Other Experimental Therapies in Neimann Pick Diseases

How to Cite This Article: Taghdiri MM. Other Experimental Therapies in Neimann Pick Diseases. Iran J Child Neurol. 2015 Autumn;9:4(Suppl.1): 25. Pls see pdf.

Neurological finding of Mitochondrial Syndromes (MERRF and MELAS)

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Adreno Leukodystrophy

How to Cite This Article: Taghdiri MM. Adreno Leukodystrophy. Iran J Child Neurol. Autumn 2014;8;4(Suppl.1):13.Pls see pdf

Infantile Spasm: A Review Article

How to Cite This Article: Taghdiri MM, Nemati H. Infantile Spasm: A Review Article. Iran J Child Neurol. 2014 Summer;8(3): 1-5.AbstractObjectiveInfantile spasm (IS) is a convulsive disease characterized by brief, symmetric axial muscle contraction (neck, trunk, and/or extremities). IS is a type of seizure that was first described by West in 1841, who witnessed the seizure in his own son. West’s syndrome refers to the classic triad of spasms, characteristic EEG, and neurodevelopmental regression. Most cases involve flexors and extensors,but either of the types may be involved independently.IS, as its name implies, most often occurs during the first year of life with an incidence of approximately 1 per 2000-4000 live births. Most, but not all, patients with this disorder have severe EEG abnormalities; this pattern was originallyreferred to as hypsarrhythmia by Gibbs and Gibbs. Cases with known etiology or signs of brain damage are considered as symptomatic. The Overall prognosis of the disease is poor. Peak onset age of the epileptic syndrome is 3 to 7 months, which mainly occurs before 2 years of age in 93% of patients. Hypsarrhythmia is the EEG hallmark of IS, which comprised a chaotic, bilaterally asynchronous high-voltage polyspike, and slow wave discharges interspersed with multifocal spikes and slow waves.Etiological classification is as follows: 1) Symptomatic: with identifiable prenatal, perinatal, and postnatal causes with developmental delay at the presentation time; 2) Cryptogenic: unknown underlying cause, normal development at the onset of spasms, normal neurological exam and neuroimaging, and no abnormality in the metabolic evaluation; 3) Idiopathic: pure functional cerebral dysfunction with complete recovery, no residual dysfunction, normal neuroimaging and normal etiologic evaluation, and normal neurodevelopment.ReferencesInfantile Spasms. In: Jean Aicardi: Disease of Nervous system in childhood. 3th ed. Mac Keith pres; 2009. p. 593-7.Fujii, Oquni H, Hirano Y, Shioda M, Osawa M. A longterm, clinical study on symptomatic infantile spasm with focal features. Brain Dev 2013;35(5):379-85.SankarR, Koh S, Wu J. Menkes JH. Paroxysmal disorders. In: Menkes JH, Sarnat HB,. MariaBL, editors Child neurology. 7th ed. Philadelphia: Lippincott Williams & Wilkins; 2006. p. 857-942.Kendall Nash and Joseph Sullivan. Myoclonic seizures and infantile spasms. InSwaiman KF, Ashwal S, Ferriero DM, Schor NF, editors.. Swaiman’s pediatric Neurology: principles and practice. 