Multiple Sclerosis in Children

Soroor INALOO, Saeedeh HAGHBIN

Iranian Journal of Child Neurology, Vol. 7 No. 2 (2013), 16 June 2013 , Page 1-10

How to Cite This Article: Inaloo S, Haghbin S. Multiple Sclerosis in Children. Iran J Child Neurol. 2013 Spring;7(2):1-10.


Multiple sclerosis (MS) is the most important immune-mediated demyelinated disease of human which is typically the disease of young adults. A total of 4% to 5% of MS population are pediatric. Pediatric MS is defined as the appearance of MS before the age of sixteen. About 80% of the pediatric cases and nearly all adolescent onset patients present with attacks typical to adult MS. Approximately 97% to 99% of the affected children have relapsing-remitting MS, while 85% to 95% of the adults experience such condition. MS in children is associated with more frequent and severe relapses. Treatment is the same as adults. We aimed to review the epidemiology, etiology, clinical manifestations, and treatment of MS in children.



1. Lublin F. History of modern multiple sclerosis therapy. J Neurol 2005 Sep;252(Suppl 3):iii3-iii9. Review.
2. Murray TJ. Robert Carswell: the first illustrator of MS. Int MS J 2009 Sep;16(3):98-101.
3. Kabat EA, Glusman M, Knaub V. Quantitative estimation of the albumin and gamma globulin in normal and pathologic cerebrospinal fluid by immunochemical methods. Am J Med 1948 May;4(5):653-62.
4. Kumar DR, Aslinia F, Yale SH, Mazza JJ. Jean-Martin Charcot: the father of neurology. Clin Med Res 2011 Mar;9(1):46-9.
5. Dawson JD. The histology of disseminated sclerosis.Trans of the Roy Soc Edinb. 1916;50:517-740.
6. Gadoth N. Multiple sclerosis in children. Brain Dev 2003 Jun;25(4):229-32. Review.
7. Banwell BL. Pediatric multiple sclerosis. Curr Neurol Neurosci Rep 2004 May;4(3):245-52.
8. Renoux C, Vukusic S, Mikaeloff Y, Edan G, Clanet M, Dubois B, et al. Natural history of multiple sclerosis with childhood onset. N Engl J Med 2007 Jun 21;356(25):2603-13.
9. Boiko A, Vorobeychicle G, Paty D, Devonshire V, Sondovnick D. Early onset multiple sclerosis: a long longitudinal study. Neurology 2002 Oct 8;59(7):1006-10.
10. Yavari MJ, Inaloo S, Saboori S. Multiple sclerosis in children: A review of clinical and paraclinical features in
26 cases. Iran J Child Neurol 2008;2(4):41-46.
11. Oksenberg JR, Baranzini SE, Sawcer S, Hauser SL. The genetics of multiple sclerosis: SNPs to pathways to pathogenesis. Nat Rev Genet 2008 Jul;9(7):516-26.
12. Willer CJ, Dyment DA, Risch NJ, Sadovnick AD, Ebers GC; Canadian Collaborative Study Group. Twin concordance and sibling recurrence rates in multiple sclerosis. Proc Natl Acad Sci USA 2003 Oct 28;100(22):12877-82.
13. Ramagopalan SV, Knight JC, Ebers GC. Multiple sclerosis and the major histocompatibility complex. Curr Opin Neurol 2009 Jun;22(3):219-25.
14. Banwell B, Krupp L, Kennedy J, Tellier R, Tenembaum S, Ness J, et al. Clinical features and viral serologies in children with multiple sclerosis: a multinational observational study. Lancet Neurol 2007 Sep;6(9):773-81.
15. Alotaibi S, Kennedy J, Tellier R, Stephens D, Banwell B. Epstein Barr virus in pediatric multiple sclerosis. JAMA
16. Pohl D, Knone B, Rostasy K, Kahler E, Brunner E, Lehnert M, et al. High seroprevalence of Epstein-Barr virus in children with multiple sclerosis. Neurology 2006 Dec12;67(11):2063-5.
17. Waubant E, Mowry EM, Krupp L, Chitnis T, Yeh EA, Kuntz N,et al. Antibody response to common viruses and human leukocyte antigen-DRB1 in pediatric multiple sclerosis. Mult Scler. 2012 Dec 11.
18. Waubant E, Mowry EM, Krupp L, Chitnis T, Yeh EA, Kuntz N, et al. Common viruses associated with lower pediatric multiple sclerosis risk. Neurology 2011 Jun 7;76(23):1989-95.
19. Mikaeloff Y, Caridade G, Rossier M, Suissa S, Tardieu M. Hepatitis B vaccination and the risk of childhoodonset
multiple sclerosis. Arch Pediatric Adolesc Med 2007;161:1176-82.
20. Hammord SR, English DR, Moleod JG. The age-range of risk of developing multiple sclerosis. Brain. 2000 May;123 (Pt 5):968-74.
21. Van Amerongen BM, Dijkstra CD, Lips P, Polman CH. Multiple sclerosis and vitamin D: an update. Eur J Clin Nutr 2004 Aug; 58:1095-109.
22. Willer CJ, Dyment DA, Sadovnick AD, Rothwell PM, Murray TJ, Ebers GC, et al. Timing of birth and risk of multiple sclerosis: population based study. BMJ 2005 Jan;330(7):120.
23. Mowry EM, Krupp LB, Milazzo M, Chabas D, Strober JB, Bellman AL, et al. Vitamin D status is associated with relapse rate in pediatric-onset multiple sclerosis. Ann Neurol 2010 May;67(5):618-24.
24. Banwell B, Bar-Or A, Arnold DL, Sadovnick D, Narayanan S, Mc Gowan M, et al. Clinical, environmental, and genetic determinants of multiple sclerosis in children with acute demyelination: a prospective national cohort study. Lnacet Neurol 2011 May;10(5):436-45.
25. Disanto G, Morahan JM, Ramagopalan SV. Multiple sclerosis: risk factors and their interactions. CNS Neurol
Disord Drug Targets. 2012 Aug;11(5):545-55.
26. Munger KL, Chitnis T, Ascherio A. Body size and risk of MS in two cohorts of US women. Neuroloty 2009 Nov 10;73(19):1543-50.
27. Renoux C, Vukusic S, Mikaeloff Y, Edan G, Clanet M, Dubois B, et al. Natural history of multiple sclerosis with
childhood onset. N Engl J Med 2007 Jun; 356(25):2603-13.
28. Gusev E, Boiko A, Bikova O, Maslova O, Guseva M, Boiko S, et al. The natural history of early onset multiple sclerosis: comparison of data from Moscow and Vancouver. Clin Neurol Neurosurg 2002 Jul;104(3):203-7.
29. Simone IL, Carrara D, Tortorella C, Liquori M, Lepore V, Pellegrini F, et al. Course and prognosis in early-onset
MS: comparison with adult-onset forms. Neurology 2002 Dec;59(12):1922-8.
30. McDonald WI, Compston A, Edan G, Goodkin D, Hartung HP, Lublin FD, et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol 2001 Jul; 50(1):121-7.
