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Pediatric multiple sclerosis: from clinical basis to imaging spectrum and differential diagnosis

Abstract

Pediatric multiple sclerosis (MS) deserves special attention because of its impact on cognitive function and development. Although knowledge regarding pediatric MS has rapidly increased, understanding the peculiarities of this population remains crucial for disease management. There is limited expertise about the efficacy and safety of current disease-modifying agents. Although pathophysiology is not entirely understood, some risk factors and immunological features have been described and are discussed herein. While the revised International Pediatric MS Study Group diagnostic criteria have improved the accuracy of diagnosis, the recently revised McDonald criteria also offer some new insights into the pediatric population. It is fundamental that radiologists have strong knowledge about the vast spectrum of demyelinating disorders that can occur in childhood to ensure appropriate diagnosis and provide early treatment.

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References

  1. 1.

    Tardieu M, Banwell B, Wolinsky JS et al (2016) Consensus definitions for pediatric MS and other demyelinating disorders in childhood. Neurology 87:S8–S11

  2. 2.

    Belman AL, Krupp LB, Olsen CS et al (2016) Characteristics of children and adolescents with multiple sclerosis. Pediatrics 138

  3. 3.

    Renoux C, Vukusic S, Mikaeloff Y et al (2007) Natural history of multiple sclerosis with childhood onset. N Engl J Med 356:2603–2613

  4. 4.

    Chitnis T, Glanz B, Jaffin S, Healy B (2009) Demographics of pediatric-onset multiple sclerosis in an MS center population from the northeastern United States. Mult Scler 15:627–631

  5. 5.

    Boiko A, Vorobeychik G, Paty D et al (2002) Early onset multiple sclerosis: a longitudinal study. Neurology 59:1006–1010

  6. 6.

    Cortese R, Collorone S, Ciccarelli O, Toosy AT (2019) Advances in brain imaging in multiple sclerosis. Ther Adv Neurol Disord 12:1756286419859722

  7. 7.

    Orrell RW (2005) Multiple sclerosis: the history of a disease. J R Soc Med 98:289

  8. 8.

    Duquette P, Murray TJ, Pleines J et al (1987) Multiple sclerosis in childhood: clinical profile in 125 patients. J Pediatr 111:359–363

  9. 9.

    Chitnis T, Krupp L, Yeh A et al (2011) Pediatric multiple sclerosis. Neurol Clin 29:481–505

  10. 10.

    Krupp LB, Banwell B, Tenembaum S, International Pediatric MS Study Group (2007) Consensus definitions proposed for pediatric multiple sclerosis and related disorders. Neurology 68:S7–S12

  11. 11.

    Krupp LB, Tardieu M, Amato MP et al (2013) International Pediatric Multiple Sclerosis Study Group criteria for pediatric multiple sclerosis and immune-mediated central nervous system demyelinating disorders: revisions to the 2007 definitions. Mult Scler 19:1261–1267

  12. 12.

    Wells E, Hacohen Y, Waldman A et al (2018) Neuroimmune disorders of the central nervous system in children in the molecular era. Nat Rev Neurol 14:433–445

  13. 13.

    Alroughani R, Boyko A (2018) Pediatric multiple sclerosis: a review. BMC Neurol 18:27

  14. 14.

    Simone M, Chitnis T (2016) Use of disease-modifying therapies in pediatric MS. Curr Treat Options Neurol 18:36

  15. 15.

    Chitnis T, Tenembaum S, Banwell B et al (2012) Consensus statement: evaluation of new and existing therapeutics for pediatric multiple sclerosis. Mult Scler 18:116–127

  16. 16.

    Saade C, Bou-Fakhredin R, Yousem DM et al (2018) Gadolinium and multiple sclerosis: vessels, barriers of the brain, and glymphatics. AJNR Am J Neuroradiol 39:2168–2176

  17. 17.

    Vasileiadis GK, Dardiotis E, Mavropoulos A et al (2018) Regulatory B and T lymphocytes in multiple sclerosis: friends or foes? Auto Immun Highlights 9:9

  18. 18.

    Bar-Or A, Hintzen RQ, Dale RC et al (2016) Immunopathophysiology of pediatric CNS inflammatory demyelinating diseases. Neurology 87:S12–S19

  19. 19.

