Thaís Armangue1, Gemma Olivé-Cirera2, Eugenia Martínez-Hernandez3, Maria Sepulveda3, Raquel Ruiz-Garcia4, Marta Muñoz-Batista3, Helena Ariño3, Veronica González-Álvarez5, Ana Felipe-Rucián6, Maria Jesús Martínez-González7, Veronica Cantarín-Extremera8, Maria Concepción Miranda-Herrero9, Lorena Monge-Galindo10, Miguel Tomás-Vila11, Elena Miravet12, Ignacio Málaga13, Georgina Arrambide14, Cristina Auger15, Mar Tintoré14, Xavier Montalban16, Adeline Vanderver17, Francesc Graus3, Albert Saiz3, Josep Dalmau18. 1. Neuroimmunology Program, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, Universitat de Barcelona, Barcelona, Spain; Pediatric Neuroimmunology Unit, Neurology Department, Sant Joan de Déu Children's Hospital, University of Barcelona, Barcelona, Spain. Electronic address: tarmangue@sjdhospitalbarcelona.org. 2. Neuroimmunology Program, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, Universitat de Barcelona, Barcelona, Spain; Neurology Section, Pediatric Service, Hospital Parc Taulí, Sabadell, Barcelona, Spain. 3. Neuroimmunology Program, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, Universitat de Barcelona, Barcelona, Spain. 4. Immunology Department, Centre Diagnòstic Biomèdic, Hospital Clínic, Barcelona, Spain. 5. Pediatric Neuroimmunology Unit, Neurology Department, Sant Joan de Déu Children's Hospital, University of Barcelona, Barcelona, Spain. 6. Neurology Section, Pediatric Service, Vall d'Hebron Hospital Barcelona, Spain. 7. Neurology Section, Pediatric Service, Cruces University Hospital, Bizkaia, Spain. 8. Pediatric Neurology Section, Hospital Niño Jesús, Madrid, Spain. 9. Neurology Section, Pediatric Service, Hospital Gregorio Marañón, Madrid, Spain. 10. Neurology Section, Pediactric Service, Hospital Miguel Servet, Zaragoza, Spain. 11. Neurology Section, Pediatric Service, Hospital La Fe, Valencia, Spain. 12. Pediatric Neurology Unit, Pediatric Service, Hospital Son Espases Palma de Mallorca, Spain. 13. Child Neurology Unit, Hospital Universitario Central de Asturias, Oviedo, Spain. 14. Centre d'Esclerosi Múltiple de Catalunya, Department of Neurology, Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca, Universitat Autònoma de Barcelona, Barcelona, Spain. 15. Section of Neuroradiology and Magnetic Resonance Unit, Department of Radiology, Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca, Universitat Autònoma de Barcelona, Barcelona, Spain. 16. Centre d'Esclerosi Múltiple de Catalunya, Department of Neurology, Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca, Universitat Autònoma de Barcelona, Barcelona, Spain; Division of Neurology, University of Toronto, St Michael's Hospital, Toronto, ON, Canada. 17. Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, USA; Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. 18. Neuroimmunology Program, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, Universitat de Barcelona, Barcelona, Spain; Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Catalan Institute for Research and Advanced Studies, Barcelona, Spain. Electronic address: jdalmau@clinic.cat.
Abstract
BACKGROUND: Investigations of myelin oligodendrocyte glycoprotein (MOG) antibodies are usually focused on demyelinating syndromes, but the entire spectrum of MOG antibody-associated syndromes in children is unknown. In this study, we aimed to determine the frequency and distribution of paediatric demyelinating and encephalitic syndromes with MOG antibodies, their response to treatment, and the phenotypes associated with poor prognosis. METHODS: In this prospective observational study, children with demyelinating syndromes and with encephalitis other than acute disseminated encephalomyelitis (ADEM) recruited from 40 secondary and tertiary centres in Spain were investigated for MOG antibodies. All MOG antibody-positive cases were included in our study, which assessed syndromes, treatment and response to treatment (ie, number of relapses), outcomes (measured with the modified Rankin scale [mRS]), and phenotypes associated with poor prognosis. We used Fisher's exact and Wilcoxon rank sum tests to analyse clinical features, and survival Cox regression to analyse time to antibody negativity. FINDINGS: Between June 1, 2013, and Dec 31, 2018, 239 children with demyelinating syndromes (cohort A) and 296 with encephalitis other than ADEM (cohort B) were recruited. 116 patients had MOG antibodies, including 94 (39%) from cohort A and 22 (7%) from cohort B; 57 (49%) were female, with a median age of 6·2 years (IQR 3·7-10·0). Presenting syndromes in these 116 patients included ADEM (46 [68%]), encephalitis other than ADEM (22 [19%]), optic neuritis (20 [17%]), myelitis (13 [11%]), neuromyelitis optica spectrum disorders (six [5%]), and other disorders (nine [8%]). Among the patients with autoimmune encephalitis in cohort B (n=64), MOG antibodies were more common than all neuronal antibodies combined (22 [34%] vs 21 [33%]). After a median follow-up of 42 months (IQR 22-67), 33 (28%) of the 116 patients had relapses, including 17 (17%) of 100 diagnosed at first episode. Steroids, intravenous immunoglobulin, or plasma exchange were used in 100 (86%) patients at diagnosis, and 32 (97%) of 33 at relapses. Rituximab was mainly used at relapses (11 [33%]). 99 (85%) of 116 patients had substantial recovery (mRS <2) and 17 (15%) moderate to severe deficits (mRS >2; one died). Phenotypes of poor prognosis included ADEM-like relapses progressing to leukodystrophy-like features, and extensive cortical encephalitis evolving to atrophy. Time to antibody negativity was longer in patients with relapses (HR 0·18, 95% CI 0·05-0·59). INTERPRETATION: The spectrum of paediatric MOG antibody-associated syndromes is wider than previously reported and includes demyelinating syndromes and encephalitis. Recognition of these disorders has important clinical and prognostic implications. FUNDING: Mutua Madrileña Foundation; ISCIII-Subdirección General de Evaluación y Fomento de la Investigación Sanitaria; Fondo Europeo de Desarrollo Regional; Pediatrics Spanish Society; Departament de Salut, Generalitat de Catalunya; Marato TV3 Foundation; Red Española de Esclerosis Múltiple; La Caixa Foundation; and Fundació CELLEX.
