Therapeutic approaches in adults with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD): A review of current evidence.

Treatment strategies of AQP4-IgG positive neuromyelitis optica spectrum disorder and MOG antibody-associated disorder in Switzerland: a nationwide survey.

Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is an inflammatory demyelinating disease of the central nervous system (CNS) with the presence of conformation-sensitive antibodies against MOG. The spectrum of MOGAD includes monophasic/relapsing optic neuritis, myelitis, neuromyelitis optica spectrum disorder (NMOSD) phenotype without aquaporin 4 (AQP4) antibodies, acute/multiphasic demyelinating encephalomyelitis (ADEM/MDEM)-like presentation, and brainstem and cerebral cortical encephalitis. There is no apparent female preponderance in MOGAD, and MOGAD can onset in all age groups (age at onset is approximately 30 years on average, and approximately 30% of cases are in the pediatric age group). While prevalence and incidence data have been available for AQP4+ NMOSD globally, such data are only beginning to accumulate for MOGAD. We reviewed the currently available data from population-based MOGAD studies conducted around the world: three studies in Europe, three in Asia, and one joint study in the Americas. The prevalence of MOGAD is approximately 1.3-2.5/100,000, and the annual incidence is approximately 3.4-4.8 per million. Among White people, the prevalence of MOGAD appears to be slightly higher than that of AQP4+ NMOSD. No obvious latitude gradient was observed in the Japanese nationwide survey. The data available so far showed no obvious racial preponderance or strong HLA associations in MOGAD. However, precedent infection was reported in approximately 20-40% of MOGAD cases, and this is worthy of further investigation. Co-existing autoimmune disorders are less common in MOGAD than in AQP4+ NMOSD, but NMDAR antibodies may occasionally be positive in patients with MOGAD. More population-based studies in different populations and regions are useful to further inform the epidemiology of this disease.

Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is a demyelinating disease of the central nervous system (CNS) that manifests as optic neuritis, transverse myelitis, acute disseminated encephalomyelitis, and cortical encephalitis. Some patients with MOGAD present with tumor-like brain lesions. However, hydrocephalus as an initial presentation is rare. We present the case of a 23-year-old Japanese man with an acute onset of headache, nausea, and diplopia, who was initially suspected of having a germinoma but was later diagnosed with MOGAD. Brain magnetic resonance imaging (MRI) revealed a tumor-like lesion with hyperintensity on fluid-attenuated inversion recovery (FLAIR) imaging and contrast enhancement on T1-weighted postcontrast images, extending from the midbrain to the thalamus with obstructive hydrocephalus. Neuroendoscopic third ventriculostomy and brain biopsy were performed. Histopathological analyses revealed demyelination, perivascular lymphocytic infiltration, and MOG loss. MOG antibody tests were positive, confirming MOGAD. The patient was treated with pulse steroid therapy (methylprednisolone 1,000 mg/day) and seven sessions of plasmapheresis, resulting in significant neurological improvement. He was discharged approximately two months after symptom onset, and at the six-month follow-up from discharge, he remained relapse-free with only mild diplopia. In this case, early diagnosis via pathological brain analysis and anti-MOG antibody testing allowed for timely treatment. We emphasize the importance of including MOGAD in the diagnostic workup of tumor-mimicking CNS lesions that can cause hydrocephalus.

