Anti-myelin Oligodendrocyte Glycoprotein Antibody Research Articles

Seropositive Neuromyelitis Optica in a Case of Undiagnosed Ankylosing Spondylitis: A Neuro-Rheumatological Conundrum

Seropositive Neuromyelitis Optica in a Case of Undiagnosed Ankylosing Spondylitis: A Neuro-Rheumatological Conundrum

Myelin oligodendrocyte glycoprotein antibodies in genetic leukodystrophies

Accumulation of intermediate metabolites due to enzyme deficiencies and demyelination can provoke inflammation in genetic leukodystrophies. Thirty patients with genetic leukodystrophy and 48 healthy control sera were tested for anti-myelin oligodendrocyte glycoprotein (MOG) antibodies by fixed and/or live cell-based assays. MOG-IgG was detected in two late infantile metachromatic leukodystrophy (MLD) cases, both of which were also weakly positive for IgG1, and one with IgG3 as the dominant anti-MOG IgG subclass. MOG-IgG was borderline positive in a vanishing white matter (VWM) disease patient. These results suggest that inherited metabolic or degenerative processes can have an autoimmune component, possibly as an epiphenomenon.

Longitudinally Extensive Transverse Myelitis: One Disease, Variable Outcomes-A Case Series.

Longitudinal extensive transverse myelitis (LETM) is a rare form of widespread inflammation of the spinal cord causing T2 hyperintensity in spinal magnetic resonance imaging (MRI) extending across three or more vertebral segments. It is an acute onset of sensory, motor, and autonomic dysfunction of variable etiology with a likely poor outcome. We present a case series of three cases wherein children between the ages of 4 and 13 years had diverse symptoms from gradual painless loss of vision in both eyes with headache, vomiting and seizure, and a normal central nervous system examination except involvement of the optic nerve to another child with abdominal pain, urinary retention and constipation for 3 days with exaggerated DTR, and patchy sensory loss without any definite sensory level, and to the third child with fever and weakness of lower limbs, hypotonia and grade 1–2/5 power in lower limbs and normal upper limb power. Contrast-enhanced MRI spine of all children showed long segment T2 hyperintensity with variable involvement of the brain. The first two children were treated with pulsed dose methylprednisolone, and the last child received intravenous immunoglobulin followed by methylprednisolone. All were followed with oral prednisolone. LETM has a varied presentation with different etiologies. Antineuromyelitis optica immunoglobulin G (IgG) antibody (Aquaporin-4 IgG) and antimyelin oligodendrocyte glycoprotein antibody are strongly recommended though they may not be locally available or not affordable. Early and aggressive immunomodulatory therapy may help faster recovery, as did with two of our three children.

Investigating myelin oligodendrocyte glycoprotein antibodies in hereditary citrullinemia

Metabolites like lipids, amino acids or peptides can affect the immune system. Citrulline is an amino acid that activates several inflammatory pathways. Serum citrulline levels are markedly elevated in hereditary citrullinemia type 1 (CTLN1), and cases with CTLN1 have have been described with inflammatory lesions of the central nervous system (CNS). This suggests the presence of a relatively proinflammatory state in CTLN1. We therefore tested sera of CTLN1 patients for anti-myelin oligodendrocyte glycoprotein (MOG) antibodies which are a frequent cause of inflammatory CNS disorders in young patients. Patients with CTLN1 (n = 15) and control groups consisting of phenylketonuria (n = 22), juvenile idiopathic arthritis (n = 13), pediatric onset systemic lupus erythematosus (n = 17) and healthy controls (n = 48) were tested for serum anti-MOG IgG and anti-MOG IgG1 antibodies in a live-cell based assay. Serum citrulline levels were elevated in 14/15 CTLN1 patients at the time of the study. No clear anti-MOG IgG positivity was detected in any of the CTLN1 or control groups. One CTLN1 and one healthy control case with anti-MOG IgG titers close to borderline were also tested for MOG-specific IgG1, with similar results. These findings did not support the role of elevated serum citrulline levels in facilitating antibody response against MOG. Other pathways that can be investigated in CTLN1 include lymphocytic responses against neural antigens or any direct effects of citrulline on neural tissue.

