Ofatumumab in Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease: A Comparison With Rituximab.

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...

A real-world comparative study on the efficacy and safety of tocilizumab and rituximab in patients with neuromyelitis optica spectrum disease and myelin oligodendrocyte glycoprotein antibody-associated disease.

Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is an immune-mediated inflammatory central nervous system (CNS) disease that has been gradually recognized in recent years and is currently considered as a distinct disease entity distinguished from multiple sclerosis and neuromyelitis optica spectrum disorder. Lately, the new diagnostic criteria for MOGAD proposed by the International MOGAD Panel were published.1 The new criteria cover six core clinical phenotypes (optic neuritis, myelitis, acute disseminated encephalomyelitis, cerebral monofocal or polyfocal deficits, brainstem or cerebellar deficits, and cerebral cortical encephalitis often with seizures), emphasize the positive serum MOG-immunoglobulin G (IgG) test (determined using cell-based assay) and exclusion of alternative causes, and include supporting clinical/neuroimaging features to offset possible deficiencies in antibody detection, aiming to provide precise diagnosis of MOGAD and avoid overdiagnosis. MOGAD, with diverse clinico-radiological manifestations, is deemed to be the “great mimic”. While the new diagnostic criteria may be relatively strict in clinical practice, we are concerned that some patients suffering from MOGAD may be omitted according to the current standards. For instance, some patients, who clearly tested positive for serum MOG-IgG, presented with fever, headache, and leptomeningeal enhancement on brain magnetic resonance imaging (MRI). In this clinical setting, MOG antibody-associated aseptic meningitis is the most reasonable diagnosis.2, 3 However, these patients are unlikely to be diagnosed with MOGAD according to the new criteria, given that meningitis does not fit into any of the six defined phenotype classifications. In another scenario, a few patients with seizures (a relatively common presentation in MOGAD4) may have normal brain MRI (especially at the disease onset),5 and may not sufficiently fulfil the new criteria, which can affect the early diagnosis of MOGAD, thus delaying immunotherapy. In addition, short segment myelitis (SSM, < 3 contiguous vertebral segments in length) is not uncommon in MOGAD. Ciron et al. evaluated 73 patients with MOGAD and found 28 (38.4%) had short lesions and 45 (61.6%) had long lesions at the first episode of myelitis.6 Moreover, the occurrence of conus medullaris involvement varied in different populations, which seems to be more uncommon in patients presenting in China (2/59 [3.4%]7), than those in Europe (22/73 [30.1%]6) and North America (21/51 [41.2%]8). Similarly, in our center with recent 5-year data, conus medullaris injury was observed in 2/17 [11.8%] cases with myelitis as the onset manifestation. SSM, with eccentric lesions and without conus medullaris involvement, can occur with low positive serum MOG-IgG. These patients would also fail to meet with the current criteria, but their clinical findings may still be relevant to MOG-IgG. Furthermore, MOG-IgG associated myelitis with negative initial spinal cord MRI occurred in 7/73 patients with MOGAD.9 For the patients with MRI-negative myelitis, if detected with low positive serum MOG-IgG, also challenge the diagnosis of MOGAD according to the new criteria, which may lead to the therapeutic dilemma. Moving forward, detailed studies of MOGAD are likely to identify additional clinico-radiological phenotypes, and the frequency of existing phenotypes will also change, and the diagnostic criteria need to be revised and updated with the times. Although there is still room for improvement, the publication of the 2023 criteria is a key step towards unifying and standardizing the diagnosis of MOGAD, pushing its research into a new era. We expect that the next version of MOGAD criteria will include the uncommon clinical phenotypes, which would allow clinicians to be more vigilant in identifying patients with MOGAD that are presenting with atypical manifestations. Furthermore, we suggest it would be beneficial to define levels of diagnostic certainty (such as possible/probable/definite MOGAD), similar to the diagnostic criteria for autoimmune encephalitis and paraneoplastic neurological syndromes. We believe that these approaches may be more advantageous in clinical diagnosis and management strategies, compensating for lower sensitivity from the current strict diagnostic criteria in the pursuit of higher specificity, so as to decrease underdiagnosis. Given that MOGAD is a treatable disease, but therapeutic regimens are still different from those for other inflammatory CNS diseases, early identification can facilitate timely and optimal treatment, thus improving the prognosis. Not applicable. The authors declare no conflict of interest. Not applicable. Data sharing is not applicable to this article as no new data were created or analyzed in this study.

