The Most Common Treatable Neurometabolic Epilepsies in Children

Epilepsy is a common neurological disorder in childhood with prominent neurological manifestations, signs, and symptoms in inherited neurometabolic disorders. Accurate diagnosis of neurometabolic disorders in epileptic patients increases the possibility of a specific treatment to improve epilepsy. Therefore, early diagnosis is essential in potentially treatable epileptic disorders. Various seizure types occur in neurometabolic disorders, which are often refractory to antiepileptic drugs (without the treatment of the underlying neurometabolic disorders). Patients with underlying disorders have severe clinical presentations, such as refractory seizures. In addition, they do not respond to antiepileptic drugs in many cases. In the epileptic patients with developmental delay and/or regression, neurometabolic disorders should be considered in the presence of abnormal neurological examination and brain imaging with specific patterns. Some of these disorders are potentially treatable. Therefore, neurologists should determine the etiology of epilepsy, especially in pediatric patients, and the treatment should not be restricted to symptomatic therapy. The present study aimed to introduce some of the treatable causes of epilepsy in pediatric patients

How Antiepileptics May Change the Serum Level of Vitamin D, Calcium, and Phosphorus in Children with Epilepsy

AbstractObjectiveStudies have shown vitamin (Vit) D deficiency and bone disease in long-term use of antiepileptics, especially in young individuals. This study aimed to determine the relationship between antiepileptic drugsand the level of Vit D, calcium (Ca), and phosphorus (P) in children with epilepsy at the Shohada Hospital from 2016 to 2017. Methods & MaterialsIn this case-control study, 60 consecutive children with epilepsy at the Shohada Hospital from 2016 to 2017 under treatment with anticonvulsions for more than six months were enrolled as the case group.The level of Vit D, Ca, and P was determined in the case group and compared with 60 children without seizure as the control group.ResultsThe mean Ca and P were alike across the groups (P > 0.05). The mean Vit D3 level was 31.3 and 40 in the case and control groups, respectively, with significant difference (P=0.0001). The mean Ca and P were alike across the types of drug in the case group (P > 0.05); however, the mean Vit D3 level was lower in the case versus controlgroup with significant difference (P=0.040). ConclusionTotally, according to the obtained results, it may be concluded that treatment with antiepileptic drugs, especially stimulant type, is related to the lower Vit D3 level, but not to the Ca and P levels.&nbsp

Hopkins Syndrome in a 14-Year-Old Boy; a Case Report

Hopkins syndrome (HS) is a flaccid paralysis resembling poliomyelitis that has been seen in some children who are recovering from an acute episode of asthma. This syndrome should be suspected based on clinical findings even before the occurrence of characteristic breathing patterns and epilepsy. We report a 14-year-old boy who had experienced an episode of HS

Evaluation of Radiographic, Neuropathological, and Demographic Findings in Children Aged 1 To 18 Years with Brain Tumor

Background: Brain tumors in children can involve different parts of the brain and cause high mortality. These tumors have different types, and they cause different conflicts and complications. So far, limited studies have been conducted in Iran on children's brain tumors. This study aimed to evaluate radiographic, neuropathological, and demographic findings in children aged 1 to 18 years with brain tumors. Materials and Methods: In this descriptive study, which was conducted for children aged 1 to 18 years with brain tumors admitted to the children's ward of Shohada Hospital (Iran-Tehran) in 2012-2018, 64 children were evaluated. Patient information was extracted from patients' files, including basic data radiological and clinical findings. A significance level was considered less than 0.05. Results: Twenty-six patients (40.6%) were girls, and 38 (59.4%) were boys. 96.9% of the children were term, and the mortality rate was 40.6%. 57.8% were diagnosed in less than one month from the onset of symptoms. 47.6% of patients had a positive family history, and none of them had a history of brain infection. The most common clinical complaint was N/V. The most common location of the tumor was the fourth ventricle (31.3%), and acute hydrocephalus was also seen in 19 patients (29.7%). The most common tumor was medulloblastoma (93.8%), and the most common stage was grade 4 (98.4%). Desmoplastic medulloblastoma was the most common form of medulloblastoma. 9.4% of patients were positive for tumor marker P53. None of the patients were positive for Beta-Catenin. Conclusion: The findings have shown that being a boy, involvement of the fourth ventricle and medulloblastoma are the most common characteristics of brain tumor involvement in Iranian children