5th ed. Edinburgh: Elsevier Saunders; 2012. p. 774-89.Paroxysmal Disorders. In: Piña-Garza J. Fenichel’s Clinical Pediatric Neurology. 7th ed. Elsevier Saunders; 2013. p. 1-46.Paciorkowski AR, Thio LL, Dobyns WB. Genetic and biologic classification of infantile spasms. Pediatr Neurol 2011;45(6):355-67.Manqanno S, Nardello R, Tripi G, Giordano G, Spitaleri C, Manfano GR. West Syndrome Followed by juvenile myoclonic epilepsy: a coincidental occurrence. BMC Neural 2013;13:48.LUX AL. Latest American and European update on infantile spasms. Curr Neural Neurosci Rep 2013;13(3):334.Hrachovy RA, Frost JD Jr. Infantile spasms. Handb Clin Neuro. 2013;111:611-8.Shumiloff NA, Lam WM, Manasco KB. Adrenocorticotropic hormone for the treatment of west syndrome in children. Ann Pharmacother 2013 47(5):744- 54.Wheless JW, Gibson PA, Rosbeck KL, Hardin M, O’Dell C, Whiltemore V. Infantile Spasms (west syndrome):  Update and resources for pediatricians and providers to share with parents. BMC Pediatr. 2012;12:108.Watemberg N. Infantile Spasms: treatment challenges. Curr Treat Options Neural. 2012;14(4): 322-31.Fukui M, Shimakawa S, Tanabe T, Nomura S, Kashiwagi M, Azumakawa K. Partial seizures during ACTH therapy in a cryptogenic West syndrome patient. Brain Dev 2013;Pii:s0387-7604(13)00003-x.Friedman D, Boqner M, Parker-Menzer K, Dviskyo. Vigabatin for partial- onset seizure treatment in patients with tuberous sclerosis complex. Epilepsy Behav 2013;27(1):118-20.Bilton JY, Sauerwein HC, Wiss SK, Donner EJ, Whiting S, Dooley JM, et al. A randomized controlled trial of flunarizine as add-on therapy and effect on cognitive outcome in children with infantile Spasms. Epilepsia 2012;53(9):1570-6.Pires ME, IIea A, Bourel E, Bellaroine V, Merdariv D, Berquin P. Ketogenic diet for infantile spasms refractory to first-line treatment: An open prospective study. Epilepsy Res 2013; 105(1-2): 189-94.Vykuntaragu KN, Bhat S, Sangay KS, Govindaagu M. Symptomatic West syndrome Secondary to Glucose transporter-1 (GluT1) Deficiency with complete response to 4:1 Ketogenic Diet. Indian J Pediatr 2013. [Epub ahead of print]Taghdiri MM, Comparative effects of Nitrazepam and ACTH on the treatment of infantile Spasms. Iran J Child Neurol 2007;1(4):25-30.Taghdiri MM, Presentation of 60 cases of infantile spasms based on etiology, clinical manifestation, EEG and brain CT scan in Mofid Children’s Hospital. JRehab 2002;3(8- 9);39-42.Taghdiri MM. Report of 40 cases of Tuberous sclerosis in Tehran. Scientific Journal of Hamadan University of Medical sciences 2002;9(1):63-7.Mytinger JR, Joshi S; Pediatric Epilepsy Research Consortium, Section on Infantile Spasms. The current evaluation and treatment of infantile spasms among members of the child Neurology Society. J child Neural 2012;227(10):1289-94.Hancock EC, Osborne JP, Edwards SW. Treatment of infantile spasms. Cochrane Database Syst Rev 2013;6:CD001770

