Review Article

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


Iranian Journal of Child Neurology, Vol. 11 No. 3 (2017), 3 July 2017, Page 1-6

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.



This study was conducted on the demographic data, clinical characteristics, electroencephalography, neuroradiological findings, and their impact on the recurrence of ataxia.

 Materials & Methods

A 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-prepared

questionnaires. 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.


Forty-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.


After 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.



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Research Article

Assessment of the Relationship between Body Mass Index and Gross Motor Development in Children


Iranian Journal of Child Neurology, Vol. 11 No. 3 (2017), 3 July 2017, Page 7-14

How to Cite This Article: Amouian S, AbbasiShaye Z, Mohammadian S, Bakhtiari M, Parsianmehr B. Assessment of the Relationship between Body Mass Index and Gross Motor Development in Children. Iran J Child Neurol.Summer 2017; 11(3):7-14.




Obesity is a growing epidemic and public health problem in children. The purpose of this study was to determine the effect of body mass index (BMI) on the gross motor development.

Materials & Methods

In this cross-sectional study conducted in 2012-13 in Gorgan, northern Iran, the gross motor development of 90 children 3-5 yr old in three groups of lean, normal and obese/overweight were evaluated by the ages and stages questionnaires (ASQ) and Denver 2 scale.


Totally, 90 children were enrolled and their developmental level was assessed with two ASQ and Denver II indices. The mean and standard deviation of the ASQ scores of the children was 53.11± 11.06 and based on Denver index, 9 children (10%) were at developmental delay status, 15 (16.7%) in the caution conditions, and 53 (58.9%) at normal developmental status. The developmental level was lower in obese/overweight group comparing with other groups according to both Denver and ASQ and there was a significant difference between obese/overweight group and normal group based in Denver and ASQ, respectively. There was no significant difference between underweight and normal and obese and underweight groups.


Overweight and obesity could affect on the gross motor development. 


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Drug-Induced Apnea in Children Admitted to Loghman Hakim Hospital, Tehran, Iran


Iranian Journal of Child Neurology, Vol. 11 No. 3 (2017), 3 July 2017, Page 15-18

How to Cite This Article: Gholami N,Alwasabi F, Farnaghi F. Drug-Induced Apnea in Children Admitted to Loghman Hakim Hospital, Tehran, Iran. Iran J Child Neurol. Summer 2017; 11(3):15-18.



Environmental hazards, including poisons, can cause irreparable effects and even be fatal for children. Poisoning in children is common and serious, but often is preventable and treatable. This study aimed to evaluate the prevalence of drugs and chemical toxicity leading to apnea. In addition, we detected type of drug that induced apnea among children.

Materials & Methods

In a retrospective cross-sectional study from Apr 2012 to Apr 2013, sampled data of all hospitalized drug-induced apnea children were collected through hospital records.


The most common cause of drug toxicity was methadone syrup (74%). The mortality rate was 3.1%; all of them due to methadone poisoning.


There was a high prevalence of apnea and poisoning of methadone in children.

Methadone poisoning should be considered in apnea.



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Therapeutic Effects of Adrenocorticotropic Hormone ACTH in Children with Severely Intractable Seizure


Iranian Journal of Child Neurology, Vol. 11 No. 3 (2017), 3 July 2017, Page 19-26

How to Cite This Article: Nasiri J, Sarajan A, Salari M, Sedghi M. Therapeutic Effects of Adrenocorticotropic Hormone ACTH in Children with
Severely Intractable Seizure. Iran J Child Neurol. Summer 2017; 11(3):19-26.



Treatment of intractable seizures other than spasms is difficult and controversial.

There are few studies on efficacy of adrenocorticotropic hormone (ACTH) in treatment of patients with intractable seizure.

Materials & Methods

Twenty-five patients with intractable seizure other than spasm including 14 boys and 11 girls with median age of 58 months referred to university clinics of Pediatric Neurology in Isfahan, Iran, during 2014-2015 were prospectively investigated. ACTH was administrated according to our protocol. All cases were followed regularly and assessed for response to treatment and probable side effects, 3 wk after beginning of ACTH therapy and three months after the ACTH therapy. EEG finding were recorded before and three months after the end of ACTH therapy. Statistical analysis using Freidman test and Wilcoxon signed – rank test were performed in order to compare seizure frequency and EEG changes, respectively.


Mean A significant reduction (>80%) in seizure frequency in 11 cases (44%) and moderate reduction (50%-80%) in 7 (28%) after 3 wk of ACTH therapy.

Despite initial positive response, recurrence of seizure was observed in 7 out of 18 cases with favorable initial response within 3 months after ACTH therapy cessation. The comparison of EEG finding before and 3 months after ACTH therapy using Wilcoxon signed – rank test showed  significant differences.