    Sepulveda M, Aldea M, Escudero D et al (2017) Epidemiology of NMOSD in Catalonia: influence of the new 2015 criteria in incidence and prevalence estimates. Mult Scler. https://doi.org/10.1177/1352458517735191

  20. 20.

    Trabatti C, Foiadelli T, Sparta MV et al (2016) Paediatric clinically isolated syndromes: report of seven cases, differential diagnosis and literature review. Childs Nerv Syst 32:69–77

  21. 21.

    Lee CG, Lee B, Lee J, Lee M (2015) The natural course of clinically isolated syndrome in pediatric patients. Brain Dev 37:432–438

  22. 22.

    Absoud M, Cummins C, Desai N et al (2011) Childhood optic neuritis clinical features and outcome. Arch Dis Child 96:860–862

  23. 23.

    Alper G, Heyman R, Wang L (2009) Multiple sclerosis and acute disseminated encephalomyelitis diagnosed in children after long-term follow-up: comparison of presenting features. Dev Med Child Neurol 51:480–486

  24. 24.

    Hacohen Y, Mankad K, Chong WK et al (2017) Diagnostic algorithm for relapsing acquired demyelinating syndromes in children. Neurology 89:269–278

  25. 25.

    Waters PJ, Komorowski L, Woodhall M et al (2019) A multicenter comparison of MOG-IgG cell-based assays. Neurology 92:e1250–e1255

  26. 26.

    Dobson R, Ramagopalan S, Davis A, Giovannoni G (2013) Cerebrospinal fluid oligoclonal bands in multiple sclerosis and clinically isolated syndromes: a meta-analysis of prevalence, prognosis and effect of latitude. J Neurol Neurosurg Psychiatry 84:909–914

  27. 27.

    Dobson R, Ramagopalan S, Giovannoni G (2012) The effect of gender in clinically isolated syndrome (CIS): a meta-analysis. Mult Scler 18:600–604

  28. 28.

    Neuteboom RF, Janssens AC, Siepman TA et al (2012) Pregnancy in multiple sclerosis: clinical and self-report scales. J Neurol 259:311–317

  29. 29.

    Tintore M, Rovira A, Rio J et al (2015) Defining high, medium and low impact prognostic factors for developing multiple sclerosis. Brain 138:1863–1874

  30. 30.

    Iaffaldano P, Simone M, Lucisano G et al (2017) Prognostic indicators in pediatric clinically isolated syndrome. Ann Neurol 81:729–739

  31. 31.

    Okuda DT, Mowry EM, Beheshtian A et al (2009) Incidental MRI anomalies suggestive of multiple sclerosis: the radiologically isolated syndrome. Neurology 72:800–805

  32. 32.

    Okuda DT, Siva A, Kantarci O et al (2014) Radiologically isolated syndrome: 5-year risk for an initial clinical event. PLoS One 9:e90509

  33. 33.

    Gorman MP, Healy BC, Polgar-Turcsanyi M, Chitnis T (2009) Increased relapse rate in pediatric-onset compared with adult-onset multiple sclerosis. Arch Neurol 66:54–59

  34. 34.

    Chitnis T, Arnold DL, Banwell B et al (2018) Trial of fingolimod versus interferon beta-1a in pediatric multiple sclerosis. N Engl J Med 379:1017–1027

  35. 35.

    Dastgir J, DiMario FJ Jr (2009) Acute tumefactive demyelinating lesions in a pediatric patient with known diagnosis of multiple sclerosis: review of the literature and treatment proposal. J Child Neurol 24:431–437

  36. 36.

    Thompson AJ, Banwell BL, Barkhof F et al (2018) Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol 17:162–173

  37. 37.

    Polman CH, Reingold SC, Banwell B et al (2011) Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 69:292–302

  38. 38.

    Hummel HM, Bruck W, Dreha-Kulaczewski S et al (2013) Pediatric onset multiple sclerosis: McDonald criteria 2010 and the contribution of spinal cord MRI. Mult Scler 19:1330–1335

  39. 39.

    Rovira A, Wattjes MP, Tintore M et al (2015) Evidence-based guidelines: MAGNIMS consensus guidelines on the use of MRI in multiple sclerosis-clinical implementation in the diagnostic process. Nat Rev Neurol 11:471–482

  40. 40.