Late onset neuromyelitis optica spectrum disorder with anti-aquaporin 4 and anti-myelin oligodendrocyte glycoprotein antibodies.

This study aimed to evaluate the clinical characteristics and prognosis of late onset (≥50years) neuromyelitis optica spectrum disorder (LO-NMOSD), and compare them with those of early onset (<50years) NMOSD (EO-NMOSD) and NMOSD with various antibody serostatuses. From January 2015 to December 2020, 360 anti-aquaporin 4 antibody (AQP4-ab)-positive and 130 anti-myelin oligodendrocyte glycoprotein antibody (MOG-ab)-positive patients presented to the Huashan Hospital, China. We retrospectively reviewed their medical records, including the Expanded Disability Status Scale (EDSS) score at each visit and the annualized relapse rate (ARR). Prognostic outcomes included the time to first relapse, blindness, motor dysfunction, severe motor dysfunction, and death. Correlations between the age at onset, lesion location, and clinical parameters were analyzed. This study included 122 (24.9%) patients with LO-NMOSD, 101 with AQP4-ab and 21 with MOG-ab. Compared with EO-NMOSD patients, those with LO-NMOSD had higher EDSS scores and more frequent disease onset with transverse myelitis, blindness, motor dysfunction, and severe motor dysfunction. Compared with LO-NMOSD patients with MOG-ab, those with AQP4-ab had a worse prognosis. Age at disease onset had a significantly positive correlation with EDSS score at the last follow-up of all NMOSD patients, but a negative correlation with ARR-1 (ARR excluding the first attack, calculated from disease onset to final follow-up) in NMOSD patients with AQP4-ab. Patients with LO-NMOSD, especially those with AQP4-ab, had a worse prognosis compared with patients with EO-NMOSD. Age at disease onset and antibody serostatus predicted blindness and motor dysfunction.

Atypical presentation of multiple sclerosis – A few points to ponder

The article by Dr. Aishwarya Angadi has brilliantly highlighted how multiple sclerosis can present as unilateral internuclear ophthalmoplegia. The author has meticulously examined the patient and presented it along with the detailed neurological findings. Early detection of multiple sclerosis can go a long way in reducing the morbidity of the disease through timely treatment and intervention. From an academic point of view, there are a few points that I would like to contribute. Since the patient complained of visual blurring, subclinical optic neuritis should have been ruled out with a visually evoked potential test.[1] In the cerebrospinal fluid study, the number of oligoclonal bands is significant for the prognosis of multiple sclerosis.[2] In a case of multiple sclerosis, NeuroMyelitis Optica Immunoglobulin G (NMOIgG) and anti-Myelin Oligodendrocyte Glycoprotein (anti-MOG) antibody should be tested.[345] Lesions on Magnetic Resonance Imaging (MRI) should fulfil McDonald's criteria to qualify as those of multiple sclerosis. MRI orbit is relevant in this case. Also, MRI brainstem should show lesions in the medial longitudinal fasciculus to explain the internuclear ophthalmoplegia. As this patient was positive for Anti Neutrophil Cytoplasmic Antibodies (ANCA), autoimmune vasculitis should also be ruled out. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

A case of anti-myelin oligodendrocyte glycoprotein antibody associated cortical encephalitis presenting only with migraine-like headache without aura

A case of anti-myelin oligodendrocyte glycoprotein antibody associated cortical encephalitis presenting only with migraine-like headache without aura

Teaching NeuroImage: Rapid Identification of Infectious Optic Neuritis by Next-Generation Sequencing.

