Deep Gray Matter Iron Deposition in NMOSD and MOGAD: A Comparative Study with MS

To investigate deep gray matter (DGM) susceptibility in neuromyelitis optica spectrum disorders (NMOSD) and myelin-oligodendrocyte glycoprotein antibody-associated disease (MOGAD) using quantitative susceptibility mapping (QSM) with multiple sclerosis (MS) as a disease comparison, and explore its clinical significance.

We prospectively recruited 200 participants with QSM images: 81 NMOSD (62 aquaporin-4 [AQP4] antibody seropositive [AQP4+] and 19 AQP4 antibody seronegative [AQP4-]), 20 MOGAD, 71 relapsing-remitting MS, and 28 healthy controls (HC). We used voxel-wise analysis to compare differences in DGM susceptibility across groups, and linear regression analysis to relate susceptibility with structural MRI measures and clinical variables. DGM susceptibility was further compared between subgroups with low and high expanded disability status scale (EDSS) scores in each disease group.

Compared with HC, AQP4+NMOSD patients showed higher susceptibility in bilateral putamen, pallidum, hippocampus, and amygdala, MOGAD showed higher susceptibility in right putamen, hippocampus, amygdala, and left thalamus, while AQP4-NMOSD showed no susceptibility alterations. Compared with MS patients, only AQP4+NMOSD showed lower DGM susceptibility. Susceptibility in several DGM subregions including right putamen, hippocampus and amygdala negatively correlated with DGM volume in AQP4+NMOSD, MOGAD and MS, and positively correlated with number of relapses and disease duration in MOGAD and MS. Higher DGM susceptibility was observed in MOGAD and MS patients with high EDSS scores than those with low EDSS scores.

We identified distinct patterns of DGM iron deposition in AQP4+NMOSD, MOGAD, and MS. These patterns were negatively associated with DGM volume and positively associated with clinical disability, especially in MOGAD and MS.