Neuromyelitis optica spectrum disorder (NMOSD) and anti-myelin oligodendrocyte glycoprotein (anti-MOG) syndromes are immune-mediated inflammatory conditions of the central nervous system that frequently involve the optic nerves and the spinal cord. Because of their similar clinical manifestations and habitual relapsing course they are frequently confounded with multiple sclerosis (MS). Early and accurate diagnosis of these distinct conditions is relevant as they have different treatments. Some agents used for MS treatment may be deleterious to NMOSD. NMOSD is frequently associated with antibodies which target aquaporin-4 (AQP4), the most abundant water channel in the CNS, located in the astrocytic processes at the blood-brain barrier (BBB). On the other hand, anti-MOG syndromes result from damage to myelin oligodendrocyte glycoprotein (MOG), expressed on surfaces of oligodendrocytes and myelin sheaths. Acute transverse myelitis with longitudinally extensive lesion on spinal MRI is the most frequent inaugural manifestation of NMOSD, usually followed by optic neuritis. Other core clinical characteristics include area postrema syndrome, brainstem, diencephalic and cerebral symptoms that may be associated with typical MRI abnormalities. Acute disseminated encephalomyelitis and bilateral or recurrent optic neuritis are the most frequent anti-MOG syndromes in children and adults, respectively. Attacks are usually treated with steroids, and relapses prevention with immunosuppressive drugs. Promising emerging therapies for NMOSD include monoclonal antibodies and tolerization.

Multiple sclerosis (MS) is an inflammatory and neurodegenerative disorder whose prevalence varies across Brazil (from 15–27 cases per 100 thousand inhabitants), and the absence of an extensive national study limits the understanding of MS epidemiology in a nation as diverse as Brazil. To compare epidemiological data, including healthcare access, among people with MS across four Brazilian regions. Data from 2,974 Brazilian MS patients in the Collaborative Latin American Database for Multiple Sclerosis (BRANDO) were analyzed. We assessed demographic and clinical outcomes, as well as healthcare access, to elucidate regional differences. The cohort was predominantly composed of female patients (72.5%) with MS onset at a mean age of 30.6 years. Regarding the regional differences, there was a lower predominance of female patients (68.7%; p = 0.003) in the Southeast, a higher rate of subjects of mixed ethnicity (p < 0.001) in the Midwest (40.3%) and Northeast (63.7%), higher scores on the Expanded Disability Status Scale (EDSS) in the Northeast (4.0; p < 0.001), a higher prevalence of relapsing-remitting MS (RRMS) in the Southeast and Midwest (87%; p < 0.001), while the Northeast presented (p < 0.001) the highest rates of primary progressive MS (PPMS) and secondary progressive MS (SPMS) (PPMS = 15.8%; SPMS = 18%). The Northeast presented the longest time (5.9 years; p < 0.01) from disease onset until MS diagnosis (range for the other regions = 1.9–3.7 years). And the Midwest showed the shortest time (2.1 years; p < 0.01) from disease onset until first access to disease-modifying therapies (DMTs; range for the other regions = 3.5–5.1 years). The present is the first nationwide epidemiological study on people with MS in Brazil. It underscores regional epidemiological variations and differences in healthcare access, advocating for tailored approaches in MS management and research.

Optic neuritis (ON) has been recognized since antiquity, but its modern clinical identity emerged only in the late 19th century and was definitively shaped by the Optic Neuritis Treatment Trial (ONTT). The ONTT established the natural history, visual prognosis, association with multiple sclerosis (MS), and therapeutic response to corticosteroids, building the foundation for contemporary ON management. Subsequent discoveries—most notably aquaporin-4 IgG-associated ON (AQP4-ON), myelin oligodendrocyte glycoprotein antibody-associated ON (MOG-ON), and double-negative ON—have fundamentally transformed this paradigm, shifting ON from a seemingly uniform demyelinating syndrome to a group of biologically distinct disorders. These subtypes differ in immunopathology, clinical course, MRI features, retinal injury patterns, CSF profiles, and long-term outcomes, making early and accurate differentiation essential. MRI provides key distinctions in lesion length, orbital tissue inflammation, bilateral involvement, and chiasmal or optic tract extension. Optical coherence tomography (OCT) offers complementary structural biomarkers, including severe early ganglion cell loss in AQP4-ON, relative preservation in MOG-ON, and variable patterns in double-negative ON. CSF analysis further refines diagnosis, with oligoclonal bands strongly supporting MS-ON. Together, these modalities enable precise early stratification and timely initiation of targeted immunotherapy, which is critical for preventing irreversible visual disability. Despite major advances, significant unmet needs persist. Access to high-resolution MRI, OCT, cell-based antibody assays, and evidence-based treatments remains limited in many regions, contributing to global disparities in outcomes. The understanding of the pathogenesis of double-negative optic neuritis, the identification of reliable biomarkers of relapse and visual recovery, and the determination of standardized cut-off values for multimodal diagnostic tools—including MRI, OCT, CSF analysis, and serological assays—remain unresolved challenges. Future research must expand biomarker discovery, refine imaging criteria, and ensure equitable global access to cutting-edge diagnostic platforms and therapeutic innovations. Four decades after the ONTT, ON remains a dynamic field of investigation, with ongoing advances holding the potential to transform care for patients worldwide. Together, these advances expose a fundamental tension between historically MS-centered diagnostic frameworks and the emerging biological heterogeneity of ON, a tension that underpins the structure and critical perspective of the present review.

Background and ObjectivesSubspecialty exchange programs in neuroimmunology are scarce and have not been formally evaluated. We assessed participant-reported outcomes of the Neuroimmunology Exchange...