Myelin Oligodendrocyte Glycoprotein Research Articles

Rare presentations of Acute Acquired Demyelinating Syndromes (ADS) among children

Acute demyelinating syndromes (ADS) in children presents with neurological symptoms with a pathology involving either single central nervous system (CNS) location (mono focal ADS) or multiple sites (poly focal ADS), with or without encephalopathy. It is a diagnostic dilemma requiring a high index of suspicion. A thorough clinical examination with neuroimaging and cerebrospinal fluid (CSF) analysis is needed for making a diagnosis. Clear cut guidelines regarding long term management and prognosis is lacking. Myelin oligodendrocyte glycoprotein (MOG) antibody must be done in all suspected cases as it helps in prognosticating and counselling parents. Recurrence is rare, recovery is usually complete and most children respond to pulse high dose methylprednisolone injection. In this case series we map out different unique presentations of acute ADS with and without Myelin oligodendrocyte glycoprotein (MOG) antibody positivity among children from a tertiary care hospital in central Kerala, India.

Deciphering the conformational dynamics of Myelin Oligodendrocyte glycoprotein in the myelin sheath

Myelin Oligodendrocyte Glycoprotein (MOG) is a transmembrane protein in the myelin sheath. It acts as an auto-antigen under certain unknown conditions causing demyelination, thus resulting in Myelin Oligodendrocyte Glycoprotein Antibody-associated Disease (MOGAD). The significance of glycosylation in the conformational dynamics of the extracellular region (EC1) of the MOG were evident from the previous computational studies. Here, in this study, we performed the molecular dynamics simulation of the entire human MOG in the myelin sheath for 100 ns using the NAMD program. The results indicated that the EC1 and cytoplasmic region (CP) dominate the conformational rigidity of the protein, and enhance its interaction with lipids. This in turn helps in maintaining the myelin integrity in the presence of glycan. The transmembrane regions have reduced interaction with lipids in the glycosylated system. Moreover, the C-terminal extracellular region 2 (EC2) behaves exactly opposite to that of EC1 in the glycan presence. This may be attributed to the glycosylation site in the EC1 region. Hence, not only the region EC1 (having 3 crucial epitopes) but even the CP region were important for understanding the proper function of MOG in the glycan presence. Communicated by Ramaswamy H. Sarma

Akt2 deficiency impairs Th17 differentiation, augments Th2 differentiation, and alters the peripheral response to immunization.

Akt1 and Akt2, isoforms of the serine threonine kinase Akt, are essential for T cell development. However, their role in peripheral T cell differentiation remains undefined. Using mice with germline deletions of either Akt1 or Akt2, we found that both isoforms are important for Th17 differentiation, although Akt2 loss had a greater impact than loss of Akt1. In contrast to defective IL-17 production, Akt2 -/- T cells exhibited enhanced IL-4 production in vitro under Th2 polarizing conditions. In vivo , Akt2 -/- mice displayed significantly diminished IL-17A and GM-CSF production following immunization with myelin oligodendrocyte glycoprotein (MOG). This dampened response was associated with further alterations in Th cell differentiation including decreased IFNγ production but preserved IL-4 production, and preferential expansion of regulatory T cells compared to non-regulatory CD4 T cells. Taken together, we identify Akt2 as an important signaling molecule in regulating peripheral CD4 T cell responses.

Features and associations of optic neuritis in the Middle East: A cross-sectional study

