In vivo evidence of differential frontal cortex metabolic abnormalities in progressive and relapsing‐remitting multiple sclerosis
Kelley M. Swanberg, Hetty Prinsen, Katherine DeStefano, Mary Bailey, Abhinav V. Kurada, David Pitt, Robert K. Fulbright, Christoph Juchem
Abstract
The pathophysiology of progressive multiple sclerosis remains elusive, significantly limiting available disease‐modifying therapies. Proton MRS ( 1 H‐MRS) enables in vivo measurement of small molecules implicated in multiple sclerosis, but its application to key metabolites glutamate, γ‐aminobutyric acid (GABA), and glutathione has been sparse. We employed, at 7 T, a previously validated 1 H‐MRS protocol to measure glutamate, GABA, and glutathione, as well as glutamine, N ‐acetyl aspartate, choline, and myoinositol, in the frontal cortex of individuals with relapsing‐remitting ( N = 26) or progressive ( N = 21) multiple sclerosis or healthy control adults ( N = 25) in a cross‐sectional analysis. Only individuals with progressive multiple sclerosis demonstrated reduced glutamate ( F 2,65 = 3.424, p = 0.04; 12.40 ± 0.62 mM versus control 13.17 ± 0.95 mM, p = 0.03) but not glutamine ( F 2,65 = 0.352, p = 0.7; 4.71 ± 0.35 mM versus control 4.84 ± 0.42 mM), reduced GABA ( F 2,65 = 3.89, p = 0.03; 1.29 ± 0.23 mM versus control 1.47 ± 0.25 mM, p = 0.05), and possibly reduced glutathione ( F 2,65 = 0.352, p = 0.056; 2.23 ± 0.46 mM versus control 2.51 ± 0.48 mM, p < 0.1). As a group, multiple sclerosis patients demonstrated significant negative correlations between disease duration and glutamate or GABA ( ρ = − 0.4, p = 0.02) but not glutamine or glutathione. Alone, only relapsing‐remitting multiple sclerosis patients exhibited a significant negative correlation between disease duration and GABA ( ρ = −0.5, p = 0.03). Taken together, these results indicate that frontal cortex metabolism is differentially disturbed in progressive and relapsing‐remitting multiple sclerosis.