The differential diagnosis between aquaporin-4-immunoglobulin G-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD), myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD), and multiple sclerosis (MS) can be complex. Kappa free light chain index (KFLC-Index) emerged as an effective biomarker for distinguishing patients with MS from patients with other conditions. The main aim of this study was to assess the diagnostic performance of KFLC-Index in differentiating MOGAD, AQP4-NMOSD, and MS and to compare it with CSF-restricted oligoclonal bands (OCB) performance. We conducted a retrospective case-control study involving 18 French centers through our national NOMADMUS database. Patients were eligible if they received MOGAD or AQP4-NMOSD diagnosis and if OCB status and KFLC-Index levels were available or could be measured retrospectively. As a comparator, we included a group of patients with MS from the Lyon center. We included 303 patients with 140 MOGAD, 37 AQP4-NMOSD, and 126 MS. The sex ratio F/M was 1/1 in the MOGAD group, 5/1 in the NMOSD group, and 4/1 in the MS group. The median age was 38 years in the MOGAD group, 52 in the NMOSD group, and 32 in the MS group. The median KFLC-Index (interquartile range) was the lowest in the MOGAD group (0.60 [0.33-2.09]) with 71% of undetectable CSF-KFLC, intermediate in the NMOSD group (8.85 [3.04-16.78]), and the highest in the MS group (49.90 [16.31-113.39]). KFLC-Index had very good diagnostic performance in differentiating MOGAD from MS (area under the curve [AUC] 0.93, 95% CI 0.9-0.96) with an optimal threshold of 5.7 (95% CI 4.74-6.85), a sensitivity of 0.89 (0.83-0.94), and a specificity of 0.89 (0.83-0.94). KFLC-Index had good performance in differentiating NMOSD from MS (AUC 0.82, 95% CI 0.74-0.88) and MOGAD from NMOSD (AUC 0.77, 95% CI 0.69-0.86). KFLC-Index did not significantly outperformed OCB in separating MOGAD from MS and NMOSD from MS; however, the combination of the 2 tests was more performant than used separately. KFLC-Index is a valuable tool in distinguishing MS from AQP4-NMOSD and MOGAD and provides additional information to that given by OCB. We suggest that KFLC-Index as an additional supporting criterion for the differential diagnosis between MOGAD and MS.

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.

Objective:The study aims to share our knowledge on myelin oligodendrocyte glycoprotein antibody (anti-MOG) seropositivity in patients with demyelinating diseases, focusing on their clinical, serologic, and radiologic characteristics, as well as treatment options for MOG associated disease (MOGAD) cases.Methods: This retrospective study included 332 of 450 demyelinating disease cases, aged 18 to 65 years, who were referred to our clinic from 2017 to 2023 with clinical and/or radiological signs of demyelination, followed by testing for the anti-MOG antibody.We applied the revised 2017 McDonald criteria and the 2023 MOGAD diagnostic criteria to those who tested positive for anti-MOG.Cases of anti-MOG seronegative multiple sclerosis (MS) and non-MOGAD were excluded.We detailed the clinical, serologic, and radiologic characteristics and treatment protocols of anti-MOG-positive/low-positive cases.Results: Among the cases, 16 were clear/low anti-MOG seropositive; of these, 10 were diagnosed with MOGAD, three were MS associated with anti-MOG seropositivity, and three were considered possible MOGAD and followed up.Four MOGAD cases (40%) were double positive for anti-MOG and oligoclonal bands.Three MOGAD cases also had autoimmune diseases.Rare clinical presentations included sixth cranial nerve palsy, tetraparesis secondary to acute disseminated Ama: almamz demyelinizan hastala sahip olgularmzda miyelin oligodendrosit glikoprotein antikoru (anti-MOG) seropozitifliini ve MOG ilikili hastalklar (MOGAD) tans alan olgularmzda klinik, serolojik, radyolojik zellikleri, tedavi seenekleri hakkndaki deneyimlerimizi paylamay amalamaktadr.Yntemler: Bu retrospektif almaya, 2017-2023 yllar arasnda kliniimize klinik ve/veya radyolojik demiyelinizasyon bulgularyla sevk edilen, 18-65 ya aralndaki 450 demiyelinizan hastalk olgusundan, anti-MOG antikor testi yaplan 332'si dahil edildi.Anti-MOG pozitif olgulara revize edilmi 2017 McDonald kriterlerini ve 2023 MOGAD tan kriterlerini uyguladk.Anti-MOG pozitif/dk pozitif vakalarn klinik, serolojik ve radyolojik zelliklerini ve tedavi protokollerini ayrntl olarak akladk.Anti-MOG seronegatif multipl skleroz (MS) ve non-MOGAD olgular alma d brakld.Anti-MOG pozitif/dk pozitif olgularn klinik, radyolojik zellikleri ve tedavi protokolleri incelendi.Bulgular: yz otuz iki olgudan anti-MOG pozitif 16 olgu tespit edildi. anti-MOG sero-pozitifliinin elik ettii MS, 10'u MOGAD tans ald. olgu ise olas MOGAD olarak deerlendirildi ve yakn takibe alnd.MOGAD'da eliki oto-immun hastalklar 3 olgumuzda mevcuttu.

