Proportion and Clinical Characteristics of Double-Seronegative NMOSD in a Multicenter Real-World Cohort.
4 affiliations
- 1Department of Neurology, Research Institute and Hospital of National Cancer Center, Goyang, Republic of Korea.
- 2Department of Neurology, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
- 3Department of Neurology, Chonnam National University Hospital and Medical School, Gwangju, Republic of Korea.
- 4Department of Neurology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Abstract
Background
Recent 2025 neuromyelitis optica spectrum disorder (NMOSD) criteria distinguish AQP4-IgG-positive disease from seronegative-syndromic groups, into which double-seronegative-NMOSD (DN-NMOSD) may be reclassified, suggesting the need to better characterize DN-NMOSD within prior diagnostic frameworks.Objective
To determine the proportion and clinical characteristics of DN-NMOSD using rigorously applied 2015 NMOSD criteria with cell-based assays (CBAs).Methods
In this multicenter retrospective cohort study across four Korean referral centers, 634 individuals fulfilling the 2015 criteria were identified. AQP4-IgG and MOG-IgG were assessed using CBAs, with repeated testing in initially seronegative individuals.Results
DN-NMOSD accounted for 8.4% (53/634). Median onset age was 36 years, with mild female predominance (59%). At disease onset, classical NMO phenotype (simultaneous optic neuritis and myelitis) was rare (2%), and isolated brain involvement without myelitis, optic neuritis, or area postrema syndrome was uncommon (13%). Over a median 9-year follow-up, 93% showed a relapsing course, and maintenance immunosuppressive therapy was used in 91% with reduction in relapse rate after treatment (p < 0.001).Conclusions
In a large multicenter cohort, DN-NMOSD represents a small proportion of NMOSD when stringent diagnostic criteria and repeated CBA testing are applied. These findings may provide data relevant to ongoing discussions on classification of the seronegative-syndromic group within evolving diagnostic frameworks.
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BibTeX
@article{hyun2026proportion,
title = {{Proportion and Clinical Characteristics of Double-Seronegative NMOSD in a Multicenter Real-World Cohort.}},
author = {Jae-Won Hyun and Ki Hoon Kim and Seung Woo Kim and Ha Young Shin and You-Ri Kang and Tai-Seung Nam and Woojun Kim and Su-Hyun Kim and Ho Jin Kim},
journal = {European journal of neurology},
year = {2026},
month = nov,
doi = {10.1111/ene.70808},
url = {https://europepmc.org/article/MED/42974736},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Proportion and Clinical Characteristics of Double-Seronegative NMOSD in a Multicenter Real-World Cohort.
AU - Jae-Won Hyun
AU - Ki Hoon Kim
AU - Seung Woo Kim
AU - Ha Young Shin
AU - You-Ri Kang
AU - Tai-Seung Nam
AU - Woojun Kim
AU - Su-Hyun Kim
AU - Ho Jin Kim
PY - 2026
DA - 2026/11/01
JO - European journal of neurology
DO - 10.1111/ene.70808
UR - https://europepmc.org/article/MED/42974736
AB - Background Recent 2025 neuromyelitis optica spectrum disorder (NMOSD) criteria distinguish AQP4-IgG-positive disease from seronegative-syndromic groups, into which double-seronegative-NMOSD (DN-NMOSD) may be reclassified, suggesting the need to better characterize DN-NMOSD within prior diagnostic frameworks.Objective To determine the proportion and clinical characteristics of DN-NMOSD using rigorously applied 2015 NMOSD criteria with cell-based assays (CBAs).Methods In this multicenter retrospective cohort study across four Korean referral centers, 634 individuals fulfilling the 2015 criteria were identified. AQP4-IgG and MOG-IgG were assessed using CBAs, with repeated testing in initially seronegative individuals.Results DN-NMOSD accounted for 8.4% (53/634). Median onset age was 36 years, with mild female predominance (59%). At disease onset, classical NMO phenotype (simultaneous optic neuritis and myelitis) was rare (2%), and isolated brain involvement without myelitis, optic neuritis, or area postrema syndrome was uncommon (13%). Over a median 9-year follow-up, 93% showed a relapsing course, and maintenance immunosuppressive therapy was used in 91% with reduction in relapse rate after treatment (p < 0.001).Conclusions In a large multicenter cohort, DN-NMOSD represents a small proportion of NMOSD when stringent diagnostic criteria and repeated CBA testing are applied. These findings may provide data relevant to ongoing discussions on classification of the seronegative-syndromic group within evolving diagnostic frameworks.
SN - 1351-5101
SN - 1468-1331
ER -