31. Polman CH, Reingold SC, Edan G, Filippi M, Hartung HP, Kappos L, et al. Diagnostic criteria for multiple sclerosis: 2005 revisions to the “McDonald Criteria”. Ann Neurol 2005 Dec;58:840-6.
32. Swanton JK, Rovira A, Tintore M, Altmann DR, Barkhof F, et al. MRI criteria for multiple sclerosis in patients presenting with clinically isolated syndromes: a multicentre retrospective study. Lancet Neurol 2007 Aug;6(8):677-86.
33. Rovira A, Swanton J, Tintore M, Sastre-Garriga J, Horga A, et al. A single, early magnetic resonance imaging study in the diagnosis of multiple sclerosis. Arch Neurol 2009 May;66(5):587-92.
34. Poser CM, Paty DW, Scheinberg L, McDonald WI, Davis FA, Ebers GC, et al. New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol 1983 Mar;13(3):227-31.
35. Polman CH, Reingold SC, Banwell B, et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 2011 Feb; 69(2):292-302.
36. Mikaeloff Y, Adamsbaum C. Husson B, Vallee L, Ponsot G, Confavreux C. et al. MRI prognostic factors for relapse after acute CNS inflammatory demyelination in childhood. Brain 2004 Sep;127(Pt9):1942-7.
37. Chabas D, Castillo-Trivino T, Mowry EM, Strober JB, Glenn OA, Woubant E, et al. Vanishing MS T2-bright lesions before puberty: a distinct MRI phenotype? Neurology 2008 Sep;71(14):1090-3.
38. Krupp LB, Banwell B, Tenembaum S. Consensus definitions proposed for pediatric multiple sclerosis and
related disorder. Neurology 2007 Apr;68(16 Suppl 2):S7-S12.
39. Yeh EA, Chitnis T, Krupp L, Ness J, Chabas D, Kuntz N, et al. Pediatric multiple sclerosis. Nat Rev Neurol 2009 Nov;5(11):621-31.
40. Banwell B, Ghezzi A, Bar-Or A, Mikaeloff Y, Tardien M. Multiple sclerosis in children: clinical diagnosis, therapeutic strategies, and future directions. Lancet Neurol 2007 Oct;6(10):887-902.
41. Venkateswaran S, Banwell B. Pediatric multiple sclerosis. Neurologist 2010 Mar;16(2):92-105.
42. Waubant E, Chabas D, Okuda DT, Glenn O, Mowry E, Henry RG, et al. Difference in disease burden and activity in pediatric patients on brain magnetic resonance imaging at time of multiple sclerosis onset vs adults. Arch Neurol 2009 Aug; 66(8):967-71.
43. Ghassemi R, Antel SB, Narayanan S, Francis J, Bar-or A, Sadovnick AD, et al. Lesion distribution in children with clinically isolated syndromes. Aim Neurol 2008 Mar;63(3);401-5.
44. Yeh EA, Weinstock-Guttman B, Ramanathan M, Ramasamy DP, Willis L, Cox JL, et al. Magnetic resonance imaging characteristics of children and adults with paediatric-onset multiple sclerosis. Brain 20 Dec;132:3392-400.
45. Mikaeloff Y, Suissa S, Vallee L, Lubetzki C, Ponsot G, Confavreux C, et al. First episode of acute CNS inflammatory demyelination in childhood: prognostic factors for multiple sclerosis and disability. J Pediatr 2004 Feb;144(2):246-52.
46. Chabas D, Ness J, Belman A, Yeh EA, Kuntz N, Gorman MP, et al. Younger children with MS have a distinct CSF inflammatory profile at disease onset. Neurology 2010 Feb 2;74(5):399-405.
47. Gronseth GS, Ashman U. Practice parameter: the usefulness of evoked potentials in identifying clinically
silent lesions in patients with suspected multiple sclerosis (an evidence-based review): Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2000 May 9;54(9):11720-5.
48. Boutin B, Esquivel E, Mayer M, Chaumet S, Ponsot G, Arthuis M, et al. Multiple sclerosis in children: report of clinical and paraclinical features of 19 cases. Neuropediatrics 1988 Aug;19(3):118-23.
49. Waldman AT, Gorman MP, Rensel MR, Austin TE, Hertz NL. Management of pediatric central nervous system demyelinating disorders: consensus of United States neurologists. J Child Neurol 2011 Jun;26(6):675-82.
50. Banwell BL. Pediatric multiple sclerosis. Curr Neurol Neurosci Rep 2004 May;4(3):245-52. 
51. Yeh EA, Weinstock-Guttman B. The management of pediatric multiple sclerosis. J Child Neurol 2012;27:1384-
52. Ghezzi A, Amato MP, Capobianco M, Gallo P, Marrosu G, Matinelli V, et al. Disease-modifying drugs in childhood-juvenile multiple sclerosis: results of an Italian co-operative study. Mult Scler 2005 Aug;11(4):420-4.
53. Banwell B, Reder AT, Krupp L, Tenembaum S, Eraksoy M, Alexy B, et al. Safety and tolerability of interferon beta-1 b in pediatric multiple sclerosis. Neurology 2006 Feb;66(4):472-6.
54. Tenembaum SN, Segura MJ. Interferon beta-la treatment in childhood and juvenile-onset multiple sclerosis. Neurology 2006 Aug 8;67(3):511-3.
55. Pohl D, Waubant E, Banwell B, Chabas D, Chitnis T, Weinstock-Guttman B, et al. Treatment of pediatric multiple sclerosis and variants. Neurology 2007 Apr;68(16 suppl):S54-65.
56. Makhani N, Gorman MP, Branson HM, Stazzone L, Banwell BL, Chitnis T, et al. Cyclophosphamide therapy in pediatric multiple sclerosis. Neurology 2009 Jun;72(24):2076-80.
57. Goodin DS, Amason BG, Coyle PK, Frohman EM, Paty DW, et al. The use of mitoxantrone (Novantrone) for the treatment of multiple sclerosis: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 2003 Nov 25;61(10):1332-8.
58. Ghezzi A, Pozzilli C, Grimaldi LM, Brescia Morra V, Bartolon F, Capra R, et al. Safety and efficacy of natalizumab in children with multiple sclerosis. Neurology 2010 Sep ;75(10):912-7.
59. Mancordi GL, Saccardi R. Autologous heamatopoietic stem cell transplantation in multiple sclerosis. Lancet Neurol 2008 7:626-636.
60. Attarian HP, Brown KM, Duntley SP, Carter JD, Cross AH, et al. The relationship of sleep disturbances and fatigue in multiple sclerosis. Arch Neurol 2004 Apr;61(4):525-30.
61. Krupp LB, Alvarez LA, LaRocca NG, Scheinberg LC. Fatigue in multiple sclerosis. Arch Neurol 1988 Apr;45(4):435-7.
62. MacAllister WS, Belman AL, Milazzo M, Weisbrot DM, Christodoulou C, Scheri WF, et al. Cognitive functioning
in children and adolescents with multiple sclerosis. Neurology 2005 Apr;64(8):1422-5.

