Document Type : Original Article
- Masoud Etemadifar 1
- Amir Parsa Abhari 2
- Ghasem Yadegarfar 3
- Mehri Salari 4
- Mohammadreza Ghazavi 5
- Milad Rayani 2
- Hosein Nouri 2
- Parisa Kargaran 6
- Shahrbanoo Mazaheri 7
- Homa Saadat 7
1 Department of Neurology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
2 Alzahra Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran
3 Department of Statistics and Epidemiology, School of Health, Isfahan University of Medical Sciences, Isfahan, Iran
4 Department of Neurological Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
5 Department of Pediatric Neurology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
6 Department of Cardiovascular Medicine, Center for Regenerative Medicine, Mayo Clinic, Rochester, Minnesota, USA
7 Department of Diseases and Transplantation, Isfahan University of Medical Sciences, Isfahan, Iran
Background: Pediatric-onset multiple sclerosis (POMS) is an autoimmune demyelinating disorder of the central nervous system (CNS), affecting individuals younger than 18 years of age. We sought to characterize the epidemiological and clinical features of patients with POMS in Isfahan, Iran, from April 1997 to March 2020.
Methods: The medical records of patients with POMS in the databases of Isfahan Department of Public Health and Isfahan Multiple Sclerosis Society (IMSS) were retrospectively reviewed. The 2006 and 2016 Isfahan Province population censuses were used as reference values for assessing the temporal trend of POMS.
Results: From April 1997 to March 2020, 509 individuals under18 years of age were diagnosed with POMS in Isfahan. 404 of these patients (79.4%) were girls, and 105 patients (20.6%) were boys (a female to male ratio of 3.85:1). Most of the patients (83%) were monosymptomatic at onset, with optic neuritis and brainstem-cerebellar disorders being the most frequent initial presentations. Mean ± standard
deviation (SD) of age at disease diagnosis was 15.8 ± 2.5 years (ranging from 3 to 18, mode = 18). From April 2019 to March 2020, the crude prevalence and the crude incidence rate of the POMS were 5.42 per 100000 and 1.86 per 100000, respectively. Poisson regression analysis revealed a 3.4% increase in the incidence rate of POMS from April 1997 to March 2020 [relative rate:1.034, 95% confidence interval (CI): 1.021-1.048].
Conclusion: The female to male ratio in our cohort was significantly higher than any other studies conducted previously. The high female to male ratio and increasing incidence of the disease suggest increasing regionalization of care.
- Dobson R, Giovannoni G. Multiple sclerosis - a review. Eur J Neurol 2019; 26(1): 27-40.
- Ruet A. Update on pediatric-onset multiple sclerosis. Rev Neurol (Paris) 2018; 174(6): 398-407.
- Yan K, Balijepalli C, Desai K, Gullapalli L, Druyts E. Epidemiology of pediatric multiple sclerosis: A systematic literature review and meta-analysis. Mult Scler Relat Disord 2020; 44: 102260.
- Pugliatti M, Sotgiu S, Rosati G. The worldwide prevalence of multiple sclerosis. Clin Neurol Neurosurg 2002; 104(3): 182-91.
- Fisher KS, Cuascut FX, Rivera VM, Hutton GJ. Current advances in pediatric onset multiple sclerosis. Biomedicines 2020; 8(4): 71.
- Etemadifar M, Izadi S, Nikseresht A, Sharifian M, Sahraian MA, Nasr Z. Estimated prevalence and incidence of multiple sclerosis in Iran. Eur Neurol 2014; 72(5-6): 370-4.
- Zipoli V, Portaccio E, Siracusa G, Pracucci G, Sorbi S, Amato MP. Interobserver agreement on Poser's and the new McDonald's diagnostic criteria for multiple sclerosis. Mult Scler 2003; 9(5): 481-5.
- Csepany T. Diagnosis of multiple sclerosis: A review of the 2017 revisions of the McDonald criteria. Ideggyogy Sz 2018; 71(9-10): 321-9. [In Hu].