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

Methylmalonic Acidemia: Diagnosis and Neuroimaging Findings of This Neurometabolic Disorder (An Iranian Pediatric Case Series)

How To Cite This Article: Karimzadeh P, Jafari N, Jabbehdari S, Taghdiri MM, Nemati H, Saket S, Alaee MR, Ghofrani M, Tonakebni SH. Methylmalonic Acidemia: Diagnosis and Neuroimaging Findings of This Neurometabolic Disorder (An Iranian Pediatric Case Series). Iran J Child Neurol. 2013 Summer; 7(3): 63-66. ObjectiveMethylmalonic acidemia is one of the inborn errors of metabolism resulting in the accumulation of acylcarnitine in blood and increased urinary methylmalonic acid excretion. This disorder can have symptoms, such as neurological and gastrointestinal manifestations, lethargy, and anorexia.Materials & MethodsThe patients who were diagnosed as methylmalonic acidemia in the Neurology Department of Mofid Children’s Hospital in Tehran, Iran, between 2002 and 2012 were included in our study. The disorder was confirmed by clinical findings, neuroimaging findings, and neurometabolic and geneticassessment in reference laboratory in Germany. We assessed the age, gender, past medical history, developmental status, clinical manifestations, and neuroimaging findings of 20 patients with methylmalonic acidemia.ResultsEighty percent of the patients were offspring of consanguineous marriages. Half of the patients had Failure to thrive (FTT) due to anorexia; 85% had history of developmental delay or regression, and 20% had refractory seizure, which all of them were controlled. The patients with methylmalonic acidemia were followed for approximately 5 years and the follow-up showedthat the patients with early diagnosis had a more favorable clinical response in growth index, refractory seizure, anorexia, and neurodevelopmental delay. Neuroimaging findings included brain atrophy, basal ganglia involvement (often in putamen), and periventricular leukomalacia.ConclusionAccording to the results of this study, we suggest that early assessment and diagnosis have an important role in the prevention of disease progression and clinical signs.References:1. Trinh BC, Melhem ER, Barker PB. Multi-slice proton MR spectroscopy and diffusion-weighted imaging in methylmalonic acidemia: report of two cases and review of the literature. AJNR Am J Neuroradiol 2001;22(5):831-3.2. Mahoney MJ, Bick D. Recent advances in the inherited methylmalonic acidemias. Acta Paediatr Scand1987;76(5):689-96.3. Radmanesh A, Zaman T, Ghanaati H, Molaei S, Robertson RL, ZamaniAA. Methylmalonic acidemia: brain imaging findings in 52 children and a review of the literature.Pediatr Radiol 2008 Oct;38(10):1054-61.4. Cantani A. [Methylmalonic acidemia: classification, diagnosis and therapy]. KlinPadiatr 1983;195(6):388-93.5. Avery ME, First LR, Pediatric Medicine, 2nd ed. Williams & Wilkins, Waverly Company; 1994. p.1075.6. Matsui SM, Mahoney MJ, Resenberg LE. The natural history of the inherited methylmalonic acidemias. N Engl J Med 1983;308(15):857-61.7. Holliday MA, Barrat M, Arner ED. Pediatric Nephrology, 3rd ed. William and Wilkins 1994; p. 890.8. Soda H, Yoshida I, Aramaki S, Kuriya N, Aoki K, Inokuchi T, et al. Renal handling of methylmalonic acid in a uraemic patient with vitamin B12 unresponsive methylmalonica cidaemia. J Inherit Metab Dis 1996;19(1):90-1.9. Imen M, Hanene B, Ichraf K, Aida R, Ilhem T, Naziha K, et al. Methylmalonic acidemia and hyperglycemia: an unusual association. Brain Dev 2012;34(2):113-4.10. Ma X, Zhang Y, Yang Y, Liu X, Yang Z, Bao X, et al. Epilepsy in children with methylmalonic acidemia: electroclinical features and prognosis. Brain Dev 2011;33(9):790-5.11. Brismar J, Ozand PT. CT and MR of the brain in disorders of the propionate and methylmalonatemetabolism. AJNR Am J Neuroradiol 1994;15(8):1459-73.12. Nicolaides P, Leonard J, Surtees R. Neurological outcome of methylmalonic acidaemia. Arch Dis Child 1998;78:508-12.

