Neuromyelitis optica spectrum disorders: a review with a focus on children and adolescents

Abstract

Neuromyelitis optica spectrum disorder (NMOSD) is a rare and severe inflammatory disorder of the central nervous system (CNS). It is strongly associated with anti-aquaporin 4 antibodies (AQP4-IgG), and it mainly affects young women from non-white ethnicities. However, ∼ 5 to 10% of all cases have onset during childhood. Children and adolescents share the same clinical, radiologic, and laboratory presentation as adults. Thus, the same NMOSD diagnostic criteria are also applied to pediatric-onset patients, but data on NMOSD in this population is still scarce. In seronegative pediatric patients, there is a high frequency of the antibody against myelin oligodendrocyte glycoprotein (MOG-IgG) indicating another disease group, but the clinical distinction between these two diseases may be challenging. Three drugs (eculizumab, satralizumab, and inebilizumab) have been recently approved for the treatment of adult patients with AQP4-IgG-positive NMOSD. Only satralizumab has recruited adolescents in one of the two pivotal clinical trials. Additional clinical trials in pediatric NMOSD are urgently required to evaluate the safety and efficacy of these drugs in this population.

Resumo

O espectro da neuromielite óptica (ENMO) é uma rara e grave doença inflamatória do sistema nervoso central (SNC), fortemente associada ao anticorpo anti-aquaporina 4 (AQP4-IgG) e que afeta preferencialmente mulheres jovens de etnias não-caucasianas. No entanto, aproximadamente de 5 a 10% de todos os casos se iniciam na infância. Crianças e adolescentes compartilham as mesmas características clínicas, radiológicas e laboratoriais dos adultos. Além disso, o mesmo critério diagnóstico de ENMO é aplicado para pacientes com início na infância. No entanto, dados da população pediátrica são escassos. Em pacientes pediátricos soronegativos, existe uma alta frequência de positividade ao anticorpo contra a glicoproteína na mielina do oligodendrócito (MOG-IgG), indicando outra patologia; porém, a distinção clínica entre as duas doenças é desafiadora. Três medicações (eculizumabe, inebilizumabe e satralizumabe) foram recentemente aprovadas para pacientes adultos com AQP4-IgG. Apenas um dos ensaios pivotais do satralizumabe recrutou adolescentes. Novos ensaios clínicos em pacientes pediátricos com ENMO são necessários para avaliar a segurança e eficácia destas drogas nesta população.

Keywords

Aquaporin 4 - Multiple Sclerosis - Myelin-Oligodendrocyte Glycoprotein - Myelitis - Optic Neuritis - Neuromyelitis Optica

Palavras-chave

Aquaporina 4 - Esclerose Múltipla - Glicoproteína Mielina-Oligodendrócito - Mielite - Neurite Óptica - Neuromielite Óptica

Authors' Contritbutions

RBP: conceptualization, methodology, visualization, writing – original draft, review, and editing; JAP, SLAP, CMR, DC: review and editing; DKS: conceptualization, methodology, validation, review, and editing.