A Case Report of Incontinentia Pigmenti

ObjectiveIncontinentia Pigmenti (IP) (Bloch_Sulzberg syndrome) is a rare neurocutaneous syndrome characterized by multisystemic involvement that is prenatally lethal in the majority of affected males and shows great clinical variability when expressed in women. The diagnosis of IP is performed based on clinical features and the family history with the support of histological findings.We report a 10-day-old female neonate with typical skin lesions and frequent seizure. Skin biopsy showed second stage IP

Hyperkinetic Movement Disorders in Children- A Brief Review

Movement disorders are common neurologic disturbances in childhood. There are two major types movement disorders. Hypokinetic disorders are with paucity of voluntary movements and are very uncommon in pediatric age group. Hyperkinetic movement abnormalities are very common in children and defined as abnormal repetitive involuntary movements. Movement disorders in childhood and even in adolescents are different in etiology, timing, treatment and prognosis versus adulthood movement abnormalities. In this brief article, we reviewed common types of hyperkinetic abnormal movements in children and adolescents with emphasis on etiologies, new classifications and recent treatment strategies.     

Zonisamide Efficacy as Adjunctive Therapy in Children With Refractory Epilepsy

How to Cite This Article: Karimzadeh P, Ashrafi MR, Bakhshandeh Bali MK, Nasehi MM, Taheri Otaghsara SM, Taghdiri MM, Ghofrani M. ZonisamideEfficacy as Adjunctive Therapy in Children With Refractory Epilepsy. Iran J Child Neurol. 2013 Spring; 7(2):37-42.ObjectiveApproximately 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 & MethodsFrom 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 seizurefrequency or severity known as response to the drug.ResultsIn 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.ConclusionThis study confirms the short term efficacy and safety of Zonisamide in children with refractory epilepsies. References1. 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 stumed 2005:Vol 5;470-473.4. Berto P. Quality of life in patients with epilepsy and impactof 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 epilepsyJapanese 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 Res2006 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

Comparative Efficacy of Zonisamide and Pregabalin as an Adjunctive Therapy in Children with Refractory Epilepsy

How to Cite This Article: Taghdiri MM, Bakhshandeh Bali MK, Karimzadeh P, Ashrafi MR, Tonekaboni SH, Ghofrani M. Comparative Efficacy of Zonisamide and Pregabalin as an Adjunctive Therapy in Children with Refractory Epilepsy. Iran J Child Neurol. 2015 Winter;9(1):49-55.AbstractObjectiveApproximately one third of epileptic children are resistant to anticonvulsant drugs. This study evaluates the effectiveness, safety, and tolerability of pregabalin as adjunctive therapy in epileptic children relative to Zonisamide.Materials & MethodsFrom April 2012 to November 2012,121 children were referred to MofidChildren’s Hospital with intractable epilepsy and enrolled in the study. The patients were divided into two groups (A and B) randomly. Group A was treated with Zonisamide and group B was treated with Pregabalin in addition to prior medication. We assessed seizure frequency and severity during a 4-week interval from the beginning of the drug treatment and compared the efficacy of each in these two groups.ResultsGroup A consists of 61 patients, 26 (42.6%) girls, and35 (57.4%) boys with an age range from 1.5 months–14 years (mean, 73.9± 44.04 months). Group B consists of 60 patients, 31(51.7%) girls, 29 (48.3%) boys with an age range from 6 months–16 years (mean, 71±42.9 months). Age, gender, seizure onset, seizure frequency, seizure type, and previous antiepileptic medications showed that there was no significant difference between the groups (P>0.05). Zonisamide and pregabalin reduced more than 50% of seizure intensity in 40.2%; 45.8% of patients also had a seizure frequency decline between35.8–44.4%, respectively and there was no significant superiority between these two novel anticonvulsants (P>0.05).ConclusionIn this survey both pregabalin and Zonisamide were impressive for seizure control in children with intractable epilepsy and well sustained with mild complications that were completely reversible.