BackgroundDifferences exist in the clinical profile of optic neuritis (ON) among various populations. The present study outlines the features of optic neuritis and its associations in Middle Eastern population. MethodsIn a single tertiary care neuro-ophthalmology clinic, we reviewed charts between 2016 and 2021, to identify patients with optic neuritis. Patients with at least one single episode of ON, and a follow up for at least 6 months were only included. Patients from countries outside the Middle East were not eligible. We performed a sub-analysis using data from the clinic, laboratory, and radiological findings to classify patients with optic neuritis into 4 groups: idiopathic ON, multiple sclerosis associated optic neuritis (MS-ON), neuromyelitis optica spectrum disorder associated optic neuritis (NMOSD-ON), and myelin oligodendrocyte glycoprotein associated disease optic neuritis (MOGAD-ON). Results77 patients met the criteria for inclusion in the study. Approximately, two thirds of the patients (64%, 95% CI [0.52–0.74]) had MS-ON, 17 patients had idiopathic ON (22.6%, 95% CI [0.13–0.33]), 6 patients were diagnosed with NMOSD-ON (8%, 95% CI [0.02–0.16]), and 4 patients had MOG-ON (5.3%, 95% CI [0.01–0.13]). More than half of patients with idiopathic ON were found to have clinically isolated syndrome (CIS) and thus to be at high risk of developing MS. Among all patients enrolled in the study, the mean age was 29.8 ± 9.53 years. Patients with MS-ON and MOG-ON were relatively younger compared to patients from other groups (P = 0.0005). There was a female preponderance among all groups except MOG-ON, where 80% were males (P = 0.11). The pre- and post-treatment logMAR visual acuity (VA) tended to be worse in NMOSD-ON than other categories (P = 0.062). Optic disc swelling was more common among patients with MOGAD-ON, and least common in patients with NMOSD (100% vs 0%, P = 0.001). 5 patients presented with simultaneous bilateral involvement, and all but one had NMOSD-ON. 29% of patients had recurrence during the time of the study with significant difference in prevalence across groups. There was no difference in the involvement of the chiasm, or the retro-chiasmal pathways across groups. ConclusionsOur study demonstrates that multiple sclerosis (MS) is the predominant CNS demyelinating disease associated with optic neuritis (ON) in the Middle Eastern population, mirroring trends observed in Western populations. The clinical and radiological features of each subtype showed no significant divergence compared to findings from studies conducted in other regions globally. These insights contribute to a deeper understanding of ON's clinical spectrum and aid in refining diagnostic and management strategies in the Middle Eastern population.

Autoantibodies-Abzymes with Amylase Activity in Experimental Autoimmune Encephalomyelitis Mice

The exact mechanisms of multiple sclerosis evolution are still unknown. However, the progress in C57BL/6 mice of experimental autoimmune encephalomyelitis (EAE, similar to human multiple sclerosis) happens as a result of the contravention of bone marrow hematopoietic stem cells differentiation profiles integrated with the production of toxic for human’s auto-antibodies-abzymes splitting myelin basic protein (MBP), myelin oligodendrocyte glycoprotein (MOG), histones, DNA and RNA as well as IgGs with catalase and peroxidase activities. Here, we first analyzed the change in the relative amylase activity of IgGs from C57BL/6 mice blood over time at different stages of the EAE evolution: onset, acute, and remission phases. It was shown that the amylase activity of IgGs during spontaneous development of EAE first noticeably increases from 50 to 80, then sharply decreases to 100-130, and again sharply increases to 150 days of mice life. Immunization of 3-month-old mice (time zero) with the DNA-histone complex leads to a decrease, while their treatment with MOG results in a substantial increase in the amylase activity of IgGs. The relative activities of all IgG-abzymes indicated above corresponding to various stages of EAE development were compared. The data shows that spontaneous EAE and immunization of mice with DNAhistones complex and MOG leads to a different and very expanded formation of various B lymphocytes, producing abzymes with several diverse catalytic activities. In addition, the relative number of lymphocytes producing diverse antibodies with distinct enzymatic activities (including their relative activities) significantly depend both on the stages of spontaneous and antigen-induced accelerations of EAE development.

Myelin oligodendrocyte glycoprotein reactive Th17 cells drive Janus Kinase 1 dependent transcriptional reprogramming in astrocytes and alter cell surface cytokine receptor profiles during experimental autoimmune encephalomyelitis

Multiple sclerosis (MS) is an autoimmune demyelinating disease affecting the central nervous system (CNS). T helper (Th) 17 cells are involved in the pathogenesis of MS and its animal model of experimental autoimmune encephalomyelitis (EAE) by infiltrating the CNS and producing effector molecules that engage resident glial cells. Among these glial cells, astrocytes have a central role in coordinating inflammatory processes by responding to cytokines and chemokines released by Th17 cells. In this study, we examined the impact of pathogenic Th17 cells on astrocytes in vitro and in vivo. We identified that Th17 cells reprogram astrocytes by driving transcriptomic changes partly through a Janus Kinase (JAK)1-dependent mechanism, which included increased chemokines, interferon-inducible genes, and cytokine receptors. In vivo, we observed a region-specific heterogeneity in the expression of cell surface cytokine receptors on astrocytes, including those for IFN-γ, IL-1, TNF-α, IL-17, TGFβ, and IL-10. Additionally, these receptors were dynamically regulated during EAE induced by adoptive transfer of myelin-reactive Th17 cells. This study overall provides evidence of Th17 cell reprogramming of astrocytes, which may drive changes in the astrocytic responsiveness to cytokines during autoimmune neuroinflammation.

