Skip to main content
Erschienen in: Neurological Sciences 9/2020

03.04.2020 | Original Article

Possible clinical role of MOG antibody testing in children presenting with acute neurological symptoms

verfasst von: Giulia Musso, Margherita Nosadini, Nicoletta Gallo, Stefano Sartori, Mara Seguso, Mario Plebani

Erschienen in: Neurological Sciences | Ausgabe 9/2020

Einloggen, um Zugang zu erhalten

Abstract

The differential diagnosis between acquired inflammatory demyelinating syndromes of the central nervous system (CNS), such as multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD) and acute disseminated encephalomyelitis (ADEM) can be very challenging at onset. Apart from cerebrospinal fluid oligoclonal bands and anti-aquaporin-4 antibodies (AQP4-Ab), definite diagnostic biomarkers are lacking. Anti-myelin oligodendrocyte glycoprotein antibodies (MOG-Abs) have been increasingly described in children with AQP4-seronegative NMOSD, ADEM and other inflammatory demyelinating CND syndromes; despite partial overlaps with AQP4-Ab disease, a novel “MOG-Ab-disorder” phenotype has been suggested. In this study, we tested the presence of MOG-Ab and AQP4-Ab in 57 children at first onset of acute neurological symptoms; three clinical subgroups were identified: 12 patients had acquired inflammatory demyelinating CNS syndromes, 11 had other autoimmune/immune-mediated disorders of the central and peripheral nervous system and 34 had non-immune-mediated CNS disorders. MOG-Abs were found positive only in a subset of cases in the subgroup with acquired inflammatory demyelinating CNS syndromes (in 2/12 patients, both with non-MS phenotype) and in none of the patients with other autoimmune and immune-mediated disorders of the central and peripheral nervous system or with non-immune-mediated disorders of the CNS.
Data from the literature review support clinical and analytical observations.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Comabella M, Montalban X (2014) Body fluid biomarkers in multiple sclerosis. Lancet Neurol 13:113–126CrossRef Comabella M, Montalban X (2014) Body fluid biomarkers in multiple sclerosis. Lancet Neurol 13:113–126CrossRef
2.
Zurück zum Zitat Thompson AJ, Banwell BL, Barkhof F, Carroll WM, Coetzee T, Comi G, Correale J, Fazekas F, Filippi M, Freedman MS, Fujihara K, Galetta SL, Hartung HP, Kappos L, Lublin FD, Marrie RA, Miller AE, Miller DH, Montalban X, Mowry EM, Sorensen PS, Tintoré M, Traboulsee AL, Trojano M, Uitdehaag BMJ, Vukusic S, Waubant E, Weinshenker BG, Reingold SC, Cohen JA (2018) Diagnosis of multiple sclerosis: 2017 revision of the McDonald criteria. Lancet Neurol 17:162–173CrossRef Thompson AJ, Banwell BL, Barkhof F, Carroll WM, Coetzee T, Comi G, Correale J, Fazekas F, Filippi M, Freedman MS, Fujihara K, Galetta SL, Hartung HP, Kappos L, Lublin FD, Marrie RA, Miller AE, Miller DH, Montalban X, Mowry EM, Sorensen PS, Tintoré M, Traboulsee AL, Trojano M, Uitdehaag BMJ, Vukusic S, Waubant E, Weinshenker BG, Reingold SC, Cohen JA (2018) Diagnosis of multiple sclerosis: 2017 revision of the McDonald criteria. Lancet Neurol 17:162–173CrossRef
3.
Zurück zum Zitat Wingerchuk DM, Lennon VA, Lucchinetti CF, Pittock SJ, Weinshenker BG (2007) The spectrum of neuromyelitis optica. Lancet Neurol 6:805–815CrossRef Wingerchuk DM, Lennon VA, Lucchinetti CF, Pittock SJ, Weinshenker BG (2007) The spectrum of neuromyelitis optica. Lancet Neurol 6:805–815CrossRef
4.
Zurück zum Zitat Lennon VA, Wingerchuk DM, Kryzer TJ, Pittock SJ, Lucchinetti CF, Fujihara K, Nakashima I, Weinshenker BG (2004) A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet 364:2106–2112CrossRef Lennon VA, Wingerchuk DM, Kryzer TJ, Pittock SJ, Lucchinetti CF, Fujihara K, Nakashima I, Weinshenker BG (2004) A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet 364:2106–2112CrossRef