GM2-Gangliosidosis (Sandhoff and Tay Sachs disease): Diagnosis and Neuroimaging Findings (An Iranian Pediatric Case Series)

How to Cite This Article: Karimzadeh P, Jafari N, Nejad Biglari H, Jabbeh Dari S, Ahmad Abadi F, Alaee MR, Nemati H, Saket S,Tonekaboni SH, Taghdiri MM, Ghofrani M. GM2-Gangliosidosis (Sandhoff and Tay Sachs disease): Diagnosis and Neuroimaging Findings (An Iranian Pediatric Case Series) Iran J Child Neurol. 2014 Summer;8(3): 55-60. AbstractObjectiveGM2-Gangliosidosis disease is a rare autosomal recessive genetic disorder that includes two disorders (Tay–Sachs and Sandhoff disease).These disorders cause a progressive deterioration of nerve cells and inherited deficiency in creatinghexosaminidases A, B, and AB.Materials & MethodsPatients who were diagnosed withGM2-Gangliosidosis in the Neurology Department of Mofid Children’s Hospital in Tehran, Iran from October 2009 to February 2014were included in our study. The disorder was confirmed by neurometabolic and enzyme level detection of hexosaminidases A, B, and ABin reference to Wagnester Laboratory in Germany. We assessed age, gender, past medical history, developmental status, clinical manifestations, and neuroimaging findings of 9 patients with Sandhoff disease and 9 with Tay Sachs disease.Results83% of our patients were the offspring of consanguineous marriages. All of them had a developmental disorder as a chief complaint.38%of patients had a history of developmental delay or regression and 22% hadseizures. The patients with Sandhoff and Tay Sachs disease were followed for approximately 5 years and the follow-up showed all patients were bedridden or had expired due to refractory seizures, pneumonia aspiration, or swallowingdisorders.Neuro-imaging findings included bilateral thalamic involvement, brain atrophy, and hypo myelination in near half of our patients (48%). ConclusionAccording to the results of this study, we suggest that cherry-red spots, hyperacusis, refractory seizures, and relative parents in children with developmental delay and/or regression should be considered for assessment of GM2-Gangliosidosis disease. ReferencesYun YM, Lee SN. A case refort of Sandhoff disease. Korean journal of ophthalmology: KJO. 2005;19(1):68-72. Epub 2005/06/03.O’Dowd BF, Klavins MH, Willard HF, Gravel R, Lowden JA, Mahuran DJ. Molecular heterogeneity in the infantile and juvenile forms of Sandhoff disease (O-variant GM2 gangliosidosis). The Journal of biological chemistry. 1986;261(27):12680-5. Epub 1986/09/25.Der Kaloustian VM, Khoury MJ, Hallal R, Idriss ZH, Deeb ME, Wakid NW, et al. Sandhoff disease: a prevalent form of infantile GM2 gangliosidosis in Lebanon. American journal of human genetics. 1981;33(1):85-9. Epub 1981/01/01.Cashman NR, Antel JP, Hancock LW, Dawson G, Horwitz AL, Johnson WG, et al. N-acetyl-beta-hexosaminidase beta locus defect and juvenile motor neuron disease: a case study. Annals of neurology. 