Approach To The First Unprovoked Seizure- PART I


Iranian Journal of Child Neurology, Vol. 7 No. 3 (2013), 28 August 2013 , Page 1-5

How to Cite This Article: Ghofrani M. Approach To The First Unprovoked Seizure- PART I. Iran J Child Neurol. 2013 Summer; 7(3): 1- 5.


The approach to a child who has experienced a first unprovoked generalized tonic-clonic seizure is challenging and at the same time controversial.
How to establish the diagnosis, ways and means of investigation and whether treatment is appropriate, are different aspects of this subject.
In this writing the above mentioned matters are discussed.

1. Bluvstein JS, Moshe SL. First unprovoked seizure Current
Management in child Neurology, third ed. 2005.P.89-92.
2. Hirtz D, Berg A, Bettis D, et al. Practice Parameter: treatment of the child with a first unprovoked seizure. American Academy of Neurology 2003;60:166-175.
3. Verity GM, Ross EN, Golding J. Epilepsy in the first ten years of life: finding of the child health and education study. Br Med J 1992;305:857-861.
4. Camfiled CS, Camfield PB, Gordon K, et al. Incidence of epilepsy in childhood and adolescence: A populationbased
study in Nova Scotia from 1977 to 1985. Epilepsia 1996;37:19-23.
5. Hauser W, Annegers J, Kurland L. Incidence of epilepsy and unprovoked seizure in Rochester, Minnisota, 1935- 1984. Epilepsia 1993;34:453-468.
6. Jallon P, Goumaz M, Haenggeli G, Morabia A. Incidence
of first epileptic seizure in the canton of Geneve Switzerland. Epilepsia 1997;38:547-552.
7. Camfiled PR, Camfiled CS. Pediatric Epilepsy: An overview. Swaiman’s pediatric Neurology, 5th ed, 2012. P.703-710.
8. Gowers WB. Epilepsy and other chronic convulsive diseases; their causes, symptoms and treatment. London: J&A Churchill,1881. P.242.
9. Goddard GV, Mc Intyre DC, Leech CK. A permanent change in brain function resulting from daily electrical stimulation- Exp Neural 1969;25:295-330.
10. Berg AT, Shinnar S. Do seizures beget seizure? An assessment of the clinical evidence in human. J Clinical
Neurophysiol 1993: 14: 102-110.
11. Wasterlain CG. Recurrent seizures in developing brain are harmful. Epilepsia 1997;38:728-734.
12. Meldrum B. Physiologic changes during prolonged seizure and epileptic brain damage. Neuropediatric 1978;9:203-212.
13. Chen K, Baram TZ, Soltesz I. Febrile seizure in developing
brain results in persistent modification of neuronal excitability in limbic circuits. Nat Med 1999;5:888-894.
14. Schemid B, Tandon P, Stafstrom CE, Holmes CL. Effect of neonatal seizures on subsequent seizure-induced brain injury. Neurology 1999;53: 1754-1761.
15. Camfeild PB. Recurrent seizures in the developing brain are not harmful. Epilepsia 1997; 38:735-737.
16. Maytal J, Shinnar S, Moshe SL, Alvarez LA. Low morbidity and mortality of status epilepticus in children.Pediatrics 1989; 83:323-331.
17. Harvey As, Nolan T, Carlin JB. Community-Based study of mortality in children with epilepsy. Epilepsia 1993;34:597-603.
18. Callenbach PM, Westendorp RG, Geerts At, et al. Mortality risk in children with epilepsy: The Dutch Study of epilepsy in childhood. Pediatrics 2001;107:1259-1263.
19. Donner EJ, Smith CR. Snead OC. Sudden unexplained death in children with wpilepsy. Neurology 2001;57: 430- 434.
20. Camfield CS, Camfiels PR, Veugelers P. Deathe in children with epilepsy; A population-based study. Lancet 2002;315:1891-1895.
21. Austin JK. Concerns and fears of children with seizures. Clin Nurs Practice Epilepsy 1993;1:4-10.
22. Shinnar Sh, O’Dell Ch, Mitnick R, et al. Neuroimaging abnormalities in children with an apparent first unprovoked seizure. Epilepsy Research 2001;43:261-269.
23. Bachman DS, Hodges F, Freeman JM. Computerized axial tomography in chronic seizure disorders of childhood. Pediatrics 1976;58:828-832.
24. Nordli DR, Pedley TA. Evaluation of Children with seizure. In: shinnar S, Amir N, Branski D (Eds). Childhood Seizure. S. Kagerm Basel, 1995.P.66-77.
25. Gilliam F, Wyllie E. Diagnostic testing of seizure disorders. Neurolo Clin 1996;14: 61-84.
26. Kuzniecky RI. Neuroimaging in pediatric epilepsy. Epilepsia 1996;37:S10-S21.
27. Scheuer ML, Pedly TA. The evaluation and treatment of seizure. N Eng J Med 1990;232:1468-1474.
28. Greenberg MK, Barsan WG, Starkman S. Neuroimaging in the emergency patient with seizure.Neurology 1996 47;26-32.
29. King MA, Newton MR, Graeme Gh, et al. Epileptology of the first seizure presentation: A clinical, electroencephalographic and magnetic Resonance Imaging study of 300 consecutive casese.
Lancet 1998;352:1007-1011.
30. Hirtz D, Ashwal S, Berg A, et al. Practice Parameter. Evaluating a first nonfebrile seizure in children. Report of the quality standards subcommittee of the American Academy of Neurology, The Child Neurology Society. Neurology 2000;55:616-623.

Paraneoplastic Neurologic Syndromes in Children: A Review Article


Iranian Journal of Child Neurology, Vol. 7 No. 3 (2013), 28 August 2013 , Page 6-14

How to Cite This Article: Alavi S. Paraneoplastic Neurologic Syndromes in Children: A Review Article. Iran J Child Neurol. 2013
Summer; 7(3): 6- 14.

Paraneoplastic neurological syndromes (PNS) were initially defined as neurological syndromes with unknown etiology that often associate with cancer. This broad definition may lead to misconception that any neurological syndrome, which coincides with a cancer might be considered as PNS. In the last two decades it has been suggested that PNSs are mainly immune-mediated. The detection of onconeural antibodies has been very helpful in indicating the existence of a tumor and defining a given neurological syndrome as paraneoplastic. However, PNS may occur without onconeural antibodies, and the antibodies can occur with no neurological syndrome; thus, their presence should not be the only condition to define a neurological syndrome as paraneoplastic. Diagnosis of paraneoplastic syndromes in children may result in early detection and treatment of the pediatric cancer and can reduce the neurological damage that is the major source of morbidity in children with successfully treated tumors. This study reviews the presenting symptoms, immunology, and management options for paraneoplastic syndromes, focusing on those most commonly reported in children.

1. Darnell RB, Posner JB. Paraneoplastic syndromes involving the nervous system. N Engl J Med 200316; 349(16):1543-54.
2. Siu LL, Chapman W, Moore MJ. Use of the somatostatin
analogue octreotide acetate in the treatment of encephalopathy associated with carcinoid tumor. Case report. Am J Clin Oncol 1997; 20(6): 558-61.