ACTH therapy may be useful in treatment of children with intractable seizures who are resistant to usual antiepileptic drugs. However further studies should be performed to determine the long-term efficacy of ACTH in treatment of intractable seizure.


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Circadian Rhythm and the Seasonal Variation in Childhood Febrile Seizure


Iranian Journal of Child Neurology, Vol. 11 No. 3 (2017), 3 July 2017, Page 27-30

How to Cite This Article: Sharafi R, Hassanzadeh Rad A, Aminzadeh V. Circadian Rhythm and the Seasonal Variation in Childhood Febrile Seizure. Iran J Child Neurol. Summer 2017; 11(3):27-30.




We aimed to assess the circadian rhythm and the seasonal variation in childhood febrile seizure (FS).

Materials & Methods

This descriptive cross-sectional study was conducted retrospectively on patients’ records. Investigators assessed the records of patients with simple FS aged 6 to 60 months referred to Emergency Department of 17-Shahrivar Hospital, Rasht northern Iran during Jan 2010 to Jan 2013. Data were gathered by a checklist including age, sex, temperature, duration of seizure, seasonal, months, diurnal variation, and level of consciousness.


Totally, 349 patients including 193 (55.3%) boys and 156 (44.7%) girls with the mean age of 22.85±18.34 months were enrolled in this study. The mean temperature of patients was 38.45±0.53°C. The mean duration of seizure was 97.91±57 sec. Awake, drowsy and slept patients were noted in 170 (48.7%), 33 (9.5%) and 146 (41.8%) cases, respectively. Most of the FS occurred in winter 118 (33.8%), afternoon 132 (37.8%) and in Jan 55 (15.8%).


Body temperature adjusted by hypothalamus affecting by circadian rhythm. FS is the most common form of seizure in childhood occurred by multifactorial issues. Otherwise, the occurrence of seizure in patients with epilepsy may be affected by the circadian rhythm. Seizures happen more frequent at a specific time in 24 h during a day.


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Treatment of Cystic Craniopharyngioma with Intracystic Stereotactic Instillation of Phosphorus 32


Iranian Journal of Child Neurology, Vol. 11 No. 3 (2017), 3 July 2017, Page 31-36

How to Cite This Article: Shahzadi S, Soltani A, Shahzadi A, Parsa Kh. Treatment of Cystic Craniopharyngioma with Intracystic Stereotactic Instillation of Phosphorus 32. Iran J Child Neurol. Summer 2017; 11(3):31-36.



Cystic craniopharyngiomas are considered the most common intracranial nonglial tumor in children with the tendency for cyst formations. The aim of this study was to evaluate the effect of intracystic phosphorus 32 (P32) therapies on controlling the growth of the cystic component of craniopharyngioma.

Materials & Methods

This clinical study was conducted on 47 patients with cystic craniopharyngioma from March 1998 to June 2012 at Shohada Tajrish Hospital, Tehran, Iran.

Patients were treated with stereotactic intracystic P32. The mean cyst volume was 23.5 ml, and the dose of radiation to the inner cyst wall was 250 Gy.


The overall response rate was 78.1% and the mean survival was 113.1±11months.

The survival rate at 1, 3, 5, and 10 years after p32 therapy was 91%, 77%, 73%, and 52%, respectively. There was no mortality related to the procedure and no visual or endocrinal deterioration. Visual improvement occurred in 88% of patients presented with recent deterioration due to the cyst enlargement.


Intracystic p32 therapy was an effective and almost safe procedure for the treatment of cystic component of craniopharyngioma.



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17. Barriger RB, Chang A, Lo SS, Timmerman RD, Des Rosiers C, Boaz JC, et al. Phosphorus-32 therapy for cystic craniopharyngiomas. Radiother Oncol 2011;98(2):207-12.

18. Tian ZM. Stereotactic intracavitary irradiation of huge cystic craniopharyngiomas. Zhonghua Wai Ke Za Zhi 1992;30(2):102-3.

19. Pollock BE, Lunsford LD, Kondziolka D, ad et al. Phosphorus-32 intracavitary irradiation of cystic craniopharyngiomas: current technique and long-term results. Int J Radiat Oncol Biol Phys 1995 ;33(2):437-46.

20. Voges J, Sturm V, Lehrke R, et al. Cystic craniopharyngioma: long-term results after intracavitary irradiation with stereotactically applied colloidal beta-emitting radioactive sources. Neurosurgery 1997;40(2):263-9.

21. Julow J, Backlund EO, Lányi F, et al. Long-term results and late complications after intracavitary yttrium-90 colloid irradiation of recurrent cystic craniopharyngiomas. Neurosurgery 2007;61(2):288-95.

22. Hasegawa T, Kondziolka D, Hadjipanayis CG, Lunsford LD. Management of cystic craniopharyngiomas with phosphorus-32 intracavitary irradiation. Neurosurgery 2004;54(4):813-20.

