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Investigating the 2023 MOGAD Criteria in Children and Adults With MOG-Antibody Positivity Within and Outside Attacks
Elianet Fonseca1, Gemma Olivé-Cirera1, Eugenia Martinez-Hernandez1
1From the Neuroimmunology Program (E.F., G.O.-C., E.M.-H., M.G., E.C., J.M.C.-M., S.L., Y.B., A.S., J.D., M.S., T.A.), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic de Barcelona, Pediatric Neuroimmunology Unit (E.F., V.G.-Á., V.D., T.A.), Neurology Department, Sant Joan de Déu Children's Hospital, and Sant Joan de Déu Private Foundation for Research and Education (IRSJD) Sant Joan de Déu Children's Hospital (E.F.), University of Barcelona; Pediatric Neurology Department (G.O.-C.), Hospital Parc Taulí de Sabadell; Immunology Service (L.N., R.R.G.), Hospital Clinic, and Ophtalmology Service (G.R., C.d.-P.-S.), Sant Joan de Déu Children's Hospital, University of Barcelona; Department of Neurology (J.B.-L.), University Hospital "12 de Octubre"; Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12) (J.B.-L.); Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED) (J.B.-L.); Department of Medicine, Faculty of Medicine (J.B.-L.), Complutense University, Madrid; Neurology Service (C.I.), Hospital Clínico Universitario, Zaragoza; Neurology Service (J.M.G.D.), Hospital General Universitario Gregorio Marañón, Madrid; Neurology Service (C.C.), Hospital Universitario Son Espases, Palma de Mallorca; Neurology Service (A.C.), Hospital de Mataró, Barcelona; Unit of Neuroimmunology and Multiple Sclerosis of Girona (UNIEMTG) (G.Á.B.), Department of Neurology, University Hospital Dr. Josep Trueta of Girona; Neurology Service (I.G.-S.), Hospital Álvaro Cunqueiro, Vigo; Department of Neurology (C.O.-G.), Hospital Clinico San Carlos, IdISSC, Madrid; Departament of Medicine (C.O.-G.), Medicine Faculty, Universidad Complutense de Madrid (UCM); Neurology Service (M.R.), Hospital Parc Taulí, Sabadell, Barcelona; Multiple Sclerosis CSUR and Clinical Neuroimmunology Unit (J.M.-P., J.E.M.-L.), Neurology Department, Hospital Clínico Universitario Virgen de la Arrixaca (IMIB-Arrixaca), Clinical Neuroimmunology and Multiple Sclerosis Cathedra, UCAM, Universidad Católica San Antonio de Murcia; Neurology Service (L.B.C.), Hospital Universitario Fundación Alcorcón, Madrid; Neurology Service (J.M.-M.), Hospital Universitario Miguel Servet, Zaragoza; Neurology Service (M.P., J.G.), Complejo Hospitalario Universitario de Albacete; Neurology Service (R.V.-G.), Hospital Universitario JM Morales Meseguer, Internal Medicine Department, Universidad de Murcia, Spain; Department of Neurology (J.D.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; and Catalan Institution for Research and Advanced Studies (ICREA) (J.D.), Barcelona, Spain.
Background And Objectives:
The 2023 criteria for myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) perform well in adults but have not been assessed in children.
Methods:
This prospective observational nationwide study includes children and adults with demyelinating syndromes or encephalitis, whose serum or CSF was found MOG-immunoglobulin G (IgG) positive at Institut d'Investigacions Biomèdiques August Pi i Sunyer-Hospital Clínic of Barcelona (Spain). Exclusion criteria were lack of clinical information and follow-up <1 year, and serum unavailable for antibody testing. The primary outcome was to assess the accuracy of the 2023 MOGAD criteria, using as gold standard the most plausible diagnosis after a follow-up >1 year. MOGAD criteria were retrospectively applied assessing core syndromes, supportive clinical-radiological features, and MOG-IgG titers. Patients tested ≤3 months of a disease attack (acute phase) or afterward (remission) were considered separately. The positive predictive value (PPV) of the criteria (true-positive [patients classified as MOGAD and MOGAD diagnosis last follow-up] divided by total positive [all patients classified as MOGAD]), and its 95% CI, was calculated with the Wilson procedure.
Results:
A total of 257 patients (133 children) were included in the study (median age 15 years [interquartile range 6-38], 54% female). Among 202 patients assessed during a disease attack, 158 (78%) had high MOG-IgG serum titers, 36 (18%) low titers, and 8 (4%) antibodies only in CSF. No differences were identified between patients with high and low titers, but those with low titers were more likely to have an alternative diagnosis at last follow-up (2/36 [6%] vs 0/158, p = 0.012). Supportive features were present in 230 of 257 (89%) patients, regardless of age, MOG-IgG titers, and core syndromes except for optic neuritis in adults whose assessment with orbital MRI was not systematic. Overall, 240 of 257 (94%) patients were well classified by the MOGAD criteria (e.g., 236 eventually having MOGAD and 4 alternative diagnoses), and 17 were wrongly classified (e.g., 11 eventually having MOGAD and 6 alternative diagnoses). Although the criteria classified better during disease attacks than during remissions (187 [96%] vs 49 [89%] serum MOG-IgG-positive patients were well-classified, p = 0.038), the PPV was high in both settings (99% [95% CI 97-100] vs 98% [95% CI 89-100]).
Discussion:
The 2023 MOGAD criteria correctly identified most children and adults with MOGAD. The highest accuracy occurred when they were applied during disease attacks.
Classification Of Evidence:
This study provides Class IV evidence that the 2023 MOGAD criteria accurately identify adults and children with MOGAD.
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