    Ketelslegers IA, Catsman-Berrevoets CE, Neuteboom RF et al (2012) Incidence of acquired demyelinating syndromes of the CNS in Dutch children: a nationwide study. J Neurol 259:1929–1935

  41. 41.

    Fromont A, Binquet C, Sauleau EA et al (2010) Geographic variations of multiple sclerosis in France. Brain 133:1889–1899

  42. 42.

    Pohl D, Hennemuth I, von Kries R, Hanefeld F (2007) Paediatric multiple sclerosis and acute disseminated encephalomyelitis in Germany: results of a nationwide survey. Eur J Pediatr 166:405–412

  43. 43.

    Langer-Gould A, Zhang JL, Chung J et al (2011) Incidence of acquired CNS demyelinating syndromes in a multiethnic cohort of children. Neurology 77:1143–1148

  44. 44.

    Hacohen Y, Brownlee W, Mankad K et al (2019) Improved performance of the 2017 McDonald criteria for diagnosis of multiple sclerosis in children in a real-life cohort. Mult Scler. https://doi.org/10.1177/1352458519863781

  45. 45.

    Rocha AJ, Littig IA, Nunes RH, Tilbery CP (2013) Central nervous system infectious diseases mimicking multiple sclerosis: recognizing distinguishable features using MRI. Arq Neuropsiquiatr 71:738–746

  46. 46.

    Dutra BG, da Rocha AJ, Nunes RH, Maia ACMJ (2018) Neuromyelitis optica spectrum disorders: spectrum of MR imaging findings and their differential diagnosis. Radiographics 38:169–193

  47. 47.

    Rubin JP, Kuntz NL (2013) Diagnostic criteria for pediatric multiple sclerosis. Curr Neurol Neurosci Rep 13:354

  48. 48.

    da Rocha AJ, Barros BR, Guedes BV, Maia AC Jr (2011) Idiopathic inflammatory demyelinating disorders of the central nervous system in children. Top Magn Reson Imaging 22:223–237

  49. 49.

    Callen DJ, Shroff MM, Branson HM et al (2009) Role of MRI in the differentiation of ADEM from MS in children. Neurology 72:968–973

  50. 50.

    Callen DJ, Shroff MM, Branson HM et al (2009) MRI in the diagnosis of pediatric multiple sclerosis. Neurology 72:961–967

  51. 51.

    Banwell B, Krupp L, Kennedy J et al (2007) Clinical features and viral serologies in children with multiple sclerosis: a multinational observational study. Lancet Neurol 6:773–781

  52. 52.

    Bulut E, Karakaya J, Salama S et al (2019) Brain MRI findings in pediatric-onset neuromyelitis optica spectrum disorder: challenges in differentiation from acute disseminated encephalomyelitis. AJNR Am J Neuroradiol 40:726–731

  53. 53.

    Hynson JL, Kornberg AJ, Coleman LT et al (2001) Clinical and neuroradiologic features of acute disseminated encephalomyelitis in children. Neurology 56:1308–1312

  54. 54.

    Atzori M, Battistella PA, Perini P et al (2009) Clinical and diagnostic aspects of multiple sclerosis and acute monophasic encephalomyelitis in pediatric patients: a single centre prospective study. Mult Scler 15:363–370

  55. 55.

    Wong AM, Simon EM, Zimmerman RA et al (2006) Acute necrotizing encephalopathy of childhood: correlation of MR findings and clinical outcome. AJNR Am J Neuroradiol 27:1919–1923

  56. 56.

    Kim HJ, Paul F, Lana-Peixoto MA et al (2015) MRI characteristics of neuromyelitis optica spectrum disorder: an international update. Neurology 84:1165–1173

  57. 57.

    Lennon VA, Wingerchuk DM, Kryzer TJ et al (2004) A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet 364:2106–2112

  58. 58.

    Lechner C, Baumann M, Hennes EM et al (2016) Antibodies to MOG and AQP4 in children with neuromyelitis optica and limited forms of the disease. J Neurol Neurosurg Psychiatry 87:897–905

  59. 59.

    van Pelt ED, Wong YY, Ketelslegers IA et al (2016) Neuromyelitis optica spectrum disorders: comparison of clinical and magnetic resonance imaging characteristics of AQP4-IgG versus MOG-IgG seropositive cases in the Netherlands. Eur J Neurol 23:580–587

  60. 60.

