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. https://doi.org/10.1016/j.msard.2020.102260.

Article  PubMed  Google Scholar 

Gorman MP, Healy BC, Polgar-Turcsanyi M, Chitnis T. Increased relapse rate in pediatric-onset compared with adult-onset multiple sclerosis. Arch Neurol. 2009;66(1):54–9. https://doi.org/10.1001/archneurol.2008.505.

Article  PubMed  Google Scholar 

Waubant E, Chabas D, Okuda DT, Glenn O, Mowry E, Henry RG, et al. Difference in disease burden and activity in pediatric patients on brain magnetic resonance imaging at time of multiple sclerosis onset vs adults. Arch Neurol. 2009;66(8):967–71. https://doi.org/10.1001/archneurol.2009.135.

Article  PubMed  Google Scholar 

Yeh EA, Weinstock-Guttman B, Ramanathan M, Ramasamy DP, Willis L, Cox JL, et al. Magnetic resonance imaging characteristics of children and adults with paediatric-onset multiple sclerosis. Brain. 2009;132(Pt 12):3392–400. https://doi.org/10.1093/brain/awp278.

Article  CAS  PubMed  Google Scholar 

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. https://doi.org/10.1056/NEJMoa067597.

Article  CAS  PubMed  Google Scholar 

Hittle M, Culpepper WJ, Langer-Gould A, Marrie RA, Cutter GR, Kaye WE, et al. Population-based estimates for the prevalence of multiple sclerosis in the united states by race, ethnicity, age, sex, and geographic region. JAMA Neurol. 2023;80(7):693–701. https://doi.org/10.1001/jamaneurol.2023.1135.

Article  PubMed  PubMed Central  Google Scholar 

Walton C, King R, Rechtman L, Kaye W, Leray E, Marrie RA, et al. Rising prevalence of multiple sclerosis worldwide: Insights from the Atlas of MS, third edition. Mult Scler. 2020;26(14):1816–21. https://doi.org/10.1177/1352458520970841.

Article  PubMed  PubMed Central  Google Scholar 

Thompson AJ, Banwell BL, Barkhof F, Carroll WM, Coetzee T, Comi G, et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol. 2018;17(2):162–73. https://doi.org/10.1016/S1474-4422(17)30470-2.

Article  PubMed  Google Scholar 

Fadda G, Brown RA, Longoni G, Castro DA, O’Mahony J, Verhey LH, et al. MRI and laboratory features and the performance of international criteria in the diagnosis of multiple sclerosis in children and adolescents: a prospective cohort study. Lancet Child Adolesc Health. 2018;2(3):191–204. https://doi.org/10.1016/S2352-4642(18)30026-9.

Article  PubMed  Google Scholar 

Solomon AJ, Arrambide G, Brownlee WJ, Flanagan EP, Amato MP, Amezcua L, et al. Differential diagnosis of suspected multiple sclerosis: an updated consensus approach. Lancet Neurol. 2023;22(8):750–68. https://doi.org/10.1016/S1474-4422(23)00148-5.

Article  PubMed  Google Scholar 

Benson LA, Healy BC, Gorman MP, Baruch NF, Gholipour T, Musallam A, et al. Elevated relapse rates in pediatric compared to adult MS persist for at least 6 years. Mult Scler Relat Disord. 2014;3(2):186–93. https://doi.org/10.1016/j.msard.2013.06.004.

Article  CAS  PubMed  Google Scholar 

Chitnis T, Aaen G, Belman A, Benson L, Gorman M, Goyal MS, et al. Improved relapse recovery in paediatric compared to adult multiple sclerosis. Brain. 2020;143(9):2733–41. https://doi.org/10.1093/brain/awaa199.

Article  PubMed  Google Scholar 

Baroncini D, Simone M, Iaffaldano P, Brescia Morra V, Lanzillo R, Filippi M, et al. Risk of persistent disability in patients with pediatric-onset multiple sclerosis. JAMA Neurol. 2021;78(6):726–35. https://doi.org/10.1001/jamaneurol.2021.1008.

Article  PubMed  Google Scholar 

Iaffaldano P, Portaccio E, Lucisano G, Simone M, Manni A, Guerra T, et al. Multiple sclerosis progression and relapse activity in children. JAMA Neurol. 2024;81(1):50–8. https://doi.org/10.1001/jamaneurol.2023.4455.

Article  PubMed  Google Scholar 

Lublin FD, Haring DA, Ganjgahi H, Ocampo A, Hatami F, Cuklina J, et al. How patients with multiple sclerosis acquire disability. Brain. 2022;145(9):3147–61. https://doi.org/10.1093/brain/awac016.