Publikationsverlauf

Eingereicht: 17. Dezember 2021

Angenommen: 06. März 2022

Artikel online veröffentlicht:
22. März 2023

• References

• 1 Wingerchuk DM, Banwell B, Bennett JL, Cabre P, Carroll W, Chitnis T. et al; International Panel for NMO Diagnosis. International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology 2015; 85 (02) 177-189
• 2 Pittock SJ, Lucchinetti CF. Neuromyelitis optica and the evolving spectrum of autoimmune aquaporin-4 channelopathies: a decade later. Ann N Y Acad Sci 2016; 1366 (01) 20-39
• 3 Wingerchuk DM, Lennon VA, Lucchinetti CF, Pittock SJ, Weinshenker BG. The spectrum of neuromyelitis optica. Lancet Neurol 2007; 6 (09) 805-815
• 4 Weinshenker BG, Wingerchuk DM. Neuromyelitis Spectrum Disorders. Mayo Clin Proc 2017; 92 (04) 663-679
• 5 Tenembaum S, Chitnis T, Nakashima I, Collongues N, McKeon A, Levy M. et al. Neuromyelitis optica spectrum disorders in children and adolescents. Neurology 2016; 87 (9, Suppl 2) S59-S66
• 6 Gombolay GY, Chitnis T. Pediatric Neuromyelitis Optica Spectrum Disorders. Curr Treat Options Neurol 2018; 20 (06) 19
• 7 Tenembaum S, Yeh EA. Guthy-Jackson Foundation International Clinical Consortium (GJCF-ICC). Pediatric NMOSD: A Review and Position Statement on Approach to Work-Up and Diagnosis. Front Pediatr 2020; 8: 339
• 8 Jarius S, Wildemann B. The history of neuromyelitis optica. J Neuroinflammation 2013; 10: 8
• 9 Jarius S, Wildemann B. The case of the Marquis de Causan (1804): an early account of visual loss associated with spinal cord inflammation. J Neurol 2012; 259 (07) 1354-1357
• 10 Lana-Peixoto MA. Devic's neuromyelitis optica: a critical review. Arq Neuropsiquiatr 2008; 66 (01) 120-138
• 11 Wingerchuk DM, Hogancamp WF, O'Brien PC, Weinshenker BG. The clinical course of neuromyelitis optica (Devic's syndrome). Neurology 1999; 53 (05) 1107-1114
• 12 Lennon VA, Kryzer TJ, Pittock SJ, Verkman AS, Hinson SR. IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel. J Exp Med 2005; 202 (04) 473-477
• 13 Wingerchuk DM, Lennon VA, Pittock SJ, Lucchinetti CF, Weinshenker BG. Revised diagnostic criteria for neuromyelitis optica. Neurology 2006; 66 (10) 1485-1489
• 14 Hacohen Y, Absoud M, Woodhall M, Cummins C, De Goede CG, Hemingway C. et al; UK & Ireland Childhood CNS Inflammatory Demyelination Working Group. Autoantibody biomarkers in childhood-acquired demyelinating syndromes: results from a national surveillance cohort. J Neurol Neurosurg Psychiatry 2014; 85 (04) 456-461
• 15 Rostasy K, Reindl M. Role of autoantibodies in acquired inflammatory demyelinating diseases of the central nervous system in children. Neuropediatrics 2013; 44 (06) 297-301
• 16 Sato DK, Callegaro D, Lana-Peixoto MA, Waters PJ, Jorge FMH, Takahashi T. et al. Distinction between MOG antibody-positive and AQP4 antibody-positive NMO spectrum disorders. Neurology 2014; 82 (06) 474-481
• 17 Marignier R, Hacohen Y, Cobo-Calvo A, Pröbstel A-K, Aktas O, Alexopoulos H. et al. Myelin-oligodendrocyte glycoprotein antibody-associated disease. Lancet Neurol 2021; 20 (09) 762-772