23. Anderson DR, Trobe JD, Taren JA, Gebarski SS. Visual outcome in cystic craniopharyngiomas treated with intracavitary phosphorus-32. Ophthalmology 1989;96(12):1786-92.

24. Kodama T, Matsukado Y, Uemura S. Intracapsular irradiation therapy of craniopharyngiomas with radioactive gold: indication and follow-up results. Neurol Med Chir (Tokyo) 1981;21(1):49-58.

25. Backlund EO, Axelsson B, Bergstrand CG, et al. Treatment of craniopharyngiomas--the stereotactic approach in a ten to twenty-three years’ perspective. I. Surgical, radiological and ophthalmological aspects. Acta Neurochir (Wien 1989;99(1-2):11-9.

26. Van den Berge JH, Blaauw G, Breeman WA, et al. Intracavitary brachytherapy of cystic craniopharyngiomas. J Neurosurg 1992;77(4):545-50.


Is Infantile Colic an Early Life Expression of Childhood Migraine?


Iranian Journal of Child Neurology, Vol. 11 No. 3 (2017), 3 July 2017, Page 37-41

How to Cite This Article: Tabrizi M, Badeli H, Hassanzadeh Rad A,  Aminzadeh V, Shokuhifard A. Is Infantile Colic an Early Life Expression
of Childhood Migraine? Iran J Child Neurol. summer 2017; 11(3):37-41.



Migraine is the most common childhood recurrent primary headache syndrome and infantile colic is a common cause of infantile cry. The pathogenesis of migraine and colic has not been well established and different factors may cause them. There is an association between infantile colic and the occurrence of childhood migraine. We aimed to assess whether infantile colic could be noted as an early life expression of childhood migraine or not.

Materials & Methods

This retrospective case-control study was conducted on 5-15-year-old children in Rasht, Iran during 2015-2016. Forty-one cases were children with migraine with or without aura. Overall, 123 Control participants were children with the same age referred to the pediatric clinic for routine care. Data were gathered by a checklist including age, sex, birth weight, family history of migraine, the occurrence of colic and type of feeding during infancy. Data were reported by descriptive statistics and analyzed by Fisher exact test using SPSS ver. 19.


Overall, 164 children with the mean age of 8.36± 2.53 yr were enrolled.

Seventeen (41.46%) children with migraine vs. 44 (35.7%) children in control group had the positive history of infantile colic and Fisher exact test noted significant relation between migraine and colic. Thirty-three children with infantile colic (46.57%) had the positive family history of migraine, which was significantly higher than 27 children without colic (29.7%). There was a significant relation between infantile feeding and migraine.


There is a probable relation between colic and migraine, therefore, migraine and colic as 2 pain syndromes may have a common pathophysiology and further investigations on this common pathophysiology is justified.


1. Richer L, Billinghurst L, Linsdell MA, Russell K, Vandermeer B, Crumley ET, Durec T, Klassen TP, Hartling L. Drugs for the acute treatment of migraine in children and adolescents. The Cochrane Library. 2016, Issue 4. Art. No.: CD005220.

2. Green A, Kabbouche M, Kacperski J, Hershey A, O’Brien H. Managing Migraine Headaches in Children and Adolescents. Expert Rev Clin Pharmacol 2016;9(3):477-82.

3. Pärtty A, Kalliomäki M, Salminen S, Isolauri E. Infantile Colic Is Associated With Low-grade Systemic Inflammation. J Pediatr Gastroenterol Nutr 2017; 64(5):691-5.

4. Bhatia J, Greer F. Use of soy protein-based formulas in infant feeding. Pediatrics 2008;121(5):1062-8.

5. Shaukat A, Levitt MD, Taylor BC, MacDonald R, Shamliyan TA, Kane RL, Wilt TJ. Systematic review: effective management strategies for lactose intolerance. Ann Int Med 2010 ;152(12):797-803.

6. Heine RG. Cow’s-milk allergy and lactose malabsorption in infants with colic. J Pediatr Gastroenterol Nutr 2013;57:S25-S7.

7. Romanello S, Spiri D, Marcuzzi E, Zanin A, Boizeau P, Riviere S, et al. Association between childhood migraine and history of infantile colic. JAMA 2013;309(15):1607- 12.

8. Jan MM, Al-Buhairi AR. Is infantile colic a migraine related phenomenon? Clin Pediatr 2001;40(5):295.

9. Bruni O, Fabrizi P, Ottaviano S, Cortesi F, Giannotti F, Guidetti V. Prevalence of sleep disorders in childhood and adolescence with headache: a case-control study. Cephalalgia 1997;17(4):492-8.

10. Sillanpää M, Saarinen M. Infantile colic associated with childhood migraine: A prospective cohort study. Cephalalgia 2015;35(14):1246-51.

