Iranian Journal of Child Neurology

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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.

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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.

Objective
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.

Results
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.

Conclusion
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.

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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.

Objective
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
studies.

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.

Result
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.

Conclusion
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.

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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.

Objective
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.

Result
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.

Conlusion
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.

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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.

How to Cite This Article: Tonekaboni SH, Ebrahimi A, Bakhshandeh Bali MK, Houshmand M, Moghaddasi M, Taghdiri MM, Nasehi MM. Sodium Channel Gene Mutations in Children with GEFS⁺ and Dravet Syndrome: A Cross Sectional Study. Iran J Child Neurol. 2013 Winter; 7 (1):25-29.

Objective

Dravet syndrome or severe myoclonic epilepsy of infancy (SMEI) is a baleful epileptic encephalopathy that begins in the first year of life. This syndrome specified by febrile seizures followed by intractable epilepsy, disturbed psychomotor development, and ataxia. Clinical similarities between Dravet syndrome and generalized epilepsy with febrile seizure plus (GEFS+) includes occurrence of febrile seizures and joint molecular genetic etiology. Shared features of these two diseases support the idea that these two disorders represent a severity spectrum of the same illness. Nowadays, more than 60 heterozygous pattern SCN1A mutations, which many are de novo mutations, have been detected in Dravet syndrome.

Materials & Methods

From May 2008 to August 2012, 35 patients who referred to Pediatric Neurology Clinic of Mofid Children Hospital in Tehran were enrolled in this study. Entrance criterion of this study was having equal or more than four criteria for Dravet syndrome. We compared clinical features and genetic findings of the patients diagnosed as Dravet syndrome or GEFS+.

Results

35 patients (15 girls and 20 boys) underwent genetic testing. Mean age of them was 7.7 years (a range of 13 months to 15 years). Three criteria that were best evident in SCN1A mutation positive patients are as follows: Normal development before the onset of seizures, onset of seizure before age of one year, and psychomotor retardation after onset of seizures.

Our genetic testing showed that 1 of 3 (33.3%) patients with clinical Dravet syndrome and 3 of 20 (15%) patients that diagnosed as GEFS+, had SCN1A mutation.

Conclusion

In this study, normal development before seizure onset, seizures beginning before age of one year and psychomotor retardation after age of two years are the most significant criteria in SCN1A mutation positive patients.

References

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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.
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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.
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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.

Objective
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.

Results
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.

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

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9. Hwang H, Kim KJ. New antiepileptic drugs in pediatric epilepsy. Brain Dev 2008;30(9):549-55.
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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.

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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.
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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.

Abstract

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.

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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.

Abstract

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
intervention.

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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.

Abstract

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.

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