• 18 Pittock SJ, Berthele A, Fujihara K, Kim HJ, Levy M, Palace J. et al. Eculizumab in Aquaporin-4-Positive Neuromyelitis Optica Spectrum Disorder. N Engl J Med 2019; 381 (07) 614-625
• 19 Yamamura T, Kleiter I, Fujihara K, Palace J, Grennberg B, Zakrzewska-Pnieska B. et al. Trial of Satralizumab in Neuromyelitis Optica Spectrum Disorder. N Engl J Med 2019; 381 (22) 2114-2124
• 20 Traboulsee A, Greenberg BM, Bennett JL, Szczechowki L, Fox E, Shkrobot S. et al. Safety and efficacy of satralizumab monotherapy in neuromyelitis optica spectrum disorder: a randomised, double-blind, multicentre, placebo-controlled phase 3 trial. Lancet Neurol 2020; 19 (05) 402-412
• 21 Cree BAC, Bennett JL, Kim HJ, Weinshenker BG, Pittock SJ, Wingerchuck DM. et al; N-MOmentum study investigators. Inebilizumab for the treatment of neuromyelitis optica spectrum disorder (N-MOmentum): a double-blind, randomised placebo-controlled phase 2/3 trial. Lancet 2019; 394 (10206): 1352-1363
• 22 Jarius S, Paul F, Weinshenker BG, Levy M, Kim HJ, Wildemann B. Neuromyelitis optica. Nat Rev Dis Primers 2020; 6 (01) 85
• 23 Fujihara K, Cook LJ. Neuromyelitis optica spectrum disorders and myelin oligodendrocyte glycoprotein antibody-associated disease: current topics. Curr Opin Neurol 2020; 33 (03) 300-308
• 24 Zhang H, Verkman AS. Longitudinally extensive NMO spinal cord pathology produced by passive transfer of NMO-IgG in mice lacking complement inhibitor CD59. J Autoimmun 2014; 53: 67-77
• 25 Furman CS, Gorelick-Feldman DA, Davidson KG, Yasumura T, Neely JD, Agre P. et al. Aquaporin-4 square array assembly: opposing actions of M1 and M23 isoforms. Proc Natl Acad Sci U S A 2003; 100 (23) 13609-13614
• 26 Papadopoulos MC, Verkman AS. Aquaporin 4 and neuromyelitis optica. Lancet Neurol 2012; 11 (06) 535-544
• 27 Saadoun S, Waters P, Bell BA, Vincent A, Verkman AS, Papadopoulos MC. Intra-cerebral injection of neuromyelitis optica immunoglobulin G and human complement produces neuromyelitis optica lesions in mice. Brain 2010; 133 (Pt 2): 349-361
• 28 Waters PJ, Pittock SJ, Bennett JL, Jarius S, Weinshenker BG, Wingerchuk DM. Evaluation of aquaporin-4 antibody assays. Clin Exp Neuroimmunol 2014; 5 (03) 290-303
• 29 Weinshenker BG, Wingerchuk DM, Vukusic S, Linbo L, Pittock SJ, Lucchinetti CF. et al. Neuromyelitis optica IgG predicts relapse after longitudinally extensive transverse myelitis. Ann Neurol 2006; 59 (03) 566-569
• 30 Mori M, Kuwabara S, Paul F. Worldwide prevalence of neuromyelitis optica spectrum disorders. J Neurol Neurosurg Psychiatry 2018; 89 (06) 555-556
• 31 Papp V, Magyari M, Aktas O, Berger T, Broadley SA, Cabre P. et al. Worldwide Incidence and Prevalence of Neuromyelitis Optica: A Systematic Review. Neurology 2021; 96 (02) 59-77
• 32 Hor JY, Asgari N, Nakashima I, Broadley SA, Leite MI, Kissani N. et al. Epidemiology of Neuromyelitis Optica Spectrum Disorder and Its Prevalence and Incidence Worldwide. Front Neurol 2020; 11: 501
• 33 Kim SH, Mealy MA, Levy M, Schmidt F, Ruprecht K, Paul F. et al. Racial differences in neuromyelitis optica spectrum disorder. Neurology 2018; 91 (22) e2089-e2099