5.
Zurück zum Zitat Ramanathan S, Dale RC, Brilot F (2016) Anti-MOG antibody: the history, clinical phenotype, and pathogenicity of a serum biomarker for demyelination. Autoimmun Rev 15:307–324CrossRef Ramanathan S, Dale RC, Brilot F (2016) Anti-MOG antibody: the history, clinical phenotype, and pathogenicity of a serum biomarker for demyelination. Autoimmun Rev 15:307–324CrossRef
6.
Zurück zum Zitat Hacohen Y, Absoud M, Deiva K, Hemingway C, Nytrova P, Woodhall M, Palace J, Wassmer E, Tardieu M, Vincent A, Lim M, Waters P (2015) Myelin oligodendrocyte glycoprotein antibodies are associated with a non-MS course in children. Neurol Neuroimmunol Neuroinflamm 2:e81CrossRef Hacohen Y, Absoud M, Deiva K, Hemingway C, Nytrova P, Woodhall M, Palace J, Wassmer E, Tardieu M, Vincent A, Lim M, Waters P (2015) Myelin oligodendrocyte glycoprotein antibodies are associated with a non-MS course in children. Neurol Neuroimmunol Neuroinflamm 2:e81CrossRef
7.
Zurück zum Zitat Hennes EM, Baumann M, Schanda K, Anlar B, Bajer-Kornek B, Blaschek A, Brantner-Inthaler S, Diepold K, Eisenkölbl A, Gotwald T, Kuchukhidze G, Gruber-Sedlmayr U, Häusler M, Höftberger R, Karenfort M, Klein A, Koch J, Kraus V, Lechner C, Leiz S, Leypoldt F, Mader S, Marquard K, Poggenburg I, Pohl D, Pritsch M, Raucherzauner M, Schimmel M, Thiels C, Tibussek D, Vieker S, Zeches C, Berger T, Reindl M, Rostásy K, BIOMARKER Study Group (2017) Prognostic relevance of MOG antibodies in children with an acquired demyelinating syndrome. Neurology 89:900–908CrossRef Hennes EM, Baumann M, Schanda K, Anlar B, Bajer-Kornek B, Blaschek A, Brantner-Inthaler S, Diepold K, Eisenkölbl A, Gotwald T, Kuchukhidze G, Gruber-Sedlmayr U, Häusler M, Höftberger R, Karenfort M, Klein A, Koch J, Kraus V, Lechner C, Leiz S, Leypoldt F, Mader S, Marquard K, Poggenburg I, Pohl D, Pritsch M, Raucherzauner M, Schimmel M, Thiels C, Tibussek D, Vieker S, Zeches C, Berger T, Reindl M, Rostásy K, BIOMARKER Study Group (2017) Prognostic relevance of MOG antibodies in children with an acquired demyelinating syndrome. Neurology 89:900–908CrossRef
8.
Zurück zum Zitat Hennes EM, Baumann M, Lechner C, Rostásy K (2018) MOG spectrum disorders and role of MOG-antibodies in clinical practice. Neuropediatrics 49:3–11CrossRef Hennes EM, Baumann M, Lechner C, Rostásy K (2018) MOG spectrum disorders and role of MOG-antibodies in clinical practice. Neuropediatrics 49:3–11CrossRef
9.
Zurück zum Zitat Peschl P, Bradl M, Höftberger R, Berger T, Reindl M (2017) Myelin oligodendrocyte glycoprotein: deciphering a target in inflammatory demyelinating diseases. Front Immunol 8:1–15CrossRef Peschl P, Bradl M, Höftberger R, Berger T, Reindl M (2017) Myelin oligodendrocyte glycoprotein: deciphering a target in inflammatory demyelinating diseases. Front Immunol 8:1–15CrossRef
10.
Zurück zum Zitat Jarius S, Ruprecht K, Kleiter I et al (2016) MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 1: frequency, syndrome specificity, influence of disease activity, long-term course, association with AQP4-IgG, and origin. J Neuroinflammation 13:279CrossRef Jarius S, Ruprecht K, Kleiter I et al (2016) MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 1: frequency, syndrome specificity, influence of disease activity, long-term course, association with AQP4-IgG, and origin. J Neuroinflammation 13:279CrossRef
11.
Zurück zum Zitat Cobo-Calvo A, Ruiz A, Maillart E et al (2018) Clinical spectrum and prognostic value of CNS MOG autoimmunity in adults: the MOGADOR study. Neurology 90:1858–1869CrossRef Cobo-Calvo A, Ruiz A, Maillart E et al (2018) Clinical spectrum and prognostic value of CNS MOG autoimmunity in adults: the MOGADOR study. Neurology 90:1858–1869CrossRef
