New insights into mapping lesion and neurotransmitter distribution comparisons in MOG-ab and AQP4-ab neuromyelitis optica spectrum disorders

Abstract

Abstract Objective: Both aquaporin-4 antibody (AQP4) associated optic neuromyelitis spectrum disease (NMOSD) and Myelin oligodendrocyte glycoprotein antibody associated disease (MOGAD) involve autoimmune-mediated neuronal damage. Brain damage can have direct or indirect effects on the neurotransmitter system, leading to disruptions and functional abnormalities in neural transmission. By examing a sizable and thoroughly characterized cohort of AQP4+ NMOSD and MOGAD patients, we aimed to compare the spatial distribution of brain lesions in the two diseases and to understand the theoretical bases for location preferences. Next, we explored and compared the association between the characteristics of lesion frequency map and the distribution of neurotransmitters in the whole brain to identify novel therapeutic targets based on neurotransmitter modulation. Methods: We gathered clinical details and MRI data to construct a lesion frequency map in AQP4+ NMOSD and MOGAD patients. Probabilistic lesion distribution maps were created after lesions automatic segmentation and spatial normalization. Lobe-wise and voxel-wise quantitative comparisons of two distributions were performed. JuSpace toolbox was performed to explore whether the lesion frequency map correlated with an abnormal distribution of specific neurotransmitters. Results: The findings showed that both AQP4+ NMOSD and MOGAD patients had supratentorial and infratentorial brain lesions, with the highest probability in the deep sublobular white matter (WM) region in both groups; The MOGAD patients' brain lesions were larger, more concentrated, and more likely to be in the deep sublobular WM, hippocampus, cerebellum, putamen, pons, medulla oblongata, cerebellum and gray matter (GM), as well as WM in the frontal, temporal, and occipital lobes. Eight neurotransmitter levels showed a substantial positive correlation with the lesion probability distribution in AQP4+ NMOSD. On the other hand, only dability distribution of MOGAD lesions and both mGluR5 and 5HT2a. Conversely, only noradrenergic (NAT) and dopaminergic (D2, DAT, FDOPA) neurotransmitters were substantially linked with the lesion probability distribution in MOGAD. Furthermore, mGluR5 and 5HT2a showed a somewhat negative correlation with the probability distribution of MOGAD lesions. The pattern of distribution of brain lesions showed also a significant spatial correspondence with a higher distribution of 5HT1a receptor in MOGAD patients comparing to AQP4+ NMOSD. Conclusion: The lesion spatial distribution results improved our understanding of imaging characteristics in the MOGAD and AQP4+ NMOSD patients. We also revealed that the distribution pattern of brain lesions showed a spatial correspondence with specific neurotransmitter, opening up a novel way to assess lesion location predilection or lesion origin.