11. Epstein LG, Zee PC. Infantile colic and migraine. JAMA 2013;309(15):1636-7.

12. Guidetti V, Ottaviano S, Pagliarini M. Childhood headache risk: warning signs and symptoms present during the first six months of life. Cephalalgia 1984;4(4):237-42.

13. Ho TW, Edvinsson L, Goadsby PJ. CGRP and its receptors provide new insights into migraine pathophysiology. Nature Rev Neurol 2010;6(10):573- 82.

14. Engel MA, Becker C, Reeh PW, Neurath MF. Role of sensory neurons in colitis: increasing evidence for a neuroimmune link in the gut. Inflamm Bowel Dis 2011;17(4):1030-3.

15. Gelfand AA, Thomas KC, Goadsby PJ. Before the headache Infant colic as an early life expression of migraine. Neurology 2012;79(13):1392-6.

16. Hall B, Chesters J, Robinson A. Infantile colic: a systematic review of medical and conventional therapies. J Paediatr Child Health 2012;48(2):128-37.

17. Critch J. Infantile colic: Is there a role for dietary interventions? Paediatr Child Health 2011;16(1):47.

18. Magis D, Schoenen J. Treatment of migraine: update on new therapies. Current Opinion Neurology 2011;24(3):203-10.

19. Katerji MA, Painter MJ. Infantile migraine presenting as colic. J Child Neurol 1994;9(3):336-7.

Neurometabolic Disorder Articles

Metabolic Screening in Children with Neurodevelopmental Delay, Seizure and/or Regression


Iranian Journal of Child Neurology, Vol. 11 No. 3 (2017), 3 July 2017, Page 42-47

How to Cite This Article: Karimzadeh P, Taghdiri MM, Abasi E, Hassanvand Amouzadeh M, Naghavi Zh, Ghazavi A, Nasehi MM, Alipour A. Metabolic Screening in Children with Neurodevelopmental Delay, Seizure and/or Regression. Iran J Child Neurol. Summer 2017; 11(3):42-47.




Neurometabolic disorder is one of the important groups of diseases that prominently has presentation early infantile period. In this study, we evaluated the result of metabolic screening of the patient with seizure, developmental delay and/or regression in development, demographic disease clinical and radiological findings on admitted and outpatient visited children.

Materials & Methods

Two-year retrospective review of 187 children with seizure, developmental delay and/or regression in the Mofid Children Hospital, Tehran, Iran was performed. The diagnosis was based on observation, findings of EEG and history of the patient, besides evaluation of patient milestones. The result of metabolic screening with Tandem mass spectrometry was evaluated using SPSS (ver.18.0) Statistical software.


Totally, 187 children with seizure, regression and/or developmental delay were evaluated by metabolic screening with tandem mass spectrometry method. The results of laboratory examination had no relationship between positive results of metabolic screening and the mentioned disease. The relations between positive results of metabolic screening and seizure, regression and/or developmental delay were not statistically meaningful.


Positive results of metabolic screening and seizure, regression and/or developmental delay were not statistically meaningful. 


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2. Mohamed S, El Melegy EM, Talaat I, et al. Neurometabolic Disorders-Related Early Childhood Epilepsy: A Single-Center Experience in Saudi Arabia. Pediatr Neonatol 2015; 56(6):393-401.

3. Berry GT, Steiner RD. Long-term management of patients with urea cycle disorders. J Pediatr 2001;138(1 Suppl): S56-60.

4. Zupec-Kania B, Zupanc ML. Long-term management of the ketogenic diet: seizure monitoring, nutrition, and supplementation. Epilepsia 2008;49 Suppl 8:23-6.

5. Weisfeld-Adams JD, Bender HA, Miley-Åkerstedt A, et al. Neurologic and neurodevelopmental phenotypes in young children with early-treated combined methylmalonic acidemia and homocystinuria, cobalamin C type. Mol Genet Metab 2013;110(3):241-7.

6. Eun SH, Hahn SH. Metabolic evaluation of children with global developmental delay. Korean J Pediatr 2015;58(4):117-22.

7. Patel KP, O’Brien TW, Subramony SH, Shuster J, Stacpoole PW. The spectrum of pyruvate dehydrogenase complex deficiency: clinical, biochemical and genetic features in 371 patients. Mol Genet Metab 2012; 105(1):34-43.

8. Bjursell MK, Blom HJ, Cayuela JA, et al. Adenosine kinase deficiency disrupts the methionine cycle and causes hypermethioninemia, encephalopathy, and abnormal liver function. Am J Hum Genet 2011; 89(4): 507-15.

9. Bolduc ME, Du Plessis AJ, Sullivan N, and et al. Spectrum of neurodevelopmental disabilities in children with cerebellar malformations. Dev Med Child Neurol 2011; 53(5):409-16.