Clinical, prognostic and pathophysiological implications of MOG-IgG detection in the CSF: the importance of intrathecal MOG-IgG synthesis

BackgroundCerebrospinal fluid myelin oligodendrocyte glycoprotein IgG (CSF MOG-IgG) are found in a proportion of patients with MOG antibody-associated disorder (MOGAD) and have been associated with severe disease presentations. However, most...

Development Perspectives for Curative Technologies in Primary Demyelinating Disorders of the Central Nervous System with Neuromyelitis Optica Spectrum Disorder (NMOSD) and Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD) at the Forefront.

Primary demyelinating disorders of the central nervous system (CNS) include multiple sclerosis and the orphan conditions neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein IgG-associated disease (MOGAD). Curative technologies under development aim to selectively block autoimmune reactions against specific autoantigens while preserving the responsiveness of the immune system to other antigens. Our analysis focused on target patient selection for such developments, carefully considering the relevant clinical, regulatory, and market-related aspects. We found that the selection of patients with orphan conditions as target populations offers several advantages. Treatments for orphan conditions are associated with limited production capacity, qualify for regulatory incentives, and may require significantly shorter and lower-scale clinical programs. Furthermore, they may meet a higher acceptable cost-effectiveness threshold in order to compensate for the low numbers of patients to be treated. Finally, curative technologies targeting orphan indications could enter less competitive markets with lower risk of generic price erosion and would benefit from additional market protection measures available only for orphan products. These advantages position orphan conditions and subgroups as the most attractive target indications among primary demyelinating disorders of the CNS. The authors believe that after successful proof-of-principle demonstrations in orphan conditions, broader autoimmune patient populations may also benefit from the success of these pioneering developments.

Clinical, Demographic, and Radiological Characteristics of Patients Demonstrating Antibodies Against Myelin Oligodendrocyte Glycoprotein

Optic neuritis, myelitis, and neuromyelitis optica spectrum disorder (NMOSD) have been associated with antibodies against myelin oligodendrocyte glycoprotein-immunoglobulin G (anti-MOG-IgG). Furthermore, patients with radiological and demographic features atypical for multiple sclerosis (MS) with optic neuritis and myelitis also demonstrate antibodies against aquaporin-4 and anti-MOG-IgG. However, data on the diagnosis, treatment, follow-up, and prognosis in patients with anti-MOG-IgG are limited. To evaluate the clinical, radiological, and demographic characteristics of patients with anti-MOG-IgG. Multicenter, retrospective, observational study. Patients with blood samples demonstrating anti-MOG-IgG that had been evaluated at the Neuroimmunology laboratory at Ondokuz Mayıs University’s Faculty of Medicine were included in the study. Of the 104 patients with anti-MOG-IgG, 56.7% were women and 43.3% were men. Approximately 2.4% of the patients were diagnosed with MS, 15.8% with acute disseminated encephalomyelitis (ADEM), 39.4% with NMOSD, 31.3% with isolated optic neuritis, and 11.1% with isolated myelitis. Approximately 53.1% of patients with spinal involvement at clinical onset demonstrated a clinical course of NMOSD. Thereafter, 8.8% of these patients demonstrated a clinical course similar to MS and ADEM, and 28.1% demonstrated a clinical course of isolated myelitis. The response to acute attack treatment was lower and the disability was higher in patients aged > 40 years than patients aged < 40 years at clinical onset. Oligoclonal band was detected in 15.5% of the patients. For patients with NMOSD and without anti-NMO antibodies, the diagnosis is supported by the presence of anti-MOG-IgG. Furthermore, advanced age at clinical onset, Expanded Disability Status Scale (EDSS) score at clinical onset, spinal cord involvement, and number of attacks may be negative prognostic factors in patients with anti-MOG-IgG.