A Comparative Study on the Sedative Effect of Oral Midazolam and Oral Promethazine Medication in Lumbar Puncture


Iranian Journal of Child Neurology, Vol. 7 No. 2 (2013), 16 June 2013 , Page 11-16

How to Cite This Article: Derakhshanfar H, Modanlookordi M, Amini A, Shahrami A. A Comparative Study of the Sedative Effect of Oral Midazolam and Oral Promethazine Medication in Lumbar Puncture. Iran J Child Neurol. 2013 Spring;7(2):11-16.


Lumbar puncture (LP) essentially is a painful and stressful procedure that indicated for diagnosis and therapeutic purposes. One way to reduce the anxiety is to administer an oral premedication. The aim of this study is to compare clinical effects of oral midazolam and oral promethazine in LP.

Materials & Methods
This prospective randomized controlled clinical trial study was
performed on 80 children aged 2-7 years that were candidate for LP. They were divided into two randomized equal groups. First group received oral midazolam syrup 0.5 mg/kg and the other group received oral promethazine syrup 1mg/kg. Level of sedation, hemodynamic changes and any other complications were monitored every 5 minutes from 30 minutes before the start of the procedure.

Midazolam group and promethazine group were similar in age, gender and weight. Midazolam had significantly shorter onset of sedation and also shorter duration to maximal sedation. The two groups were similar with respect to sedative effect at all time. The only complication that was significantly more in midazolam group was nausea and vomiting.

Midazolam syrup and promethazine syrup have same sedative effect in children. Both of these medications are easy to use in preschool children and none of them appeared to be superior to another.


1. Ellenby MS, Tegtmeyer K, Lai S, Braner DA. Lumbar Puncture. N Engl J Med 2006;28;355(13):e12.
2. Crock C, Olsson C, Phillips R, Chalkiadis G, Sawyer S, Ashley D, et al. General anesthesia or conscious sedation for painful procedures in childhood cancer: The family’s perspective. Arch Dis Child 2003;88(3):253−7.
3. Holdsworth MT, Raisch DW, Winter SS, Frost JD, Moro MA, Doran NH, et al. Pain and distress from Bone marrow aspirations and lumbar punctures. Ann Pharmacother 2003;37(1):17-22.
4. Ellis JA, Villeneuve K, Newhook K, Ulrichsen J. Pain Management Practices for Lumbar Punctures: Are We Consistent? J Pediatr Nurs 2007 Dec;22(6):479-87.
5. Mathai A, Nazareth M, Raju RS. Preanesthetic sedation of preschool children: comparison of intranasal midazolam versus oral promethazin. Anesth Essays Res 2011;5(1):67-71.
6. McCann ME, Kain ZN. The management of preoperative anxiety in children: an update. Anesth Analg 2001; 93(1): 98–105.
7. Kain ZN, Caldwell-Andrews AA. Psychological preparation of children undergoing surgery. Anesth Clinic NA 2005;23:597–614.
8. Wolf AR, Rosenbarum A, Kain ZN, Larsson P, Lönnqvist PA. The place of premedication in pediatric practice. Paediatr Anaesth 2009;19(9):817-28.
9. Yuen VM, Hui TW, Irwin MG, Yuen MK. A Comparison of Intranasal Dexmedetomidine and Oral Midazolam for Premedication in Pediatric Anesthesia: A Double-Blinded Randomized Controlled Trial. Anesth Analg 2008;106(6):1715–21.
10. Funk W, Jakob W, Riedl T, Taeger K. Oral preanaesthetic
medication for children: double blind randomized study of a combination of midazplam and ketamine vs midazolam or ketamine alone. Br JAnaesth 2000;84(3):355-40
11. Mazurek MS. Sedation and Analgesia for Procedures outside the Operating Room. Semin in Pediatr Surg 2004;13(3):166-173.
12. Jo SH, Hong HK, Chong SH, Lee HS, Choe H. H1 antihistamine drug promethazine directly blocks hERG K+ channel. Pharmacol Res 2009;60(5):429-37.
13. Gutstein HB, Johnson KL, Heard MB, Gregory GA. Oral Ketamine Preanesthetic Medication in children, Anesthesiology 1992;76(1):28-33.
14. Almenrader N, Passariello M, Coccetti B, Haiber R, Pietropaoli P. Premedication in children: a comparison of oral midazolam and oral clonidine. Pediatr Anesth 2007;17(12):1143–9.