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.

Background and objective: Myelin-oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) frequently initiates during childbearing years. This study investigated the impact of pregnancy and post-partum on MOGAD activity. Methods: Retrospective analysis of clinical and demographic data from a multicenter French cohort of adult patients with MOGAD. All adult female patients who had a pregnancy after disease onset or in the year before disease onset were included. The annualized relapse rate was evaluated in patients who had a pregnancy after disease onset, to evaluate the impact of pregnancy and post-partum on MOGAD course. Results: Twenty-five informative pregnancies after disease onset were identified. No relapse was recorded during these pregnancies and only three relapses occurred during the first 3 months post-partum. The annualized relapse rate decreased from 0.67 (95% confidence interval: 0.40–1.10) during the pre-pregnancy period to 0 (95% confidence interval: 0–0.21) during pregnancy and to 0.22 (95% confidence interval: 0.09–0.53) during the first year post-partum. Among 144 female patients in their childbearing age recorded in the database, 18 (12.5%) reported their first symptoms during pregnancy or in the 12 months post-partum. Discussion: Our study suggests a marked reduction of MOGAD relapse rate during pregnancy and the post-partum period. Prospective studies on the role of pregnancy and delivery in MOGAD course are needed.

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.

Neuromyelitis optica spectrum disorders (NMOSD) and Myelin Oligodendrocyte Glycoprotein (MOG) antibody-associated disease (MOGAD) are neuroinflammatory conditions characterized by attacks, primarily affecting the spinal cord and the optic nerve. When left untreated, these disorders can result in severe neurological disability. Although recent advancements have improved treatment, many questions remain regarding the optimal management of these rare conditions. We conducted a national survey among neurologists in Switzerland experienced in treating NMOSD and MOGAD. The survey comprised 42 questions covering diagnostic methods, acute treatment, maintenance immunotherapy and approaches to long-term strategy. Twenty-one out of 28 invited neurologists took part in the survey (response rate 75 %). There was high consensus on treating acute attacks with high-dose steroids and with plasmapheresis in severe cases. In NMOSD, 71.4 % recommended oral steroid tapering, compared to 85.7 % in MOGAD. All participants advocated maintenance treatment after the first attack in NMOSD, compared to only 10 % in MOGAD. Indeed, many participants advised starting therapy in MOGAD after the first attack only in cases of severe attacks (38 %), persistent MOG-antibodies (10 %) or both (19 %). Rituximab was the most used first-line maintenance immunotherapy for both diseases. Approaches to treatment strategy for the long-term varied with a tendency to recommend de-escalation or discontinuation in stable patients with MOGAD, but not with NMOSD. This study highlights current treatment approaches to NMOSD and MOGAD across Switzerland. Rituximab remains the most prescribed drug for both conditions. The overall variability in recommendations underscores the need for greater awareness of disease-specific management and for further research to optimize treatment strategies for patients with NMOSD and MOGAD.

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.

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.

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.