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Background: Aquaporin-4 immunoglobulin G (AQP4-IgG) antibody-positive neuromyelitis optica spectrum disorders (NMOSD) are frequently associated with other autoimmune disorders, including systemic lupus erythematosus (SLE). Eculizumab (ECU) is a highly effective long-term treatment for NMOSD. However, ECU is known to increase significantly the risk of infection with encapsulated bacteria and sepsis. Recently, increased insulin resistance (IR) in patients with NMOSD has been suggested. Type B IR (TBIR) is a rare autoimmune condition often accompanying or preceding SLE. TBIR has not yet been reported in NMOSD. Objective: To report an ECU-treated patient with AQP4-IgG-positive NMOSD who developed fatal septic complications after the emergence of TBIR. Methods: Description of the clinical course over a period of 8 years. Results: A female patient was diagnosed with NMOSD at the age of 16 years. A variety of disease-modifying drugs failed to achieve sufficient disease control, resulting in severe tetraparesis. Treatment with ECU was started 6 years after NMOSD diagnosis and stabilized the disease. The patient developed TBIR 8 months after initiation of ECU therapy. Following high-dose intravenous methylprednisolone therapy for a clinical relapse and three further courses of ECU, the patient was admitted with severe pneumonia caused by the encapsulated bacterium Klebsiella pneumoniae and hypoglycemia. Despite multimodal therapy, the patient died from sepsis-related multiorgan failure 18 months after initiation of ECU. Conclusions: TBIR should be considered as differential diagnosis in patients with NMOSD presenting with disturbed glucose metabolism, irrespective of the presence of SLE. More real-world data are needed on the risk/benefit ratio of ECU treatment in patients who have co-existing autoimmune comorbidities that may compromise immune function. Strategies to mitigate the risk of serious infection in patients treated with ECU are discussed. [ABSTRACT FROM AUTHOR]

Background and purpose: Foveal changes were reported in aquaporin‐4 antibody (AQP4‐Ab) seropositive neuromyelitis optica spectrum disorder (NMOSD) patients; however, it is unclear whether they are independent of optic neuritis (ON), stem from subclinical ON or crossover from ON in fellow eyes. Fovea morphometry and a statistical classification approach were used to investigate if foveal changes in NMOSD are independent of ON and progressive. Methods: This was a retrospective longitudinal study of 27 AQP4‐IgG + NMOSD patients (49 eyes; 15 ON eyes and 34 eyes without a history of ON [NON eyes]), follow‐up median (first and third quartile) 2.32 (1.33–3.28), and 38 healthy controls (HCs) (76 eyes), follow‐up median (first and third quartile) 1.95 (1.83–2.54). The peripapillary retinal nerve fibre layer thickness and the volume of combined ganglion cell and inner plexiform layer as measures of neuroaxonal damage from ON were determined by optical coherence tomography. Nineteen foveal morphometry parameters were extracted from macular optical coherence tomography volume scans. Data were analysed using orthogonal partial least squares discriminant analysis and linear mixed effects models. Results: At baseline, foveal shape was significantly altered in ON eyes and NON eyes compared to HCs. Discriminatory analysis showed 81% accuracy distinguishing ON vs. HCs and 68% accuracy in NON vs. HCs. NON eyes were distinguished from HCs by foveal shape parameters indicating widening. Orthogonal partial least squares discriminant analysis discriminated ON vs. NON with 76% accuracy. In a follow‐up of 2.4 (20.85) years, no significant time‐dependent foveal changes were found. Conclusion: The parafoveal area is altered in AQP4‐Ab seropositive NMOSD patients suggesting independent neuroaxonal damage from subclinical ON. Longer follow‐ups are needed to confirm the stability of the parafoveal structure over time. [ABSTRACT FROM AUTHOR]