1986;19(6):568-72. Epub 1986/06/01.Oonk JGW, Van der Helm HJ, Martin JJ. Spinocerebellar degeneration: hexosaminidase A and B deficiency in two adult sisters. Neurology 1979;29:380–384.Federico A, Ciacci G, D’Amore I, Pallini R, Palmeri S, Rossi A, et al. GM2 Gangliosidosis with Hexosaminidase A and B Defect: Report of a Family with Motor Neuron Disease-like Phenotype. In: Addison GM, Harkness RA, Isherwood DM, Pollitt RJ, editors. Practical Developments in Inherited Metabolic Disease: DNA Analysis, Phenylketonuria and Screening for Congenital Adrenal Hyperplasia: Springer Netherlands; 1986. p. 307-10.Gomez-Lira M, Sangalli A, Mottes M, Perusi C, Pignatti PF, Rizzuto N, et al. A common beta hexosaminidase gene mutation in adult Sandhoff disease patients. Human genetics. 1995;96(4):417-22. Epub 1995/10/01.Barbeau A, Plasse L, Cloutier T, Paris S, Roy M. Lysosomal enzymes in ataxia: discovery of two new cases of late onset hexosaminidase A and B deficiency (adult Sandhoff disease) in French Canadians. The Canadian journal of neurological sciences Le journal canadien des sciences neurologiques. 1984;11(4 Suppl):601-6. Epub 1984/11/01.Haghighi A, Masri A, Kornreich R, Desnick RJ. Tay- Sachs disease in an Arab family due to c.78G>A HEXA nonsense mutation encoding a p.W26X early truncation enzyme peptide. Molecular genetics and metabolism. 2011;104(4):700-2. Epub 2011/10/05.Tay SK, Low PS, Ong HT, Loke KY. Sandhoff disease- a case report of 3 siblings and a review of potential therapies. Annals of the Academy of Medicine, Singapore. 2000;29(4):514-7. Epub 2000/11/01.Ghosh M, Hunter WS, Wedge C. Corneal changes in Tay-Sachs disease. Canadian journal of ophthalmology Journal canadien d’ophtalmologie. 1990;25(4):190-2.Epub 1990/06/01.Hittmair K, Wimberger D, Bernert G, Mallek R, Schindler EG. MRI in a case of Sandhoff’s disease. Neuroradiology. 1996;38 Suppl 1:S178-80. Epub 1996/05/01.Koelfen W, Freund M, Jaschke W, Koenig S, Schultze C. GM-2 gangliosidosis (Sandhoff’s disease): two year follow-up by MRI. Neuroradiology. 1994;36(2):152-4.Epub 1994/01/01.Kokot W, Raczynska K, Krajka-Lauer J, Iwaszkiewicz- Bilikiewicz B, Wierzba J. [Sandhoff’s and Tay-Sachs disease--based on our own cases]. Klinika oczna. 2004;106(3 Suppl):534-6. Epub 2005/01/08. Choroba Sandhoffa oraz Tay Sachsa--w oparciu o przypadki  wlasne.Barness LA, Henry K, Kling P, Laxova R, Kaback M, Gilbert-Barness E. A 7-year old white-male boy with progressive neurological deterioration. American journal of medical genetics. 1991;40(3):271-9. Epub 1991/09/01.Arisoy AE, Ozden S, Ciliv G, Ozalp I. Tay-Sachs disease: a case report. The Turkish journal of pediatrics. 1995;37(1):51-6. Epub 1995/01/01.Ozkara HA, Topcu M, Renda Y. Sandhoff disease in the Turkish population. Brain & development. 1997;19(7):469-72. Epub 1997/12/31.

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

Evaluation of One Hundred Pediatric Muscle Biopsies During A 2-Year Period in Mofid Children And Toos Hospitals

