Cargando…

Serial Anti–Myelin Oligodendrocyte Glycoprotein Antibody Analyses and Outcomes in Children With Demyelinating Syndromes

IMPORTANCE: Identifying the course of demyelinating disease associated with myelin oligodendrocyte glycoprotein (MOG) autoantibodies is critical to guide appropriate treatment choices. OBJECTIVE: To characterize serial anti-MOG antibody serologies and clinical and imaging features at presentation an...

Descripción completa

Detalles Bibliográficos
Autores principales: Waters, Patrick, Fadda, Giulia, Woodhall, Mark, O’Mahony, Julia, Brown, Robert A., Castro, Denise A., Longoni, Giulia, Irani, Sarosh R., Sun, Bo, Yeh, E. Ann, Marrie, Ruth Ann, Arnold, Douglas L., Banwell, Brenda, Bar-Or, Amit
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Medical Association 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6763982/
https://www.ncbi.nlm.nih.gov/pubmed/31545352
http://dx.doi.org/10.1001/jamaneurol.2019.2940
_version_ 1783454283783471104
author Waters, Patrick
Fadda, Giulia
Woodhall, Mark
O’Mahony, Julia
Brown, Robert A.
Castro, Denise A.
Longoni, Giulia
Irani, Sarosh R.
Sun, Bo
Yeh, E. Ann
Marrie, Ruth Ann
Arnold, Douglas L.
Banwell, Brenda
Bar-Or, Amit
author_facet Waters, Patrick
Fadda, Giulia
Woodhall, Mark
O’Mahony, Julia
Brown, Robert A.
Castro, Denise A.
Longoni, Giulia
Irani, Sarosh R.
Sun, Bo
Yeh, E. Ann
Marrie, Ruth Ann
Arnold, Douglas L.
Banwell, Brenda
Bar-Or, Amit
author_sort Waters, Patrick
collection PubMed
description IMPORTANCE: Identifying the course of demyelinating disease associated with myelin oligodendrocyte glycoprotein (MOG) autoantibodies is critical to guide appropriate treatment choices. OBJECTIVE: To characterize serial anti-MOG antibody serologies and clinical and imaging features at presentation and during follow-up in an inception cohort of prospectively monitored children with acquired demyelination. DESIGN, SETTING, AND PARTICIPANTS: In this prospective cohort study, study participants were recruited from July 2004 to February 2017 through the multicenter Canadian Pediatric Demyelinating Disease Study. Inclusion criteria included (1) incident central nervous system demyelination, (2) at least 1 serum sample obtained within 45 days from onset, and (3) complete clinical information. Of 430 participants with acquired demyelinating syndrome recruited, 274 were included in analyses. Of 156 excluded participants, 154 were excluded owing to missing baseline samples and 2 owing to incomplete clinical information. Data were analyzed from May to October 2018. MAIN OUTCOMES AND MEASURES: Presence of anti-MOG antibodies was blindly assessed in serial samples collected over a median of 4 years. Clinical, magnetic resonance imaging, and cerebrospinal fluid features were characterized at presentation, and subsequent disease course was assessed by development of new brain magnetic resonance imaging lesions, total lesion volume at last evaluation, annualized relapse rates, Expanded Disability Status Scale score and visual functional score at 4 years, and any disease-modifying treatment exposure. RESULTS: Of the 274 included participants, 140 (51.1%) were female, and the median (interquartile range) age of all participants was 10.8 (6.2-13.9) years. One-third of children were positive for anti-MOG antibodies at the time of incident demyelination. Clinical presentations included a combination of optic neuritis, transverse myelitis, and acute disseminated encephalomyelitis for 81 of 84 anti-MOG antibody–positive children (96%). Brain lesions were present in 51 of 76 anti-MOG antibody–positive participants (67%), but magnetic resonance imaging characteristics differed with age at presentation. Complete resolution of baseline lesions was observed in 26 of 49 anti-MOG antibody–positive participants (53%). On serial serum analysis, 38 of 67 participants (57%) who were seropositive at onset became seronegative (median time to conversion, 1 year). Among all participants who were positive for anti-MOG antibodies at presentation, clinical relapses occurred in 9 of 24 children (38%) who remained persistently seropositive and in 5 of 38 children (13%) who converted to seronegative status. CONCLUSIONS AND RELEVANCE: Myelin oligodendrocyte glycoprotein antibodies are common in children with acquired demyelinating syndrome and are transient in approximatively half of cases. Even when persistently positive, most anti-MOG antibody–positive children experience a monophasic disease. The presence of anti-MOG antibodies at the time of incident demyelination should not immediately prompt the initiation of long-term immunomodulatory therapy.