10. Bhardwaj P, Kaushal RK, Chandel A. Biotinidase deficiency: A treatable cause of infantile seizures. J Pediatr Neurosci 2010; 5(1):82-3.

11. López-Pisón J, García-Jiménez MC, Monge-Galindo L, et al. Our experience with the aetiological diagnosis of global developmental delay and intellectual disability: 2006-2010. Neurologia 2014; 29(7):402-7.

12. Mikati MA, Hani AJ. Seizures in Childhood. In: Kliegman RM, Stanton BF, St Geme JW, Schor NF, editors. Nelson Textbook of Pediatrics. 20th ed. Philadelphia: Elsevier;2016.p.2823-56.

13. Korman SH, Jakobs C, Darmin PS, et al. Glutaric aciduria type 1: clinical, biochemical and molecular findings in patients from Israel. Eur J Paediatr Neurol 2007; 11(2):81-9.

14. Eun SH, Hahn SH. Metabolic evaluation of children with global developmental delay. Korean J Pediatr 2015; 58(4):117-122.

15. Karimzadeh P, Ahmadabadi F, Jafari N, et al. Study on MRI Changes in Phenylketonuria in Patients Referred to Mofid Hospital/ Iran. Iran J Child Neurol 2014; 8(2):53- 56.

16. Karimzadeh P, Jafari N, Ahmad Abadi F, et al. Propionic Acidemia: Diagnosis and Neuroimaging Findings of This Neurometabolic Disorder. Iran J Child Neurol 2014; 8(1):58-61.

17. Karimzadeh P, Jafari N, Jabbehdari S, et al. Methylmalonicacidemia: Diagnosis and Neuroimaging Findings of This Neurometabolic Disorder (An Iranian Pediatric Case Series). Iran J Child Neurol 2013; 7(3): 63-66.

18. Vanderver A, Wolf NI. Genetic and Metabolic Disorders of the White Matter. In: Swaiman KF, Ashwal S, Ferriero DM, Schor NF, editors. Swaiman’s Pediatric Neurology. 5th ed. Philadelphia: Elsevier Saunders;2012.p.1020-51.

19. Youssef-Turki I, Kraoua S, Smirani K, Mariem H, BenRhouma A, Rouissi , Gouider-Khouja N. Epilepsy Aspects and EEG Patterns in Neuro-Metabolic Diseases. J Behav Brain Sci 2011; 1(2).

20. Karimzadeh P, Ahmadabadi F, Jafari N, et al. Biotinidase deficiency: a reversible neurometabolic disorder (an Iranian pediatric case series). Iran J Child Neurol 2013; 7(4):47-52.

21. Walterfang M, Bonnot O, Mocellin R, Velakoulis D. The neuropsychiatry of inborn errors of metabolism. J Inherit Metab Dis 2013; 36(4):687-702.

22. Wolf NI, Bast T, Surtees R. Epilepsy in inborn errors of metabolism. Epileptic Disord. 2005; 7(2):67-81.

23. Koul R1, Al-Yahmedy M, Al-Futaisi A. E v a l u a t i o n children with global developmental delay: a prospective study at sultan qaboos university hospital, oman. Oman Med J 2012; 27(4):310-3.

24. Alrifai MT, AlShaya MA, Abulaban A, Alfadhe M. Hereditary neurometabolic causes of infantile spasms in 80 children presenting to a tertiary care center. Pediatr Neurol 2014; 51(3):390-7.

Homocystinuria with Cerebral Venous Sinus Thrombosis: Excellent Recovery with Intravenous Recombinant Tissue Plasminogen Activator


Iranian Journal of Child Neurology, Vol. 11 No. 3 (2017), 3 July 2017, Page 48-52

How to Cite This Article: Gowda VK, Nanjundappa RC, Pendharkar H, Benakappa N. Homocystinuria with Cerebral Venous Sinus Thrombosis: Excellent Recovery with Intravenous Recombinant Tissue Plasminogen Activator. Iran J Child Neurol. Summer 2017; 11(3):48-52.



Hyperhomocysteinemia can cause cerebral venous thrombosis. Recombinant tissue plasminogen activator is one of the treatment options for cerebral venous thrombosis in selected cases. We present here a 7-year-old boy with homocysteinuria with stroke. MRI of brain showed cerebral venous sinus thrombosis. We successfully treated with intravenous recombinant tissue plasminogen activator. He recovered completely without any complications.

Recombinant tissue plasminogen activator can be considered one of the treatment options in cerebral venous thrombosis in homocystinura.


1. Fernando D. Testai, MD, PhD; Philip B. Gorelick, MD,MPH. Inherited Metabolic disorders and stroke part 2-Homocystinuria, organic acidurias, and urea cycle disorders. Arch Neurol 2010; 67 (2):148-153.