Aim/backgroundThe concept of neuromyelitis optica spectrum disorder (NMOSD) is changing, with a disease spectrum emerging that includes aquaporin 4 (AQP4) IgG-seropositive NMOSD, myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD), and double-seronegative NMOSD. The past years have seen important advances in understanding rare demyelinating central nervous system (CNS) disorders associated with AQP4-IgG and MOG-IgG antibodies. Most of the recent literature has focused on the identification of clinical and magnetic resonance imaging (MRI) features that help distinguish these diseases from each other, simultaneously highlighting major diagnostic pitfalls that may lead to misdiagnosis. The present study aims to understand the epidemiology and disease characteristics of NMOSD and MOGAD in our population and compare them with previously published reports.Materials and methodsThis was a prospective, single-center, comparative, observational study conducted over 18 months. Thirty patients were recruited and categorized into two groups: NMOSD and MOGAD. Each group consisted of 15 patients. Data regarding neurological assessment, neuroimaging, treatment, and outcome were collected. These patients were followed at one, three, six, and 12 months for treatment response, residual disability, and relapse. Disease severity and disability were assessed by using the Expanded Disability Status Scale (EDSS) and modified Rankin scale (mRS).ResultsThe average age at presentation of the NMOSD group of patients was 34.67 ± 15.66 years, which was significantly higher compared to the 26 ± 5.74 years seen for the MOGAD group (p < 0.0001). The MOGAD group of patients had a significantly higher proportion of men compared to the NMOSD group (66.67% in MOGAD versus 0% in NMOSD). Optic neuritis was seen in a significantly higher proportion of MOGAD patients compared to the NMOSD group of patients (p = 0.0061). Bilateral optic neuritis was more common in the MOGAD group (26.67% vs. 6.67% in the NMOSD group). Isolated myelitis was higher in the NMOSD group. A higher proportion of patients in the NMOSD group received steroids along with rituximab (26.67%) compared to the MOGAD subgroup of patients. In terms of the rescue treatment, intravenous immunoglobulin (IVIG) or plasma exchange (PLEX) therapy was required more in the NMOSD group than the MOGAD group. The EDSS and mRS scores of both groups were comparable at baseline. However, on follow-up, the EDSS and mRS levels were significantly lower for the MOGAD group compared to the NMOSD group (p < 0.05). The overall relapse rate was 33.33% in the NMOSD group compared to 20% in the MOGAD group at 12 months.ConclusionNMOSD and MOGAD are two distinct CNS demyelinating disorders having different demographics, clinical profiles, treatment responses, relapse rates, and short-term outcomes. MOGAD patients appear to have younger age at onset, male predominance, less severe clinical presentation, good response to first-line treatment, fewer relapses, and better one-year functional outcomes whereas NMOSD has female predominance, more severe clinical attacks of myelitis and optic neuritis, less response to first-line management of acute attack requiring rescue therapy more often, less response to conventional immunosuppressive treatment with more relapses requiring escalation of maintenance therapy with rituximab, and significant visual and locomotor residual disability at 12 months.

To clarify T-cell responses in myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD), we cultured the peripheral blood mononuclear cells of 24 patients with MOGAD and 20 with aquaporin-4 (AQP4) antibody-positive neuromyelitis optica spectrum disorders (NMOSD), and those of 17 healthy controls (HCs), in the presence of fourteen MOG peptides covering the full-length MOG, five AQP4 peptides, two myelin basic protein peptides, or two proteolipid protein peptides. Then, we measured T-cell activation markers, such as cell surface CD69 and the intracellular production of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interferon-γ in CD4-positive T-cells, with a flow cytometer. The expression of CD69 in response to MOG p16-40 and MOG p181-205 was significantly higher (Stimulation Index > 2) in MOGAD than in HCs. Also, CD69 for AQP4 p21-40, AQP4 p211-230, and MOG p166-190 were significantly increased in NMOSD than in HCs. Intracellular GM-CSF production responding to MOG p16-40 was significantly higher in MOGAD than in HCs (p < 0.05), although intracellular interferon-γ was not elevated. None of the responses to the other peptides were different between the groups. The present study showed subtle CD4-positive T-cell activation elicited by some MOG peptides alone in patients with MOGAD. Further studies of cytokines or other stimulation and alternative assay markers and metrics are needed to delineate the immunopathological roles of T-cells in MOGAD.