12.
Zurück zum Zitat O'Connor KC, McLaughlin KA, De Jager PL et al (2007) Self-antigen tetramers discriminate between myelin autoantibodies to native or denaturated protein. Nat Med 13:211–217CrossRef O'Connor KC, McLaughlin KA, De Jager PL et al (2007) Self-antigen tetramers discriminate between myelin autoantibodies to native or denaturated protein. Nat Med 13:211–217CrossRef
13.
Zurück zum Zitat Jarius S, Paul F, Aktas O et al (2018) MOG encephalomyelitis: international recommendations on diagnosis and antibody testing. J Neuroinflammation 15:134CrossRef Jarius S, Paul F, Aktas O et al (2018) MOG encephalomyelitis: international recommendations on diagnosis and antibody testing. J Neuroinflammation 15:134CrossRef
14.
Zurück zum Zitat Hacohen Y, Mankad K, Chong WK, Barkhof F, Vincent A, Lim M, Wassmer E, Ciccarelli O, Hemingway C (2017) Diagnostic algorithm for relapsing acquired demyelinating syndromes in children. Neurology 89:269–278CrossRef Hacohen Y, Mankad K, Chong WK, Barkhof F, Vincent A, Lim M, Wassmer E, Ciccarelli O, Hemingway C (2017) Diagnostic algorithm for relapsing acquired demyelinating syndromes in children. Neurology 89:269–278CrossRef
15.
Zurück zum Zitat Jurynczyk M, Geraldes R, Probert F, Woodhall MR, Waters P, Tackley G, DeLuca G, Chandratre S, Leite MI, Vincent A, Palace J (2017) Distinct brain imaging characteristics of autoantibody-mediated CNS conditions and multiple sclerosis. Brain 140:617–627CrossRef Jurynczyk M, Geraldes R, Probert F, Woodhall MR, Waters P, Tackley G, DeLuca G, Chandratre S, Leite MI, Vincent A, Palace J (2017) Distinct brain imaging characteristics of autoantibody-mediated CNS conditions and multiple sclerosis. Brain 140:617–627CrossRef
16.
Zurück zum Zitat Krupp LB, Tardieu M, Amato MP, Banwell B, Chitnis T, Dale RC, Ghezzi A, Hintzen R, Kornberg A, Pohl D, Rostasy K, Tenembaum S, Wassmer E, International Pediatric Multiple Sclerosis Study Group (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 19:1261–1267CrossRef Krupp LB, Tardieu M, Amato MP, Banwell B, Chitnis T, Dale RC, Ghezzi A, Hintzen R, Kornberg A, Pohl D, Rostasy K, Tenembaum S, Wassmer E, International Pediatric Multiple Sclerosis Study Group (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 19:1261–1267CrossRef
17.
Zurück zum Zitat Teunissen CE, Petzold A, Bennett JL, Berven FS, Brundin L, Comabella M, Franciotta D, Frederiksen JL, Fleming JO, Furlan R, Hintzen RQ, Hughes SG, Johnson MH, Krasulova E, Kuhle J, Magnone MC, Rajda C, Rejdak K, Schmidt HK, van Pesch V, Waubant E, Wolf C, Giovannoni G, Hemmer B, Tumani H, Deisenhammer F (2009) A consensus protocol for the standardization of cerebrospinal fluid collection and biobanking. Neurology 73:1914–1922CrossRef Teunissen CE, Petzold A, Bennett JL, Berven FS, Brundin L, Comabella M, Franciotta D, Frederiksen JL, Fleming JO, Furlan R, Hintzen RQ, Hughes SG, Johnson MH, Krasulova E, Kuhle J, Magnone MC, Rajda C, Rejdak K, Schmidt HK, van Pesch V, Waubant E, Wolf C, Giovannoni G, Hemmer B, Tumani H, Deisenhammer F (2009) A consensus protocol for the standardization of cerebrospinal fluid collection and biobanking. Neurology 73:1914–1922CrossRef
18.
Zurück zum Zitat Duignan S, Wright S, Rossor T, Cazabon J, Gilmour K, Ciccarelli O, Wassmer E, Lim M, Hemingway C, Hacohen Y (2018) Myelin oligodendrocyte glycoprotein and aquaporin-4 antibodies are highly specific in children with acquired demyelinating syndromes. Dev Med Child Neurol 60:958–962CrossRef Duignan S, Wright S, Rossor T, Cazabon J, Gilmour K, Ciccarelli O, Wassmer E, Lim M, Hemingway C, Hacohen Y (2018) Myelin oligodendrocyte glycoprotein and aquaporin-4 antibodies are highly specific in children with acquired demyelinating syndromes. Dev Med Child Neurol 60:958–962CrossRef
