Understanding Mechanisms of Whole Brain and Regional Grey Matter Atrophy in Children With MOGAD.

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.