Brain lesion microstructure in neuromyelitis optica spectrum disorder and myelin oligodendrocyte glycoprotein disease.

Neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) diagnosis are based on the presence of serological and magnetic resonance imaging (MRI) biomarkers. Diffusion tensor imaging (DTI), neurites orientation dispersion and density imaging (NODDI), and the Spherical Mean Technique (SMT) may be helpful to provide a microstructural characterization of the different types of white matter lesions and give an insight about their different pathological mechanisms. The aim of the study was to characterize microstructural differences between brain typical lesions (TLs) and nontypical lesions (nTLs). A total of 17 NMOSD and MOGAD patients [9 Aquaporin4 (AQP4)+NMO, 2 seronegative-NMO, 6 MOGAD] underwent MRI scans on a 3 Tesla MAGNETON PRISMA. Diffusion parameters (fractional anisotropy; mean diffusivity [MD]; intracellular volume fraction [ICVF]; extra-neurite transverse diffusivity; and extra-neurite MD; neurite signal fraction) were obtained using DTI, NODDI, and SMT. Microstructural parameters within lesions were compared through a generalized linear model using age, sex, and total lesion volume as covariates. In NMOSD/MOGAD whole cohort (total lesions=477), TLs showed increased MD and decreased ICVF compared to nTLs (p<.05), indicating higher inflammation and axonal loss. Similar results were found also in the AQP4+NMO subgroup (decreased ICVF, p<.05). Furthermore, in NMOSD/MOGAD whole cohort and in AQP4+NMO subgroup, TLs showed a trend toward higher EXRATRANS than nTLs, suggesting a more severe degree of demyelination within TLs. TLs and nTLs in NMOSD/MOGAD showed different diffusion MRI-derived microstructural features, with TLs showing a more severe degree of inflammation and fiber disruption with respect to nTLs.

Alterations of brain structural and functional connectivity networks topology and decoupling in pediatric myelin oligodendrocyte glycoprotein antibody-associated disease

ObjectiveTo investigate the alteration in structural and functional connectivity networks (SCN and FCN) as well as their coupling in pediatric myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), and determine if these properties could serve as potential biomarkers for the disease. Materials and methodsIn total of 32 children with MOGAD and 30 age- and sex-matched healthy controls (HC) were employed to construct the SCN and FCN, respectively. The graph-theoretical analyses of the global properties, node properties of the 90 brain nodes, and the structural-functional connectivity (SC-FC) coupling of the two networks were performed. The graph-theoretical properties that exhibited significant differences were analyzed using partial correlation analysis in conjunction with the clinical scales, including the expanded disability status scale (EDSS), modified Rankin scale (mRS), and pediatric cerebral performance category (PCPC) of the MOGAD group. Subsequently, a machine learning model was developed to discriminate between MOGAD and the HC group, aiming to explore the potential of these properties as biomarkers. ResultsThe SCN of the MOGAD group exhibited aberrant global properties, including an increased characteristic path length (Lp) and a decreased global efficiency (Eg), along with reduced nodal properties such as degree centrality (Dc), nodal efficiency (Ne), and local efficiency in multiple nodes. The FCN of the MOGAD group only exhibited decreased Dc, Ne, and betweenness centrality in two nodes of nodal properties. Besides, MOGAD showed a significant decrease in SC-FC coupling compared to the HC group. The analysis of partial correlation revealed significant correlations between several properties and the scales of EDSS and mRS in the MOGAD group. The machine learning method was used to extract six features and establish the model, achieving a classification accuracy of 82.3% for MOGAD. ConclusionsPediatric MOGAD showed a more pronounced impairment in the SCN along with decoupling of SC-FC. Both partial correlation analysis and discriminant modeling suggest that alterations in brain network properties have the potential as biomarkers for assessing brain damage in MOGAD.