2. Herrmann E, Lorenzl S, Obeid R. Review of the role of hyperhomocysteinemia and B-vitamin deficiency in neurological and psychiatric disorders-current evidence and preliminary recommendations. Fortschr Neurol Psychiatr 2007; 75: 515-527.

3. Online Mendelian Inheritance in Man. Homocystinuria. cgi?id=236200. Accessed March 27, 2009.

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5. Hacke W, Doonnan G, Fieschi C, Kaste M, von Kummer R, Broderick JP, et al. Association of outcome with early stroke treatment: Pooled analysis of ATLANTIS, ECASS, and NINDS rt –PA stroke trials. Lancet 2004; 363: 768-774.,

6. Roach ES, Golomb MR, Adams R, Biller J, Daniels S, Deveber G. et al. Management of stroke in infants and children: a scientific statement from a special writing group of the American Heart Association Stroke Council and the Council on cardiovascular disease in young. Stroke 2008; 39:2644-2691.

7. Soleau SW, Schmidt R, Stevens S, Osborn A, MacDonald JD. Extensive experience with dural sinus thrombosis. Neurosurgery 2003; 52: 534-544; discussion 542-544.

8. Janjua N, Nasar A, Lynch JK, Qureshi AI. Thrombolysis for ischemic stroke in children: data from the nationwide inpatient sample. Stroke 2007; 38:1850-1854.

9. Amlie-Lefond C, deVeber G, Chan AK, Benedict S, Bernard T, Carpenter J et al. Use of alteplase in childhood arterial ischaemic stroke: a multicentre, observational, cohort study. Lancet Neurol 2008; 8:530-536.

The Report of Three Rare Cases of the Niemann-pick Disease in Birjand, South Khorasan, Eastern Iran


Iranian Journal of Child Neurology, Vol. 11 No. 3 (2017), 3 July 2017, Page 53-56

How to Cite This Article: Noroozi Asl S, Vakili R, Ghaemi N, Eshraghi P. The Report of Three Rare Cases of the Niemann-pick Disease in Birjand, South Khorasan, Eastern Iran. Iran J Child Neurol. Summer 2017; 11(3):53-56.



Niemann–Pick disease type C (NP-C) is a rare neurovisceral and irreversible disease leading to premature death and disabling neurological signs. This autosomal recessive disease with incidence rate of 1:120000 is caused by mutations in either the NPC1 or the NPC2 gene, which leads to accumulation of cholesterol in body tissues especially brain and progressive neurological symptoms. NP-C is characterized by nonspecific visceral, neurological and psychiatric manifestations in infants. The neurological involvement is typically proceeded by systemic signs (cholestatic jaundice in the neonatal period or isolated spleno-or hepatosplenomegaly in infancy or childhood).

Early detection of NPC is important so that therapy with miglustat can delay onset of neurological symptoms and prolong survival. We describe here three infants from Birjand, South Khorasan, eastern Iran in 2016 with splenomegaly and different neurological signs that diagnosis was confirmed by genetic study. In all of them, NPC-509 was pathologically increased. They also had an unreported homozygous mutation (c. 1415T>C, p.Leu472Pro) in exon 9 of the NPC1 gene. We found unreported homozygous mutation in NPC gene.

Knowing this mutation is significant to our people. Genotype-phenotype correlations for this specific mutation needs to be further studied.



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2. Vanier MT: Niemann-Pick disease type C. Orphanet J Rare Dis 2010;5:16.

3. Di Rocco M1, Dardis A, Madeo A, Barone R, Fiumara A. Early miglustat therapy in infantile Niemann-Pick disease type C. Pediatr Neurol 2012;47(1):40-3.

4. Karimzadeh P, Tonekaboni SH, Ashrafi MR, et al. Effects of Miglustat on Stabilization of Neurological Disorder in Niemann–Pick Disease Type C Iranian Pediatric Case Series. J Child Neurol 2013;28(12):1599-606.

5. Wijburg F, Sedel F, Pineda M et al. Development of a Suspicion Index to aid diagnosis of Niemann-Pick disease type C. Neurology 2012;78(20):1560-7.

6. Wraith JE, Imrie J. New therapies in the management of Niemann-Pick type C disease: clinical utility of miglustat. Ther Clin Risk Manag 2009;5:877-87.

7. Patterson M, Hendriksz Ch, Walterfang M, et al. Recommendations for the diagnosis and management of Niemann–Pick disease type C: An update. Mol Genet Metab 2012;106(3):330-44.

8. Margaret M, Destinck DJ. Lipidosis(Lysosomal storage disease). Nelson Textbook of Pediatrics. 19th ed.

Philadelphia: WB Saunders Company. 2011:488-9.

9. Patterson M.C, Mengel E, Wijburg F, et al. Disease and patient characteristics in NP-C patients: findings from an international disease registry. Orphanet J Rare Dis 2013;8:12.