Article  PubMed  PubMed Central  Google Scholar 

McKay KA, Manouchehrinia A, Berrigan L, Fisk JD, Olsson T, Hillert J. Long-term cognitive outcomes in patients with pediatric-onset vs adult-onset multiple sclerosis. JAMA Neurol. 2019;76(9):1028–34. https://doi.org/10.1001/jamaneurol.2019.1546.

Article  PubMed  PubMed Central  Google Scholar 

Ruano L, Branco M, Portaccio E, Goretti B, Niccolai C, Patti F, et al. Patients with paediatric-onset multiple sclerosis are at higher risk of cognitive impairment in adulthood: an Italian collaborative study. Mult Scler. 2018;24(9):1234–42. https://doi.org/10.1177/1352458517717341.

Article  PubMed  Google Scholar 

Amato MP, Goretti B, Ghezzi A, Lori S, Zipoli V, Portaccio E, et al. Cognitive and psychosocial features of childhood and juvenile MS. Neurology. 2008;70(20):1891–7. https://doi.org/10.1212/01.wnl.0000312276.23177.fa.

Article  CAS  PubMed  Google Scholar 

Amato MP, Goretti B, Ghezzi A, Lori S, Zipoli V, Moiola L, et al. Cognitive and psychosocial features in childhood and juvenile MS: two-year follow-up. Neurology. 2010;75(13):1134–40. https://doi.org/10.1212/WNL.0b013e3181f4d821.

Article  CAS  PubMed  Google Scholar 

Portaccio E, Bellinvia A, Razzolini L, Pasto L, Goretti B, Niccolai C, et al. Long-term cognitive outcomes and socioprofessional attainment in people with multiple sclerosis with childhood onset. Neurology. 2022;98(16):e1626–36. https://doi.org/10.1212/WNL.0000000000200115.

Article  CAS  PubMed  Google Scholar 

Carotenuto A, Moccia M, Costabile T, Signoriello E, Paolicelli D, Simone M, et al. Associations between cognitive impairment at onset and disability accrual in young people with multiple sclerosis. Sci Rep. 2019;9(1):18074. https://doi.org/10.1038/s41598-019-54153-7.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Banwell B, Giovannoni G, Hawkes C, Lublin F. Editors’ welcome and a working definition for a multiple sclerosis cure. Mult Scler Relat Disord. 2013;2(2):65–7. https://doi.org/10.1016/j.msard.2012.12.001.

Article  PubMed  Google Scholar 

Giovannoni G, Cook S, Rammohan K, Rieckmann P, Sorensen PS, Vermersch P, et al. Sustained disease-activity-free status in patients with relapsing-remitting multiple sclerosis treated with cladribine tablets in the CLARITY study: a post-hoc and subgroup analysis. Lancet Neurol. 2011;10(4):329–37. https://doi.org/10.1016/S1474-4422(11)70023-0.

Article  CAS  PubMed  Google Scholar 

Havrdova E, Galetta S, Hutchinson M, Stefoski D, Bates D, Polman CH, et al. Effect of natalizumab on clinical and radiological disease activity in multiple sclerosis: a retrospective analysis of the Natalizumab Safety and Efficacy in Relapsing-Remitting Multiple Sclerosis (AFFIRM) study. Lancet Neurol. 2009;8(3):254–60. https://doi.org/10.1016/S1474-4422(09)70021-3.

Article  PubMed  Google Scholar 

Kappos L, De Stefano N, Freedman MS, Cree BA, Radue EW, Sprenger T, et al. Inclusion of brain volume loss in a revised measure of “no evidence of disease activity” (NEDA-4) in relapsing-remitting multiple sclerosis. Mult Scler. 2016;22(10):1297–305. https://doi.org/10.1177/1352458515616701.

Article  PubMed  Google Scholar 

Szilasiova J, Mikula P, Rosenberger J, Fedicova M, Gdovinova Z, Urban P, et al. Plasma neurofilament light chain levels are predictors of disease activity in multiple sclerosis as measured by four-domain NEDA status, including brain volume loss. Mult Scler. 2021;27(13):2023–30. https://doi.org/10.1177/1352458521998039.

Article  CAS  PubMed  Google Scholar 

Giovannoni G, Bermel R, Phillips T, Rudick R. A brief history of NEDA. Mult Scler Relat Disord. 2018;20:228–30. https://doi.org/10.1016/j.msard.2017.07.011.

Article  PubMed  Google Scholar 

Prosperini L, Mancinelli C, Haggiag S, Cordioli C, De Giglio L, De Rossi N, et al. Minimal evidence of disease activity (MEDA) in relapsing-remitting multiple sclerosis. J Neurol Neurosurg Psychiatry. 2020;91(3):271–7. https://doi.org/10.1136/jnnp-2019-322348.

Article  PubMed  Google Scholar