan, Iran. Journal of Isfahan Medical School, 2011;29(138.2):555- 561.15. Mazaheri S, Fazlian M, Hossein Zadeh A. Clinical and Epidemiological Features of Early and Adult Onset Multiple Sclerosis in Hamedan, Iran, 2004–2005. Yafteh 2008; 9 (4) :39-44.16. Saman-Nezhad B, Rezaee T, Bostani A, Najafi F, Aghaei A. Epidemiological Characteristics of Patients with Multiple Sclerosis in Kermanshah, Iran in 2012. J Mazand Univ Med Sci 2013; 23(104): 97-101 (In Persian).17. Renoux C, Vukusic S, Mikaeloff Y, Edan G. Natural history of multiple sclerosis with childhood onset. N Engl J Med 2007. 356(25): p. 2603-2613.18. Ness JM, Chabas D, Sadovnick AD, Pohl D, Banwell B, Weinstock-Guttman B. Clinical features of children and adolescents with multiple sclerosis. Neurology 2007; 68(16 suppl 2):S37-S45.19. Etemadifar M, Janghorbani M,Shaygannejad V, Ashtari F . Prevalence of multiple sclerosis in Isfahan. Iran. Neuroepidemiology 2006; 27(1):39-44 (In Persian).20. Saadatnia M, Etemadifar M, Maghzi AH. Multiple sclerosis in Isfahan, Iran. Int Rev Neurobiol 2007; 79: 357-75.21. Nabavi SM, Poorfarzam S, Ghassemi H. Clinical Course and prognosis of 203 patients with MS in shahid Mostafa Khomeini Hospital, Tehran 2002, Tehran University Medical Journal, 200l 64( 7)6: 90-97

Estimating the Annual Risk of Tuberculosis Infection and Disease in Southeast of Iran Using the Bayesian Mixture Method

Background: Tuberculosis is still a public health concern in Iran. The main challenge in monitoring epidemiological status of tuberculosis is to estimate its incidence accurately. Objectives: We used a newly developed approach to estimate the incidence of tuberculosis in Sistan, an endemic area in southeast of Iran in 2012-13. Patients and Methods: This cross-sectional study was conducted on school children aged 6-9 years. We estimated a required sample size of 6350. Study participants were selected using stratified two-stage cluster sampling method and recruited in a tuberculin skin test survey. Indurations were assessed after 72 hours of the injection and their distributions were plotted. Prevalence and annual risk of tuberculosis infection (ARTI) were estimated using the Bayesian mixture model and some traditional methods. The incidence of active disease was calculated using the Markov Chain Monte Carlo technique. Results: We assumed weibull, normal and normal as the best distributions for indurations due to atypical reactions, BCG (Bacillus Calmette–Guérin) reactions and Mycobacterium tuberculosis infection, respectively. The estimated infection prevalence and ARTI were 3.6% (95%CI: 3.1, 4.1) and 0.48%, respectively. These estimates were lower than those obtained from the traditional methods. The incidence of active tuberculosis was estimated as 107 (87-149) per 100000 population with a CDR of 54% (40%-68%). Conclusions: Although the mixture model showed slightly lower estimates than the traditional methods, it seems that this method might generate more accurate results for deep exploration of tuberculosis endemicity. Besides, we found that Sistan is a high endemic area for tuberculosis in Iran with a low case detection rate