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

How to Cite This Article: Karimzadeh P, Taghdiri MM, Abasi E, Hassanvand Amouzadeh M, Naghavi Zh, Ghazavi A, Nasehi MM, Alipour A. Metabolic Screening in Children with Neurodevelopmental Delay, Seizure and/or Regression. Iran J Child Neurol. Summer 2017; 11(3):42-47. AbstractObjectiveNeurometabolic disorder is one of the important groups of diseases that prominently has presentation early infantile period. In this study, we evaluated the result of metabolic screening of the patient with seizure, developmental delay and/or regression in development, demographic disease clinical and radiological findings on admitted and outpatient visited children.Materials & MethodsTwo-year retrospective review of 187 children with seizure, developmental delay and/or regression in the Mofid Children Hospital, Tehran, Iran was performed. The diagnosis was based on observation, findings of EEG and history of the patient, besides evaluation of patient milestones. The result of metabolic screening with Tandem mass spectrometry was evaluated using SPSS (ver.18.0) Statistical software.ResultsTotally, 187 children with seizure, regression and/or developmental delay were evaluated by metabolic screening with tandem mass spectrometry method. The results of laboratory examination had no relationship between positive results of metabolic screening and the mentioned disease. The relations between positive results of metabolic screening and seizure, regression and/or developmental delay were not statistically meaningful.ConclusionPositive results of metabolic screening and seizure, regression and/or developmental delay were not statistically meaningful. References1. Piña-Garza JE. Altered States of Consciousness. In: Piña- Garza JE, editor. Fenichel’s clinical pediatric neurology. 7th ed. Philadelphia: Elsevier Saunders;2013.p.47-75.2. Mohamed S, El Melegy EM, Talaat I, et al. Neurometabolic Disorders-Related Early Childhood Epilepsy: A Single-Center Experience in Saudi Arabia. Pediatr Neonatol 2015; 56(6):393-401.3. Berry GT, Steiner RD. Long-term management of patients with urea cycle disorders. J Pediatr 2001;138(1 Suppl): S56-60.4. Zupec-Kania B, Zupanc ML. Long-term management of the ketogenic diet: seizure monitoring, nutrition, and supplementation. Epilepsia 2008;49 Suppl 8:23-6.5. Weisfeld-Adams JD, Bender HA, Miley-Åkerstedt A, et al. Neurologic and neurodevelopmental phenotypes in young children with early-treated combined methylmalonic acidemia and homocystinuria, cobalamin C type. Mol Genet Metab 2013;110(3):241-7.6. Eun SH, Hahn SH. Metabolic evaluation of children with global developmental delay. Korean J Pediatr 2015;58(4):117-22.7. Patel KP, O’Brien TW, Subramony SH, Shuster J, Stacpoole PW. The spectrum of pyruvate dehydrogenase complex deficiency: clinical, biochemical and genetic features in 371 patients. Mol Genet Metab 2012; 105(1):34-43.8. Bjursell MK, Blom HJ, Cayuela JA, et