19.
Zurück zum Zitat Nosadini M, Granata T, Matricardi S, Freri E, Ragona F, Papetti L, Suppiej A, Valeriani M, Sartori S, Italian Working Group on Paediatric Anti-N-methyl-D-aspartate Receptor Encephalitis (2019) Relapse risk factors in anti-N-methyl-D-aspartate receptor encephalitis. Dev Med Child Neurol 61:1101–1107CrossRef Nosadini M, Granata T, Matricardi S, Freri E, Ragona F, Papetti L, Suppiej A, Valeriani M, Sartori S, Italian Working Group on Paediatric Anti-N-methyl-D-aspartate Receptor Encephalitis (2019) Relapse risk factors in anti-N-methyl-D-aspartate receptor encephalitis. Dev Med Child Neurol 61:1101–1107CrossRef
20.
Zurück zum Zitat Nosadini M, Toldo I, Tascini B, Bien CG, Parmeggiani L, De Gaspari P, Zuliani L, Sartori S (2019) LGI1 and CASPR2 autoimmunity in children: systematic literature review and report of a young girl with Morvan syndrome. J Neuroimmunol 335:577008CrossRef Nosadini M, Toldo I, Tascini B, Bien CG, Parmeggiani L, De Gaspari P, Zuliani L, Sartori S (2019) LGI1 and CASPR2 autoimmunity in children: systematic literature review and report of a young girl with Morvan syndrome. J Neuroimmunol 335:577008CrossRef
21.
Zurück zum Zitat Sartori S, Priante E, Pettenazzo A, Marson P, Suppiej A, Benini F, Perilongo G, Toldo I (2014) Intrathecal synthesis of oligoclonal bands in rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation syndrome: new evidence supporting immunological pathogenesis. J Child Neurol 29:421–425CrossRef Sartori S, Priante E, Pettenazzo A, Marson P, Suppiej A, Benini F, Perilongo G, Toldo I (2014) Intrathecal synthesis of oligoclonal bands in rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation syndrome: new evidence supporting immunological pathogenesis. J Child Neurol 29:421–425CrossRef
22.
Zurück zum Zitat Ramanathan S, Mohammad S, Tantsis E et al (2018) Clinical course, therapeutic responses and outcomes in relapsing MOG antibody-associated demyelination. J Neurol Neurosurg Psychiatry 89:127–137CrossRef Ramanathan S, Mohammad S, Tantsis E et al (2018) Clinical course, therapeutic responses and outcomes in relapsing MOG antibody-associated demyelination. J Neurol Neurosurg Psychiatry 89:127–137CrossRef
23.
Zurück zum Zitat Hacohen Y, Palace J (2018) Time to separate MOG-Ab-associated disease from AQP4-Ab-positive neuromyelitis optica spectrum disorder. Neurology 90:947–948CrossRef Hacohen Y, Palace J (2018) Time to separate MOG-Ab-associated disease from AQP4-Ab-positive neuromyelitis optica spectrum disorder. Neurology 90:947–948CrossRef
24.
Zurück zum Zitat Dos Passos GR, Oliveira LM, da Costa BK, Apostolos-Pereira SL, Callegaro D, Fujihara K, Sato DK (2018) MOG-IgG-associated optic neuritis, encephalitis, and myelitis: lessons learned from neuromyelitis optica spectrum disorder. Front Neurol 9:217CrossRef Dos Passos GR, Oliveira LM, da Costa BK, Apostolos-Pereira SL, Callegaro D, Fujihara K, Sato DK (2018) MOG-IgG-associated optic neuritis, encephalitis, and myelitis: lessons learned from neuromyelitis optica spectrum disorder. Front Neurol 9:217CrossRef
25.
Zurück zum Zitat Jarius S, Ruprecht K, Kleiter I et al (2016) MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Parts 2: epidemiology, clinical presentation, radiological and laboratory features, treatment responses, and long-term outcome. J Neuroinflammation 13:280CrossRef Jarius S, Ruprecht K, Kleiter I et al (2016) MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Parts 2: epidemiology, clinical presentation, radiological and laboratory features, treatment responses, and long-term outcome. J Neuroinflammation 13:280CrossRef