format Online
Article
Text
id pubmed-6763982
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher American Medical Association
record_format MEDLINE/PubMed
spelling pubmed-67639822019-10-18 Serial Anti–Myelin Oligodendrocyte Glycoprotein Antibody Analyses and Outcomes in Children With Demyelinating Syndromes Waters, Patrick Fadda, Giulia Woodhall, Mark O’Mahony, Julia Brown, Robert A. Castro, Denise A. Longoni, Giulia Irani, Sarosh R. Sun, Bo Yeh, E. Ann Marrie, Ruth Ann Arnold, Douglas L. Banwell, Brenda Bar-Or, Amit JAMA Neurol Original Investigation IMPORTANCE: Identifying the course of demyelinating disease associated with myelin oligodendrocyte glycoprotein (MOG) autoantibodies is critical to guide appropriate treatment choices. OBJECTIVE: To characterize serial anti-MOG antibody serologies and clinical and imaging features at presentation and during follow-up in an inception cohort of prospectively monitored children with acquired demyelination. DESIGN, SETTING, AND PARTICIPANTS: In this prospective cohort study, study participants were recruited from July 2004 to February 2017 through the multicenter Canadian Pediatric Demyelinating Disease Study. Inclusion criteria included (1) incident central nervous system demyelination, (2) at least 1 serum sample obtained within 45 days from onset, and (3) complete clinical information. Of 430 participants with acquired demyelinating syndrome recruited, 274 were included in analyses. Of 156 excluded participants, 154 were excluded owing to missing baseline samples and 2 owing to incomplete clinical information. Data were analyzed from May to October 2018. MAIN OUTCOMES AND MEASURES: Presence of anti-MOG antibodies was blindly assessed in serial samples collected over a median of 4 years. Clinical, magnetic resonance imaging, and cerebrospinal fluid features were characterized at presentation, and subsequent disease course was assessed by development of new brain magnetic resonance imaging lesions, total lesion volume at last evaluation, annualized relapse rates, Expanded Disability Status Scale score and visual functional score at 4 years, and any disease-modifying treatment exposure. RESULTS: Of the 274 included participants, 140 (51.1%) were female, and the median (interquartile range) age of all participants was 10.8 (6.2-13.9) years. One-third of children were positive for anti-MOG antibodies at the time of incident demyelination. Clinical presentations included a combination of optic neuritis, transverse myelitis, and acute disseminated encephalomyelitis for 81 of 84 anti-MOG antibody–positive children (96%). Brain lesions were present in 51 of 76 anti-MOG antibody–positive participants (67%), but magnetic resonance imaging characteristics differed with age at presentation. Complete resolution of baseline lesions was observed in 26 of 49 anti-MOG antibody–positive participants (53%). On serial serum analysis, 38 of 67 participants (57%) who were seropositive at onset became seronegative (median time to conversion, 1 year). Among all participants who were positive for anti-MOG antibodies at presentation, clinical relapses occurred in 9 of 24 children (38%) who remained persistently seropositive and in 5 of 38 children (13%) who converted to seronegative status. CONCLUSIONS AND RELEVANCE: Myelin oligodendrocyte glycoprotein antibodies are common in children with acquired demyelinating syndrome and are transient in approximatively half of cases. Even when persistently positive, most anti-MOG antibody–positive children experience a monophasic disease. The presence of anti-MOG antibodies at the time of incident demyelination should not immediately prompt the initiation of long-term immunomodulatory therapy. American Medical Association 2019-09-23 2020-01 /pmc/articles/PMC6763982/ /pubmed/31545352 http://dx.doi.org/10.1001/jamaneurol.2019.2940 Text en Copyright 2019 Waters P et al. JAMA Neurology. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the CC-BY License.
spellingShingle Original Investigation
Waters, Patrick
Fadda, Giulia
Woodhall, Mark
O’Mahony, Julia
Brown, Robert A.