The Optic Neuritis Treatment Trial, a landmark study completed in 1991, stratified the risk of multiple sclerosis in patients with optic neuritis. Since that time, unique biomarkers for optic neuritis have been found. The antibody against aquaporin-4 (AQP4)-immunoglobulin G (IgG) discovered in 2004 was found to be both the pathologic cause and a reliable biomarker for neuromyelitis optica spectrum disorders. This finding enabled an expanded definition of the phenotype of neuromyelitis optica spectrum disorder and improved treatment of the disease. Subsequently, myelin oligodendrocyte glycoprotein (MOG) IgG was recognized to be a marker for MOG-IgG-associated disorder, a central demyelinating disease characterized by recurrent optic neuritis, prominent disk edema, and perineural optic nerve enhancement on magnetic resonance imaging. Most multiple sclerosis disease-modifying agents are ineffective for AQP4-IgG-positive neuromyelitis optica spectrum disorder and MOG-IgG-associated disorder. Because there are crucial differences in treatment and prognosis between multiple sclerosis, AQP4-IgG-positive neuromyelitis optica spectrum disorder, and MOG-IgG-associated disorder, ophthalmologists should be aware of these new biomarkers of optic neuritis and incorporate their testing in all patients with atypical optic neuritis. [ABSTRACT FROM AUTHOR]

Background: Antibodies against myelin oligodendrocyte glycoprotein (MOG-IgG) have been reported in patients with aquaporin-4 antibody (AQP4-IgG)-negative neuromyelitis optica spectrum disorders (NMOSD). The objective of this study was to describe optic neuritis (ON)-induced neuro-axonal damage in the retina of MOG-IgG-positive patients in comparison with AQP4-IgG-positive NMOSD patients. Methods: Afferent visual system damage following ON was bilaterally assessed in 16 MOG-IgG-positive patients with a history of ON and compared with that in 16 AQP4-IgG-positive NMOSD patients. In addition, 16 healthy controls matched for age, sex, and disease duration were analyzed. Study data included ON history, retinal optical coherence tomography, visual acuity, and visual evoked potentials. Results: Eight MOG-IgG-positive patients had a previous diagnosis of AQP4-IgG-negative NMOSD with ON and myelitis, and eight of (mainly recurrent) ON. Twenty-nine of the 32 eyes of the MOG-IgG-positive patients had been affected by at least one episode of ON. Peripapillary retinal nerve fiber layer thickness (pRNFL) and ganglion cell and inner plexiform layer volume (GCIP) were significantly reduced in ON eyes of MOG-IgG-positive patients (pRNFL = 59 ± 23 μm; GCIP = 1.50 ± 0.34 mm3) compared with healthy controls (pRNFL = 99 ± 6 μm, p < 0.001; GCIP =1.97 ± 0.11 mm3, p < 0.001). Visual acuity was impaired in eyes after ON in MOG-IgG-positive patients (0.35 ± 0.88 logMAR). There were no significant differences in any structural or functional visual parameters between MOG-IgGpositive and AQP4-IgG-positive patients (pRNFL: 59 ± 21 μm; GCIP: 1.41 ± 0.27 mm3; Visual acuity = 0.72 ± 1.09 logMAR). Importantly, MOG-IgG-positive patients had a significantly higher annual ON relapse rate than AQP4-IgGpositive patients (median 0.69 vs. 0.29 attacks/year, p = 0.004), meaning that on average a single ON episode caused less damage in MOG-IgG-positive than in AQP4-IgG-positive patients. pRNFL and GCIP loss correlated with the number of ON episodes in MOG-IgG-positive patients (p < 0.001), but not in AQP4-IgG-positive patients. Conclusions: Retinal neuro-axonal damage and visual impairment after ON in MOG-IgG-positive patients are as severe as in AQP4-IgG-positive NMOSD patients. In MOG-IgG-positive patients, damage accrual may be driven by higher relapse rates, whereas AQP4-IgG-positive patients showed fewer but more severe episodes of ON. Given the marked damage in some of our MOG-IgG-positive patients, early diagnosis and timely initiation and close monitoring of immunosuppressive therapy are important. [ABSTRACT FROM AUTHOR]