A 52-year-old, HIV-negative woman presented with one year of bilateral painless central vision loss that worsened over 3 months. A medical examination revealed Argyll Robertson pupil (i.e., accommodates but does not react to light). Single-read next-generation sequencing (NGS) of the CSF identified 89 sequence reads corresponding to Treponema, elevated CSF protein, pleocytosis, negative antiaquaporin-4, antimyelin oligodendrocyte glycoprotein antibody levels, retinal nerve fiber layer thinning, and bilateral nerve sheath enhancement (Figures 1–2). The patient received penicillin and oral prednisolone, which improved her vision. Infectious causes of optic neuritis are complex (Table).1,2 NGS is an emerging method with the potential to rapidly identify atypical optic neuritis.

GRP78 Antibodies Are Associated With Blood-Brain Barrier Breakdown in Anti-Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disorder.

Background and ObjectivesTo analyze (1) the effect of immunoglobulin G (IgG) from patients with anti–myelin oligodendrocyte glycoprotein antibody (MOG-Ab)–associated disorder on the blood-brain barrier (BBB) endothelial cells and (2) the positivity of glucose-regulated protein 78 (GRP78) antibodies in MOG-Ab–associated disorders.MethodsIgG was purified from sera with patients with MOG-Ab–associated disorder in the acute phase (acute MOG, n = 15), in the stable stage (stable MOG, n = 14), healthy controls (HCs, n = 9), and disease controls (DCs, n = 27). Human brain microvascular endothelial cells (BMECs) were incubated with IgG, and the number of nuclear NF-κB p65-positive cells in BMECs using high-content imaging system and the quantitative messenger RNA change in gene expression over the whole transcriptome using RNA-seq were analyzed. GRP78 antibodies from patient IgGs were detected by Western blotting.ResultsIgG in the acute MOG group significantly induced the nuclear translocation of NF-κB and increased the vascular cell adhesion molecule 1/intercellular adhesion molecule 1 expression/permeability of 10-kDa dextran compared with that from the stable MOG and HC/DC groups. RNA-seq and pathway analysis revealed that NF-κB signaling and oxidative stress (NQO1) play key roles. The NQO1 and Nrf2 protein amounts were significantly decreased after exposure to IgG in the acute MOG group. The rate of GRP78 antibody positivity in the acute MOG group (10/15, 67% [95% confidence interval, 38%–88%]) was significantly higher than that in the stable MOG group (5/14, 36% [13%–65%]), multiple sclerosis group (4/29, 14% [4%–32%]), the DCs (3/27, 11% [2%–29%]), or HCs (0/9, 0%). Removal of GRP78 antibodies from MOG-IgG reduced the effect on NF-κB nuclear translocation and increased permeability.DiscussionGRP78 antibodies may be associated with BBB dysfunction in MOG-Ab–associated disorder.

Torticollis as an Initial Manifestation of a Seronegative Demyelinating Disorder in a Child: A Case Report

AbstractTorticollis refers to a condition in which the head is persistently tilted to one side, sometimes associated with pain. Torticollis in a child can be congenital or acquired. Torticollis as an initial manifestation of an underlying demyelinating syndrome is quite rare in children. Here, we report a 7-year-old girl who presented with persistent torticollis. Neuroimaging of the brain revealed features of a demyelinating disease. Further studies did not show any evidence of multiple sclerosis. Cerebrospinal fluid was negative for antiaquaporin-4 antibodies, antimyelin oligodendrocyte glycoprotein antibodies, and oligoclonal bands. A seronegative demyelinating disorder was considered. She was treated with pulsed methylprednisolone therapy. She responded well to steroids with no progression of illness during follow-up. Torticollis was partially improved.

