Clinical presentation, MR imaging and outcome in children with myelin oligodendrocyte glycoprotein antibody-negative acute disseminated encephalomyelitis

M Panagi; A Blaschek; A Selek; M Baumann; R Cleaveland; A Panzer; C Conrad; A Della Marina; K Egler; J Finsterwalder; T Geis; H Hartmann; M Häusler; P Hofstetter; M Karenfort; G Kluger; S Leiz; A Merkenschlager; M Nosadini; S Sartori; M Salandin; M Schimmel; B Kornek; E M Wendel; M Reindl; K Rostasy; BIOMARKER Study Group

doi:10.1016/j.ejpn.2025.05.009

Clinical presentation, MR imaging and outcome in children with myelin oligodendrocyte glycoprotein antibody-negative acute disseminated encephalomyelitis

Eur J Paediatr Neurol. 2025 May 22:57:24-34. doi: 10.1016/j.ejpn.2025.05.009. Online ahead of print.

Authors

M Panagi¹, A Blaschek², A Selek³, M Baumann⁴, R Cleaveland⁵, A Panzer⁵, C Conrad⁶, A Della Marina⁷, K Egler⁸, J Finsterwalder⁹, T Geis¹⁰, H Hartmann¹¹, M Häusler¹², P Hofstetter¹³, M Karenfort¹⁴, G Kluger¹⁵, S Leiz¹⁶, A Merkenschlager¹⁷, M Nosadini¹⁸, S Sartori¹⁸, M Salandin¹⁹, M Schimmel²⁰, B Kornek²¹, E M Wendel²², M Reindl²³, K Rostasy²⁴; BIOMARKER Study Group

Affiliations

¹ Department of Pediatric Neurology, Children's Hospital Datteln, University Witten/Herdecke, Datteln, Germany.
² LMU University Hospital, Department of Pediatrics I Division of Pediatric Neurology I MUC ISPZ Hauner - Munich University Center for Children with Medical and Developmental, Dr. von Hauner Children's Hospital, Munich, Germany.
³ Health Sciences University Gülhane Training and Research Hospital Department of Child Neurology, Ankara, Turkey.
⁴ Department of Pediatric I, Pediatric Neurology, Medical University of Innsbruck, Innsbruck, Austria.
⁵ Department of Pediatric Radiology, Children's Hospital Datteln, University Witten/Herdecke, Datteln, Germany.
⁶ Division of Pediatric Neurology, Department of Pediatrics, Marienhaus Klinikum Bendorf, Neuwied, Waldbreitbach, Germany.
⁷ Department of Pediatric Neurology, Centre for Neuromuscular Disorders, University Duisburg-Essen, Essen, Germany.
⁸ Department of Neonatology, Pediatrics, and Adolescent Medicine Klinikum Nürnberg, Germany.
⁹ Department of Pediatric Neurology, Mutterhaus der Borromäerinnen, Trier, Germany.
¹⁰ Pediatric Neurology, University Children's Hospital Regensburg (KUNO), Hospital St. Hedwig of the Order of St. John, University of Regensburg, Regensburg, Germany.
¹¹ Department of Pediatric Kidney, Liver, Metabolic and Neurological Diseases, Hannover Medical School, Hannover, Germany.
¹² Division of Neuropediatrics, Department of Pediatric and Adolescent Medicine, RWTH University Hospital, Aachen, Germany.
¹³ Division of Neuropediatrics, Department of Pediatrics, Goethe University Frankfurt, Main, Frankfurt, Germany.
¹⁴ Department of General Pediatrics, Neonatology and Pediatric Cardiology, University Children's Hospital, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.
¹⁵ Centre of Epilepsy for Children and Adolescents, Schoen Klinik Vogtareuth, Hospital for Neuropediatrics and Neurological Rehabilitation, Vogtareuth, Germany; Department of Pediatrics, Institute of Rehabilitation, Transition and Palliation of Neurologically Ill Children, Paracelsus Medical University, Salzburg, Austria.
¹⁶ Department of Pediatrics and Adolescent Medicine, Hospital Dritter Orden, Munich, Germany.
¹⁷ Department of Pediatric Neurology, University Leipzig, Leipzig, Germany.
¹⁸ Pediatric Neurology and Neurophysiology Unit, Department of Women's and Children's Health, University Hospital of Padua, Padua, Italy; Neuroimmunology Group Paediatric Research Institute "Città Della Speranza, Padova, Italy.
¹⁹ Division of Child and Adolescent Neurology and Rehabilitation, Hospital Bozen, Bozen, Italy.
²⁰ Division of Pediatric Neurology, Clinic of Pediatrics, University Hospital of Augsburg, Augsburg, Germany.
²¹ Comprehensive Center for Clinical Neurosciences & Mental Health, Medical University of Vienna, Austria.
²² Division of Pediatric Neurology, Department of Pediatrics, Olgahospital, Klinikum Stuttgart, Stuttgart, Germany.
²³ Medical University of Innsbruck, Clinical Department of Neurology Innsbruck, Austria, Innsbruck, Austria.
²⁴ Department of Pediatric Neurology, Children's Hospital Datteln, University Witten/Herdecke, Datteln, Germany. Electronic address: kevin.rostasy@uni-wh.de.

PMID: 40446499
DOI: 10.1016/j.ejpn.2025.05.009

Abstract

Background: Acute disseminated encephalomyelitis (ADEM) without myelin oligodendrocyte glycoprotein (MOG) antibodies (abs) presents a diagnostic challenge.

Objective: To investigate whether the diagnosis of MOG-negative (neg) ADEM was confirmed over time and to highlight the clinical and neuroradiological characteristics distinguishing monophasic MOG-neg ADEM from alternative diagnoses.

Material and methods: Children diagnosed with a first clinical episode of MOG-neg ADEM and a dataset including clinical presentation, MRI, CSF studies and at least 3-month follow-up were included.

Results: 47 children with MOG-neg ADEM were identified (m:f = 27:20 , median age 8.0 years. 38 (79.2 %) children maintained the initial diagnosis after a median follow-up of 34.2 months. In 9 (19.1 %) children an alternative diagnosis was assigned after a median follow-up of 4.2 months including multiple sclerosis (MS) n = 2; glioblastoma (GBM) n = 2; hemophagocytic lymphohistiocytosis (HLH) n = 2; CNS vasculitis n = 1; ADEM followed by optic neuritis (ADEMON) n = 2. Cerebral white matter lesions were identified in 84.2 % of MOG-neg ADEM children. Gadolinium enhancement was noted in 11.4 % of MOG-neg ADEM children. Of 38 MOG-neg ADEM children, 9 (23.7 %) had only one atypical MRI finding, whereas 23 (60.5 %) showed multiple atypical MRI features. All children with alternative diagnoses exhibited more than one atypical MRI feature. The outcome was favorable (mRS </ = 2) in 36/38 (94.7 %) children with MOG-neg ADEM CONCLUSION: A substantial number of children initially diagnosed with MOG-neg ADEM will have another diagnosis. Children with MOG-neg ADEM showed white matter lesions but also atypical MRI findings. Monophasic MOG-neg ADEM was associated with a favorable outcome.

Keywords: (1) acute disseminated encephalomyelitis (ADEM); (2) children; (3) myelin oligodendrocyte glycoprotein (MOG); (4) multiple sclerosis (MS); (5) HLH.