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. Am J Hum Genet 1994; 55(1):34-41.Kaul R, Gao GP, Balamurugan K, Matalon R. Cloning of the human aspartoacylase cDNA and a common missense mutation in Canavan disease. Nat Genet 1993; 5(2):118-23.Kvittingen EA, Guldal G, Borsting S, Skalpe IO, Stokke O, Jellum E. N-acetylaspartic aciduria in a child with a progressive cerebral atrophy. Clin Chim Acta 1986;158(3):217-27.Mahloudji M, Daneshbod K, Karjoo M. Familial spongy degeneration of the brain. Arch Neurol 1970; 22(4):294-8.Matalon R, Kaul R, Casanova J, Michals K, Johnson A, Rapin I, et al. SSIEM Award. Aspartoacylase deficiency: the enzyme defect in Canavan disease. J Inherit Metab Dis 1989; 12(Suppl 2):329-31.Matalon R, Michals K, Sebesta D, Deanching M, Gashkoff P, Casanova J. Aspartoacylase deficiency and N-acetylaspartic aciduria in patients with Canavan disease. Am J Med Genet 1988; 29(2):463-71.Morcaldi L, Salvati G, Giordano GG, Guazzi GC. Congenital familial spongy idiocy (van Bogaert-Bertrand syndrome) in a non-Jewish family (study of a 2d Italian family)]. Acta Genet Med Gemellol (Roma) 1969; 18(2):142-57.Ozand PT, Gascon GG, Dhalla M. Aspartoacylase deficiency, and Canavan disease in Saudi Arabia. Am J Med Genet 1990; 35(2):266-8.Schmidt H, Rott HD, Neuhauser G, Neumann W. [Spongious cerebral dystrophy at an infant age (Canavan-Bogaert-Bertrand types) in three siblings of a non-Jewish family in upper Franconia (author’s transl)]. KlinPadiatr 1978; 190(6):580-5.Shaag A, Anikster Y, Christensen E, Glustein JZ, Fois A, Michelakakis H, et al. The molecular basis of Canavan (aspartoacylase deficiency) disease in European non-Jewish patients. Am J Hum Genet 1995; 57(3):572-80.Sistermans EA, de Coo RF, van Beerendonk HM, Poll-The BT, Kleijer WJ, van Oost BA. Mutation detection in the aspartoacylase gene in 17 patients with Canavan disease: four new mutations in the non-Jewish population. Eur J Hum Genet 2000; 8(7):557-60.Toft PB, Geiss-Holtorff R, Rolland MO, Pryds O, Muller-Forell W, Christensen E, et al. Magnetic resonance imaging in juvenile Canavan disease. Eur J Pediatr 1993; 152(9):750-3.Michals K, Matalon R. Canavan’s disease. In: Raymond GV, Eichler F, Fatemi A, Naidu S, eds. Leukodystrophies. London: Mac Keith Press.2011.P.156-69.Breitbach-Faller N, Schrader K, Rating D, Wunsch R. Ultrasound findings in follow-up investigations in a case of aspartoacylase deficiency (Canavan disease). Neuropediatrics 2003; 34:96–9.Matalon RM, Michals-Matalon K. Spongy degeneration of the brain, Canavan disease: biochemical and molecular findings. Front Biosci 2000; 5:D307–11.Matalon R, Michals K, Kaul R. Canavan disease: from spongy degeneration to molecular analysis. J Pediatr 1995; 127:511–7

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

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Association between Iron Deficiency Anemia and Febrile Seizure: a Systematic Review and Meta-Analysis

Background and objective: Febrile seizure is the most common convulsive disorder in children and different studies reported controversial results about the association between this disorder and iron deficiency, in some studies, iron level in children with febrile seizures is higher than control and in some reports is less than the control group. So, we systematically reviewed all the studies in this field and analyzed their findings using meta-analysis methods. Material and methods: This review and meta-analysis was conducted by iron and fever keywords on articles published in the databases Pubmed, Googlescholar and Federated search of medical digital library includes a variety of international databases. All articles by the end of March 2012 were studied. Case-control studies were selected and quality assessment of studies were surveyed by STROB criteria and information requirements, including the status of iron deficiency anemia, iron levels and ferritin level of eligible studies were extracted and analyzed by Comprehensive Meta Analysis Version 2.0 software and The Forest and Funnel chart was drawn. Results: Finally 11 studies included 1357 children with febrile seizure and 1347 children in the control group were evaluated. The odds ratio of iron deficiency anemia in children with febrile seizure in comparison to the control group was 1.27 (OR = 1.27, CI95%: 1.03 -1.56). Ferritin level was not significant between the two groups (p=0.022), but iron levels in the two groups was significant (p=0.000). Conclusion: Iron deficiency considered as a risk factor in the incidence of febrile seizure and interventional studies can be helpful to confirm this hypothesis