{"doi":"10.1002/nbm.4590","title":"In vivo evidence of differential frontal cortex metabolic abnormalities in progressive and relapsing‐remitting multiple sclerosis","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.","journal":"NMR in Biomedicine","year":2021,"id":183468,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":13,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9621,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":737879,"name":"Hetty Prinsen","orcid":null,"position":1,"is_corresponding":false},{"id":737880,"name":"Katherine DeStefano","orcid":null,"position":2,"is_corresponding":false},{"id":415179,"name":"Mary Bailey","orcid":null,"position":3,"is_corresponding":false},{"id":737881,"name":"Abhinav V. Kurada","orcid":null,"position":4,"is_corresponding":false},{"id":469584,"name":"David Pitt","orcid":"0000-0002-6407-9542","position":5,"is_corresponding":false},{"id":434717,"name":"Robert K. Fulbright","orcid":"0000-0002-8204-3594","position":6,"is_corresponding":false},{"id":385456,"name":"Christoph Juchem","orcid":"0000-0002-1505-201X","position":7,"is_corresponding":false},{"id":737159,"name":"Kelley M. Swanberg","orcid":"0000-0002-1254-190X","position":0,"is_corresponding":true}],"reference_count":85,"raw_metadata":null,"created_at":"2026-07-18T23:48:22.008011Z","pmid":"34318959","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}