• 34 Fadda G, Armangue T, Hacohen Y, Chitnis T, Banwell B. Paediatric multiple sclerosis and antibody-associated demyelination: clinical, imaging, and biological considerations for diagnosis and care. Lancet Neurol 2021; 20 (02) 136-149
• 35 Alvarenga MP, Fernandez O, Leyva L, Campanella L, Vasconcelos CF, Alvarenga M. et al. The HLA DRB1*03:01 allele is associated with NMO regardless of the NMO-IgG status in Brazilian patients from Rio de Janeiro. J Neuroimmunol 2017; 310: 1-7
• 36 Kay CSK, Scola RH, Arndt RC, Lorenzoni PJ, Werneck LC. HLA-alleles class I and II associated with genetic susceptibility to neuromyelitis optica in Brazilian patients. Arq Neuropsiquiatr 2019; 77 (04) 239-247
• 37 Paz ÉS, Maciel PMCT, D'Almeida JAC, Silva BYC, Sampaio HAC, Pinheiro ADV. et al. Excess weight, central adiposity and pro-inflammatory diet consumption in patients with neuromyelitis optica spectrum disorder. Mult Scler Relat Disord 2021; 54 (54) 103110
• 38 Haji Molla Rabi S, Shahmirzaei S, Sahraian MA, Mozdabadi RSK, Aliabadi HR, Gheini MR. et al. Sleep disorders as a possible predisposing attack factor in neuromyelitis optica spectrum disorder (NMOSD): A case-control study. Clin Neurol Neurosurg 2021; 204: 106606
• 39 Mealy MA, Cook LJ, Pache F, Velez DL, Borisow N, Becker D. et al. Vaccines and the association with relapses in patients with neuromyelitis optica spectrum disorder. Mult Scler Relat Disord 2018; 23: 78-82
• 40 Zhong X, Zhou Y, Lu T, Wang Z, Fang L, Peng L. et al. Infections in neuromyelitis optica spectrum disorder. J Clin Neurosci 2018; 47: 14-19
• 41 Kim HJ, Paul F, Lana-Peixoto MA, Tenembaum S, Asgari N, Palace J. et al; Guthy-Jackson Charitable Foundation NMO International Clinical Consortium & Biorepository. MRI characteristics of neuromyelitis optica spectrum disorder: an international update. Neurology 2015; 84 (11) 1165-1173
• 42 Ciccarelli O, Cohen JA, Reingold SC, Weinshenker BG. International Conference on Spinal Cord Involvement and Imaging in Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorders. Spinal cord involvement in multiple sclerosis and neuromyelitis optica spectrum disorders. Lancet Neurol 2019; 18 (02) 185-197
• 43 Shosha E, Dubey D, Palace J, Nakshima I, Jacob A, Fujihara K. et al. Area postrema syndrome: Frequency, criteria, and severity in AQP4-IgG-positive NMOSD. Neurology 2018; 91 (17) e1642-e1651
• 44 Iorio R, Papi C. Neuromyelitis optica, aquaporin-4 antibodies, and neuroendocrine disorders. Handb Clin Neurol 2021; 181: 173-186
• 45 Salama S, Levy M. Bright spotty lesions as an imaging marker for neuromyelitis optica spectrum disorder. Mult Scler 2022; 28 (11) 1663-1666
• 46 Shahmohammadi S, Doosti R, Shahmohammadi A, Mohammadianinejad SE, Sahraian MA, Azimi AR. et al. Autoimmune diseases associated with Neuromyelitis Optica Spectrum Disorders: A literature review. Mult Scler Relat Disord 2019; 27: 350-363
• 47 Akaishi T, Takahashi T, Nakashima I, Abe M, Ishii T, Aoki M. et al. Repeated follow-up of AQP4-IgG titer by cell-based assay in neuromyelitis optica spectrum disorders (NMOSD). J Neurol Sci 2020; 410: 116671
• 48 Holroyd KB, Manzano GS, Levy M. Update on neuromyelitis optica spectrum disorder. Curr Opin Ophthalmol 2020; 31 (06) 462-468