BACKGROUND: Investigations of myelin oligodendrocyte glycoprotein (MOG) antibodies are usually focused on demyelinating syndromes, but the entire spectrum of MOG antibody-associated syndromes in children is unknown. In this study, we aimed to determine the frequency and distribution of paediatric demyelinating and encephalitic syndromes with MOG antibodies, their response to treatment, and the phenotypes associated with poor prognosis. METHODS: In this prospective observational study, children with demyelinating syndromes and with encephalitis other than acute disseminated encephalomyelitis (ADEM) recruited from 40 secondary and tertiary centres in Spain were investigated for MOG antibodies. All MOG antibody-positive cases were included in our study, which assessed syndromes, treatment and response to treatment (ie, number of relapses), outcomes (measured with the modified Rankin scale [mRS]), and phenotypes associated with poor prognosis. We used Fisher's exact and Wilcoxon rank sum tests to analyse clinical features, and survival Cox regression to analyse time to antibody negativity. FINDINGS: Between June 1, 2013, and Dec 31, 2018, 239 children with demyelinating syndromes (cohort A) and 296 with encephalitis other than ADEM (cohort B) were recruited. 116 patients had MOG antibodies, including 94 (39%) from cohort A and 22 (7%) from cohort B; 57 (49%) were female, with a median age of 6·2 years (IQR 3·7-10·0). Presenting syndromes in these 116 patients included ADEM (46 [68%]), encephalitis other than ADEM (22 [19%]), optic neuritis (20 [17%]), myelitis (13 [11%]), neuromyelitis optica spectrum disorders (six [5%]), and other disorders (nine [8%]). Among the patients with autoimmune encephalitis in cohort B (n=64), MOG antibodies were more common than all neuronal antibodies combined (22 [34%] vs 21 [33%]). After a median follow-up of 42 months (IQR 22-67), 33 (28%) of the 116 patients had relapses, including 17 (17%) of 100 diagnosed at first episode. Steroids, intravenous immunoglobulin, or plasma exchange were used in 100 (86%) patients at diagnosis, and 32 (97%) of 33 at relapses. Rituximab was mainly used at relapses (11 [33%]). 99 (85%) of 116 patients had substantial recovery (mRS <2) and 17 (15%) moderate to severe deficits (mRS >2; one died). Phenotypes of poor prognosis included ADEM-like relapses progressing to leukodystrophy-like features, and extensive cortical encephalitis evolving to atrophy. Time to antibody negativity was longer in patients with relapses (HR 0·18, 95% CI 0·05-0·59). INTERPRETATION: The spectrum of paediatric MOG antibody-associated syndromes is wider than previously reported and includes demyelinating syndromes and encephalitis. Recognition of these disorders has important clinical and prognostic implications. FUNDING: Mutua Madrileña Foundation; ISCIII-Subdirección General de Evaluación y Fomento de la Investigación Sanitaria; Fondo Europeo de Desarrollo Regional; Pediatrics Spanish Society; Departament de Salut, Generalitat de Catalunya; Marato TV3 Foundation; Red Española de Esclerosis Múltiple; La Caixa Foundation; and Fundació CELLEX.
Authors: Elia Sechi; Laura Cacciaguerra; John J Chen; Sara Mariotto; Giulia Fadda; Alessandro Dinoto; A Sebastian Lopez-Chiriboga; Sean J Pittock; Eoin P Flanagan Journal: Front Neurol Date: 2022-06-17 Impact factor: 4.086
Authors: Amy Kunchok; Eoin P Flanagan; Karl N Krecke; John J Chen; J Alfredo Caceres; Justin Dominick; Ian Ferguson; Revere Kinkel; John C Probasco; Miguel Ruvalcaba; Jonathan D Santoro; Kurt Sieloff; Jeremy Timothy; Brian G Weinshenker; Andrew McKeon; Sean J Pittock Journal: Mult Scler Date: 2020-09-10 Impact factor: 6.312
Authors: Saurabh Sinha; Brenda Banwell; Alexander Tucker; Phillip B Storm; Jimmy Huh; Shih-Shan Lang Journal: Childs Nerv Syst Date: 2021-04-02 Impact factor: 1.475