Case Report

Limb Girdle Muscular Dystrophy Type 2E Due to a Novel Large Deletion in SGCB Gene


Iranian Journal of Child Neurology, Vol. 11 No. 3 (2017), 3 July 2017, Page 57-60

How to Cite This Article: Ghafouri-Fard S, Hashemi-Gorji F, Fardaei M, Miryounesi M. Limb Girdle Muscular Dystrophy Type 2E Due to a Novel Large Deletion in SGCB Gene. Iran J Child Neurol. Summer 2017; 11(3):57-60.




Autosomal recessive limb-girdle muscular dystrophies (LGMD type 2) are a group of clinically and genetically heterogeneous diseases with the main characteristics of weakness and wasting of the pelvic and shoulder girdle muscles. Among them are sarcoglycanopathies caused by mutations in at least four genes named SGCA, SGCB, SGCG and SGCD. Here we report a consanguineous Iranian family with two children affected with LGMD type 2E.

Mutation analysis revealed a novel homozygous exon 2 deletion of SGCB gene in the patients with the parents being heterozygous for this deletion. This result presents a novel underlying genetic mechanism for LGMD type 2E.


1. Lo HP, Cooper ST, Evesson FJ, Seto JT, Chiotis M, Tay V et al. Limb-girdle muscular dystrophy: diagnostic evaluation, frequency and clues to pathogenesis. Neuromuscul Disord 2008;18(1):34-44.

2. Bushby KM, Beckmann JS. The 105th ENMC sponsored workshop: pathogenesis in the non-sarcoglycan limbgirdle muscular dystrophies, Naarden, April 12-14, 2002. Neuromuscul Disord 2003;13(1):80-90.

3. Zatz M, de Paula F, Starling A, Vainzof M. The 10 autosomal recessive limb-girdle muscular dystrophies. Neuromuscul Disord 2003;13(7-8):532-44.

4. Araishi K, Sasaoka T, Imamura M, Noguchi S, Hama H, Wakabayashi E et al. Loss of the sarcoglycan complex and sarcospan leads to muscular dystrophy in beta-sarcoglycan-deficient mice. Hum Mol Genet 1999;8(9):1589-98.

5. Pegoraro E, Hoffman EP. Limb-girdle muscular dystrophy overview. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017. 2012.

6. Straub V, Bushby K. The childhood limb-girdle muscular dystrophies. Semin Pediatr Neurol 2006;13(2):104-14.

7. Kaindl AM, Jakubiczka S, Lucke T, Bartsch O, Weis J, Stoltenburg-Didinger G, et al. Homozygous microdeletion of chromosome 4q11-q12 causes severe limb-girdle muscular dystrophy type 2E with joint hyperlaxity and contractures. Hum Mut 2005;26(3):279- 80.

8. Trabelsi M, Kavian N, Daoud F, Commere V, Deburgrave N, Beugnet C et al. Revised spectrum of mutations in sarcoglycanopathies. European journal of human genetics. Europ J Hum Gene 2008;16(7):793- 803.

9. Rivas E, Teijeira S, dos Santos MR, Porrit I, Leturcq F, Fernandez JM et al. Beta-sarcoglycanopathy (LGMD 2E) in a Spanish family. Acta Myol 2004;23(3):159-62.

10. Barresi R, Di Blasi C, Negri T, Brugnoni R, Vitali A, Felisari G et al. Disruption of heart sarcoglycan complex and severe cardiomyopathy caused by beta sarcoglycan mutations. J Med Gene 2000;37(2):102-7.

Semi Lobar Holoprosencephaly with Vertebral Segmentation Defects

Birendra RAI, Farhana SHARIF

Iranian Journal of Child Neurology, Vol. 11 No. 3 (2017), 3 July 2017, Page 61-65

How to Cite This Article: Rai B, Sharif F. Semi Lobar Holoprosencephaly with Vertebral Segmentation Defects. Iran J Child Neurol. Summer 2017; 11(3):61-65.



Holoprosencephaly is the most common embryonic brain defect. Foetuses who survive during intrauterine life are born with varying grades of brain and facial deformities. Extra craniofacial manifestations are common. Vertebral segmentation defects are rarely seen with holoprosencephaly, mainly in association with holoprosencephaly diencephalic hamartoblastoma (HDH) association. A female infant was born at term by normal delivery. Birth head circumference was below the 3rd percentile. Antenatal scan had showed microcephaly as the only abnormality. Physical examination revealed microcephaly, ocular hypotelorism, left ear skin tag and short neck. MRI of the brain showed semilobar holoprosencephaly. Neck radiograph revealed gross vertebral segmentation defect involving cervical and upper thoracic vertebrae.

She had initial feeding difficulties. She showed severe global developmental delay and had underlying central diabetes insipidus. Vertebral segmentation defect is rare in holoprosencephaly.