15. Singh N, Pandey RK, Saksena AK, Jaiswal JN. A comparative evaluation of oral midazolam with oral sedatives as  premedication in pediatric dentistry. J Clin Pediatr Dent 2002;26(2):161-4.

16. Naziri F, Alijanpour E, Rabei SM, Seifi S, Mir M, Hosseinpour M, et al. Comparison of oral Midazolam with oral Promethazine on decreasing anxiety of children when separated from their parents before anesthesia. J Babol Univ Medl Sci  2007;9(4):29-32.
17. Parkinson L, Hughes J, Gill A, Billingham I, Ratcliffe J, Choonara I. A randomized controlled trial of sedation in the critically ill. Paediatr Anaesth 1997;7(5): 405-10.
18. Crean P. Sedation and neuromuscular blockade in paediatric intensive care;practice in the United Kingdom and North America. Paediatr Anaesth 2004;14(6):439-42.
19. Schmidt AP, Valinetti EA, Bandeira D, Bertacchi MF, Simões CM, Auler JO Jr. Effects of preanesthetic administration of midazolam, clonidine, or dexmedetomidine on postoperative pain and anxiety in children. Paediatr Anaesth 2007;17(7):667-74.
20. Pfeil N, Uhlig U, Kostev K, Carius R, Schröder H, Kiess W, et al. Antiemetic edications in children with presumed infectious gastroenteritis--harmacoepidemiology in Europe and Northern America. J Pediatr 2008;153(5):659-62.

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


Iranian Journal of Child Neurology, Vol. 7 No. 2 (2013), 16 June 2013 , Page 17-21


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.


Muscle 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 paraclinic

Materials & Methods
We 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.

Sixty-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.

This study confirms the high diagnostic yields of muscle biopsy
especially 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.


1. 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 The
Motore 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.


A novel deletion mutation in ASPM gene in an Iranian family with autosomal recessive primary microcephaly

Elinaz AKBARIAZAR, Mohammad Reza EBRAHIMPOUR, Saeedeh AKBARI, Sanaz ARZHANGHI, Seydeh Sedigheh ABEDINI, Hossein NAJMABADI, Kimia KAHRIZI

Iranian Journal of Child Neurology, Vol. 7 No. 2 (2013), 16 June 2013 , Page 23-30

How to Cite This Article: Akbarizar E, Ebrahimpour M, Akbari S, Arzhanghi S, Abedini SS, Najmabadi H, Kahrizi K. A Novel Deletion Mutation in ASPM Gene in an Iranian Family with Autosomal Recessive Primary Microcephaly. Iran J Child Neurol.  2013 Spring;7(2):23-30.


Autosomal recessive primary microcephaly (MCPH) is a neurodevelopmental and genetically heterogeneous disorder with decreased head circumference due to the abnormality in fetal brain growth. To date, nine loci and nine genes responsible for the situation have been identified. Mutations in the ASPM gene (MCPH5) is the most common cause of MCPH. The ASPM gene with 28 exons is essential for normal mitotic spindle function in embryonic neuroblasts.

Materials & Methods
We have ascertained twenty-two consanguineous families with
intellectual disability and different ethnic backgrounds from Iran. Ten out of twenty-two families showed primary microcephaly in clinical examination. We investigated MCPH5 locus using homozygosity mapping by microsatellite marker.

Sequence analysis of exon 8 revealed a deletion of nucleotide (T) in donor site of splicing site of ASPM in one family. The remaining nine families were not linked to any of the known loci. More investigation will be needed to detect the causative defect in these families.

We detected a novel mutation in the donor splicing site of exon 8 of the ASPM gene. This deletion mutation can alter the ASPM transcript leading to functional impairment of the gene product.


1. Pattison L, Crow YJ, Deeble VJ, Jackson AP, Jafri H, Rashid Y, et al. A Fifth Locus for Primary Autosomal Recessive Microcephaly Maps to Chromosome 1q31. Am J Hum Genet 2000;67(6):1578-80.
2. Darvish H, Esmaeeli-Nieh S, Monajemi G, Mohseni M, Ghasemi-Firouzabadi S, Abedini S, et al. A clinical and molecular genetic study of 112 Iranian families with primary microcephaly. Journal of Medical Genetics 2010;47(12):823-8.
3. Tolmie JL, M M, JB S, D D, JM C. Microcephaly: genetic counselling and antenatal diagnosis after the birth of an affected child. Am JMed Genet 1987;27583-94.
4. Cowie V. The genetics and sub-classification of microcephaly. J Ment Defic Res 1960;4:42-7.
5. Woods C. Human microcephaly. Curr Opin Neurobiol 2004;14(1):112-7.
6. Kaindl AM PS, Kumar P, Kraemer N, Issa L, Zwirner A, Gerard B, Verloes A MS,et al.Many roads lead to primary autosomal recessive microcephaly. Prog Neurobiol 2010;90:363-83.
7. Kumar A BS, Babu M, Markandaya M, Girimaji SC. Genetic analysis of primary microcephaly in Indian families: novel ASPM mutations. Clin Genet 2004;66:341-8.
8. Jackson AP, Eastwood H, Bell SM, Adu J, Toomes C, Carr IM, et al. Identification of microcephalin, a protein implicated in determining the size of the human brain. The American Journal of Human Genetics 2002;71(1):136-42.

