BACKGROUND: Previous studies have indicated that progression independent of relapse activity (PIRA) is uncommon in patients with aquaporin- 4 antibody-positive (AQP4-IgG) neuromyelitis optica spectrum disorder (NMOSD). However, the patterns of disability accumulation in seronegative NMOSD are unknown. This study aimed to evaluate the prevalence of PIRA and relapse-associated worsening (RAW) in seronegative NMOSD. METHODS: We conducted a retrospective, multicentre cohort study of seronegative NMOSD patients from the MSBase registry. Inclusion criteria required at least three recorded expanded disability status scale (EDSS) scores: baseline, progression, and 6 months confirmed disability progression (CDP). For those with 6-month CDP, the presence or absence of relapse between baseline and progression determined the classification as RAW or PIRA, respectively. Descriptive statistics were employed to present the data. RESULTS: This study included 93 patients, with a median follow-up duration of 5.0 years (Q1 2.8, Q3 8.4). The cohort predominantly consisted of female patients (77.4%), with a median age of onset of 33.9 years (Q1 26.1, Q3 41.2). PIRA was observed in 1 case (1.1%), whilst RAW was documented in 7 cases (7.5%). CONCLUSION: This international cohort study confirms that CDP is uncommon in seronegative NMOSD. Given more than three quarters of CDP occur due to RAW, therapeutic strategies should focus primarily on preventing relapses.

• Keywords
• Disability, EDSS, NMOSD, Progression independent of relapses, Relapse-associated worsening, Seronegative,
• MeSH
• Aquaporin 4 immunology   MeSH
• Autoantibodies blood   MeSH
• Adult MeSH
• Cohort Studies MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Follow-Up Studies MeSH
• Neuromyelitis Optica * physiopathology   epidemiology   blood   immunology   MeSH
• Disability Evaluation MeSH
• Disease Progression * MeSH
• Recurrence MeSH
• Registries MeSH
• Retrospective Studies MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Names of Substances
• Aquaporin 4 MeSH
• AQP4 protein, human MeSH Browser
• Autoantibodies MeSH