Optic perineuritis: A Canadian case series and literature review

BackgroundOptic perineuritis (OPN) is a rare orbital inflammatory disorder that primarily involves the optic nerve sheath (ONS). This study aimed to describe the clinical features of idiopathic OPN as well as OPN secondary to other infectious and inflammatory conditions in a Canadian case series as current literature on secondary OPN in Western countries is mostly limited to case reports. MethodsRetrospective case series of all patients seen in a tertiary neuro-ophthalmology practice with a diagnosis of OPN from 2014 to 2020. ResultsA total of 21 patients (14 women, mean age 55.8) corresponding to 29 eyes with OPN were identified. Fifteen cases were associated with inflammatory or infectious conditions and only 6 were idiopathic. All idiopathic cases were unilateral. The most common secondary causes of OPN were anti-myelin oligodendrocyte glycoprotein (MOG) antibody disease (n = 4), syphilis (n = 3), sarcoidosis (n = 3), and giant cell arteritis (n = 3). At initial presentation, best-corrected visual acuity (BCVA) was 20/20 or better in 24% (n = 7) and visual field mean deviation (VF MD) was better than −5 dB in 34% of eyes (10/29). Treatment consisted of intravenous penicillin for syphilitic OPN and high-dose corticosteroids followed by oral taper with or without immunosuppressive therapy for non-syphilitic OPN. BCVA improved in 34% (10/29) and VF MD improved in 45% (13/29) eyes. ConclusionOPN primarily occurred in association with systemic inflammatory conditions, especially in bilateral cases. Syphilis must be ruled out in all patients. Anti-MOG antibody disease is an important, newly recognized secondary cause of OPN, and serologic testing should be included in the investigation of all patients with OPN.

Delayed Visual Improvement in Pediatric Myelin Oligodendrocyte Glycoprotein Antibody-Associated Optic Neuritis

Bilateral involvement and severe visual impairment can occur in the acute phase of pediatric myelin oligodendrocyte glycoprotein (MOG) antibody–associated optic neuritis (ON), but few patients have residual severe vision loss. 1 Giacomini T. Foiadelli T. Annovazzi P. et al. Pediatric optic neuritis and anti MOG antibodies: a cohort of Italian patients. Mult Scler Relat Disord. 2019; 39: 101917 Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar Limited data exist regarding the prognosis of refractory pediatric MOG antibody–associated ON. We present the case of an adolescent with severe MOG antibody–associated ON followed by delayed but significant improvement.

Longitudinally extensive transverse myelitis with anti-myelin oligodendrocyte glycoprotein antibodies following SARS-CoV-2 infection

We report the case of a patient with symptoms of myelopathy following acute SARS-CoV-2 infection. MRI documented a longitudinally extensive transverse myelitis and further investigation was unremarkable with the exception of positivity for MOG-IgG in serum. This report extends the spectrum of post-COVID-19 neurological syndromes, and documents a very significant improvement to long-term oral corticosteroid therapy in this setting. Further prospective studies are needed to establish the risk of recurrence in this subset of patients.

Epilepsy in patients with MOG antibody disease

Introduction. MOG (anti-myelin oligodendrocyte glycoprotein) antibody disease is a group of demyelinating disorders of the central nervous system, in which antibodies attack the glycoproteins on the oligodendrocyte myelin membrane. The aim of the study was to evaluate the course of the disease in patients with MOG antibody disease with epilepsy.&#x0D; Materials and methods. We examined 11 patients (5 men and 6 women) with MOG antibody disease aged from 2 months to 46 years. Three case studies were described when patients with MOG antibody disease had epileptic seizures.&#x0D; Results and discussion. Epileptic seizures preceded the diagnosis of MOG antibody disease in the first patient. The disease presented as right-sided optic neuritis in the second patient. Seven years later, an epileptic seizure occurred after childbirth, when the BBB could have become permeable to circulating MOG antibodies. The disease presented with headache in the third patient. Right-sided optic neuritis and ataxia developed after an acute viral respiratory infection. Myelitis was diagnosed, and an epileptic seizure occurred one year later. The patient had a combination of CADASIL syndrome with MOG antibody disease.&#x0D; Conclusion. Epileptic seizures are common in patients with MOG antibody disease. In addition to antiepileptic therapy, treatment of MOG antibody disease is crucial. This leads to good seizure control and a favourable prognosis.