• 49 Savransky A, Rubstein A, Rios MH, Vergel SL, Velasquez MC, Sierra SP. et al. Prognostic indicators of improvement with therapeutic plasma exchange in pediatric demyelination. Neurology 2019; 93 (22) e2065-e2073
• 50 Mealy MA, Wingerchuk DM, Palace J, Greenberg BM, Levy M. Comparison of relapse and treatment failure rates among patients with neuromyelitis optica: multicenter study of treatment efficacy. JAMA Neurol 2014; 71 (03) 324-330
• 51 Damato V, Evoli A, Iorio R. Efficacy and Safety of Rituximab Therapy in Neuromyelitis Optica Spectrum Disorders: A Systematic Review and Meta-analysis. JAMA Neurol 2016; 73 (11) 1342-1348
• 52 Paolilo RB, Hacohen Y, Yazbeck E, Armangue T, Bruijstens A, Lechner C. et al. Treatment and outcome of aquaporin-4 antibody-positive NMOSD: A multinational pediatric study. Neurol Neuroimmunol Neuroinflamm 2020; 7 (05) e837
• 53 Abboud H, Salazar-Camelo A, George N, Planchon SM, Matiello M, Mealy MA, Goodman A. On-behalf of the Guthy-Jackson Foundation NMO International Clinical Consortium. Symptomatic and restorative therapies in neuromyelitis optica spectrum disorders. J Neurol. 2022 Apr;269(4):1786-1801. doi: 10.1007/s00415-021-10783-4. Epub 2021 Sep 5. PMID: 34482456; PMCID: PMC8940781
• 54 Tillema JM, McKeon A. The spectrum of neuromyelitis optica (NMO) in childhood. J Child Neurol 2012; 27 (11) 1437-1447
• 55 Krupp LB, Tardieu M, Amato MP, Banwell B, Chitnis T, Dale RC. et al; International Pediatric Multiple Sclerosis Study Group. 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 2013; 19 (10) 1261-1267
• 56 Chitnis T, Ness J, Krupp L, Waubant E, Hunt T, Olsen CS. et al. Clinical features of neuromyelitis optica in children: US Network of Pediatric MS Centers report. Neurology 2016; 86 (03) 245-252
• 57 Camera V, Messina S, Elhadd KT, Sanpera-Iglesias J, Mariano R, Hacohen Y. et al. Early predictors of disability of paediatric-onset AQP4-IgG-seropositive neuromyelitis optica spectrum disorders. J Neurol Neurosurg Psychiatry 2022; 93 (01) 101-111
• 58 Lechner C, Breu M, Wendel EM, Kornek B, Schanda K, Baumann M. et al. Epidemiology of Pediatric NMOSD in Germany and Austria. Front Neurol 2020; 11: 415
• 59 Zhou J, Zhang Y, Ji TY, Jin YW, Bao XH, Zhang YH, Xiong H, Chang XZ, Jiang YW, Wu Y. [Clinical analysis of neuromyelitis optica spectrum disorders in childhood]. Zhonghua Er Ke Za Zhi. 2019 Feb 2;57(2):118-124. Chinese. doi: 10.3760/cma.j.issn.0578-1310.2019.02.011. PMID: 30695886
• 60 Dahan A, Brilot F, Leventer R, Kornberg AJ, Dale RC, Yiu EM. Neuromyelitis Optica Spectrum Disorder and Anti-Aquaporin 4 Channel Immunoglobulin in an Australian Pediatric Demyelination Cohort. J Child Neurol 2020; 35 (04) 291-296
• 61 Zhou Y, Zhong X, Shu Y, Cui C, Wang J, Wang Y, Li X, Chen Z, Peng L, Kermode A, Qiu W. Clinical course, treatment responses and outcomes in Chinese paediatric neuromyelitis optica spectrum disorder. Mult Scler Relat Disord. 2019 Feb;28:213-220. doi: 10.1016/j.msard.2018.12.038. Epub 2019 Jan 3. PMID: 30623860