Therapeutic role of interferon-γ in experimental autoimmune encephalomyelitis is mediated through a tolerogenic subset of splenic CD11b+ myeloid cells

Cumulative evidence has established that Interferon (IFN)-γ has both pathogenic and protective roles in Multiple Sclerosis and the animal model, Experimental Autoimmune Encephalomyelitis (EAE). However, the underlying mechanisms to the beneficial effects of IFN-γ are not well understood. In this study, we found that IFN-γ exerts therapeutic effects on chronic, relapsing-remitting, and chronic progressive EAE models. The frequency of regulatory T (Treg) cells in spinal cords from chronic EAE mice treated with IFN-γ was significantly increased with no effect on Th1 and Th17 cells. Consistently, depletion of FOXP3-expressing cells blocked the protective effects of IFN-γ, indicating that the therapeutic effect of IFN-γ depends on the presence of Treg cells. However, IFN-γ did not trigger direct in vitro differentiation of Treg cells. In vivo administration of blocking antibodies against either interleukin (IL)-10, transforming growth factor (TGF)-β or program death (PD)-1, revealed that the protective effects of IFN-γ in EAE were also dependent on TGF-β and PD-1, but not on IL-10, suggesting that IFN-γ might have an indirect role on Treg cells acting through antigen-presenting cells. Indeed, IFN-γ treatment increased the frequency of a subset of splenic CD11b+ myeloid cells expressing TGF-β-Latency Associated Peptide (LAP) and program death ligand 1 (PD-L1) in a signal transducer and activator of transcription (STAT)-1-dependent manner. Furthermore, splenic CD11b+ cells from EAE mice preconditioned in vitro with IFN-γ and myelin oligodendrocyte glycoprotein (MOG) peptide exhibited a tolerogenic phenotype with the capability to induce conversion of naïve CD4+ T cells mediated by secretion of TGF-β. Remarkably, adoptive transfer of splenic CD11b+ cells from IFN-γ-treated EAE mice into untreated recipient mice ameliorated clinical symptoms of EAE and limited central nervous system infiltration of mononuclear cells and effector helper T cells. These results reveal a novel cellular and molecular mechanism whereby IFN-γ promotes beneficial effects in EAE by endowing splenic CD11b+ myeloid cells with tolerogenic and therapeutic activities.

Myelin Oligodendrocyte Glycoprotein (MOG)35-55 Mannan Conjugate Induces Human T-Cell Tolerance and Can Be Used as a Personalized Therapy for Multiple Sclerosis.

We have previously performed preclinical studies with the oxidized mannan-conjugated peptide MOG35-55 (OM-MOG35-55) in vivo (EAE mouse model) and in vitro (human peripheral blood) and demonstrated that OM-MOG35-55 suppresses antigen-specific T cell responses associated with autoimmune demyelination. Based on these results, we developed different types of dendritic cells (DCs) from the peripheral blood monocytes of patients with multiple sclerosis (MS) or healthy controls presenting OM-MOG35-55 or MOG-35-55 to autologous T cells to investigate the tolerogenic potential of OM-MOG35-55 for its possible use in MS therapy. To this end, monocytes were differentiated into different DC types in the presence of IL-4+GM-CSF ± dexamethasone (DEXA) ± vitamin D3 (VITD3). At the end of their differentiation, the DCs were loaded with peptides and co-cultured with T cells +IL-2 for 4 antigen presentation cycles. The phenotypes of the DC and T cell populations were analyzed using flow cytometry and the secreted cytokines using flow cytometry or ELISA. On day 8, the monocytes had converted into DCs expressing the typical markers of mature or immature phenotypes. Co-culture of T cells with all DC types for 4 antigen presentation cycles resulted in an increase in memory CD4+ T cells compared to memory CD8+ T cells and a suppressive shift in secreted cytokines, mainly due to increased TGF-β1 levels. The best tolerogenic effect was obtained when patient CD4+ T cells were co-cultured with VITD3-DCs presenting OM-MOG35-55, resulting in the highest levels of CD4+PD-1+ T cells and CD4+CD25+Foxp3+ Τ cells. In conclusion, the tolerance induction protocols presented in this work demonstrate that OM-MOG35-55 could form the basis for the development of personalized therapeutic vaccines or immunomodulatory treatments for MS.

Myelin Oligodendrocyte Glycoprotein Antibody-Associated Bilateral Optic Neuritis (Mogad) in a Five Year Old Girl.