- Krupp LB, Banwell B, Tenembaum S. Consensus definitions proposed for pediatric multiple sclerosis and related disorders. Neurology 2007; 68(16 Suppl 2): S7-12.
- Magyari M, Sorensen PS. Comorbidity in multiple sclerosis. Front Neurol 2020; 11: 851.
- Pohl D, Hennemuth I, von Kries R, Hanefeld F. Paediatric multiple sclerosis and acute disseminated encephalomyelitis in Germany: Results of a nationwide survey. Eur J Pediatr 2007; 166(5): 405-12.
- Reinhardt K, Weiss S, Rosenbauer J, Gartner J, von Kries R. Multiple sclerosis in children and adolescents: incidence and clinical picture - new insights from the nationwide German surveillance (2009-2011). Eur J Neurol 2014; 21(4): 654-9.
- Alroughani R, Akhtar S, Ahmed SF, Behbehani R, Al-Abkal J, Al-Hashel J. Incidence and prevalence of pediatric onset multiple sclerosis in Kuwait: 1994-2013. J Neurol Sci 2015; 353(1-2): 107-10.
- Marrie RA, O'Mahony J, Maxwell C, Ling V, Yeh EA, Arnold DL, et al. Incidence and prevalence of MS in children: A population-based study in Ontario, Canada. Neurology 2018; 91(17): e1579-e1590.
- Boesen MS, Magyari M, Koch-Henriksen N, Thygesen LC, Born AP, Uldall PV, et al. Pediatric-onset multiple sclerosis and other acquired demyelinating syndromes of the central nervous system in Denmark during 1977-2015: A nationwide population-based incidence study. Mult Scler 2018; 24(8): 1077-86.
- Gianfrancesco MA, Barcellos LF. Obesity and multiple sclerosis susceptibility: A review. J Neurol Neuromedicine 2016; 1(7): 1-5.
- Yamaguchi Y, Torisu H, Kira R, Ishizaki Y, Sakai Y, Sanefuji M, et al. A nationwide survey of pediatric acquired demyelinating syndromes in Japan. Neurology 2016; 87(19): 2006-15.
- Achiron A, Garty BZ, Menascu S, Magalashvili D, Dolev M, Ben-Zeev B, et al. Multiple sclerosis in Israeli children: incidence, an clinical, cerebrospinal fluid and magnetic resonance imaging findings. Isr Med Assoc J 2012; 14(4): 234-9.
- Eskandarieh S, Sahraiain MA, Molazadeh N, Moghadasi AN. Pediatric multiple sclerosis and its familial recurrence: A population based study (1999-2017). Mult Scler Relat Disord 2019; 36: 101377.
- Inaloo S, Haghbin S, Moradi M, Dashti H, Safari N. Acquired CNS demyelinating syndrome in children referred to Shiraz Pediatric Neurology Ward. Iran J Child Neurol 2014; 8(2): 18-23.
- Banwell B, Bar-Or A, Arnold DL, Sadovnick D, Narayanan S, McGowan M, et al. Clinical, environmental, and genetic determinants of multiple sclerosis in children with acute demyelination: A prospective national cohort study. Lancet Neurol 2011; 10(5): 436-45.
- Renoux C, Vukusic S, Mikaeloff Y, Edan G, Clanet M, Dubois B, et al. Natural history of multiple sclerosis with childhood onset. N Engl J Med 2007; 356(25): 2603-13.
- Ramphul K, Mejias SG, Joynauth J. Pediatric multiple sclerosis in the United States in children ages 0-18. Mult Scler Relat Disord 2020; 38: 101874.
- Dell'Avvento S, Sotgiu MA, Manca S, Sotgiu G, Sotgiu S. Epidemiology of multiple sclerosis in the pediatric population of Sardinia, Italy. Eur J Pediatr 2016; 175(1): 19-29.
- Ismail FY, Gordon-Lipkin E, Huether K, Blair I, Szolics M, Alsaadi T, et al. Pediatric multiple sclerosis in the United Arab Emirates: Characteristics from a multicenter study and global comparison. J Child Neurol 2018; 33(6): 422-7.