Acute disseminated encephalomyelitis associated with anti-myelin oligodendrocyte glycoprotein (MOG-IGG) antibody in a patient with recent vaccination against SARS-CoV-2

Vaccines are one of the greatest achievements of modern medicine and are safely administered, but they can give rise to autoimmune diseases which include Central Neurvous System or trigger/exacerbate chronic diseases such as multiple sclerosis, neuromyelitis optic and Myelin Oligodendrocyte Glicoprotein Antibody Disease (MOGAD). The SARS-CoV 2 is a human respiratory virus with neuroinvasive and neurotropic capabilities. Several SARS-CoV-2 vaccines have been developed, some with messenger RNA and other with viral vectors.

Overlapping syndrome mimicking infectious meningoencephalitis in a patient with MOG and GFAP IgG

BackgroundCentral nervous system overlapping autoimmune syndromes are uncommon, especially with the coexistence of MOG-IgG and GFAP-IgG.Case presentationA 23-year-old woman presented with transient convulsions, a loss of consciousness, persistent fever, headache, and vomiting. Cerebrospinal fluid (CSF) analysis revealed elevated cellularity, and magnetic resonance imaging (MRI) showed diffuse leptomeningeal enhancement. She had fever and headache with antiviral and antibiotic treatment for 2 weeks, and she had empirical anti-tuberculosis treatment and oral prednisolone therapy. She was followed for 3 months after presentation with improved symptoms and normal CSF analysis. A 3-month follow-up MRI showed asymmetric lesions in the cerebellum, corona radiata, and white matter with enhancement. The anti-tuberculosis treatment was continued, and steroid therapy was discontinued. After she stopped taking prednisolone, an interrupted headache gradually appeared. MRI at 4 months after presentation revealed a partial reduction in lesions but enlarged areas in the left cerebellum and right parietal white matter and a new lesion in the region of the right ependyma with linear enhancement. Her CSF was positive for anti-myelin oligodendrocyte glycoprotein (MOG) and anti-glial fibrillary acidic protein (GFAP) antibodies using a transfected cell-based assay. She was diagnosed with overlapping syndrome of MOG‑IgG‑associated disease and GFAP astrocytopathy. She received steroid pulse therapy (methylprednisolone, 1 g for 5 days), followed by a gradual tapering of oral prednisolone and the addition of an immunosuppressant (tacrolimus, 3 mg per day). Six months after the initial presentation, she had no symptoms. An MRI showed that the lesions had diminished, and no enhancement was found.ConclusionsWe report a case that was positive for double antibodies, which was initially misdiagnosed as infectious meningoencephalitis. This case broadens the clinical and phenotypic presentation of the overlapping syndrome spectrum.

Application of deep-learning to the seronegative side of the NMO spectrum.