9. Roberts E, Jackson AP, Carradice AC, Deeble VJ, Mannan J, Rashid Y, et al. The second locus for autosomal recessive primary microcephaly (MCPH2) maps to chromosome 19q13. 1-13.2. European journal of human genetics: EJHG  1999;7(7):815.
10. Kousar R, Hassan MJ, Khan B, Basit S, Mahmood S, Mir A, et al. Mutations in WDR62 gene in Pakistani families with autosomal recessive primary microcephaly. BMC neurology 2011;11(1):119.
11. Evans PD, Vallender EJ, Lahn BT. Molecular evolution
of the brain size regulator genes<i> CDK5RAP2</i>and<i> CENPJ</i>. Gene 2006;375:75-9.
12. Nagase T, Nakayama M, Nakajima D, Kikuno R, Ohara O. Prediction of the coding sequences of unidentified human genes. XX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. DNA research 2001;8(2):85-95.
13. Jamieson CR GC, Abramowicz MJ. Primary autosomal recessive microcephaly: homozygosity mapping of MCPH4 to chromosome 15. Am J Hum Genet 1999;65:1465-9.
14. Genin A, Desir J, Lambert N, Biervliet M, Van Der Aa N, Pierquin G, et al. Kinetochore KMN network gene CASC5 mutated in Primary Microcephaly. Human molecular genetics 2012.
15. Bond J, Roberts E, Mochida GH, Hampshire DJ, Scott S, Askham JM, et al. ASPM is a major determinant of cerebral cortical size. Nature genetics 2002;32(2):316-20.
16. Fish JL, Kosodo Y, Enard W, Pääbo S, Huttner WB. Aspm specifically maintains symmetric proliferative divisions of neuroepithelial cells. Proceedings of the National Academy of Sciences 2006;103(27):10438-43.
17. Leal G, Roberts E, Silva E, Costa S, Hampshire D, Woods C. A novel locus for autosomal recessive primary microcephaly (MCPH6) maps to 13q12.2. Journal of Medical Genetics 2003;40(7):540-2.
18. Kumar A. Mutations in STIL, encoding a pericentriolar and centrosomal protein, cause primary microcephaly. The American Journal of Human Genetics 2009;84(2):286-90.
19. Hussain MS, Baig SM, Neumann S, Nurnberg G, Farooq M, Ahmad I, et al. Atruncating mutation on CEP135 causes primary microcephaly and disturbed centrosomal function.AMJ,HumGenet 2012;90:871-8.
20. Guernsey DL, Jiang H, Hussin J, Arnold M, Bouyakdan K, Perry S, et al. Mutations in centrosomal protein CEP152 in primary microcephaly families linked to MCPH4. The American Journal of Human Genetics 2010;87(1):40-51.
21. Gul A, Hassan MJ, Mahmood S, Chen W, Rahmani S, Naseer MI, et al. Genetic studies of autosomal recessive primary microcephaly in 33 Pakistani families: novel sequence variants in ASPM gene. Neurogenetics 2006;7(2):105-10.
22. Roberts E, Hampshire D, Springell K, Pattison L, Y C, Jafri H, et al. Autosomal recessive primary microcephaly: an analysis of locus heterogeneity and phenotypic variation. J Med Genet 2002;39:718–721.
23. Woods CG BJ, Enard W. Autosomal recessive primary microcephaly (MCPH): a review of clinical, molecular, and evolutionary findings. Am J Hum Genet 2005 May;76(5):717-28.
24. Kouprina N, Pavlicek A, Collins NK, Nakano M, Noskov VN, Ohzeki JI, et al. The microcephaly ASPM gene is expressed in proliferating tissues and encodes for a mitotic spindle protein. Human Molecular Genetics 2005;14(15):2155-65.
25. Bond J, Scott S, Hampshire DJ, Springell K, Corry P, Abramowicz MJ, et al. Protein-Truncating Mutations in< i> ASPM</i> Cause Variable Reduction in Brain Size. The American Journal of Human Genetics 2003;73(5):1170-7.
26. Pichon B, Vankerckhove S, Bourrouillou G, Duprez L, Abramowicz MJ. A translocation breakpoint disrupts the ASPM gene in a patient with primary microcephaly. European journal of Human Genetics 2004;12(5):419-21.
27. Garshasbi.M, Motazacker M, Kahrizi K, Behjati F, Abedini S, Nieh S, et al. SNP array-based homozygosity mapping reveals MCPH1 deletion in family with autosomal recessive mental retardation and mild microcephaly. Hum Genet 2006 Feb;118(6):708-15.
28. Jackson A, McHale D, Campbell D, Jafri H, Rashid Y, Mannan J, et al. Primary autosomal recessive microcephaly (MCPH1) maps to chromosome 8p22-pter. Am J Hum Genet 1998 Aug;63(2):541-6.
29. Moynihan L, Jackson A, Roberts E, Karbani G, Lewis I, Corry P, et al. A third novel locus for primary autosomal recessive microcephaly maps to chromosome 9q34. Am J Hum Genet 2000 Feb;66(2):724-7.
30. Bond J, Roberts E, Springell K, Lizarraga S, Scott S, Higgins J, et al. A centrosomalmechanism involving CDK5RAP2 and CENPJ controls brain size. Nat Genet.2005 Apr;37(4):353-5. Nat Genet 2005 Apr;37(4):353-5.
31. Jamieson C, Govaerts C, Abramowicz M, J. Primary autosomal recessive microcephaly: homozygosity mapping of MCPH4 to chromosome 15. Am J Hum Genet. 1999;65:1465-9.

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

Seyed Hassan TONEKABONI, Ahmad EBRAHIMI, MohammadKazem BAKHSHANDEH BALI, Massoud HOUSHMAND, Mehdi MOGHADDASI, Mohammad Mahdi TAGHDIRI, Mohammad Mahdi NASEHI

Iranian Journal of Child Neurology, Vol. 7 No. 2 (2013), 16 June 2013 , Page 31-36


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.



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+.


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.


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.


  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  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.
  8. 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.
  9. 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.
  10. 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.
  11. 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.
  12. 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.
  13. Lossin C. A catalog  of  SCN1A variants.  Brain  Dev 2009;31:114-30.
  14. 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.
  15. 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.
  16. 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.
  17. 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.
  18. 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.
  19. 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.
  20. 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.
  21. 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.
  22. 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.
  23. 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.

Zonisamide Efficacy as Adjunctive Therapy in Children With Refractory Epilepsy

Parvaneh KARIMZADEH, Mahmoud Reza ASHRAFI, MohammadKazem BAKHSHANDEH BALI, Mohammad Mahdi NASEHI, Seyedeh Mohadeseh TAHERI OTAGHSARA, Mohammad Mahdi TAGHDIRI, Mohammad GHOFRANI

Iranian Journal of Child Neurology, Vol. 7 No. 2 (2013), 16 June 2013 , Page 37-42

How to Cite This Article: Karimzadeh P, Ashrafi MR, Bakhshandeh Bali MK, Nasehi MM, Taheri Otaghsara SM, Taghdiri MM, Ghofrani M. Zonisamide
Efficacy as Adjunctive Therapy in Children With Refractory Epilepsy. Iran J Child Neurol. 2013 Spring; 7(2):37-42.