MOG antibody-associated disease after vaccination with ChAdOx1 nCoV-19

ObjectivesTo analyze the differences in laboratory data between patients with myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD), multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD).MethodsThe study included 26 MOGAD patients who visited Beijing Tiantan Hospital from 2018 to 2021. MS and NMOSD patients who visited the clinic during the same period were selected as controls. Relevant indicators were compared between the MOGAD group and the MS/NMOSD groups, and the diagnostic performance of meaningful markers was assessed.ResultsThe MOGAD group showed a slight female preponderance of 57.7%, with an average onset age of 29.8 years. The absolute and relative counts of neutrophils were higher in the MOGAD group than in the MS group, while the proportion of lymphocytes was lower. The cerebrospinal fluid (CSF) IgG level, IgG index, 24-h IgG synthesis rate, and positive rate of oligoclonal bands (OCB) were lower in MOGAD patients than in the MS group. The area under ROC curve (AUC) was 0.939 when combining the relative lymphocyte count and IgG index. Compared to the NMOSD group, the MOGAD group had higher levels of serum complement C4 and lower levels of serum IgG. The AUC of serum C4 combined with FT4 was 0.783.ConclusionStatistically significant markers were observed in the laboratory data of MOGAD patients compared to MS/NMOSD patients. The relative lymphocyte count combined with IgG index had excellent diagnostic efficacy for MOGAD and MS, while serum C4 combined with FT4 had better diagnostic efficacy for MOGAD and NMOSD.

Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) covers a wide spectrum of manifestations and is defined by the presence of MOG seropositivity. However, in a proportion of patients, there may be an overlap in some of the clinical and radiological manifestations between MOGAD and multiple sclerosis (MS). Being wary of this entity is critical to ensure appropriate therapy. Herein, we present a case with recurrent episodes of short-segment myelitis typical for multiple sclerosis, but later diagnosed as MOGAD by MOG antibody seropositivity. This case, along with previous reports, highlights an increasingly recognized subgroup in MOGAD with initial clinical phenotypes suggestive of MS, but later showing a disease course and therapeutic response compatible with MOGAD. Given the potential overlap of some clinical phenotypes in patients with MS and those with MOGAD, we recommend MOG antibody testing in all patients with recurrent short-segment myelitis, conus medullaris involvement, and those who demonstrated steroid dependence.

Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is an immune-mediated demyelinating disease that is challenging to differentiate from multiple sclerosis (MS), as the clinical phenotypes overlap, and people with MOGAD can fulfil the current MRI-based diagnostic criteria for MS. In addition, the MOG antibody assays that are an essential component of MOGAD diagnosis are not standardized. Accurate diagnosis of MOGAD is crucial because the treatments and long-term prognosis differ from those for MS. This Expert Recommendation summarizes the outcomes from a Magnetic Resonance Imaging in MS workshop held in Oxford, UK in May 2022, in which MS and MOGAD experts reflected on the pathology and clinical features of these disorders, the contributions of MRI to their diagnosis and the clinical use of the MOG antibody assay. We also critically reviewed the literature to assess the validity of distinctive imaging features in the current MS and MOGAD criteria. We conclude that dedicated orbital and spinal cord imaging (with axial slices) can inform MOGAD diagnosis and also illuminate differential diagnoses. We provide practical guidance to neurologists and neuroradiologists on how to navigate the current MOGAD and MS criteria. We suggest a strategy that includes useful imaging discriminators on standard clinical MRI and discuss imaging features detected by non-conventional MRI sequences that demonstrate promise in differentiating these two disorders.