3. Bataller L, Dalmau JO. Paraneoplastic disorders of the central nervous system: update on diagnostic criteria and treatment.Semin Neurol 2004 Dec; 24(4): 461-71.
4. Graus F, Keime-Guibert F, Reñe R, Benyahia B, Ribalta
T, Ascaso C, et al. Anti-Hu-associated paraneoplastic encephalomyelitis: analysis of 200 patients. Brain 2001;124(Pt 6):1138-48.
5. Honnorat J, Antoine JC. Paraneoplastic neurological syndromes. Orphanet J Rare Dis 2007 May 4; 2:22.
6. Vianello M, Vitaliani R, Pezzani R, Nicolao P, Betterle C,Keir G, et al. The spectrum of antineuronal autoantibodies in a series of neurological patients. J Neurol Sci 2004;220(1-2):29-36.
7. Graus F, Delattre JY, Antoine JC, Dalmau J, Giometto B, Grisold W, et al. Recommended diagnostic criteria for paraneoplastic neurological syndromes. J Neurol Neurosurg Psychiatry 2004;75(8):1135-40.
8. Scheid R, Honnorat J, Delmont E, Urbach H, Biniek R. A new anti-neuronal antibody in a case of paraneoplastic limbic encephalitis associated with breast cancer. J Neurol Neurosurg Psychiatry 2004;75(2):338-40.
9. Altman AJ, Baehner RL. Favorable prognosis for survival in children with coincident opso-myoclonus and neuroblastoma. Cancer 1976;37:846-52.
10. O’Neill JH, Murray NM, Newsom-Davis J. The Lambert- Eaton myasthenic syndrome. A review of 50 cases. Brain 1988;111(Pt 3):577-96.
11. Bernal F, Shams’ili S, Rojas I, Sanchez-Valle R, Saiz A, et al. Anti-Tr antibodies as markers of paraneoplastic cerebellar degeneration and Hodgkin’s disease. Neurology 2003;60(2):230-4.
12. Croft PB, Urich H, Wilkinson M. Peripheral neuropathy of sensorimotor type associated with malignant disease. Brain 1967;90(1):31-66.
13. Dalmau J, Rosenfeld MR: Paraneoplastic syndromes of
the CNS. Lancet Neurol 2008;7(4):327-40.
14. Albert ML, Austin LM, Darnell RB. Detection and treatment of activated T cells in the cerebrospinal fluid of patients with paraneoplastic cerebellar degeneration. Ann Neurol 2000;47(1):9-17.
15. Okano HJ, Park WY, Corradi JP, Darnell RB. The cytoplasmic Purkinje onconeural antigen cdr2 down-regulates c-Myc function: implications for neuronal and tumor cell survival. Genes Dev 1999;13(16):2087-97.
16. Furneaux HM, Reich L, Posner JB. Autoantibody synthesis in the central nervous system of patients with paraneoplastic syndromes. Neurology 1990;40(7):1085-91.
17. Darnell RB. Onconeural antigens and the paraneoplastic neurologic disorders: at the intersection of cancer, immunity, and the brain. Proc Natl Acad Sci U S A 1996; 93(10):4529-36
18. Albert ML, Jegathesan M, Darnell RB. Dendritic cell maturation is required for the cross-tolerization of CD8+
T cells. Nat Immunol 2001; 2(11):1010-7.
19. Posner JB. Paraneoplastic opsoclonus/myoclonus: B cells, T cells, both, or neither? Neurology 2004; 62(9):1466–7.
20. Jan H. de Graaf, Rienk Y. J. Tamminga, Willem A. Kamps. Paraneoplastic manifestations in children. Eur J Pediatr 1994;153(11):784-91.
21. Turkel SB, Brumm VL, Mitchell WG, Tavare CJ. Mood and behavioral dysfunction with opsoclonus-myoclonus ataxia. J Neuropsychiatry Clin Neurosci 2006;18(2): 239-41.
22. Brissaud HE, Beauvais P. Opsoclonus and neuroblastoma.
N Engl J Med 1969; 280:1242.
23. Harel S, Yurgenson U, Rechavi G, Burstein Y, Spirer Z.  Cerebellar ataxia and opsoclonus as the initial manifestations of myoclonic encephalopathy associated with neuroblastoma. Child Nerv Syst 1987; 3(4):245-247.
24. Connolly AM, Pestronk A, Mehta S, Pranzatelli MR 3rd, Noetzel MJ. Serum autoantibodies in childhood opsoclonus-myoclonus syndrome: an analysis of antigenic targets in neural tissues. J Pediatr 1997; 130(6): 878 -884.
25. Blaes F, Pike MG, Lang B. Autoantibodies in childhood opsoclonus-myoclonus syndrome. J Neuroimmunol 2008; 201–202: 221-6. Epub 2008 Aug 6.
26. Kirsten A, Beck S, Fühlhuber V, Kaps M, Kreutz T, Korfei M, et al: New autoantibodies in pediatric opsoclonus myoclonus syndrome. Ann N Y Acad Sci 2007; 1110:256-60.
27. Sabater L, Xifró X, Saiz A, Alberch J, Graus F. Analysis of antibodies to neuronal surface antigens in adult opsoclonus-myoclonus. J Neuroimmunol 2008; 196(1-2):188–91.
28. Pohl KR, Pritchard J, Wilson J. Neurological sequelae of the
dancing eye syndrome. Eur J Pediatr 1996;155(3):237-44.
29. Younes-Mhenni S, Janier MF, Cinotti L, Antoine JC, Tronc F, Cottin V, et al. FDG-PET improves tumour detection in patients with paraneoplastic neurological syndromes. Brain 2004 Oct;127 (Pt 10):2331–8. Epub 2004 Sep 10.
30. Titulaer MJ, Soffietti R, Dalmau J, Gilhus NE, Giometto
B, Graus F, et al. Screening for tumours in paraneoplastic
syndromes: report of an EFNS Task Force. Eur J Neurol 2010; 18(1):19-e3. Epub 2010 Sep 29.
31. Wells EM, Dalmau J. Paraneoplastic neurologic disorders in children. Curr Neurol Neurosci Rep 2011;11(2):187-94.
32. Haberlandt E, Bast T, Ebner A, Holthausen H, Kluger G,
Kravljanac R, et al. Limbic encephalitis in children and adolescents. Arch Dis Child. 2010; 96(2):186-91.
33. Yeung WL, Li CK, Nelson EA, Chik KW, Joynt GM, Yuen E, et al. Unusual neurological presentation of neuroblastoma. Hong Kong Med J 2003; 9(2):142–4.
34. Gultekin SH, Rosenfeld MR, Voltz R, Eichen J, Posner JB, Dalmau J. Paraneoplastic limbic encephalitis:neurological symptoms, immunological findings and tumour association in 50 patients. Brain 2000;123 (Pt 7):1481-94.
35. Vedeler CA, Antoine JC, Giometto B, Graus F, Grisold W, Hart IK, et al. Paraneoplastic Neurological Syndrome Euronetwork. Management of paraneoplastic neurological syndromes: report of an EFNS Task Force. Eur J Neurol. 2006 Jul; 13(7): 682-90.
36. Darnell RB: NMDA receptor as a target in paraneoplastic
encephalitis. Ann Neurol 2007; 61(1): 3-4.
37. Dalmau J, Tüzün E, Wu HY, Masjuan J, Rossi JE, Voloschin A, et al. Paraneoplastic anti-Nmethyl-Daspartate receptor encephalitis associated with ovarian teratoma. Ann Neurol 2007; 61(1): 25-36.
38. Dalmau J, Gleichman AJ, Hughes EG, Rossi JE, Peng X, Lai M, et al. Anti- NMDA receptor encephalitis: case series and analysis of the effects of antibodies. Lancet Neurol 2008; 7(12):1091-98.
39. Florance NR, Davis RL, Lam C, Szperka C, Zhou L,
Ahmad S, et al. Anti-N-methyl-Daspartate receptor (NMDAR) encephalitis in children and adolescents. Ann Neurol 2009; 66(1):11-8.
40. Drukker CA, Heij HA, Wijnaendts LC, Verbeke JI, Kaspers GJ. Paraneoplastic gastro-intestinal anti-Hu syndrome in neuroblastoma. Pediatr Blood Cancer 2009; 52(3):396-8.
41. Emir S, Kutluk MT, Göğüş S, Büyükpamukçu M.
Paraneoplastic cerebellar degeneration and Horner syndrome: association of two uncommon findings in a child with Hodgkin disease. J Pediatr Hematol Oncol 2000; 22(2):158–61.
42. de Buys Roessingh AS, Loriot MH, Wiesenauer C, Lallier
M. Lambert-Eaton myasthenic syndrome revealing an abdominal neuroblastoma. Pediatr Surg 2009; 44(8):E5–7.
43. Dalmau J, Graus F, Rosenblum MK, Posner JB. Anti-Hu associated paraneoplastic encephalomyelitis/sensory neuropathy: a clinical study of 71 patients. Medicine
(Baltimore) 1992; 71(2):59–72.
44. Ertle F, Behnisch W, Al Mulla NA, Bessisso M, Rating
D, Mechtersheimer G, et al. Treatment of neuroblastoma- related opsoclonus - myoclonus-ataxia syndrome with high-dose dexamethasone pulses. Pediatr Blood Cancer 2008; 50(3):683–7.
45. Pranzatelli MR, Tate ED, Swan JA, Travelstead AL, Colliver JA, Verhulst SJ, et al. B cell depletion therapy for new-onset opsoclonus-myoclonus. Mov Disord. 2010; 25(2): 238-42.
46. Shams’ili S, de Beukelaar J, Gratama JW, Hooijkaas H,
van den Bent M, van ‘t Veer M, et al. An uncontrolled trial of rituximab for antibody associated paraneoplastic neurological syndromes. J Neurol 2006; 253(1):16-20.
47. Alavi S, Kord Valeshabad A, Moradveisi B, Aminasnafi A, Arzanian MT. Clinical responses to rituximab in a case of neuroblastoma with refractory opsoclonus myoclonus ataxia syndrome. Case Rep Oncol Med 2012;2012:164082.
48. Alavi S, Fahimzad A, Jadali F, Ghazizadeh F, Rashidi
A. Concurrent adrenal neuroblastoma and kawasaki disease: a report of a rare case.Case Rep Pediatr 2013;2013:931703.


