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Understanding Mechanisms of Whole Brain and Regional Grey Matter Atrophy in Children With MOGAD
Ermelinda De Meo1,2, Riccardo Nistri1, Michael Eyre3,4
1Department of Neuroinflammation, Queen Square MS Centre, UCL Queen Square Institute of Neurology, London, UK.
Insights
Brain lesions and relapsing disease significantly impact grey matter atrophy in paediatric MOGAD patients. Persistent MOG-Ab positivity also contributes to brain volume loss and clinical impairment.
Area of Science:
- Neuroscience
- Immunology
- Pediatric Neurology
Background:
- Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is an immune-mediated condition affecting the central nervous system in children.
- Understanding the neuroanatomical changes and their clinical relevance in paediatric MOGAD is crucial for management.
Purpose of the Study:
- To investigate the mechanisms of whole brain and grey matter (GM) volume changes in paediatric MOGAD.
- To identify the clinical correlates of these volumetric changes.
Main Methods:
- MRI scans were performed on 109 paediatric MOGAD patients at onset and follow-up.
- Volumetric analysis using SynthSeg+ compared patient data to normative trajectories from typically developing children.
- Linear mixed-effects models assessed the impact of lesions, disease course, MOG-Ab serostatus, and age on brain volumes.
Main Results:
- 71% of patients had brain lesions at onset, associated with reduced brain growth.
- 46% developed GM atrophy over time, linked to lesion presence and relapsing disease.
- Brain lesions drove progressive atrophy, while relapsing disease and persistent MOG-Ab positivity correlated with specific regional GM atrophy.
Conclusions:
- Brain lesions at onset, their persistence, relapsing disease, and MOG-Ab positivity are key risk factors for GM atrophy in paediatric MOGAD.
- These factors are associated with clinical impairment, including disability progression and learning difficulties.
Objective:
To investigate the mechanisms driving whole brain and regional grey matter (GM) volume changes along with their clinical correlates in paediatric myelin oligodendrocyte glycoprotein antibody (MOG-Ab)-associated disease (MOGAD).
Methods:
One-hundred-nine paediatric MOGAD patients from two UK centres underwent MRI at attack nadir and follow-up (at least 1) ≥ 6 weeks later. Normative trajectories from 317 typically developing children informed volumetric comparisons. MRI segmentation with SynthSeg+ enabled volumetric analysis. Linear mixed-effects models examined impact of brain lesions, disease course, MOG-Ab serostatus and age at onset on brain volumes and changes over time, along with clinical correlates.
Results:
Brain lesions were present in 71/109 patients, who were younger and more likely to present with acute disseminated encephalomyelitis. At onset, 79% showed reduced brain growth, particularly those with brain lesions. Over time, 46% developed atrophy, associated with lesion presence and relapsing disease. All patients exhibited cortical and deep GM growth reduction at onset, with brain lesions driving progressive atrophy. Brian lesion complete resolution mitigated atrophy in the left supramarginal and right inferior parietal gyri. Relapsing disease was linked to greater GM atrophy in the frontal, temporal and parietal lobes. Persistent MOG-Ab positivity correlated with GM atrophy in the cingulate and entorhinal cortices and temporal pole. Disability progression was linked to deep GM, temporal pole and lateral orbitofrontal atrophy, while learning difficulties were associated with lateral occipital and parietal atrophy.
Interpretation:
Brain lesions at onset and their persistence, relapsing disease and MOG-Ab positivity are key risk factors for GM atrophy and clinical impairment in paediatric MOGAD.