26.
Zurück zum Zitat Zuliani L, Nosadini M, Gastaldi M, Spatola M, Iorio R, Zoccarato M, Mariotto S, De Gaspari P, Perini F, Ferrari S, Evoli A, Sartori S, Franciotta D, Giometto B (2019) Management of antibody-mediated autoimmune encephalitis in adults and children: literature review and consensus-based practical recommendations. Neurol Sci 40:2017–2030CrossRef Zuliani L, Nosadini M, Gastaldi M, Spatola M, Iorio R, Zoccarato M, Mariotto S, De Gaspari P, Perini F, Ferrari S, Evoli A, Sartori S, Franciotta D, Giometto B (2019) Management of antibody-mediated autoimmune encephalitis in adults and children: literature review and consensus-based practical recommendations. Neurol Sci 40:2017–2030CrossRef
27.
Zurück zum Zitat Chen JJ, Flanagan EP, Jitprapaikulsan J et al (2018) Myelin oligodendrocyte glycoprotein antibody-positive optic neuritis: clinical characteristics, radiologic clues, and outcome. Am J Ophtalmol 195:8–15CrossRef Chen JJ, Flanagan EP, Jitprapaikulsan J et al (2018) Myelin oligodendrocyte glycoprotein antibody-positive optic neuritis: clinical characteristics, radiologic clues, and outcome. Am J Ophtalmol 195:8–15CrossRef
28.
Zurück zum Zitat Reindl M, Jarius S, Rostasy K, Berger T (2017) Myelin oligodendrocyte glycoprotein antibodies: how clinically useful are they? Curr Opin Neurol 30:295–301CrossRef Reindl M, Jarius S, Rostasy K, Berger T (2017) Myelin oligodendrocyte glycoprotein antibodies: how clinically useful are they? Curr Opin Neurol 30:295–301CrossRef
29.
Zurück zum Zitat Waters PJ, Komorowski L, Woodhall M, Lederer S, Majed M, Fryer J, Mills J, Flanagan EP, Irani SR, Kunchok AC, McKeon A, Pittock SJ (2019) A multicenter comparison of MOG-IgG cell-based assays. Neurology 92:e1250–e1255PubMedPubMedCentral Waters PJ, Komorowski L, Woodhall M, Lederer S, Majed M, Fryer J, Mills J, Flanagan EP, Irani SR, Kunchok AC, McKeon A, Pittock SJ (2019) A multicenter comparison of MOG-IgG cell-based assays. Neurology 92:e1250–e1255PubMedPubMedCentral
30.
Zurück zum Zitat Reindl M, Di Pauli F, Rostásy K, Berger T (2013) The spectrum of MOG autoantibody-associated demyelinating diseases. Nat Rev Neurol 9:455–461CrossRef Reindl M, Di Pauli F, Rostásy K, Berger T (2013) The spectrum of MOG autoantibody-associated demyelinating diseases. Nat Rev Neurol 9:455–461CrossRef
31.
Zurück zum Zitat Wells E, Hacohen Y, Waldman A, Tillema JM, Soldatos A, Ances B, Benseler S, Bielekova B, Dale RC, Dalmau J, Gaillard W, Gorman M, Greenberg B, Hyslop A, Pardo CA, Tasker RC, Yeh EA, Bar-Or A, Pittock S, Vanderver A, Banwell B, attendees of the International Neuroimmune Meeting (2018) Neuroimmune disorders of the central nervous system in children in the molecular era. Nat Rev Neurol 14:433–445CrossRef Wells E, Hacohen Y, Waldman A, Tillema JM, Soldatos A, Ances B, Benseler S, Bielekova B, Dale RC, Dalmau J, Gaillard W, Gorman M, Greenberg B, Hyslop A, Pardo CA, Tasker RC, Yeh EA, Bar-Or A, Pittock S, Vanderver A, Banwell B, attendees of the International Neuroimmune Meeting (2018) Neuroimmune disorders of the central nervous system in children in the molecular era. Nat Rev Neurol 14:433–445CrossRef
Metadaten
Titel
Possible clinical role of MOG antibody testing in children presenting with acute neurological symptoms
verfasst von
Giulia Musso
Margherita Nosadini
Nicoletta Gallo
Stefano Sartori
Mara Seguso
Mario Plebani
Publikationsdatum
03.04.2020
Verlag
Springer International Publishing
Erschienen in
Neurological Sciences / Ausgabe 9/2020
Print ISSN: 1590-1874
Elektronische ISSN: 1590-3478
DOI
https://doi.org/10.1007/s10072-020-04379-5

Weitere Artikel der Ausgabe 9/2020

Neurological Sciences 9/2020 Zur Ausgabe

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.