Ullrich Congenital Muscular Dystrophy (UCMD): Clinical and Genetic Correlations


Iranian Journal of Child Neurology, Vol. 7 No. 3 (2013), 28 August 2013 , Page 15-22

How to Cite This Article: Bozorgmehr B, Kariminejad A, Nafissi Sh, Jebelli B, Andoni U, Gartioux C, Ledeuil C, Allamand Y, Richard P, Kariminejad MH. Ullrich Congenital Muscular Dystrophy (UCMD):Clinical and Genetic Correlations. Iran J Child Neurol. 2013 Summer; 7(3): 15-22.



Ullrich congenital muscular dystrophy (UCMD) corresponds to the severe end of the clinical spectrum of neuromuscular disorders caused by mutations in the genes encoding collagen VI (COL VI). We studied four unrelated families with six affected children that had typical UCMD with dominant and recessive inheritance.

Materials & Methods
Four unrelated Iranian families with six affected children with typical UCMD were analyzed for COLVI secretion in skin fibroblast culture and the secretion of COLVI in skin fibroblast culture using quantitative RT–PCR (Q-RT-PCR), and mutation identification was performed by sequencing of complementary DNA.

COL VI secretion was altered in all studied fibroblast cultures. Two affected sibs carried a homozygous nonsense mutation in exon 12 of COL6A2, while another patient had a large heterozygous deletion in exon 5-8 of COL6A2. The two other affected sibs had homozygote mutation in exon 24 of COL6A2, and the last one was homozygote in COL6A1.

In this study, we found out variability in clinical findings and genetic inheritance among UCMD patients, so that the patient with complete absence of COLVI was severely affected and had a large heterozygous deletion in COL6A2. In contrast, the patients with homozygous deletion had mild to moderate decrease in the secretion of COL VI and were mildly to
moderately affected.

1. Voit T. Congenital Muscular Dystrophies Brain Dev 1998;20(2): 65-74.
2. Ullrich OZ Ges. Scleroatonic Muscular Dystrophy. Neurol
Psychiatr 1930;126:171-201.
3. Ullrich O. Monatsschr. Kinderheilkd 1930;47:502-10.
4. Mercuri E, Yuva Y, Brown SC, Brockington M, Kinali M, Jungbluth H, et al. Collagen VI involvement in Ullrich Syndrome: A Clinical, genetic and Immunohistochemical study. Neurology 2002;58(9):1354-9.
5. Lampe AK, Bushby KM. Collagen VI related muscle disorders. J Med Genet 2005;42(9):673-85.
6. Mercuri E, Muntoni F. Congenital Muscular Dystrophies. In: Emery AEH, editors. The muscular dystrophies. Oxford: Oxford University Press: 2001. p. 10-38.
7. Furukawa T, Toyokura Y. Congenital Hypotonic-Sclerotic muscular dystrophy. J Med Genet 1977;14(6):426-9.
8. Nonaka I, Une Y, Ishihara T, Miyoshino S, Nakashima T, Sugita H. A clinical and histological study of Ullrich’s disease (congenital atonic-sclerotic muscular dystrophy). Neuropediatrics 1981; 12(3):197-208.
9. Pan TC, Zhang RZ, Sudano DG, Marie SK, Bonnemann CG, Chu ML. New molecular mechanism for Ullrich Congenital Muscular Dystrophy: A heterozygous inframe deletion in the COL6A1 gene causes a severe phenotype. Am J Hum Genet 2003;73(2):355-69.
10. Baker NL, Morgelin M, Peat R, Goemans N, North KN, Baterman JF, et al. Dominant Collagen VI Mutations are a
common cause of ullrich congenital muscular dystrophy. Hum Mol Genet 2005;14(2]):279-93.

11. Pace RA, Peat RA, Baker NL, Zamurs L, Morgelin M, Irving M et al. Collagen VI glycine mutations: Perturbed assembly and a spectrum of clinical severity. Ann Neurol 2008;64(3):294-303.
12. Bethlem J, Wijngaarden GK. Benign myopathy, with autosomal dominant inheritance. A report on three pedigress. Brain 1976;99(1):91-100.

13. Gualandi F, Urciuolo A, Martoni E, Sabatelli P, Squarzoni S, Bovolenta M, et al Auotosomal recessive Bethlem myopath. Neurology 2009;73(22):1883-91.
14. Foley AR, Hu Y, Zou Y, Columbus A, Shoffiner J, Dunn DM, et al. Autosomal recessive Bethlam Myopathy. Neuromuscular Disord 2009;19(10):813-7.


Antiepileptic Drug-Related Adverse Reactions and Factors Influencing These Reactions


Iranian Journal of Child Neurology, Vol. 7 No. 3 (2013), 28 August 2013 , Page 23-27

How to Cite This Article: Karimzadeh P, Bakrani V. Antiepileptic Drug-Related Adverse Reactions And Factors Influencing These Reactions. Iran J Child Neurol. 2013 Summer; 7(3):23-27.


According to the basic role of drug side effects in selection of
an appropriate drug, patient compliance and the quality of life in
epileptic patients, and forasmuch as new dugs with unknown side effect have been produced and introduced, necessity of this research and similar studies is explained. This study was conducted to evaluate the incidence and clinical characteristics of anti epileptic drug (AED) related adverse reactions in children treated with AEDs.

Material & Methods
In this descriptive study, children less than 14 years old with AED
side effects referred to the Children’s Medical Center and Mofid
Childeren’s Hospital (Tehran, Iran) were evaluated during 2010-2012.
The informations were: sex, age, incriminating drug, type of drug side effect, incubation period, history of drug usage, and patient and family allergy history. Exclusive criterions were age more than 14 years old and reactions due to reasons other than AEDs (Food, bite, non-AEDs, etc.).