To apply a deep-learning algorithm to brain MRIs of seronegative patients with neuromyelitis optica spectrum disorders (NMOSD) and NMOSD-like manifestations and assess whether their structural features are similar to aquaporin-4-seropositive NMOSD or multiple sclerosis (MS) patients. We analyzed 228 T2- and T1-weighted brain MRIs acquired from aquaporin-4-seropositive NMOSD (n = 85), MS (n = 95), aquaporin-4-seronegative NMOSD [n = 11, three with anti-myelin oligodendrocyte glycoprotein antibodies (MOG)], and aquaporin-4-seronegative patients with NMOSD-like manifestations (idiopathic recurrent optic neuritis and myelitis, n = 37), who were recruited from February 2010 to December 2019. Seventy-three percent of aquaporin-4-seronegative patients with NMOSD-like manifestations also had a clinical follow-up (median duration of 4years). The deep-learning neural network architecture was based on four 3D convolutional layers. It was trained and validated on MRI scans of aquaporin-4-seropositive NMOSD and MS patients and was then applied to aquaporin-4-seronegative NMOSD and NMOSD-like manifestations. Assignment of unclassified aquaporin-4-seronegative patients was compared with their clinical follow-up. The final algorithm differentiated aquaporin-4-seropositive NMOSD and MS patients with an accuracy of 0.95. All aquaporin-4-seronegative NMOSD and 36/37 aquaporin-4-seronegative patients with NMOSD-like manifestations were classified as NMOSD. Anti-MOG patients had a similar probability of being NMOSD or MS. At clinical follow-up, one unclassified aquaporin-4-seronegative patient evolved to MS, three developed NMOSD, and the others did not change phenotype. Our findings support the inclusion of aquaporin4-seronegative patients into NMOSD and suggest a possible expansion to aquaporin-4-seronegative unclassified patients with NMOSD-like manifestations. Anti-MOG patients are likely to have intermediate brain features between NMOSD and MS.

Variation in Evolving Optic Neuritis.

The typical natural history of optic neuritis is subjected to important exceptions. Recognition of these exceptions has led to valuable insights regarding specific etiologies of optic neuritis. Exceptions to the natural history of recovering optic neuritis are well-defined (e.g., chronic relapsing inflammatory optic neuropathy), but exceptions to the natural history of evolving optic neuritis are less so. Medical records of patients illustrating an atypical course of evolving optic neuritis were reviewed in a retrospective manner. Each patient was treated by at least one of the authors. Four patients were identified who illustrated an atypical natural history of incipient optic neuritis. Diagnoses included idiopathic optic neuritis, seropositive neuromyelitis optica spectrum disease, anti-myelin oligodendrocyte glycoprotein antibody disease, and multiple sclerosis in 1 patient each. Features of interest included an atypical temporal relationship between development of pain and onset of clinical optic neuropathy, an unusually protracted duration of pain, and an unusually long duration of worsening optic neuropathy before stabilization. This case series illustrates the substantial clinical heterogeneity which may be observed in the evolution of optic neuritis. The temporal relationship between development of pain and onset of clinical optic neuropathy, the duration of pain, and duration of worsening optic neuropathy before stabilization are all subjected to significant variability. Although most patients with optic neuritis present with painful vision loss which progresses over 1 week or less, careful attention to the exceptions described herein may facilitate earlier recognition of diagnostically challenging cases.

Immunotherapies for Anti-N-M-methyl-D-aspartate Receptor Encephalitis: Multicenter Retrospective Pediatric Cohort Study in China.

Background: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis has been discovered for more than a decade, but the establishment of standardized immunotherapy protocol for pediatric patients still needs more clinical evidence.Methods: A multicenter, retrospective study was conducted on pediatric patients diagnosed with anti-NMDAR encephalitis between November 2011 and December 2018. The clinical records including clinical manifestations, immunotherapy strategies, and outcomes were collected and analyzed.Results: A total of 386 patients were included in our study and the median onset age was 8.00 (IQR 4.83–10.90) years. All patients received first-line immunotherapy and the majority (341, 88.3%) used the standard combination of methylprednisolone pulses (MEP) and intravenous immunoglobulins (IVIG), but 211 patients did not show satisfactory improvement (mRS ≥ 3). Mainly three treatment strategies were applied after first-line immunotherapy: second-line immunotherapy, repetitive first-line immunotherapy, and maintaining oral prednisolone. For patients with mRS ≥ 4 after first-line immunotherapy, the incidence of poor outcome (mRS ≥ 3) in oral prednisolone group was higher than that in other treatment groups (p = 0.039). No difference in complete recovery rate (mRS = 0) was found between patients receiving second-line and repetitive first-line immunotherapy, or patients using long-term and short-term prednisolone. Out of 149 patients who received anti-myelin oligodendrocyte glycoprotein antibody (MOG-Ab) test, 27 (18.12%) were positive. Patients with concomitantly positive MOG-Ab showed milder conditions compared to patients with typical anti-NMDAR encephalitis and were more inclined to relapses. We also identified female, MOG-Ab positive, and not receiving second-line and/or repetitive first-line immunotherapy were risk factors for relapses.Conclusions: For patients with mRS ≥ 4 after first-line immunotherapy and patients with concomitantly positive MOG-Ab, second-line immunotherapy is recommended. When second-line immunotherapy is not applicable, repetitive first-line immunotherapy can be considered as an option. Both second-line and repetitive first-line immunotherapy are beneficial to reduce relapse rate. The duration of sequential oral prednisolone can be shortened after fully evaluating patients' conditions.