Background and Objective: Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is a significant component of demyelinating diseases in pediatric populations. Recently, diagnostic criteria for MOGAD were established. This study aims to evaluate and compare the diagnostic efficacy of the fixed-cell-based assay (Fixed-CBA) and the live cell-based assay (Live-CBA) in patients who meet the 2023 clinical diagnostic criteria for MOGAD. Methods: This retrospective study included patients suspected of having MOGAD who were enrolled between June 2023 and June 2024. Patients were selected based on the “core clinical demyelinating events” outlined in the 2023 proposed criteria of the International MOGAD Panel. Patients with multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD) with aquaporin-4 antibody-positive (AQP4-Abs-positive), and non-central nervous system (non-CNS) inflammatory diseases were chosen as controls. Serum samples were simultaneously tested for MOG-Abs using Fixed-CBA and Live-CBA. Results: A total of 86 patients were enrolled in the study: 52 in the suspected MOGAD group and 34 in the control group. Out of these patients studied, 16 presented with optic neuritis (ON), 5 with myelitis, 8 with acute disseminated encephalomyelitis (ADEM), and 7 with cortical encephalitis. Sixteen patients could not be classified by clinical phenotype. The highest MOG-Ab positivity rate was among patients with cortical encephalitis [85.7% (Live-CBA)/71.4% (Fixed-CBA)]. Both assays identified 22 positive samples, with Fixed-CBA and Live-CBA sensitivities at 44.2% and 55.8%, respectively, and a specificity of 97%. Of the patients suspected of having MOGAD, 19 cases were confirmed using the Fixed-CBA, while 28 cases were confirmed using the Live-CBA. This resulted in an upgrade in diagnostic classification for nine cases. This led to a diagnostic reclassification in nine cases. Conclusions: Both the Fixed-CBA and Live-CBA were associated with higher sensitivity for patients selected based on the 2023 MOGAD clinical diagnostic criteria. The Live-CBA exhibited an 11.6% increase in sensitivity, contributing to a 17.3% (9/52) enhancement in clinical diagnostic accuracy.

The immune imbalance between follicular regulatory and helper T cells in myelin oligodendrocyte glycoprotein IgG-associated disease

Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is a recently identified autoimmune demyelinating disorder of the CNS affecting both adults and children. Diagnostic criteria for MOGAD have recently been published. We aimed to validate the 2023 MOGAD diagnostic criteria in a real-world cohort of patients with atypical CNS inflammation. All patients referred to the National neuromyelitis optica spectrum disorder (NMOSD) specialized service at The Walton Center NHS Foundation Trust between 2012 and 2023 with an atypical demyelinating syndrome were evaluated. We systematically applied the 2023 MOGAD diagnostic criteria and previous 2018 International Diagnostic Recommendations for MOG encephalomyelitis to our retrospective cohort. 474 patients were screened and 66 were excluded for lack of clinical information. Preexisting diagnoses within our cohort included the following: MOGAD, n = 127; AQP4-IgG NMOSD, n = 125; seronegative NMOSD, n = 33; multiple sclerosis (MS), n = 10; and other diagnoses, n = 113. Of patients with preexisting MOGAD, 97% (123/127) fulfilled the 2023 MOGAD diagnostic criteria. Three patients with a low-positive MOG-IgG did not meet supportive features though 2/3 had insufficient investigations. Alternative diagnoses could not be excluded in 1 patient with MS-MOGAD overlap. No patients with a non-MOGAD diagnosis were found to fulfill the 2023 diagnostic criteria. The sensitivity and specificity of the 2023 MOGAD diagnostic criteria were 97% and 100% with no false positives, improving on 2018 International Diagnostic Recommendations for MOG encephalomyelitis. Low-positive MOG-IgG results were more often associated with a longer time from disease onset to sampling (p < 0.001). In addition, in patients with a MOG-IgG1 test within 6 months of clinical onset, approximately 25% can become low positive by 6 months. Of patients with preexisting MOGAD, 9% (12/127) had insufficient investigations and examinations to fully evaluate additional supportive features. However, in those who were completely evaluated, supportive features were fulfilled in 97% (111/115). The 2023 MOGAD diagnostic criteria were highly sensitive and specific and closely align with historically established cases of MOGAD. However, because additional supportive features are stipulated for patients with a low-positive MOG-IgG result, missed diagnoses may occur due to delayed testing or insufficient investigations.