A total of 70 patients with AED reaction were enrolled in this
study. They included 26 (37%) females and 44 (63 %) males. The maximum rate of incidence was seen at age less than 5 years old. All the patients had cutaneous eruptions that the most common cutaneous drug eruption was maculopapular rash. The incidence of systemic and laboratory adverse events was less than similar studies. The most common culprit was phenobarbital (70%) and the least common was lamotrigine (1.4%).

In this study, we found higher rates of drug rash in patients treated with aromatic AEDs and lower rates with non-aromatic AEDs. Various endogenous and environmental factors may influence the propensity to develop these reactions.



1. Blume WT, Lu¨ders HO, Mizrahi E, et al. Glossary of descriptive terminology for ictal semiology: report of the ILAE task force on classification and terminology. Epilepsia 2001; 42: 1212Y1218.

2. Atlas:Epilepsy care in the world 2005.Available at: Accessed October 9, 2010.
3. Noorbala AA, Bagheri Yazdi SA, Yasamy MT, et al. Mental health survey of the adult population in Iran. Br J Psychiatry 2004;184:70Y73.
4. Mohammadi MR, Ghanizadeh A, Davidian H, et al. Prevalence of epilepsy and comorbidity of psychiatric disorders in Iran. Seizure 2006;15:476Y482.
5. McAuley JW, Lott RS. Seizure disorders. In: Koda-Kimble MA, Young LY, Kradjan WA, et al, eds.Applied Therapeutics: The Clinical Use of Drugs. 9th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2008:54-1Y54-38.
6. Perucca E, Beghi E, Dulac O, et al. Assessing risk to benefit ratio in antiepileptic drug therapy. Epilepsy Res 2000; 41: 107Y139.
7. Mansur AT, Pekcan Yasar S, Goktay F. Anticonvulsant hypersensitivity syndrome. Clinical and laboratory features. Int J Dermatol 2008; 47: 1184-9.
8. Bahareh Malekafzali,Franak Najibi, Cutaneous reactions of anticonvulsant drugs, in Jdermatology 2012;47:1.

9. Brandon D. Newell, Maryam Moinfar,_ Anthony J. Mancini,_and Amy Jo Nopper. Retrospective Analysis of 32 Pediatric Patients with Anticonvulsant Hypersensitivity Syndrome   (ACHSS).2009; Pediatric Dermatology 26 : 5; 536–546.
10. Sharma VK, Sethuraman G, kumear B. Cotaneous adverse drug reactions: Clinical pattern and causative agents, A 6 years Series from chandigarh, India. Postgrad Med 2001; 47: 95-9.
11. Sushma M, Noel MV, Ripika MC, Jamef J,.Guido S. Cutaneous adverse drug reactions: A 9 Year Study from a sath Indian hospital. Safety 2005; 14(8): 567-70.

A Study on Causes and Types of Abnormal Increase in Infants’ Head Circumference in Kashan/Iran


Iranian Journal of Child Neurology, Vol. 7 No. 3 (2013), 28 August 2013 , Page 28-33

How to Cite This Article: Talebian A, Soltani B, Moravveji AR, Salamati L, Davami M. A Study on Causes and Types of Abnormal Increase in infants’ Head Circumference in Kashan/Iran. Iran J Child Neurol. 2013 Summer; 7(3): 28- 33.


Head circumference is a valuable index of brain growth and its disturbances can indicate different disorders of nervous system. Abnormal increased head circumference (macrocephaly) is common and observed in about 2% of infants. In this study, the causes and clinical types of abnormal increase in infants’ head circumference were investigated in Kashan, Iran.

Materials & Methods
This cross-sectional study was performed on 90 infants less than 2 years of age with abnormal increase in head circumference in Kashan, during 2009- 2011. The data were collected by history taking, physical examination, growth chart, and imaging.

65 (72%) cases out of 90 infants were male and 25 ( 28%) cases were female. Fifty-three (58.8%) cases had familial megalencephaly, 30 (33.4%) had hydrocephalus, and other causes were observed in 7 (7.8%) cases. Eighty-three percent of Infants with familial megalencephaly and 50% with hydrocephalus had normal fontanels. In 90.6% of cases with
familial megalencephaly, family history for large head was positive. Motor development was normal in 100% of cases with familial megalencephaly and 76.7% of hydrocephalic infants.

Familial megalencephaly was the most common cause of macrocephaly in the studied infants, and most of them had normal physical examination and development, so, parental head circumferences should be considered in the interpretation of infant’s head circumference and in cases of abnormal physical examination or development, other diagnostic modalities, including brain imaging should be done.


1. Lunde A, Melve KK, Gjessing HK, Skjaerven R, Irgens LM. Genetic and environmental influences on birth weight, Birth length, Head circumference, and gestational age by use of population-based parentoffspring data. American J Epidemiol 2007;165(7):734-41.
2. Sankaran S, Das A, Bauer CR, Bada HS, Lester B, Wright LL, et al. Association between patterns of maternal substance use and infant birth weight, length and head circumference.Pediatrics 2004;114(2):e226-34.
3. Demestre Guasch X, Raspall Torrent F, Vila Ceren C, Sala Castellvi P, Elizari Saco MJ, Martinez-Nadal S, et al. Influence of socioeconomic factors on weight, length and head circumference measurements in newborns from 35 to 42 weeks gestational. An Pediatr (Barc) 2009;70(3):241-52.
4. Fenichel, GM. Disorders of cranial volume and shape. In: Clinical Pediatric Neurology: A Signs and Symptoms Approach, 6th ed. Philadelphia: Elsevier Saunders; 2009.p. 368.
5. Kinsman SL, , Johnston MV. Hydrocephalus. In: Kliegman RM, Stanton BF, St Geme JW, Schor NF, Behrman RE, editors. Nelson textbook of pediatrics. 19th ed. Philadelphia, PA: Elsevier/Saunders, Philadelphia; 2011. p. 2008-11.
6. Nard, JA. Abnormal head size and shape. In: Gartner JC,
Zitelli BJ, editors. Common and Chronic Symptoms in Pediatrics. St. Louis: Mosby; 1997.
7. Menkes JH, Sarnat HB, Flores-Sarnat L. Malformations of the central nervous system. In: Menkes JH, Sarnat HB, Maria BL, editors. Child Neurology. 7th ed. Philadelphia:  Lippincott Williams & Wilkins; 2006. p. 284.
8. Williams CA, Dagli A, Battaglia A. Genetic disorders associated with macrocephaly. Am J Med Genet A 2008;146A(15):2023-37.
9. Varma R, Williams SD, Wessel HB. Neurology. In: Zitelli BJ, Davis HW, edtors. Atlas of Pediatric Physical Diagnosis. 5th ed. Philadelphia: Mosby Elsevier; 2007. p. 563.
10. Rekate HL. Hydrocephalus in children. In: Winn HR, Youmans JR, editors. Youmans Neurological Surgery. 5th ed. St Louis: Saunders. 2003. 3387-404.
11. Gupta SN, Belay B. Intracranial incidental findings on brain MR images in a pediatric neurology practice: a retrospective study. J Neurol Sci 2008;264(1-2):34-7.
12. Alper G, Ekinci G, Yilmaz Y, Arikan C, Telyar G, Erzen C. Magnetic resonance imaging characteristics of benign macrocephaly in children. J Child Neurol 1999;14(10):678-82.
13. Smith R, Leonidas JC, Maytal J. The value of head ultrasound in infants with macrocephaly. Pediatr Radiol 1998;28(3):143-6.
14. Day RE, Schutt WH. Normal children with large heads benign familial megalencephaly. Arch Dis Child 1979;54(7):512-7.
15. Kumar R. External hydrocephalus in small children. Childs Nerv Syst 2006;22(10):1237-41.
16. Rollins JD, Collins JS, Holden KR. United states head circumference growth reference charts: birth to 21 years. J Pediatr 2010;156(6):907-13.
17. Medina LS, Frawley K, Zurakowski D, Buttros D, DeGrauw AJ, Crone KR. Children with macrocrania: Clinical and imaging predictors of disorders requiring surgery. AJNR Am J Neuroradiol 2001;22(3):564-70.
18. Lorber J, Priestly BL. Children with large heads: a practical approach to diagnosis in 557 children, with special reference to 109 children with megalencephaly. Dev Med Child Neurol 1981;23(4):494-504.
19. Zahl SM, Wester K. Routine measurement of head circumference as a tool for detecting intracranial expansion in infants: what is the gain? A nationwide survey. Pediatrics 2008;121(3):e416-20.
20. Alvarez LA, Maytal J, Shinnar S. Idiopathic external hydrocephalus: natural history and relationship to benign
familial macrocephaly. Pediatrics 1986;77(6):901-7.
21. Yew AY, Maher CO, Muraszko KM, garton HJ. Longterm health status in benign external hydrocephalus. Pediatr Neurosurg 2011;47(1):1-6.
22. Muenchberger H, Assad N, Joy P, Brunsdon R, Shores EA. Idiopathic macrocephaly in the infant: long-term neurological and neuropsychological outcome. Childs Nerv Syst 2006;22(10):1242-48.

