Gray matter sodium accumulation and atrophy in relapsing-remitting multiple sclerosis correspond to neurotransmitter...

To explore gray matter (GM) sodium accumulation and volume reduction in relapsing-remitting multiple sclerosis (RRMS) patients by sodium magnetic resonance imaging (²³Na-MRI) and proton MRI (¹H-MRI), respectively, and to investigate the relationship between regional GM damage, atlas-based neurotransmitter distribution, and clinical characteristics.

Fifty-five RRMS patients and 55 healthy controls (HC) were included in this study. We compared the differences in GM total sodium concentration (TSC) and volume between the two groups by voxel-based and region of interest-based analyses, respectively, and then explored the relationship between regional GM damage and clinical characteristics. Spatial correlations between GM damage patterns and atlas-based neurotransmitter maps were investigated using the JuSpace toolbox.

Compared with HC, RRMS patients showed significant TSC increases in bilateral frontal, temporal, occipital cortices, fusiform gyrus, as well as in the right hippocampus and parahippocampal gyrus. The TSC of bilateral inferior temporal gyrus, right superior occipital gyrus and fusiform gyrus was significantly positively correlated with expanded disability status scale (r = 0.371-0.383, p ≤ 0.01), whereas the volumes of left hippocampus, putamen and pallidum were significantly negatively correlated with disease duration (r = -0.351 to -0.412, p ≤ 0.01). The GM sodium accumulation or atrophy in RRMS correlated with the spatial distribution of serotonin, dopamine, GABAergic, opioid, and noradrenaline neurotransmitters, and the degree of above alignment was related to clinical characteristics.

Sodium accumulation occurs primarily in cortical regions of RRMS patients and is associated with physical disability. Regional GM damage with specific neurotransmitter systems may explain some clinical manifestations.

Question ²³Na-MRI can detect early metabolic damage, but the relationship between brain metabolic damage and the vulnerability of specific neurotransmitter systems in multiple sclerosis patients remains unclear. Findings Alterations in GM sodium concentration were widespread across cortical regions, and the GM damage pattern was spatially correlated with neurotransmitter distribution. Clinical relevance ²³Na-MRI could reveal potential metabolic alterations in the GM of multiple sclerosis patients, reflecting neural axonal damage early in the disease. GM damage corresponding to specific neurotransmitter distribution may help to reveal some clinical manifestations and further guide clinical treatment.