 How to Cite This Article:Nilipor Y, Shariatmadari F, Abdollah gorji F, Rouzrokh M, Ghofrani M, Karimzadeh P, Taghdiri MM,  Delavarkasmaei H, Ahmadabadi F, Bakhshandeh bali MK, Nemati H, Saket S, Jafari N, Yaghini O, Tonekaboni SH.  Evaluation of One Hundred Pediatric Muscle Biopsies During A 2-Year Period in Mofid Children And Toos Hospitals. Iran J Child Neurol. 2013 Spring;7(2):17-21. ObjectiveMuscle biopsy is a very important diagnostic test in the investigation of a child with suspected neuromuscular disorder. The goal of this study was to review and evaluate pediatric muscle biopsies during a 2-year period with focus on histopathology diagnosis and correlations with other paraclinicstudies.Materials & MethodsWe investigated 100 muscle biopsies belonging to patients with clinical impression of neuromuscular disorder. These patients have been visited consecutively by pediatric neurologists during 2010 to 2012. Samples were investigated by standard enzyme histochemical and immunohistochemical techniques.ResultSixty-nine (69%) males and 39 (39%) females with a mean age of 5.7 years were evaluated. Major pathologic diagnoses were Muscular dystrophy (48 cases), Neurogenic atrophy (18 cases), nonspecific myopathic atrophy (12cases), congenital myopathy (6 cases), storage myopathies (4 cases) and in 6 cases there was no specific histochemical pathologic finding. EMG was abnormal in 79 cases. Degree of correlation between EMG and biopsy result was significant in children ≥ 2 years of age.ConclusionThis study confirms the high diagnostic yields of muscle biopsyespecially only if standard and new techniques such as enzyme study and immunohistochemistry are implemented. Also, we report 11 cases of Merosin negative congenital muscular dystrophy. This is the largest documented case series of Merosin deficient congenital muscular dystrophy reported from Iran. References1. Harvey B. Sarnat. Evaluation and Investigation. In:Kliegman. Stanton.Schor. Behrman.Nelson Text Book of Pediatrics.19th edition.Philadelphia: Elsevier,2011. P.2109-2112. 2. Harvey B. Sarnat and John H Menkes. Disease of TheMotore Unit. In: John H Menkes, Harvey B Sarnat, Bernard L Maria. Child Neurology. 7th edition.california: lippincott,2006.p.969-972.3. Marius Kuras Skram, Sasha Gulati, Erik Larrson. Muscle Biopsies In Children-An Evaluation Of Histopathology And Clinical Valueduring A 5-Year Period. Upsala J Med Sci 2009 March:114 (1);41-45.4. Owji M, Modaressi F. Diagnosis of Myopathies Using Histology. Histochemistry, Immunohistochemistry and Electron Microscopy 2010,12 (4):434 -440.5. Dua T, Das M, Kabra M. Spectrum of Floppy Children in Indian Scenario. Indian Pediatric J 2001, 38:1236-1243.6. Rabie M, Jossiphov J, Nevo Y. Electromyography accuracy compared to muscle biopsy in childhood. J Child Neurol 2007 jul; 22(7):803.8.

prevalence and types of congenital heart disease in babies born in the city of Khorramabad (2007- 2011)

Background: Congenital heart disease is the most common congenital malformations in newborns. The aim of this study was to determine the prevalence and types of congenital heart disease in babies born in the city of Khorramabad. Materials and Methods: The present study was a descriptive cross-sectional. Sampling method was census. All babies born in the city of Khorramabad from 2007 to 2011, whom their first echocardiogram was diagnosed with congenital heart disease, were studied. The studied variables included sex, premature birth, cyanosis, anomalies of other organs, maternal age over 40 years, consanguineous parents, drug use during pregnancy, maternal medical history, a history of congenital heart disease in the mother and types of heart abnormality. Data collected through questionnaire and statistically analyzed by SPSS software. Results: Of 43195 newborns177 cases had congenital heart disease. The incidence of congenital heart disease per 1,000 live births in the study was 4.2. In this study ventricular septal defect (44%) and atrial septal defect (21 %) were the most common congenital malformations of the heart. 63.8% of neonates with congenital heart disease were male(p=0.005), 80.4 % term infants(p<0.001) , 93.5 % of them had no cyanosis, consanguineous parents 28%,congenital heart diseases in parents 10.3 %, history of diabetes in 9.3 % of mothers and 5.6% of newborns had other anomalies such as cleft lip and palate. Conclusion: In this study, ventricular septal defect and atrial septal defect were the most common congenital malformations of the heart and frequency of boys was approximately twice of girl