CSWS Versus SIADH as the Probable Causes of Hyponatremia in Children With Acute CNS Disorders


Iranian Journal of Child Neurology, Vol. 7 No. 3 (2013), 28 August 2013 , Page 34-39

How to Cite This Article: Sorkhi H, Salehi Omran MR, Barari Savadkoohi R, Baghdadi F, Nakhjavani N, Bijani A. CSWS versus SIADH as the probable Causes of Hyponatremia in Children with Acute CNS Disorders. Iran J Child Neurol. 2013 Summer;7(3): 34-39.


There is a major problem about the incidence, diagnosis, and differentiation of cerebral salt wasting syndrome (CSWS) and syndrome of inappropriate secretion of antidiuretic hormone (SIADH) in patients with acute central nervous system (CNS) disorders. According to rare reports of these cases, this study was performed in children with acute CNS disorders for diagnosis of CSWS versus SIADH.

Materials & Methods
This prospective study was done on children with acute CNS disorders. The definition of CSWS was hyponatremia (serum sodium ≤130 mEq/L), urine volume output ≥3 ml/kg/hr, urine specific gravity ≥1020 and urinary sodium concentration ≥100 mEq/L. Also, patients with hyponatremia (serum sodium ≤130 mEq/L), urine output < 3 ml/kg/hr, urine specific gravity ≥1020, and urinary sodium concentration >20 mEq/L were considered to have SIADH.

Out of 102 patients with acute CNS disorders, 62 (60.8%) children were male with mean age of 60.47±42.39 months. Among nine children with hyponatremia (serum sodium ≥130 mEq/L), 4 children had CSWS and 3 patients had SIADH.
In 2 cases, the cause of hyponatremia was not determined. The mean day of hyponatremia after admission was 5.11±3.31 days. It was 5.25±2.75 and 5.66± 7.23 days in children with CSWS and SIADH, respectively. Also, the urine sodium (mEq/L) was 190.5±73.3 and 58.7±43.8 in patients with CSWS and SIADH, respectively.

According to the results of this study, the incidence of CSWS was more than SIADH in children with acute CNS disorders. So, more attention is needed to differentiate CSWS versus SIADH in order to their different management.

1. Peters JP, Welt LG, Sims EAH. A salt wasting syndrome
associated with cerebral disease. Trans Assoc Am Physiciants 1957;63:57-64.
2. Schwartz WB, Bennett W, Curelop S. A syndrome of renal sodium loss and hyponatremia probably resulting from inappropriate secretion of antiduretic hormone. Am J Med 1950:23(4); 529-42.
3. Hasan D, Wijdicks EF, Vermeulen M. Hyponatremia is associated with cerebral ischemia in patients with aneurysmal subarachnoid hemorrhage. Ann Neurol 1990;27(1):106-8.
4. Sherlock M, O’Sullivan E, Agha A, Behan LA, Rawluk D, Brennan P, et al. The incidence and pathophysiology of hyponatraemia after subarachnoid haemorrhage. Clin Endocrinol (Oxf). 2006;64(3):250-4.
5. Wartenberg KE, Schmidt JM, Claassen J, Temes RE, Frontera JA, Ostapkovich N, et al. Impact of medical complications on outcome after subarachnoid hemorrhage. Crit Care Med 2006;34(3):617-23; quiz 624.
6. Qureshi AI, Suri MF, Sung GY, Straw RN, Yahia AM, Saad M, et al. Prognostic significance of hypernatremia and hyponatremia among patients with aneurysmal subarachnoid hemorrhage. Neurosurgery 2002;50(4):749-55.
7. Bianchetti MG, Simonetti GD, Bettinelli A. Body fluids and salt metabolism - Part I. Ital J Pediatr 200919;35(1):36.
8. Peruzzo M, Milani GP, Garzoni L, Longoni L, Simonetti GD, Bettinelli A, et al. Body fluids and salt metabolism - part II. Ital J Pediatr 2010;36(1):78.
9. Moritz ML, Ayus JC. New aspects in the pathogenesis, prevention, and treatment of hyponatremic encephalopathy in children. Pediatr Nephrol. 2010;25(7):1225-38.
10. Albanese A, Hindmarsh P, Stanhope R. Management of
hyponatraemia in patients with acute cerebral insults. Arch Dis Child 2001;85(3):246-51.
11. Brimioulle S, Orellana-Jimenez C, Aminian A, Vincent JL. Hyponatremia in neurological patients: cerebral salt wasting versus inappropriate antidiuretic hormone secretion. Intensive Care Med 2008;34(1):125-31.
12. Yee AH, Burns JD, Wijdicks EF. Cerebral salt wasting: pathophysiology, diagnosis, and treatment. Neurosurg Clin N Am 2010;21(2):339-52.
13. Palmer BF. Hyponatraemia in a neurosurgical patient: syndrome of inappropriate antidiuretic hormone secretion versus cerebral salt wasting. Nephrol Dial Transplant 2000;15(2):262-8.
14. Rivkees SA. Differentiation appropriate antiduretic hormone secretion, inappropriate antiduretic secretion and cerebral salt wasting: the common, uncommon, and misnamed. Curr Opin Pediatr 2008;20(4):448-52.
15. Sterns RH, Silver SM. Cerebral salt wasting versus SIADH:
What difference? J Am Soc Nephrol 2008;19(2):194-6.
16. Jiménez R, Casado-Flores J, Nieto M, García-Teresa MA. Cerebral salt wasting syndrome in children with acute central nervous system injury. Pediatr Neurol 2006;35(4):261-3.
17. Bartter FC, Schwartz WB. Syndrome of inappropriate secretion of antidiuretic hormone. Am J Med 1967;42:790- 806.
18. Verbalis JG. Pathogenesis of hyponatremia in an experimental model of the syndrome of inappropriate antidiuresis. Am J Physiol 1994;267(6 Pt 2):R1617-25.
19. Harrigan MR. Cerebral salt wasting syndrome: a review.
Neurosurgery 1996;38(1):152-60.
20. Inatomi J, Yokoyama Y, Sekine T, Igarashi T. A case of cerebral salt-wasting syndrome associated with aseptic meningitis in an 8-year-old boy. Pediatr Nephrol 2008;23(4):659-62.
21. Brookes MJ, Gould TH. Cerebral salt wasting syndrome in meningoencephalitis: a case report. J Neurol Neurosurg Psychiatry 2003;74(2):277.
22. Cuardrado-Godia E, Cerda M, Rodriguez-Campello A, Puig de Dou J. Sindrome pierde sal cerebral en las infeccioned del sistema nervioso central. Med Clin (Barc) 2007;24:128(7);229-9.
23. Roca-Ribas F, Ninno JE, Gasperin A, Lucas M, Liubia C. Cerebral salt wasting syndrome as a postoperative complication after surgical resection of acoustic neuroma. Otol Neurotol 2002;23:992-5.
24. Bussmann C, Bast T, Rating D. Hyponatraemia in children
with acute CNS disease: SIADH or cerebral salt wasting? Childs Nerv Syst 2001;17(1-2):58-62.
25. Hardesty DA, Kilbaugh TJ, Storm PB. Cerebral Salt Wasting Syndrome in Post-Operative Pediatric Brain Tumor Patients. Neurocrit Care 2012;17(3):382-7.
26. Agha A, Thornton E, O’Kelly P, Tormey W, Phillips J, Thompson CJ. Posterior pituitary dysfunction after traumatic brain injury. J Clin Endocrinol Metab 2004;89(12):5987-92.
27. Singh S, Bohn D, Carlotti AP, Cusimano M, Rutka JT, Halperin ML. Cerebral salt wasting: truths, fallacies, theories, and challenges. Crit Care Med. 2002 Nov;30(11):2575-9.
28. Carlotti AP, Bohn D, Rutka JT, Singh S, Berry WA, Sharman A, et al. A method to estimate urinary electrolyte excretion in patients at risk for developing cerebral salt wasting. J Neurosurg 2001;95(3):420-4.
29. International committee for Standardization in Haematology. Recommended methods for measurement of red-cell and plasma volume. J Nucl Med 1980:21(8);793-800.
30. Byeon JH, Yoo G. Cerebral salt wasting syndrome after calvarial remodeling in craniosynostosis. J Korean Med Sci 2005;20(5):866–9.
31. Gutierrez OM, Lin HY. Refractory hyponatremia. Kidney Int 2007; 71(1):79-82.
32. Maesaka JK, Imbriano LJ, Ali NM, Ilamathi E. Is it cerebral or renal salt wasting? Kidney Int 2009; 76(9):934-8.
33. Maesaka JK, Venkatesan J, Piccione JM, Decker R, Dreisbach AW, Wetherington JD. Abnormal urate transport in patients with intracranial disease. Am J Kidney Dis 1992;19(1):10-5.
34. Berendes E, Walter M, Cullen P, Prien T, Van Aken H, Horsthemke J, et al. Secretion of brain natriuretic peptide in patients with aneurysmal subarachnoid haemorrhage. Lancet 1997 Jan 25;349(9047):245-9.
35. Kurokawa Y, Uede T, Ishiguro M, Honda O, Honmou O,
Kato T, et al. Pathogenesis of hyponatremia following subarachnoid hemorrhage due to ruptured cerebral aneurysm. Surg Neurol 1996;46(5):500-7.
36. Khurana VG, Wijdicks EF, Heublein DM, McClelland RL, Meyer FB, Piepgras DG, et al. A pilot study of dendroaspis natriuretic peptide in aneurysmal subarachnoid hemorrhage. Neurosurgery 2004;55(1):69- 75.
37. Kaneko T, Shirakami G, Nakao K, Nagata I, Nakagawa O, Hama N, et al. C-type natriuretic peptide (CNP) is the major natriuretic peptide in human cerebrospinal fluid. Brain Res 1993;612(1-2):104-9.
38. Damaraju SC, Rajshekhar V, Chandy MJ. Validation study of a central venous pressure-based protocol for the management of neurosurgical patients with hyponatremia and natriuresis. Neurosurgery 1997;40(2):312-6.
39. Sivakumar V, Rajshekhar V, Chandy MJ. Management of
neurosurgical patients with hyponatremia and natriuresis.
Neurosurgery 1994;34(2):269-74; discussion 274.

