Optic neuritis in Asian type opticospinal multiple sclerosis (OSMS-ON) in a non-Asian population: A functional-structural paradox.

BACKGROUND: Biomarkers have improved the classification of autoimmune inflammatory disorders, including optic neuritis (ON) as a frequent presentation of multiple sclerosis, neuromyelitis spectrum disorders, MOG antibody-related disease (MOGAD), and opticospinal multiple sclerosis (OSMS). The phenotype of OSMS in non-Asian populations is less well known. OBJECTIVE: We investigated the clinical features and prognosis of OSMS-ON in a Brazilian cohort. METHODS: This was a single-center cohort study of patients from Rio de Janeiro (Brazil) with OSMS. All individuals were MOG- and AQP4-seronegative, clinically diagnosed with ON, and had magnetic resonance imaging-confirmed transverse myelitis (TM). Subjects and healthy controls (HCs) were assessed for visual acuity (logMAR VA), automated perimetry mean deviation (MD), intraocular pressure, and spectral-domain optical coherence tomography (OCT), followed by automated retinal layer segmentation of the peripapillary retinal nerve fiber layer (pRNFL) and macular ganglion cell and inner plexiform layer (mGCIPL). Receiver operator characteristic curves were plotted and the area under the curve (AUC) was calculated for group comparisons of retinal asymmetry of the pRNFL and mGCIPL. RESULTS: The 30 patients with OSMS were predominantly female and white. The mean age was 48 years (range 20-70 years). Unilateral ON was the index event in 83.3% of patients. Over the average 18-year follow-up period, there were 89 relapses of ON. In individuals with OSMS, the average VA was 0.07±0.14 in the right eye (RE) and 0.13±0.30 in the left eye (LE). The MD was -5.37±5.88 dB and -5.23±3.34 dB for the RE and LE, respectively. There was a significant cumulative loss of VA (p = 0.0003) and MD (p = 0.0001) with a higher number of recurrent episodes. Atrophy of the pRNFL thickness was significant in OSMS (RE, 78.62 ± 16.01 µm; LE, 79.86 ± 13.79 µm) relative to the HC group (RE, 98.87 ± 10.68 µm; LE, 97.87 ± 10.85 µm, p = 0.0001). Likewise, there was significant mGCIPL atrophy in patients with OSMS (RE, 74.96 ± 14.46 µm; LE, 73.88 ± 13.79 µm) relative to the HC group (RE, 90.50 ± 6.74 µm; LE, 90.41± 6.89 µm; p = 0.0001). Retinal asymmetry, inter-eye percentage, and absolute differences accurately separated patients with unilateral ON from HCs (AUC=0.89 and AUC=0.85, respectively). CONCLUSION: A structural-functional paradox was found in OSMS with a high diagnostic value for a novel metric based on retinal asymmetry. The functional visual outcome are excellent despite significant structural damage to the inner retinal layers in patients with a high ON relapse rate and long-term bilateral sequential involvement.

Lower frequency of antibodies to MOG in Brazilian patients with demyelinating diseases: An ethnicity influence?

OBJECTIVE: Antibodies against Myelin Oligodendrocyte glycoprotein (MOG-Ab) have been investigated as potential biological marker for neuromyelitis optica (NMO) and high-risk syndromes (HR) negative for AQP4-Ab in populations with different ethnic background. We tested AQP4 and MOG antibodies in a Brazilian population with high African ethnic background. METHOD: The study population was composed of adult patients from Rio de Janeiro with inflammatory demyelinating diseases (new and old cases). Blood samples were sent blindly to test the AQP4 and MOG antibodies by CBA. The frequency of positive MOG-Ab was estimated in the NMOHR and the NMO spectrum disorders (NMOSD). A systematic review with meta-analysis assessed the frequency of MOG-Ab in Caucasians and non-Caucasians. RESULTS: 200 adult patients (52% Afro-Brazilian) 115 of them with NMOHR were tested. MOG antibodies were found in 5/68 negative cases of AQP4-Ab negative (7%). The criteria for NMOSD were fulfilled by 70 patients with NMOHR and none of them was positive for MOG-Ab. A low prevalence of MOG antibodies and a predominant phenotype of bilateral Optic Neuritis were found in most non-Caucasian patients. CONCLUSION: The low frequency of MOG Ab in patients from Rio de Janeiro and in other non-Caucasian populations suggests a racial/ancestral influence.