Castro, Denise A.
Longoni, Giulia
Irani, Sarosh R.
Sun, Bo
Yeh, E. Ann
Marrie, Ruth Ann
Arnold, Douglas L.
Banwell, Brenda
Bar-Or, Amit
Serial Anti–Myelin Oligodendrocyte Glycoprotein Antibody Analyses and Outcomes in Children With Demyelinating Syndromes
title Serial Anti–Myelin Oligodendrocyte Glycoprotein Antibody Analyses and Outcomes in Children With Demyelinating Syndromes
title_full Serial Anti–Myelin Oligodendrocyte Glycoprotein Antibody Analyses and Outcomes in Children With Demyelinating Syndromes
title_fullStr Serial Anti–Myelin Oligodendrocyte Glycoprotein Antibody Analyses and Outcomes in Children With Demyelinating Syndromes
title_full_unstemmed Serial Anti–Myelin Oligodendrocyte Glycoprotein Antibody Analyses and Outcomes in Children With Demyelinating Syndromes
title_short Serial Anti–Myelin Oligodendrocyte Glycoprotein Antibody Analyses and Outcomes in Children With Demyelinating Syndromes
title_sort serial anti–myelin oligodendrocyte glycoprotein antibody analyses and outcomes in children with demyelinating syndromes
topic Original Investigation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6763982/
https://www.ncbi.nlm.nih.gov/pubmed/31545352
http://dx.doi.org/10.1001/jamaneurol.2019.2940
work_keys_str_mv AT waterspatrick serialantimyelinoligodendrocyteglycoproteinantibodyanalysesandoutcomesinchildrenwithdemyelinatingsyndromes
AT faddagiulia serialantimyelinoligodendrocyteglycoproteinantibodyanalysesandoutcomesinchildrenwithdemyelinatingsyndromes
AT woodhallmark serialantimyelinoligodendrocyteglycoproteinantibodyanalysesandoutcomesinchildrenwithdemyelinatingsyndromes
AT omahonyjulia serialantimyelinoligodendrocyteglycoproteinantibodyanalysesandoutcomesinchildrenwithdemyelinatingsyndromes
AT brownroberta serialantimyelinoligodendrocyteglycoproteinantibodyanalysesandoutcomesinchildrenwithdemyelinatingsyndromes
AT castrodenisea serialantimyelinoligodendrocyteglycoproteinantibodyanalysesandoutcomesinchildrenwithdemyelinatingsyndromes
AT longonigiulia serialantimyelinoligodendrocyteglycoproteinantibodyanalysesandoutcomesinchildrenwithdemyelinatingsyndromes
AT iranisaroshr serialantimyelinoligodendrocyteglycoproteinantibodyanalysesandoutcomesinchildrenwithdemyelinatingsyndromes
AT sunbo serialantimyelinoligodendrocyteglycoproteinantibodyanalysesandoutcomesinchildrenwithdemyelinatingsyndromes
AT yeheann serialantimyelinoligodendrocyteglycoproteinantibodyanalysesandoutcomesinchildrenwithdemyelinatingsyndromes
AT marrieruthann serialantimyelinoligodendrocyteglycoproteinantibodyanalysesandoutcomesinchildrenwithdemyelinatingsyndromes
AT arnolddouglasl serialantimyelinoligodendrocyteglycoproteinantibodyanalysesandoutcomesinchildrenwithdemyelinatingsyndromes
AT banwellbrenda serialantimyelinoligodendrocyteglycoproteinantibodyanalysesandoutcomesinchildrenwithdemyelinatingsyndromes
AT baroramit serialantimyelinoligodendrocyteglycoproteinantibodyanalysesandoutcomesinchildrenwithdemyelinatingsyndromes