West Syndrome in South Iran: Electro-Clinical Manifestations


Iranian Journal of Child Neurology, Vol. 7 No. 3 (2013), 28 August 2013 , Page 40-44

How to Cite This Article: Asadi-Pooya AA, Sharifzade M. West Syndrome in South Iran: Electro-Clinical Manifestations. Iran J Child Neurol. 2013 Summer; 7(3): 40-44.

We aimed to determine the clinical and electroencephalographic (EEG) characteristics of the patients with West syndrome (WS) in south Iran.

Materials & Methods
In this retrospective study, all patients with a clinical diagnosis of WS were recruited in the outpatient epilepsy clinic at Shiraz University of Medical Sciences between September 2008 and May 2012. Age, gender, age at seizure onset, seizure type(s), epilepsy risk factors, EEG and imaging studies of all patients were registered routinely.

During the study period, 2500 patients with epilepsy were registered at our epilepsy clinic. Thirty-two patients (1.3%) were diagnosed to have WS. Age of onset (mean ± standard deviation) was 4.99 ± 3.06 months. Sixteen patients were male and 16 were female. Nine (28.1%) were reported to have two or more seizure types and 23 (71.8%) had one seizure type (epileptic spasms). At referral, no developmental delay was detected in two patients and in the rest, a mild to severe delay was noted.
Electroencephalography showed typical hypsarrhythmia in 59.4% of our patients and modified hypsarrhythmia or atypical presentations were seen in 40.6%. Two patients had pyridoxine (B6)-dependent seizures, confirmed by oral B6 trial.

Variants of the classical triad of WS including other seizure types, atypical EEG findings, and normal psychomotor function at the beginning could be observed in some patients. Rarely, treatable genetic disorders (e.g., pyridoxine-dependent seizures) should be considered in those in whom no other diagnosis is evident.


1. Blume WT, Lüders HO, Mizrahi E, Tassinari C, van Emde Boas W, Engel J Jr. Glossary of descriptive terminology for ictal semiology: report of the ILAE task force on classification and terminology. Epilepsia. 2001 Sep;42(9):1212-8.
2. Carmant L. Infantile spasms: West syndrome. Arch Neurol. 2002 Feb;59(2):317-8.
3. Hrachovy RA. West’s syndrome (infantile spasms).Clinical description and diagnosis. Adv Exp Med Biol.2002;497:33-50. Review.
4. Riikonen R, Donner M. Incidence and aetiology of infantile spasms from 1960 to 1976: a population study in Finland. Dev Med Child Neurol. 1979 Jun;21(3):333-43.
5. Dulac O. What is West syndrome? Brain Dev. 2001 Nov;23(7):447-52. Review.
6. Wong V. West syndrome-The University of Hong Kong experience (1970-2000). Brain Dev. 2001 Nov;23(7):609-15.
7. Kalra V, Gulati S, Pandey RM, Menon S. West syndrome and other infantile epileptic encephalopathies -Indian hospital experience. Brain Dev. 2001 Nov; 23(7):593-602. Corrected and republished in: Brain Dev. 2002 Mar;24(2):130-9.
8. Young C; Taiwan Child Neurology Society. National survey of West syndrome in Taiwan. Brain Dev. 2001 Nov;23(7):570-4.
9. Asadi-Pooya AA, Mintzer S, Sperling MR. Nutritional supplements, foods, and epilepsy: is there a relationship?Epilepsia. 2008 Nov;49(11):1819-27.

10. Mikati MA, Trevathan E, Krishnamoorthy KS, Lombroso CT. Pyridoxine - dependent epilepsy: EEG investigations and long-term follow-up. Electroencephalogr Clin Neurophysiol. 1991 Mar;78(3):215-21.
11. Nabbout R, Soufflet C, Plouin P, Dulac O. Pyridoxine dependent epilepsy: a suggestive electroclinical pattern. Arch Dis Child Fetal Neonatal Ed. 1999 Sep;81(2):F125-9.

12. Gospe SM Jr. Pyridoxine-dependent seizures: new genetic and biochemical clues to help with diagnosis and treatment. Curr Opin Neurol. 2006 Apr;19(2):148-53. Review.

13.Riikonen R. The latest on infantile spasms. Curr Opin Neurol. 2005 Apr;18(2):91-5. Review.