al. Adenosine kinase deficiency disrupts the methionine cycle and causes hypermethioninemia, encephalopathy, and abnormal liver function. Am J Hum Genet 2011; 89(4): 507-15.9. Bolduc ME, Du Plessis AJ, Sullivan N, and et al. Spectrum of neurodevelopmental disabilities in children with cerebellar malformations. Dev Med Child Neurol 2011; 53(5):409-16.10. Bhardwaj P, Kaushal RK, Chandel A. Biotinidase deficiency: A treatable cause of infantile seizures. J Pediatr Neurosci 2010; 5(1):82-3.11. López-Pisón J, García-Jiménez MC, Monge-Galindo L, et al. Our experience with the aetiological diagnosis of global developmental delay and intellectual disability: 2006-2010. Neurologia 2014; 29(7):402-7.12. Mikati MA, Hani AJ. Seizures in Childhood. In: Kliegman RM, Stanton BF, St Geme JW, Schor NF, editors. Nelson Textbook of Pediatrics. 20th ed. Philadelphia: Elsevier;2016.p.2823-56.13. Korman SH, Jakobs C, Darmin PS, et al. Glutaric aciduria type 1: clinical, biochemical and molecular findings in patients from Israel. Eur J Paediatr Neurol 2007; 11(2):81-9.14. Eun SH, Hahn SH. Metabolic evaluation of children with global developmental delay. Korean J Pediatr 2015; 58(4):117-122.15. Karimzadeh P, Ahmadabadi F, Jafari N, et al. Study on MRI Changes in Phenylketonuria in Patients Referred to Mofid Hospital/ Iran. Iran J Child Neurol 2014; 8(2):53- 56.16. Karimzadeh P, Jafari N, Ahmad Abadi F, et al. Propionic Acidemia: Diagnosis and Neuroimaging Findings of This Neurometabolic Disorder. Iran J Child Neurol 2014; 8(1):58-61.17. Karimzadeh P, Jafari N, Jabbehdari S, et al. Methylmalonicacidemia: Diagnosis and Neuroimaging Findings of This Neurometabolic Disorder (An Iranian Pediatric Case Series). Iran J Child Neurol 2013; 7(3): 63-66.18. Vanderver A, Wolf NI. Genetic and Metabolic Disorders of the White Matter. In: Swaiman KF, Ashwal S, Ferriero DM, Schor NF, editors. Swaiman’s Pediatric Neurology. 5th ed. Philadelphia: Elsevier Saunders;2012.p.1020-51.19. Youssef-Turki I, Kraoua S, Smirani K, Mariem H, BenRhouma A, Rouissi , Gouider-Khouja N. Epilepsy Aspects and EEG Patterns in Neuro-Metabolic Diseases. J Behav Brain Sci 2011; 1(2).20. Karimzadeh P, Ahmadabadi F, Jafari N, et al. Biotinidase deficiency: a reversible neurometabolic disorder (an Iranian pediatric case series). Iran J Child Neurol 2013; 7(4):47-52.21. Walterfang M, Bonnot O, Mocellin R, Velakoulis D. The neuropsychiatry of inborn errors of metabolism. J Inherit Metab Dis 2013; 36(4):687-702.22. Wolf NI, Bast T, Surtees R. Epilepsy in inborn errors of metabolism. Epileptic Disord. 2005; 7(2):67-81.23. Koul R1, Al-Yahmedy M, Al-Futaisi A. E v a l u a t i o n children with global developmental delay: a prospective study at sultan qaboos university hospital, oman. Oman Med J 2012; 27(4):310-3.24. Alrifai MT, AlShaya MA, Abulaban A, Alfadhe M. Hereditary neurometabolic causes of infantile spasms in 80 children presenting to a tertiary care center. Pediatr Neurol 2014; 51(3):390-7