Status of the neuromyelitis optica spectrum disorder in Latin America

BackgroundNeuromyelitis optica spectrum disorders (NMOSD) is an increasing diagnostic and therapeutic challenge in Latin America (LATAM). Despite the heterogeneity of this population, ethnic and socioeconomic commonalities exist, and epidemiologic studies from the region have had a limited geographic and population outreach. Identification of some aspects from the entire region are lacking. ObjectivesTo determine ethnic, clinical characteristics, and utilization of diagnostic tools and types of therapy for patients with NMOSD in the entire Latin American region. MethodsThe Latin American Committee for Treatment and Research in MS (LACTRIMS) created an exploratory investigational survey addressed by Invitation to NMOSD Latin American experts identified through diverse sources. Data input closed after 30 days from the initial invitation. The questionnaire allowed use of absolute numbers or percentages. Multiple option responses covering 25 themes included definition of type of practice; number of NMOSD cases; ethnicity; utilization of the 2015 International Panel criteria for the diagnosis of Neuromyelitis optica (IPDN); clinical phenotypes; methodology utilized for determination of anti-Aquaporin-4 (anti­ AQP4) antibodies serological testing, and if this was performed locally or processed abroad; treatment of relapses, and long-term management were surveyed. ResultsWe identified 62 investigators from 21 countries reporting information from 2154 patients (utilizing the IPDN criteria in 93.9% of cases), which were categorized in two geographical regions: North-Central, including the Caribbean (NCC), and South America (SA). Ethnic identification disclosed Mestizos 61.4% as the main group. The most common presenting symptoms were concomitant presence of optic neuritis and transverse myelitis in 31.8% (p=0.95); only optic neuritis in 31.4% (more common in SA), p<0.001); involvement of the area postrema occurred in 21.5% and brain stem in 8.3%, both were more frequent in the South American cases (p<0.001). Anti-AQP4 antibodies were positive in 63.9% and anti-Myelin Oligodendrocyte Glycoprotein (MOG) antibodies in 4.8% of total cases. The specific laboratorial method employed was not known by 23.8% of the investigators. Acute relapses were identified in 81.6% of cases, and were treated in 93.9% of them with intravenous steroids (IVS); 62.1% with plasma exchange (PE), and 40.9% with intravenous immunoglobulin-G (IVIG). Therapy was escalated in some cases due to suboptimal initial response. Respondents favored Rituximab as long-term therapy (86.3%), whereas azathioprine was also utilized on 81.8% of the cases, either agent used indistinctly by the investigators according to treatment accessibility or clinical judgement. There were no differences among the geographic regions. ConclusionsThis is the first study including all countries of LATAM and the largest cohort reported from a multinational specific world area. Ethnic distributions and phenotypic features of the disease in the region, challenges in access to diagnostic tools and therapy were identified. The Latin American neurological community should play a determinant role encouraging and advising local institutions and health officials in the availability of more sensitive and modern diagnostic methodology, in facilitating the the access to licensed medications for NMOSD, and addressing concerns on education, diagnosis and management of the disease in the community.