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<jats:sec><jats:title>Objective</jats:title><jats:p>To determine whether unsupervised principal component analysis (PCA) of comprehensive clinico-radiologic data can identify phenotypic subgroups within antibody-negative patients with overlapping features of multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSDs), and to validate the phenotypic classifications using high-resolution nuclear magnetic resonance (NMR) plasma metabolomics with inference to underlying pathologies.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Forty-one antibody-negative patients were recruited from the Oxford NMO Service. Thirty-six clinico-radiologic parameters, focusing on features known to distinguish NMOSD and MS, were collected to build an unbiased PCA model identifying phenotypic subgroups within antibody-negative patients. Metabolomics data from patients with relapsing-remitting MS (RRMS) (n = 34) and antibody-positive NMOSD (Ab-NMOSD) (aquaporin-4 antibody n = 54, myelin oligodendrocyte glycoprotein antibody n = 20) were used to identify discriminatory plasma metabolites separating RRMS and Ab-NMOSD.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>PCA of the 36 clinico-radiologic parameters revealed 3 phenotypic subgroups within antibody-negative patients: an MS-like subgroup, an NMOSD-like subgroup, and a low brain lesion subgroup. Supervised multivariate analysis of metabolomics data from patients with RRMS and Ab-NMOSD identified myoinositol and formate as the most discriminatory metabolites (both higher in RRMS). Within antibody-negative patients, myoinositol and formate were significantly higher in the MS-like vs NMOSD-like subgroup; myoinositol (mean [SD], 0.0023 [0.0002] vs 0.0019 [0.0003] arbitrary units [AU]; <jats:italic>p</jats:italic> = 0.041); formate (0.0027 [0.0006] vs 0.0019 [0.0006] AU; <jats:italic>p</jats:italic> = 0.010) (AU).</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>PCA identifies 3 phenotypic subgroups within antibody-negative patients and that the metabolite discriminators of RRMS and Ab-NMOSD suggest that these groupings have some pathogenic meaning. Thus, the identified clinico-radiologic discriminators may provide useful diagnostic clues when seeing antibody-negative patients in the clinic.</jats:p></jats:sec>

Original publication

DOI

10.1212/nxi.0000000000000626

Type

Journal article

Journal

Neurology - Neuroimmunology Neuroinflammation

Publisher

Ovid Technologies (Wolters Kluwer Health)

Publication Date

11/2019

Volume

6

Pages

e626 - e626