Risk Factors for Birth Asphyxia in an Urban Health Facility in Cameroon

Andreas CHIABI, Seraphin NGUEFACK, Evelyne MAH, Sostenne NODEM, Lawrence MBUAGBAW, Elie MBONDA, Pierre-Fernand TCHOKOTEU, Anderson DOH

Iranian Journal of Child Neurology, Vol. 7 No. 3 (2013), 28 August 2013 , Page 46-54

How to Cite This Article: Chiabi A, Nguefack S, Mah E, Nodem S, Mbuagbaw L, Mbonda E, Tchokoteu PF, Doh A. Risk Factors for Birth Asphyxia in an Urban Health Facility in Cameroon. Iran J Child Neurol. 2013 Summer; 7(3):46-54.

The World Health Organization (WHO) estimates that 4 million children are born with asphyxia every year, of which 1 million die and an equal number survive with severe neurologic sequelae. The purpose of this study was to identify the risk factors of birth asphyxia and the hospital outcome of affected neonates.

Materials & Methods
This study was a prospective case-control study on term neonates in a tertiary hospital in Yaounde, with an Apgar score of < 7 at the 5th minute as the case group, that were matched with neonates with an Apgar score of ≥ 7 at the 5th minute as control group. Statistical analysis of relevant variables of the mother and neonates was carried out to determine the significant risk factors.

The prevalence of neonatal asphyxia was 80.5 per 1000 live births. Statistically significant risk factors were the single matrimonial status, place of antenatal visits, malaria, pre-eclampsia/eclampsia, prolonged labor, arrest of labour,
prolonged rupture of membranes, and non-cephalic presentation. Hospital mortality was 6.7%, that 12.2% of them had neurologic deficits and/or abnormal transfontanellar ultrasound/electroencephalogram on discharge, and 81.1% had
a satisfactory outcome.

The incidence of birth asphyxia in this study was 80.5% per1000 live birth with a mortality of 6.7%. Antepartum risk factors were: place of antenatal visit, malaria during pregnancy, and preeclampsia/eclampsia. Whereas prolonged labor, stationary labor, and term prolonged rupture of membranes were intrapartum risk faktors. Preventive measures during prenatal  visits through informing and communicating with pregnant women should be reinforced.


1. World Health Organisation. Perinatal mortality: a listing
of available information. WHO/frh/msm/96.7.Geneva: WHO;1996.
2. Lawn JE, Cousens S, Zupan J; Lancet Neonatal Survival
Steering Team. 4 million neonatal deaths: When? Where?
Why? Lancet 2005;365;891-900.
3. Bryce J, Boschi-Pinto C, Shibuya K, Black RE, WHO Child Health Epidemiology Reference Group. WHO estimates of the causes of death in children. Lancet 2005;365:1147-52.
4. United Nations. The Millenium Development Goals Report 2010. New York; 2010
5. Boog G. La souffrance foetale aigue. J Gynecol Obstet
Biol Reprod 2001;30:393-432.
6. Zupan-Simunek V. Définition de l’asphyxie intrapartum
et conséquences sur le devenir. J Gynecol Obstet Biol
Reprod 2008;37S: S7-S15.
7. McGuire W. Perinatal asphyxia. Available from: http:// background/0320.html. (Accessed 2/3/2010).
8. De Vries LS, Jongmans MJ. Long-term outcome after
neonatal hypoxic-ischaemic encephalopathy. Arch Dis
Child Fetal Neonatal Ed 2010;95:F220-F4.
9. Dilenge ME, Majnemer A, Shevell MI. Long-term  developmental outcome of asphyxiated term neonates. J
Child Neurol 2001;16:781-92.
10. Haider BA, Bhutta ZA. Birth asphyxia in developing countries: Current status and public health implications. Curr Probl Pediatr Adolesc Health Care 2006;6:178-88.
11. Badawi N, Kurinczuk JJ, Keogh JM, Alessandri LM, O’Sullivan F, Burton PR, et al. Intrapartum risk factors for newborn encephalopathy: the Western Australian case-control study. BMJ 1998;317(7172):1554-8.
12. Badawi N, Kurinczuk JJ, Keogh JM, Alessandri LM, O’Sullivan F, Burton PR, et al. Antepartum risk factors for newborn encephalopathy: the Western Australian case-control study. BMJ 1998;317(7172):1549-53.
13. Arniel-Tison C, Ellison P. Birth asphyxia in the full term newborn: early assessment and outcome. Dev Med Child Neurol 1986;28: 671-82.
14. Sarnat HB, Sarnat MS. Neonatal encephalopathy following fetal distress. Arch Neurol 1976;33:696-705.
15. Sullivan KM, Soe MM: Sample size for a cross-sectional, cohort, or clinical trial studies. Available from: http:// 25/4/2011)
16. Zupan-Simunek V, Razafimahefa H, Caeymaex L. Pronostic neurologique des asphyxies perinatales à terme. J Gynecol Obstet Biol Reprod 2003;32:85-90.
17. Monebenimp F, Tietche F, Eteki N. Asphyxie néonatale au centre hospitalier universitaire de Yaoundé. Clin Mother Child Health 2005;2:335-8.
18. Douba EC. Souffrance cérébrale asphyxique du nouveauné
a terme au Centre Mère-Enfant de Yaoundé. MD thesis. Faculty of Medicine and Biomedical Sciences, University of Yaounde I; 2007.
19. Airede AI. Birth asphyxia and hypoxic- ischemic encephalopathy incidence and severity. Ann Trop Pediatr
1991;11(4): 331-5.
20. Ogunlesi TA, Oseni SB. Severe birth asphyxia in Wesley
Guild hospital: A persistent plague!. Niger Med Pract 2008;53(3):40-3.
21. Thornberg E, Thiringer K, Odeback A, Milson I. Birth asphyxia: incidence, clinical course and outcome in a
Swedish population. Acta Pediatr 1995;84(8):1927-32.
22. Gonzales de Dios J, Moya M. Perinatal difference in asphyxic full terms newborn: an epidemiological study. Rev Neurol 1996; 24:812-9.
23. Chandra S, Ramji S, Thirupuram S. Perinatal asphyxia: multivariate analysis of risk factors in hospital births. India Pediatr 1997;34(3):206-12.
24. Muhammad A. Birth asphyxia. Professional Med J
2004;11(4): 416-22.
25. Johnston MV, Hagberg H. Sex and the pathogenesis of
cerebral palsy. Dev Med Child Neurol 2007;49:74-8.
26. Raatikainen K, Heiskanen N, Heinoven S. Marriage still
protects pregnancy. BJOG 2003;112(10): 1411-6.
27. Houndjahoué GFH. Etude de la mortalité néonatale due à
l’asphyxie dans le district sanitaire de Kolokani au Mali (Thèse de Doctorat en Médecine). Faculté de Médecine, de Pharmacie et d’Odonto-Stomatologie. Université de Bamako; 2004.
28. Kinoti SN. Asphyxia of the newborn in East, Central and
Southern Africa. East Afr Med J 1993;70(7):422-33.
29. Rehana M, Yasmeen M, Farrukh M, Naheed PS, Uzma DM. Risk factors of birth asphyxia. J A M C. 2007;19(3):67-71.
30. Diallo S, Kourouma ST, Camara YB. Mortalité néonatale à l’institut de nutrition et de santé de l’enfant (INSE), Conakry-République de Guinée. Med Afr Noire 1998;45(5):326-9.
31. Victory R, Penava D, Dasilva O, Natale R, Richardson B. Umbilical cord pH and base excess values in relation to adverse outcome events for infants delivering at term. Am J Obstet Gynecol 2004;191(6):2021-8.
32. Meka LR. Evaluation de la prise en charge des nouveaunés
en salle de naissance : cas de l’Hôpital Gynéco- Obstétrique et Pédiatrique de Yaoundé (MD Thesis). Faculty of Medicine and Biomedical Sciences. Yaoundé: University of Yaounde I; 2008.
33. World Health Organization. WHO Antenatal care randomized trial: manual for the implementation of the new model. Geneva: World Health Organization; 2002.
34. Institut National de la Statistique (INS) et ORC Macro.
Enquête démographique et de santé du Cameroun. Calverton Maryland, USA : INS et ORC Macro; 2004
35. Kumari S, Sharma M, Yuadav M, Saraf A, Kabra M,
Merha R. Trends in neonatal outcome with low Apgar score. India J Pediatr 1993; 60(3):415-22.
36. Boeuf P, Tan A, Romagosa C, Radford J, Mwapasa V, Molyneux ME, et al. Placental hypoxia during placental
malaria. J Infect Dis 2008;197(5):757-65.
37. Brahim BJ, Johnson PM. Placental malaria and preeclampsia
through the looking glass backwards? J Reprod Immunol 2005; 65(1):1-15.
38. Ellis M, Manandhar N, Manandhar DS, Costello AM. Risk factors for neonatal encephalopathy in Kathmandu, Nepal, a developing country: unmatched case-control study. BMJ 2000;320:1229-36.