1. Shiota K, Yamada S, Komada M, et al. Embryogenesis of holoprosencephaly. Am J Med Genet A 2007; 43A(24):3079-87.

2. Verloes A, Gillerot Y, Langhendries JP, et al. Variability versus heterogeneity in syndromal hypothalamic  hamartoblastoma and related disorders: review and delineation of the cerebro-acro-visceral early lethality (CAVE) multiplex syndrome. Am J Med Genet 1992 Jul 1;43(4):669-77

3. Guimiot F, Marcorelles P, Aboura A, et al. Giant diencephalic harmartoma and related anomalies: a newly recognized entity distinct from the Pallister-Hall syndrome. Am J Med Genet A 2009; 149A(6):1108-15.

4. Castori M, Douzgou S, Silvestri E, et al. Reassessment of holoprosencephaly-diencephalic hamartoblastoma (HDH) association. Am J Med Genet A 2007; 143(3):277- 84.

5. Croen LA, Shaw GM, Lammer EJ. Holoprosencephaly: epidemiologic and clinical characteristics of a California population. Am J Med Genet 1996; 64(3):465-72.

6. Christèle Dubourg, Claude Bendavid, Laurent Pasquier, et al. Holoprosencephaly. Orphanet J Rare Dis 2007; 2: 8. Published online 2007 February 2.

7. Orioli IM, Castilla EE. Epidemiology of holoprosencephaly: Prevalence and risk factors. Am J Med Genet C Semin Med Genet 2010; 154C(1):13-21.

8. Plawner LL, Delgado MR, Miller VS, et al. Neuroanatomy of holoprosencephaly as predictor of function: beyond the face predicting the brain. Neurology 2002; 59(7):1058- 66.

9. Barr M Jr, Cohen MM Jr. Holoprosencephaly survival and performance. Am J Med Genet 1999; 89(2):116-20.

10. Lewis AJ, Simon EM, Barkovich AJ, et al. Middle interhemispheric variant of holoprosencephaly: a distinct cliniconeuroradiologic subtype. Neurology 2002; 59(12):1860-5.

11. Bellone S, De Rienzo F, Prodam F, et al. Etiopathogenetic advances and management of holoprosencephaly: from bench to bedside. Panminerva Med 2010; 52(4):345-54.

12. Wallis D, Muenke M. Mutations in holoprosencephaly. Hum Mutat 2000; 16(2):99-108.

13. Miller EA, Rasmussen SA, Siega-Riz AM, et al. National Birth Defects Prevention Study. Risk factors for nonsyndromic holoprosencephaly in the National Birth Defects Prevention Study. Am J Med Genet C Semin Med Genet 2010; 154C(1):62-72.

14. Cohen MM Jr, Shiota K. Teratogenesis of holoprosencephaly. Am J Med Genet 2002; 109(1):1-15.

15. Kline-Fath BM, Calvo-Garcia MA. Prenatal imaging of congenital malformations of the brain. Semin Ultrasound CT MR 2011; 32(3):167-88.

Letter to Editor

Zinc and Copper Metabolism and Risk of Autism: a reply to Sayehmiri et al


Iranian Journal of Child Neurology, Vol. 11 No. 3 (2017), 3 July 2017, Page 66-69

How to Cite This Article: Fluegge K. Zinc and copper metabolism and risk of autism: a reply to Sayehmiri et al. Iran J Child Neurol. Summer 2017; 11(3):66-69.



Sayehmiri et al. recently conducted a meta-analysis to explore the relationship between zinc and copper metabolism and autism spectrum disorders (ASD).

Recent reports have elucidated a full behavioral profile of mice exposed to prenatal zinc deficiency and documented a phenotype similar to that found in autism spectrum disorders (ASD). These studies suggest that significant alterations in Zn metabolism may be an important nutritional component in the development of ASD.

Materials & Methods

The idea that prenatal zinc deficiency may be to blame is cursorily challenged. Epidemiological studies show that high-income countries with a low estimated prevalence of inadequate zinc intake report the highest prevalence of ASD.

Consistent with other reports indicating a link between air pollution and ASD, it has recently been proposed that use of the herbicide, glyphosate, in agriculture may serve as an instrumental variable in predicting later neurodevelopmental impairment via emissions of the agricultural air pollutant, nitrous oxide (N2O).


Work in anesthesiology has demonstrated the neurological effects from subanesthetic doses of N2O, including its inhibition of the alpha 7 nicotinic acetylcholine receptor (α7), a receptor coupled to both central nitric oxide (NO) metabolism and peripheral anti-inflammation.


This correspondence explores how the aforementioned nutritional phenotypes found by Sayehmiri et al. in their systematic review may be a compensatory mechanism to counter the effects (namely, α7 inhibition) of air pollutant exposures occurring during the most critical stages of fetal development.



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