RT Journal Article SR Electronic T1 Classifying the antibody-negative NMO syndromes JF Neurology - Neuroimmunology Neuroinflammation JO Neurol Neuroimmunol Neuroinflamm FD Lippincott Williams & Wilkins SP e626 DO 10.1212/NXI.0000000000000626 VO 6 IS 6 A1 Yeo, Tianrong A1 Probert, Fay A1 Jurynczyk, Maciej A1 Sealey, Megan A1 Cavey, Ana A1 Claridge, Timothy D.W. A1 Woodhall, Mark A1 Waters, Patrick A1 Leite, Maria Isabel A1 Anthony, Daniel C. A1 Palace, Jacqueline YR 2019 UL http://nn.neurology.org/content/6/6/e626.abstract AB Objective 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.Methods 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.Results 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]; p = 0.041); formate (0.0027 [0.0006] vs 0.0019 [0.0006] AU; p = 0.010) (AU).Conclusions 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.Ab-NMOSD=antibody-positive NMOSD; ANOVA=analysis of variance; AQP4-Ab=aquaporin-4 antibody; AU=arbitrary units; AUC=area under the curve; CPMG=Carr-Purcell-Meiboom-Gill; LBL=low brain lesion; MOG-Ab=myelin oligodendrocyte glycoprotein antibody; MRS=magnetic resonance spectroscopy; NMOSD=neuromyelitis optica spectrum disorders; OPLS-DA=orthogonal partial least square discriminant analysis; PCA=principal component analysis; ppm=parts per million; RRMS=relapsing-remitting MS; VIP=variable importance in projection