Neurological Manifestations of an Old Disease: A Case Report


Iranian Journal of Child Neurology, Vol. 7 No. 3 (2013), 28 August 2013 , Page 55-57

How to Cite This Article: Islami Z, Ataee Nakhaei MH. Neurological Manifestations of An Old Disease: A Case Report. Iran J Child Neurol. 2013 Summer; 7(3): 55-57.


Neurological manifestations of neonatal disorders have various causes, among them neonatal tetanus, albeit rare, is a potentially fatal and preventable disease, which is seen in underdeveloped and developing countries. Although the
disease has been eradicated from I.R. Iran, pregnant women immigrating to Iran from neighboring countries, especially from eastern border, may carry a risk of neonatal tetanus to the child due to inadequate tetanus immunization and inappropriate post-delivery care. It is then important to maintain a high index of suspicion for early diagnosis and prompt treatment, when infants present with poor feeding and abnormal behavior.
Case presentation Here, we report the clinical course of a newborn with neonatal tetanus, who was admitted with complaints of poor feeding and muscle rigidity, more than a decade after eradication of the disorder.



1. WHO. Immunization, Vaccines and Biologicals. Available
en/; 2008 [Access 25.10.2011].
2. Lum SH, Chew MF. Neonatal Tetanus: A Study of Five Cases in Sandakan, Sabah. Med J Malaysia 2009;64(1):80-2.
3. Ilic M, Pejcic L, Tiodorovic B, Hasani B, Stankovic S, Milojevic D, et al. Neonatal tetanus – report of a case. Turk J pediatr 2010;52:404-8.
4. Chang SC, Wang CL. Neonatal tetanus after home delivery:
report of one case. Pediatr Neonatol 2010;51(3):182-5.
5. Cook TM, Protheroe RT, Handel JM. Tetanus: a review of
the literature. Br J Anaesth 2001;87(3):477-87.
6. Richard F. Edlich, MD, PhD, Lisa G. Hill, Chandra A.
Mahler, et al. Management and Prevention of Tetanus.
Long Term Eff Med Implants 2003;13(3)139–54.
7. Ministry of Health and Medical Education. Pediatric
immunization. Available from:
pro=nobak;2011 [Access 28.10.2011].
8. S. Beheshti MD, A. Khajehdehi MD, G-R. Rezaian MD,
P. Khajehdehi MD. CURRENT STATUS OF TETANUS IN IRAN. Arch Iranian Med 2002;5(4):216-18.

9. World Health Organization. WHO-Recommended standards for surveillance of selected vaccinepreventable diseases. Available from:; 2003[Access 25.10.2011].
10. World Health Organization. Immunization surveillance,
assessment and monitoring. Available from: http://www. _ monitoring/ diseases/ MNTE_
initiative/en/index.html; 2011 [Access 25.10.2011].


Mirror Movements and Myelomeningocele: Report of A Single Case and Review of Literature


Iranian Journal of Child Neurology, Vol. 7 No. 3 (2013), 28 August 2013 , Page 58-61

How to Cite This Article: IIbtihel Rébai I, Benrhouma H, Kraoua I, Drissi C, Ben Hammouda M, Gouider-khouja N. Mirror Movements and Myelomeningocele: Report of A Single Case and Review of Literature. Iran J Child Neurol. 2013 Summer;7(3):58-61.


Mirror movements (MM) have been described in several pathological conditions. Their association with neural tube defects is rare, and only 5 cases have been reported in literature to date. We report on a case of MM associated with cervical myelomeningocele, and we discuss the diffusion tensor imaging findings and the underlying mechanism.


1. Cohen LG, Meer J, Tarkka I, Bierner S, Leiderman DB,
Dubinsky RM, et al. Congenital Mirror Movements. Abnormal organization of motor pathways in two patients. Brain 1991;114(Pt 1B):381-403.
2. Rasmussen P. Persistent mirror movements: a clinical
study of 17 children, adolescents and young adults. Dev
Med Child Neurol 1993;35(8):699-707.
3. Forget R, Boghen D, Attig E, Lamarre Y. Electromyographic
studies of congenital mirror movements. Neurology 1986;36(10):1316-22.
4. Erdincler P. Cervical cord tethering and congenital mirror
movements: is it an association rather than a coincidence?
Br J Neurosurg 2002;16(5):519–22.
5. Odabasi Z, Gökçil Z, Kütükçü Y, Vural O, Yardim M.
Mirror movements associated with cervical meningocele:
case report. Minim Invas Neurosurg 1998;41(2):99–100.
6. Erol FS, Topsakal C, Ozveren MF, Akdemir I, Cobanoglu
B. Meningocele with cervical dermoid sinus tract presenting with congenital mirror movement and recurrent meningitis. Yonsei Med J 2004;45(3):568–72.
7. Andrabi Y, Nejat F, El Khashab, Ashrafi MR. Mirror movement associated with neural tube defects. Neuropsychiatr Dis Treat 2008;4(6):1273–76.
8. Avery LW, Rentfro CC. The Klippel–Feil syndrome. A pathological report. Arch Neurol Psychiat 1936;36:1068- 76.
9. Gunderson CH, Solitaire GB. Mirror movements in patients with Klippel–Feil syndrome. Arch Neurol 1968;18(6):675–9.
10. Tuch DS, Reese TG, Wiegell MR, Makris N, Belliveau JW, Wedeen VJ. High angular resolution diffusion imaging reveals intravoxel white matter fiber heterogeneity. Magn Reson Med 2002;48(4):577-82.

11. Mamata H, Mamata Y, Westin CF, Shenton ME, Kikinis R, Jolesz FA, et al. High-resolution line scan diffusion tensor MR imaging of white matter fiber tract anatomy. AJNR Am J Neuroradiol 2002;23(1):67-75.
12. Galléa C, Popa T, Billot S, Méneret A, Depienne C, Roze
E. Congenital mirror movements: a clue to understanding
bimanual motor control. J Neurol 2011;258(11):1911-9.


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

Parvaneh KARIMZADEH, Narjes JAFARI, Farzad AHMADABADI, Sayena JABBEDARI, MohammadMahdi TAGHDIRI, Hamid NEMATI, Sasan SAKET, Fakhreddin SHARIATMADARI, Mohammad Reza ALAEE, Mohammad GHOFRANI, Seyed Hasan TONEKABONI

Iranian Journal of Child Neurology, Vol. 7 No. 3 (2013), 28 August 2013 , Page 63-66

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.


Methylmalonic 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 & Methods
The 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 genetic
assessment 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.

Eighty 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 showed
that 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.

According 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.


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 Scand


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.