• 62 Fragoso YD, Sousa NAC, Saad T, Alves-Leon SV, Pimentel MLV, Goncalves MVM. et al. Clinical Characteristics of Patients With Neuromyelitis Optica Spectrum Disorders With Early Onset. J Child Neurol 2019; 34 (09) 487-490
• 63 Baghbanian SM, Sahraian MA, Naser Moghadasi A, Asgari N. Disability and Therapeutic Response in Paediatric Neuromyelitis Optica Spectrum Disorder: A Case Series from Iran. Iran J Child Neurol 2019; 13 (03) 99-104
• 64 Sepúlveda M, Sola-Valls N, Escudero D, Rojc B, Barón M, Hernández-Echebarría L. et al. Clinical profile of patients with paraneoplastic neuromyelitis optica spectrum disorder and aquaporin-4 antibodies. Mult Scler 2018; 24 (13) 1753-1759
• 65 Boesen MS, Magyari M, Born AP, Thygesen LC. Pediatric acquired demyelinating syndromes: a nationwide validation study of the Danish National Patient Register. Clin Epidemiol 2018; 10: 391-399
• 66 Fragomeni MO, Bichuetti DB, Oliveira EML. Pediatric-onset multiple sclerosis in Brazilian patients: Clinical features, treatment response and comparison to pediatric neuromyelitis optica spectrum disorders. Mult Scler Relat Disord 2018; 25: 138-142
• 67 Hacohen Y, Mankad K, Chong WK, Barkhof F, Vincent A, Lim M. et al. Diagnostic algorithm for relapsing acquired demyelinating syndromes in children. Neurology 2017; 89 (03) 269-278
• 68 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) 2006-2015
• 69 Lechner C, Baumann M, Hennes EM, Schanda K, Marquard K, Karenfort M. et al. Antibodies to MOG and AQP4 in children with neuromyelitis optica and limited forms of the disease. J Neurol Neurosurg Psychiatry 2016; 87 (08) 897-905
• 70 Absoud M, Lim MJ, Appleton R, Jacob A, Kitley J, Leite MI. et al. Paediatric neuromyelitis optica: clinical, MRI of the brain and prognostic features. J Neurol Neurosurg Psychiatry 2015; 86 (04) 470-472
• 71 Fragoso YD, Ferreira ML, Oliveira EM, Domingues RB, Ribeiro TAGJ, Brooks JBB. et al. Neuromyelitis optica with onset in childhood and adolescence. Pediatr Neurol 2014; 50 (01) 66-68
• 72 Rostasy K, Mader S, Schanda K, Huppke P, Gärtner J, Kraus V. et al. Anti-myelin oligodendrocyte glycoprotein antibodies in pediatric patients with optic neuritis. Arch Neurol 2012; 69 (06) 752-756
• 73 Peña JA, Ravelo ME, Mora-La Cruz E, Montiel-Nava C. NMO in pediatric patients: brain involvement and clinical expression. Arq Neuropsiquiatr 2011; 69 (01) 34-38
• 74 Collongues N, Marignier R, Zéphir H, Papeix C, Fontaine B, Blanc F. et al. Long-term follow-up of neuromyelitis optica with a pediatric onset. Neurology 2010; 75 (12) 1084-1088
• 75 Huppke P, Blüthner M, Bauer O, Stark W, Reinhardt K, Huppke B. et al. Neuromyelitis optica and NMO-IgG in European pediatric patients. Neurology 2010; 75 (19) 1740-1744
• 76 Banwell B, Tenembaum S, Lennon VA, Ursell E, Kennedy J, Bar-Or A. et al. Neuromyelitis optica-IgG in childhood inflammatory demyelinating CNS disorders. Neurology 2008; 70 (05) 344-352
• 77 Lotze TE, Northrop JL, Hutton GJ, Ross B, Schiffman JS, Hunter JV. Spectrum of pediatric neuromyelitis optica. Pediatrics 2008; 122 (05) e1039-e1047
• 78 McKeon A, Lennon VA, Lotze T, Tenenbaum S, Ness JM, Rensel M. et al. CNS aquaporin-4 autoimmunity in children. Neurology 2008; 71 (02) 93-100