Approximately one third of epileptic children do not achieve complete seizure improvement. Zonisamide is a new antiepileptic drug which is effective as adjunctive therapy in treatment of intractable partial seizures.
The purpose of the current study was to evaluate the effectiveness, safety, and tolerability of Zonisamide in epileptic children.

Materials & Methods
From November 2011 until October 2012, 68 children who referred to Children’s Medical Center and Mofid Children Hospital due to refractory epilepsy (failure of seizure control with the use of two or more anticonvulsant drugs) entered the study. The patients were treated with Zonisamide by dose of 2- 12 mg/kg daily in addition to the previous medication. We followed the children every three to four-weeks intervals based on daily frequency, severity and duration of seizures. During the follow-up equal and more than fifty percent reduction in seizure
frequency or severity known as response to the drug.

In this study 68 patients were examined that 61 children reached the last stage.35 (57.4%) were male and 26 (42.6%) patients were female.
After first and six months of Zonisamide administration daily seizure frequency decreased to 2.95±3.54 and 3.73±3.5 respectively. There was significant difference between seizure frequency in first and six month after Zonisamide toward initial attacks. After six months ZNS therapy a little side effects were created in 10 patients (16.4%) including stuttering(4.9%), decreased appetite (4.9%), hallucination (1.6%), dizziness(1.6%), blurred vision(1.6%) and suspiring(1.6%) as all of them eliminated later dosage reduction.

This study confirms the short term efficacy and safety of Zonisamide in children with refractory epilepsies.


1. Michal V. Johnston. Seizure in childhood. In: Robert M. Kliegman, Richad E. Behrman. Nelson Text book of pediatrics.18th edition; Philadelphia:Saunders,2010,p 2457-70.
2. Icardi J.Epilepsy in children .3th Ed. Lippincott Williams &Wilkins .edition .2004:38.

3. Barbara Olson.Treatment of refractory epilepsy.Adv stu
med 2005:Vol 5;470-473.
4. Berto P. Quality of life in patients with epilepsy and impact
of treatments. Pharmacoeconomics 2002;20:1039-59.
5. Lepikk IE. Zonisamide: chemistry, mechanism of action,
and pharmacokinetics. Seizure 2004;13S: S5-9.
6. Sobieszek G, Borowicz KK, Kimber-Trojnar Z, Małek R, Piskorska B, Czuczwar SJ. Zonisamide: a new antiepileptic drug. Pol J Pharmacol 2003 Sep- Oct; 55(5): 683-9.
7. Ohtahara, S. Zonisamide in the management of epilepsy
Japanese experience. Epilepsy Res 2006;68 (Suppl. 2):25-33.
8. Baulac M. Introduction to zonisamide. Epilepsy Res 2006;68(Suppl. 2):S3-S9.

9. Hwang H, Kim KJ. New antiepileptic drugs in pediatric epilepsy. Brain Dev 2008;30(9):549-55.
10. Kyoung Heo, Byung In Lee, Sang Do Yi, Yong Won Cho, Dong Jin Shin, Hong Ki Song, et al. Shortterm efficacy and safety of zonisamide as adjunctive treatment for refractory partial seizures: A multicenter open-label single-arm trial in Korean patients. Seizure 2012;21:188-193.
11. Schulze-Bonhage A. Zonisamide in the treatment of epilepsy. Expert Opin Pharmacother 2010;11(1):115-26.
12. Lee YJ, Kang HC, Seo JH, Lee JS, Kim HD. Efficacy and tolerability of adjunctive therapy with zonisamide in childhood intractable epilepsy. Brain Dev 2010;32(3):208-12.
13. Marmaroua A, Pellockb JM. Zonisamide: Physician and patient experiences. Epilepsy Res 2005 Mar-Apr;64(1-2):63-9.
14. Fallah R, Divesalar S, Babaei A. The efficacy and safety of zonisamide as an add-on drug in the treatment of lennox–gastaut syndrome. Iran J Child Neurol 2010 Nov;l4(3):45-50.

15. Shah J, Shellenberger K, Canafax DM. Zonisamide: chemistry, biotransformation, and pharmacokinetics. Healthcare, Philadelphia (2002), pp. 873-879.

16. Baulac M. Introduction to zonisamide. Epilepsy Res
2006 Feb;68 (Suppl 2):S3-9.
17. Baulac M, Ilo E. Leppik. Efficacy and safety of adjunctive zonisamide therapy for refractory partial seizures. Epilepsy Research 2007;75:75-83.
18. Coppola G, Grosso S, Verrotti A, Parisi P, Luchetti A,
Franzoni E, et al. Zonisamide in children and young adults with refractory epilepsy: An open label, multicenter Italian study. Epilepsy Research 2009;83:112-116.
19. Tan HJ, Martland TR, Appleton RE, Kneen R. Effectiveness and tolerability of zonisamide in children with epilepsy: A retrospective review. Seizure 2010;19:31-35.
20. Stephen LJ, Kelly K, Wilson EA, Parker P, Brodie MJ. A prospective audit of adjunctive zonisamide in an everyday clinical setting. Epilepsy Behav 2010 Apr;17(4):455-60.
21. Catarino CB, Bartolini E, Bell GS, Yuen AWC, Duncan JS, Sander JW.The long-term retention of zonisamide in a large cohort of people with epilepsy at a tertiary referral centre. Epilepsy Research 2011;96:39-44.
22. Loscher W, Schmidt D. Experimental and clinical evidence for loss of effect(tolerance) during prolonged treatment with antiepileptic drugs. Epilepsia 2006;47(8):1253-84.
23. Eun SH, Kim HD, Eun BL, Lee IK, Chung HJ, Kim JS, et al. Comparative trial of low- and high-dose zonisamide as monotherapy for childhood epilepsy.Seizure 2011;20(7):558-63.