    Kitley J, Waters P, Woodhall M et al (2014) Neuromyelitis optica spectrum disorders with aquaporin-4 and myelin-oligodendrocyte glycoprotein antibodies: a comparative study. JAMA Neurol 71:276–283

  61. 61.

    Jarius S, Ruprecht K, Kleiter I et al (2016) MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 2: epidemiology, clinical presentation, radiological and laboratory features, treatment responses, and long-term outcome. J Neuroinflammation 13:280

  62. 62.

    Dos Passos GR, Oliveira LM, da Costa BK et al (2018) MOG-IgG-associated optic neuritis, encephalitis, and myelitis: lessons learned from neuromyelitis optica spectrum disorder. Front Neurol 9:217

  63. 63.

    Fadda G, Brown RA, Longoni G et al (2018) 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 2:191–204

  64. 64.

    Hinnell CJ, Lu JQ, Rajapakse T, Mah JK (2011) Acute tumefactive inflammatory demyelination in a child. Pediatr Neurol 44:394–395

  65. 65.

    Yiu EM, Laughlin S, Verhey LH et al (2014) Clinical and magnetic resonance imaging (MRI) distinctions between tumefactive demyelination and brain tumors in children. J Child Neurol 29:654–665

  66. 66.

    Suh DC, Song Y, Park D et al (2018) New grading system for the clinical evaluation of patients with spinal vascular lesions. Neuroradiology 60:1035–1041

  67. 67.

    Kepes JJ (1993) Large focal tumor-like demyelinating lesions of the brain: intermediate entity between multiple sclerosis and acute disseminated encephalomyelitis? A study of 31 patients. Ann Neurol 33:18–27

  68. 68.

    Mikaeloff Y, Suissa S, Vallee L et al (2004) First episode of acute CNS inflammatory demyelination in childhood: prognostic factors for multiple sclerosis and disability. J Pediatr 144:246–252

  69. 69.

    Chitnis T (2013) Disease-modifying therapy of pediatric multiple sclerosis. Neurotherapeutics 10:89–96

  70. 70.

    Yapici Z, Eraksoy M (2002) Bilateral demyelinating tumefactive lesions in three children with hemiparesis. J Child Neurol 17:655–660

  71. 71.

    Puri V, Chaudhry N, Gulati P et al (2005) Recurrent tumefactive demyelination in a child. J Clin Neurosci 12:495–500

  72. 72.

    Kumar K, Toth C, Jay V (1998) Focal plaque of demyelination mimicking cerebral tumor in a pediatric patient. Pediatr Neurosurg 29:60–63

  73. 73.

    Suh CH, Kim HS, Jung SC et al (2018) MRI findings in tumefactive demyelinating lesions: a systematic review and meta-analysis. AJNR Am J Neuroradiol 39:1643–1649

  74. 74.

    Huppke B, Ellenberger D, Rosewich H et al (2014) Clinical presentation of pediatric multiple sclerosis before puberty. Eur J Neurol 21:441–446

  75. 75.

    Tenembaum SN, Banwell B, Pohl D et al (2013) Subcutaneous interferon beta-1a in pediatric multiple sclerosis: a retrospective study. J Child Neurol 28:849–856

  76. 76.

    Makhani N, Ngan BY, Kamath BM, Yeh EA (2013) Glatiramer acetate-induced acute hepatotoxicity in an adolescent with MS. Neurology 81:850–852

  77. 77.

    Alroughani R, Das R, Penner N et al (2018) Safety and efficacy of delayed-release dimethyl fumarate in pediatric patients with relapsing multiple sclerosis (FOCUS). Pediatr Neurol 83:19–24

  78. 78.

    Waubant E, Banwell B, Wassmer E et al (2019) Clinical trials of disease-modifying agents in pediatric MS: opportunities, challenges, and recommendations from the IPMSSG. Neurology 92:e2538–e2549

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Correspondence to Igor G. Padilha.

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Padilha, I.G., Fonseca, A.P.A., Pettengill, A.L.M. et al. Pediatric multiple sclerosis: from clinical basis to imaging spectrum and differential diagnosis. Pediatr Radiol (2020) doi:10.1007/s00247-019-04582-3

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Keywords

  • Brain
  • Central nervous system
  • Children
  • Demyelination
  • Diagnostic criteria
  • Differential diagnosis
  • Magnetic resonance imaging
  • Multiple sclerosis
  • Spinal cord