Background: Magnetic resonance imaging (MRI) T2-lesions resolve more often in myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) than aquaporin-4 IgG-positive neuromyelitis optica spectrum disorder (AQP4 + NMOSD) and multiple sclerosis (MS) in adults but few studies analyzed children. Objective: The main objective of this study is to investigate MRI T2-lesion evolution in pediatric MOGAD, AQP4 + NMOSD, and MS. Methods: Inclusion criteria were as follows: (1) first clinical attack; (2) abnormal MRI (⩽6 weeks); (3) follow-up MRI beyond 6 months without relapses in that region; and (4) age < 18 years. An index T2-lesion (symptomatic/largest) was identified, and T2-lesion resolution or persistence on follow-up MRI was determined. Results: We included 56 patients (MOGAD, 21; AQP4 + NMOSD, 8; MS, 27) with 69 attacks. Index T2-lesion resolution was more frequent in MOGAD (brain 9 of 15 [60%]; spine 8 of 12 [67%]) than AQP4 + NMOSD (brain 1 of 4 [25%]; spine 0 of 7 [0%]) and MS (brain 0 of 18 [0%]; spine 1 of 13 [8%]), p < 0.01. Resolution of all T2-lesions occurred more often in MOGAD (brain 6 of 15 [40%]; spine 7 of 12 [58%]) than AQP4 + NMOSD (brain 1 of 4 [25%]; spine 0 of 7 [0%]), and MS (brain 0 of 18 [0%]; spine 1 of 13 [8%]), p < 0.01. Reductions in median index T2-lesion area were greater in MOGAD (brain, 305 mm; spine, 23 mm) than MS (brain, 42 mm [p<0.001]; spine, 10 mm [p<0.001]) without differing from AQP4 + NMOSD (brain, 133 mm [p=0.42]; spine, 19.5 mm [p=0.69]). Conclusion: In children, MRI T2-lesions resolved more often in MOGAD than AQP4 + NMOSD and MS which is similar to adults suggesting these differences are related to pathogenesis rather than age.

BackgroundThe link between multiple sclerosis (MS) and Epstein-Barr virus (EBV) is well established in adults but less clear in paediatric cases. In addition, the role of EBV and other viral...

BackgroundThere are challenges in the diagnosis of myelin-oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD), and a current lack of targeted treatments. This study investigated the disease management and burden of MOGAD in a real-world setting.MethodsData were derived from the Adelphi MOGAD Disease Specific Programme (DSP)™, a cross-sectional survey of neurologists and their consulting patients with MOGAD, conducted in Europe and the United States in 2022. Neurologists reported on patient demographics, clinical characteristics, disease management history, treatments prescribed and burden of disease. Patients voluntarily reported on their perceptions on burden of disease. All analyses were descriptive.ResultsOverall, 74 neurologists provided data for 268 consecutively consulting patients with MOGAD, of whom 66 completed voluntary questionnaires. Sixty four percent of patients received a preliminary/alternative diagnoses, and patients underwent a median (Q1, Q3) of 12.0 (9.0; 19.0) blood tests, assessments and/or scans to confirm MOGAD diagnosis. The median (interquartile range, Q1, Q3) physician-reported time from symptom onset to preliminary/alternative diagnosis was 19.0 (0.0; 59.0) days, and from symptom onset to definitive diagnosis 64.0 (31.0; 150.2) days. At time of the survey, 91.8% and 83.5% of patients were prescribed acute and maintenance treatment, respectively. Symptomatic burden remained moderately high, with patients reporting quality of life (QoL) and work productivity impairments.ConclusionPatients with MOGAD may suffer from challenges in diagnosis, and disease management remains suboptimal, with burden to patients affecting their QoL and ability to work. Both the diagnosis and treatment of MOGAD should continue to be the subject of further research.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00415-025-13233-7.