Joubert Syndrome with Variable Features: Presentation of Two Cases


Iranian Journal of Child Neurology, Vol. 7 No. 2 (2013), 16 June 2013 , Page 43-46

How to Cite this Article: Barzegar M, Malaki M, Sadegi-Hokmabadi E. Joubert Syndrome with Variable Features: Presentation of Two Cases. Iran J Child Neurol. 2013  Spring;7(2):43-46.



Joubert syndrome is a very rare disorder characterized by respiratory irregularities, nystagmus, hypotonia, and global developmental delay with abnormalities of cerebellum. We present two cases of this syndrome with different phenotypes. The first case was an 8-month-old girl with hypotonia, apnea, and mild developmental delay as well as retinal degeneration and unilateral renal cystic dysplasia. The second case was a 27-month-old boy who presented with episodes of hyperpnea, apnea, retinal dystrophy, and severe global developmental delay. Both patients had normal metabolic profile and prototype imaging of joubert syndrome including vermis agenesis and molar tooth sign.


1. Zamponi N, Rossi B, Messori A, Polonara G, Regnicolo L, Cardinali C. Joubert syndrome with associated corpus callosum agenesis. Eur J Paediatr Neurol 2002;6(1):63-6.
2. Ishikawa T, Zhu BL, Li DR, Zhao D, Michiue T, Maeda H. An autopsy case of an infant with Joubert syndrome who died unexpectedly and a review of the literature. Forensic Sci Int 2008 Aug 6;179(2-3):e67-73.
3. Joubert Syndrome Foundation, 2003. Available at Accessed February 19, 2003.
4. Joubert M, Eisenring JJ, Robb JP, Andermann F. Familial
agenesis of the cerebellar vermis. A syndrome of episodic
hyperpnea, abnormal eye movements, ataxia, and retardation. Neurology 1969 Sep;19(9):813-25.
5. Maria BL, Boltshauser E, Palmer SC, Tran TX. Clinical features and revised diagnostic criteria in Joubert syndrome. J Child Neurol 1999 Sep;14(9):583-90; discussion 590-1.
6. Badano JL, Mitsuma N, Beales PL, Katsanis N. The ciliopathies: an emerging class of human genetic disorders. Annu Rev Genomics Hum Genet 2006;7:125-48. Review.
7. Chance PF, Cavalier L, Satran D, Pellegrino JE, Koenig M, Dobyns WB. Clinical nosologic and genetic aspects of Joubert and related syndromes. J Child Neurol 1999 Oct;14(10):660-6; discussion 669-72. Review.
8. Doherty D, Glass IA, Siebert JR, Strouse PJ, Parisi MA, Shaw DW, et al. Prenatal diagnosis in pregnancies at risk for Joubert syndrome by ultrasound and MRI. Prenat Diagn 2005 Jun;25(6):442-7. Review.
9. Brancati F, Dallapiccola B, Valente EM. Joubert Syndrome and related disorders. Orphanet J Rare Dis 2010 Jul 8;5:20. doi: 10.1186/1750-1172-5-20. Review.

10. Brancati F, Barrano G, Silhavy JL, Marsh SE, Travaglini L, Bielas SL, et al. CEP290 mutations are frequently identified in the oculo-renal form of Joubert syndromerelated disorders. Am J Hum Genet 2007 Jul;81(1):104-13.
11. Salomon R, Saunier S, Niaudet P. Nephronophthisis. Pediatr Nephrol 2009 Dec;24(12):2333-44.
12. Ferland RJ, Eyaid W, Collura RV, Tully LD, Hill RS, Al-Nouri D, et al. Abnormal cerebellar development and axonal decussation due to mutations in AHI1 in Joubert syndrome. Nat Genet 2004 Sep;36(9):1008-13.
13. Joubert M, Eisenring JJ, Andermann F. Familial dysgenesis of the vermis: a syndrome of hyperventilation, abnormal eye movements and retardation. Neurology 1968 Mar;18(3):302-3.
14. Boltshauser E, Herdan M, Dumermuth G, Isler W. Joubert
syndrome: clinical and polygraphic observations in a further case. Neuropediatrics 1981 May;12(2):181-9.

Spontaneous Ventral Spinal Epidural Hematoma in an Infant: An Unusual Presentation

Asad ABBAS, Kamran AFZAL, Athar A. MUJEEB, Tabassum SHAHAB, Mohd. KHALID

Iranian Journal of Child Neurology, Vol. 7 No. 2 (2013), 16 June 2013 , Page 47-50

How to Cite This Article: Abbad A, Afzal K, Mujeeb AA, Shahab T, Khalid M. Spontaneous Ventral Spinal Epidural Hematoma in an Infant: An Unusual Presentation. Iran J Child Neurol. 2013  Spring;7(2):47-50.


Spontaneous ventral spinal epidural hematomas are extremely rare in children and clinically recognized by the appearance of acute asymmetric focal motor and sensory involvement. In infants, the initial presenting symptoms are very non-specific and irritability is often the only initial manifestation. Appearance of other neurological signs may be delayed up to hours or even days later. In the absence of significant precipitating factors such as severe trauma or previously known coagulopathies,
the diagnosis is usually delayed until the full picture of severe cord compression is developed. The diagnosis is finally made by performing magnetic resonance imaging. We report a 5-month-old infant with spinal epidural hematoma who presented with symmetrical upper limb weakness and diaphragmatic involvement to highlight the importance of recognizing the atypical manifestations for early diagnosis and


1. Phillips TW, Kling TF Jr, McGillicuddy JE. Spontaneous ventral spinal epidural hematoma with anterior cord

syndrome: report of a case. Neurosurgery 1981;9:440-3.

2. Patel H, Boaz JC, Phillips JP, Garg BP. Spontaneous spinal epidural hematoma in children. Pediatr Neurol

1998;19:302-7. Review.

3. Penar PL, Fischer DK, Goodrich I, Bloomgarden GM, Robinson F. Spontaneous spinal epidural hematoma. Int

Surg 1987;72:218-21.

4. Noth I, Hutter JJ, Meltzer PS, Damiano ML, Carter LP. Spinal epidural hematoma in a hemophilic infant. Am J

Pediatr Hematol Oncol 1993;15:131-4. Review.