- Ysrraelit MC, Correale J. Impact of sex hormones on immune function and multiple sclerosis development. Immunology 2019; 156(1): 9-22.
- Yilmaz U, Anlar B, Gucuyener K. Characteristics of pediatric multiple sclerosis: The Turkish pediatric multiple sclerosis database. Eur J Paediatr Neurol 2017; 21(6): 864-72.
- Cerqueira Pinto SC, Ferreira Vasconcelos CC, Aurencao JCK, Alvarenga MP, das Gracas Gomes Camargo SM, Santos Thuler LC, et al. Pediatric multiple sclerosis in Rio de Janeiro: Secondary progression and disability. Pediatr Neurol 2019; 94: 48-54.
- Moussavi M, Heidarpour R, Aminorroaya A, Pournaghshband Z, Amini M. Prevalence of vitamin D deficiency in Isfahani high school students in 2004. Horm Res 2005; 64(3): 144-8.
- Olsson T, Barcellos LF, Alfredsson L. Interactions between genetic, lifestyle and environmental risk factors for multiple sclerosis. Nat Rev Neurol 2017; 13(1): 25-36.
- Miclea A, Bagnoud M, Chan A, Hoepner R. A brief review of the effects of vitamin D on multiple sclerosis. Front Immunol 2020; 11: 781.
- Blaschek A, Langhagen T, Bechtold-Dalla Pozza S, Heinen F, Muller-Felber W. Vitamin D levels in pediatric Multiple Sclerosis patients. Neuropediatrics 2011; 42(S 01): 058.
- Lysandropoulos AP, Jaquiery E, Jilek S, Pantaleo G, Schluep M, Du Pasquier RA. Vitamin D has a direct immunomodulatory effect on CD8+ T cells of patients with early multiple sclerosis and healthy control subjects. J Neuroimmunol 2011; 233(1-2): 240-4.
- Rocca MA, Absinta M, Amato MP, Moiola L, Ghezzi A, Veggiotti P, et al. Posterior brain damage and cognitive impairment in pediatric multiple sclerosis. Neurology 2014; 82(15): 1314-21.
- Boesen MS, Blinkenberg M, Thygesen LC, Eriksson F, Magyari M. School performance, psychiatric comorbidity, and healthcare utilization in pediatric multiple sclerosis: A nationwide population-based observational study. Mult Scler 2021; 27(2): 259-67.
- Banwell B, Ghezzi A, Bar-Or A, Mikaeloff Y, Tardieu M. Multiple sclerosis in children: Clinical diagnosis, therapeutic strategies, and future directions. Lancet Neurol 2007; 6(10): 887-902.
- Ozakbas S, Idiman E, Baklan B, Yulug B. Childhood and juvenile onset multiple sclerosis: clinical and paraclinical features. Brain Dev 2003; 25(4): 233-6.
- Ruggieri M, Polizzi A, Pavone L, Grimaldi LM. Multiple sclerosis in children under 6 years of age. Neurology 1999; 53(3): 478-84.
- Koch M, Uyttenboogaart M, Polman S, De KJ. Seizures in multiple sclerosis. Epilepsia 2008; 49(6): 948-53.
- Chabas D, Green AJ, Waubant E. Pediatric multiple sclerosis. NeuroRx 2006; 3(2): 264-75.
- Schorner A, Weissert R. Patients with epileptic seizures and multiple sclerosis in a multiple sclerosis center in southern Germany between 2003-2015. Front Neurol 2019; 10: 613.
- Huppke B, Ellenberger D, Rosewich H, Friede T, Gartner J, Huppke P. Clinical presentation of pediatric multiple sclerosis before puberty. Eur J Neurol 2014; 21(3): 441-6.
- Yeh EA, Chitnis T, Krupp L, Ness J, Chabas D, Kuntz N, et al. Pediatric multiple sclerosis. Nat Rev Neurol 2009; 5(11): 621-31.
- Chitnis T, Glanz B, Jaffin S, Healy B. Demographics of pediatric-onset multiple sclerosis in an MS center population from the Northeastern United States. Mult Scler 2009; 15(5): 627-31.