Clinical and Epidemiological Aspects of Multiple Sclerosis in Children

How to Cite This Article: Nasehi MM, Sahraian MA, Naser Moghaddasi A, Ghofrani M, Ashtari F, Taghdiri MM, Tonekaboni SH, Karimzadeh P, Afshari M, Moosazadeh M. Clinical and Epidemiological Aspects of Multiple Sclerosis in Children. Iran J Child Neurol. Spring 2017; 11(2):37-43.AbstractObjectiveOverall, 2%-5% of patients with multiple sclerosis (MS) experienced the first episode of disease before the age 18 years old. Since the age of onset among children is not similar to that in general population, clinicians often fail to early diagnose the disease. This study aimed to determine the epidemiological and clinical patterns of MS among Iranian children.Materials & Methods In this cross-sectional study carried out in Iran in 2014-2015, information was collected using a checklist with approved reliability and validity. Method sampling was consensus. Data were analyzed using frequency, mean and standard deviation indices by means of SPSS ver. 20 software.Results Totally, 177 MS children were investigated. 75.7% of them were female. Mean (SD), minimum and maximum age of subjects were 15.9 (2), 7 and 18 yr, respectively. The most reported symptoms were sensory (28.2%), motor (29.4%), diplopia (20.3%) and visual (32.8%). Primary MRI results showed 91.5% and 53.1% periventricular and spinal cord lesions, respectively.Conclusion MS is significantly more common among women. The most common age of onset is during the second decades. Sensory and motor problems are the most symptoms, while, periventricular and spinal cord lesions are the most MRI results. References 1. Ascherio A, Munger K. Epidemiology of multiple sclerosis: from risk factors to prevention. Semin Neurol 2008; 28(1): 17-28.2. Abedidni M, Habibi Saravi R, Zarvani A, Farahmand M. Epidemiologic study of multiple sclerosis in Mazandaran,Iran, 2007. J Mazandaran Univ Med Sci 2008; 18(66): 82-6.3. Taghdiri MM, Gofrani M, Barzegar M, Moayyedi A, Tonekaboni H. The survey of 20 cases of multiple sclerosis in children in mofid hospital of Tehran. J Rehabil, 2001; 4(6-7):61-67.4. Benito-Leon J, Martinez P. Health-related quality of life in multiple sclerosis. Neurologia 2003; 18: 207-10.5. Nedjat S, Montazeri A, Mohammad K, Majdzadeh R, Nabavi N, Nedjat F, et al . Quality of Life in Multiple Sclerosis Compared to the Healthy Population in Tehran. Iran J Epidemiol 2006; 2 (3 and 4) :19-24.6. Marrie RA. Environmental risk factors in multiple sclerosis aetiology. Lancet Neurol 2004; 3(12):709-18.7. Milo R, Kahana E. Multiple sclerosis:geoepidemiology, genetics and the environment. Autoimmun Rev 2010; 9(5): A387-A394.8. Banwell B, Ghezzi A, Bar-Or A, Mikaeloff Y. Multiple sclerosis in children: clinical diagnosis, therapeutic strategies, and future directions. The Lancet Neurol, 2007;6(10):887-902.9. Ebers GC. Environmental factors and multiple sclerosis. The Lancet Neurol, 2008;7(3):268-277.10. Noseworthy JH, Lucchinetti C, Rodriguez M, Weinshenker BG. Multiple Sclerosis. N Engl J Med 2000; 343(13):938-52.11. Rudick RA, Cohen JA, Weinstock-Guttman B, Kinkel RP, Ransohoff RM. Management of multiple sclerosis. N Engl J Med 1997: 337(22): 1604-11.12. Greer JM, McCombe PA. Role of gender in multiple sclerosis: clinical effects and potential molecular mechanisms. J Neuroimmunol 2011;234(1-2): 7-18.13. Boiko A, Vorobeychik G, Paty D, Devonshire V, Sadovnick D. Early onset multiple sclerosis A longitudinal study. Neurology 2002; 59(7):1006-1010.14. . Ashtari F, Shaygannejad V, Heidari F, Akbari M. Prevalence of Familial Multiple Sclerosis in Isfahan, Iran. Journal of Isfahan Medical School, 2011;29(138.2):555- 561.15. Mazaheri S, Fazlian M, Hossein Zadeh A. Clinical and Epidemiological Features of Early and Adult Onset Multiple Sclerosis in Hamedan, Iran, 2004–2005. Yafteh 2008; 9 (4) :39-44.16. Saman-Nezhad B, Rezaee T, Bostani A, Najafi F, Aghaei A. Epidemiological Characteristics of Patients with Multiple Sclerosis in Kermanshah, Iran in 2012. J Mazand Univ Med Sci 2013; 23(104): 97-101 (In Persian).17. Renoux C, Vukusic S, Mikaeloff Y, Edan G. Natural history of multiple sclerosis with childhood onset. N Engl J Med 2007. 356(25): p. 2603-2613.18. Ness JM, Chabas D, Sadovnick AD, Pohl D, Banwell B, Weinstock-Guttman B. Clinical features of children and adolescents with multiple sclerosis. Neurology 2007; 68(16 suppl 2):S37-S45.19. Etemadifar M, Janghorbani M,Shaygannejad V, Ashtari F . Prevalence of multiple sclerosis in Isfahan. Iran. Neuroepidemiology 2006; 27(1):39-44 (In Persian).20. Saadatnia M, Etemadifar M, Maghzi AH. Multiple sclerosis in Isfahan, Iran. Int Rev Neurobiol 2007; 79: 357-75.21. Nabavi SM, Poorfarzam S, Ghassemi H. Clinical Course and prognosis of 203 patients with MS in shahid Mostafa Khomeini Hospital, Tehran 2002, Tehran University Medical Journal, 200l 64( 7)6: 90-97