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