Performance of the international 2023 myelin oligodendrocyte glycoprotein antibody-associated disease panel criteria in a Japanese cohort: combined assessment of myelin oligodendrocyte glycoprotein immunoglobulin G in serum and CSF

Abstract

In the 2023 International Panel’s diagnostic criteria for myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), one of six core clinical demyelinating events (core events) is required: optic neuritis (ON), myelitis, acute disseminated encephalomyelitis (ADEM), cerebral monofocal or polyfocal deficits, brainstem or cerebellar deficits, and cerebral cortical encephalitis. If myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG) in serum is not clearly positive or is CSF-restricted, the criteria require supporting clinical and MRI features (supporting features). We assessed the performance of the MOGAD panel criteria in relation to MOG-IgG titers in serum and CSF, and explored the diagnostic implications of CSF MOG-IgG as well as atypical clinical presentations.

In this cross-sectional cohort study, we analyzed 405 cases of non-multiple-sclerosis CNS demyelinating diseases with aquaporin 4 immunoglobulin G negativity, all of whom underwent MOG-IgG testing using paired serum and CSF samples collected across Japan from 2015 to 2018. Endpoint titers were determined by two-fold serial dilutions (starting at 1:16 for serum and 1:1 for CSF), with ≥1:128 in serum defined as the cutoff to minimize false-positive results, as we previously established. Two independent investigators evaluated whether each patient met the core events and the supporting features.

A total of 141 cases exhibited MOG-IgG positivity in serum and/or CSF. The core events included ON (n = 50, 36%), myelitis (n = 61, 43%), ADEM (n = 31, 22%), cerebral deficits (n = 22, 16%), brainstem/cerebellar deficits (n = 26, 18%), cortical encephalitis (n = 22, 16%) with overlap. Five cases (3.5%) did not meet the criteria; two cases of meningitis with headache and prolonged fever lacked core events, while one case of optic neuritis and two cases of myelitis lacked the supporting features and showed either low-positive serum or CSF-restricted MOG-IgG. The rate of meeting the supporting features showed a titer-dependent trend; 1:16-1:64, 88%; 1:128-1:512, 97%; ≥ 1:1024, 100% in serum; negative–1:4, 92%; 1:8–1:32, 100%; ≥ 1:64, 100% in CSF.

Overall, the criteria demonstrated good performance. In our cohort, all cases with high CSF positivity (≥1:8) fulfilled the supporting features. Future revisions may need to incorporate less common presentations, such as meningitis or prolonged fever with clear positivity and the supporting features, and recognize high CSF MOG-IgG titers as diagnostic. Additionally, in some cases with low positivity or CSF-restricted MOG-IgG that do not meet the supporting features, MOGAD may remain a possible diagnosis after careful exclusion of alternative diagnoses.