5. Beatty RM, Winston KR. Spontaneous cervical epidural hematoma. A consideration of etiology. J Neurosurg


6. Alva NS. Traumatic spinal epidural hematoma of a 10-month-old male: a clinical note. Pediatr Neurol

2000;23:88-9. Review.

7. Aminoff MJ: Vascular disorders of the spinal cord, in Davidoff RA (ed): Handbook of the Spinal Cord.

Infections and Cancer, Vol 5. New York: Marcel Dekker, 1986, pp 271-273.

8. Blount J, Doughty K, Tubbs RS, Wellons JC, Reddy A, Law C, et al. In utero spontaneous cervical thoracic

epidural hematoma imitating spinal cord birth injury. Pediatr Neurosurg 2004;40:23-7.

9. Iguchi T, Ito Y, Asai M, Ito J, Okada N, Murakami M. [A case of spontaneous spinal epidural hematoma]. No To

Hattatsu 1993;25:267-70. Review. Japanese.

10. Nagel MA, Taff IP, Cantos EL, Patel MP, Maytal J, Berman D. Spontaneous spinal epidural hematoma in a

7-year-old girl. Diagnostic value of magnetic resonance imaging. Clin Neurol Neurosurg 1989;91:157-60.

11. Metzger G, Singbartl G. Spinal epidural hematoma following epidural anesthesia versus spontaneous spinal

subdural hematoma. Two case reports. Acta Anaesthesiol Scand 1991;35:105-7.

12. Patel H, Garg BP. Increasing irritability with sudden onset of flaccid weakness. Semin Pediatr Neurol 1996;3:192-7.

13. Tewari MK, Tripathi LN, Mathuriya SN, Khandelwal N, Kak VK. Spontaneous spinal extradural hematoma

in children. Report of three cases and a review of the literature. Childs Nerv Syst 1992;8:53-5. Review.

14. Pecha MD, Able AC, Barber DB, Willingham AC. Outcome after spontaneous spinal epidural hematoma in children: case report and review of the literature. Arch Phys Med Rehabil 1998;79:460-3. Review.

Acute Necrotizing Encephalopathy of Childhood; A Case Report

Mohammad Reza SALEHIOMRAN, Hajighorban NOOREDDINI, Fatemeh BAGHDADI

Iranian Journal of Child Neurology, Vol. 7 No. 2 (2013), 16 June 2013 , Page 51-54

How to Cite this Article: Salehi Omran MR, Nooreddini H, Baghdadi F. Acute Necrotizing Encephalopathy of Childhood; A Case Report. Iran J Child Neurol. 2013 Spring;7(2):51-54.



Acute Necrotizing Encephalopathy of Childhood (ANEC) is an atypical disease followed by respiratory or gastrointestinal infection, high fever, which is accompanied with rapid alteration of consciousness and seizures. This disease is seen nearly exclusively in East Asian infants and children who had previously a good health. Serial MRI examinations demonstrated symmetric lesions involving the thalami, brainstem, cerebellum, and white matter. This disease has a poor prognosis, often culminating in profound morbidity and mortality. A 22-month infant with ANEC hospitalized in Amirkola Children Hospital has been evaluated.

1. Mizuguchi M. Acute necrotizing encephalopathy of childhood: a novel form of acute encephalopathy prevalent in Japan and Taiwan. Brain Dev. 1997 Mar;19(2):81-92. Review.
2. Wang HS, Huang SC. Acute necrotizing encephalopathy of childhood. Chang Gung Med J 2001 Jan;24(1):1-10.

3. Campistol J, Gassió R, Pineda M, Fernandez-Alvarez E. Acute necrotizing encephalopathy of childhood (infantile bilateral  thalamic necrosis): two non-Japanese cases. Dev Med Child Neurol 1998 Nov;40(11):771-4.
4. Ito Y, Ichiyama T, Kimura H, Shibata M, Ishiwada N, Kuroki H, Furukawa S, Morishima T. Detection of influenza virus RNA by reverse transcription-PCR and proinflammatory cytokines in influenza-virus-associated encephalopathy. J Med Virol 1999 Aug;58(4):420-5.
5. Sugaya N. Influenza-associated encephalopathy in Japan. Semin Pediatr Infect Dis 2002 Apr;13(2):79-84. Review.
6. Skelton BW, Hollingshead MC, Sledd AT, Phillips CD, Castillo M. Acute necrotizing encephalopathy of childhood: typical findings in an atypical disease. Pediatr Radiol 2008 Jul; 38(7):810-3.
7. Wong AM, Simon EM, Zimmerman RA, Wang HS, Toh CH, Ng SH. Acute necrotizing encephalopathy of childhood: correlation of MR findings and clinical outcome. AJNR Am J Neuroradiol 2006 Oct; 27(9): 1919-23.
8. Mizuguchi M. [Acute necrotizing encephalopathy of childhood]. Ryoikibetsu Shokogun Shirizu 2000; (30 Pt 5):527-30. Review. Japanese.

9. San Millan B, Teijeira S, Penin C, Garcia JL, Navarro C. Acute necrotizing encephalopathy of childhood: report of a Spanish case. Pediatr Neurol 2007 Dec; 37(6): 438- 41.
10. Mizuguchi M, Abe J, Mikkaichi K, Noma S, Yoshida K, Yamanaka T, et al. Acute necrotising encephalopathy of childhood: a new syndrome presenting with multifocal, symmetric brain lesions. J Neurol Neurosurg Psychiatry 1995 May; 58(5): 555-61.

11. Weng WC, Peng SS, Lee WT. Acute necrotizing encephalopathy of childhood with spinal cord involvement: a case report. J Child Neurol 2010 Dec; 25(12):1539-41.
12. Ozawa T, Nakashima Y, Ito R, Hirano A, Kondo T. EEG findings in a case of acute necrotizing encephalopathy of childhood associated with influenza A virus infection. No To Hattatsu 2001 Jan;33(1):63-8. Japanese.
13. Kurachi Y, Kawahara H, Hatakeyama K, Yazawa K, Kubota M, Oka A, et al. Acute necrotizing encephalopathy with horizontal gaze palsy. No To Shinkei 1997 Aug;49(8): 753-8. Japanese.