To characterize clinical features, treatment outcomes, and access barriers in seronegative neuromyelitis optica spectrum disorder (NMOSD) in a predominantly Hispanic safety-net population.

Seronegative NMOSD accounts for up to 25% of cases. No randomized controlled trial data guide disease-modifying therapy (DMT) selection in this population, and Hispanic patients remain underrepresented in published cohorts. Access-barrier outcomes have not been systematically reported in seronegative NMOSD cohorts.

Single-center retrospective case series, January 2010 to March 2026. Inclusion required 2015 IPND criteria for seronegative NMOSD, AQP4-IgG negativity on validated cell-based assay (Mayo FACS or ARUP ELISA), and minimum 6-month follow-up. The pre-specified primary endpoint was relapse on current DMT, defined as relapse occurring after initiation of currently listed therapy; pre-treatment events, gap-related relapses, off-therapy relapses, and prior-therapy relapses were excluded.

Of 179 charts reviewed (133 unique patients), 10 met inclusion criteria. Cohort: 80% Hispanic, 70% female; median follow-up 10 years. Index syndromes: longitudinally extensive transverse myelitis 60%, optic neuritis 30%, area postrema syndrome 10%. Two patients were non-assessable for the on-treatment endpoint (Patient 6, prednisone monotherapy; Patient 8, off DMT since 2022). Among the 8 assessable, 7 (87.5%) were relapse-free on current DMT. The single on-treatment relapse (Patient 10) had 3 relapses despite CD19 <10 at each, supporting pharmacodynamic rituximab failure. Among 8 with surveillance imaging on current DMT (Patients 3 and 6 lacked recent imaging due to clinical stability and access barriers), 0 showed new T2 or gadolinium-enhancing lesions. Treatment delays from insurance, financial, or access barriers were documented in 5 of 10 patients (50%); 3 had gaps with measurable clinical harm.

Seronegative NMOSD in this predominantly Hispanic South Texas safety-net cohort is clinically heterogeneous and associated with significant treatment access barriers. These findings support prospective registries enrolling seronegative and underserved populations with access-related outcomes alongside clinical measures.