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Assessing the applicability of the 2023 international MOGAD panel criteria in real-world clinical settings.

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a recently identified demyelinating disorder with a diverse clinical spectrum. Diagnosing MOGAD traditionally relies on clinical judgment, highlighting the necessity for precise diagnostic criteria. Banwell et al. proposed criteria, aiming to refine the diagnostic spectrum. This study evaluates these criteria in a real-life cohort, comparing their performance with clinical judgment and describe the cohort of MOGAD patients. This retrospective study, conducted at Hadassah Medical Center, included 88 patients with MOG-IgG antibodies. Patients with a positive or borderline MOG-IgG antibodies by cell-based assay were included. Demographics, clinical and MRI data were recorded. Cases were divided into definite MOGAD and Non-MOGAD groups as determined by the treating physician. We assessed the sensitivity and specificity of the new criteria in comparison to treating physicians' evaluations. Additionally, we examined clinical differences between the MOGAD and Non-MOGAD groups. We observed a strong concordance (98%) between the new MOGAD criteria and treating physicians' diagnoses. Clinical disparities between MOGAD and Non-MOGAD groups included lower EDSS scores, normal MRI scans, preserved brain volume, negative OCB results, and distinct relapse patterns. Also, compared to relapsing patients, monophasic MOGAD patients have greater brain volume and a lower age at onset. The study demonstrates robust accuracy of new MOGAD criteria, emphasizing their potential to enhance diagnostic precision. Treatment response integration into the MOGAD diagnosis is crucial, as it could aid in distinguishing MOGAD from other demyelinating disorders. Distinct clinical profiles highlight the importance of informed decisions in managing MOGAD and similar disorders.

Radiologic Lag and Brain MRI Lesion Dynamics During Attacks in MOG Antibody-Associated Disease.

Knowledge of the evolution of CNS demyelinating lesions within attacks could assist diagnosis. We evaluated intra-attack lesion dynamics in patients with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) vs multiple sclerosis (MS) and aquaporin-4 antibody seropositive neuromyelitis optica spectrum disorder (AQP4+NMOSD). This retrospective observational multicenter study included consecutive patients from Mayo Clinic (USA) and Great Ormond Street Hospital for Children (UK). Inclusion criteria were as follows: (1) MOGAD, MS, or AQP4+NMOSD diagnosis; (2) availability of ≥2 brain MRIs (within 30 days of attack onset); and (3) brain involvement (i.e., ≥1 T2 lesion) on ≥1 brain MRI. The initial and subsequent brain MRIs within a single attack were evaluated for the following: new T2 lesions(s); resolved T2 lesion(s); both; or no change. This was compared between MOGAD, MS, and AQP4+NMOSD attacks. We used the Mann-Whitney U test and χ2/Fisher exact test for statistical analysis. Our cohort included 55 patients with MOGAD (median age, 14 years; interquartile range [IQR] 5-34; female sex, 29 [53%]) for a total of 58 attacks. The comparison groups included 38 patients with MS, and 19 with AQP4+NMOSD. In MOGAD, the initial brain MRI (median of 5 days from onset [IQR 3-9]) was normal in 6/58 (10%) attacks despite cerebral symptoms (i.e., radiologic lag). The commonest reason for repeat MRI was clinical worsening or no improvement (33/56 [59%] attacks with details available). When compared with the first MRI, the second intra-attack MRI (median of 8 days from initial scan [IQR 5-13]) showed the following: new T2 lesion(s) 27/58 (47%); stability 24/58 (41%); resolution of T2 lesion(s) 4/58 (7%); or both new and resolved T2 lesions 3/58 (5%). Findings were similar between children and adults. Steroid treatment was associated with resolution of ≥1 T2 lesion (6/28 [21%] vs 1/30 [3%], p = 0.048) and reduced the likelihood of new T2 lesions (9/28 vs 18/30, p = 0.03). Intra-attack MRI changes favored MOGAD (34/58 [59%]) over MS (10/38 [26%], p = 0.002) and AQP4+NMOSD (4/19 [21%], p = 0.007). Resolution of ≥1 T2 lesions was exclusive to MOGAD (7/58 [12%]). Radiologic lag is common within MOGAD attacks. Dynamic imaging with frequent appearance and occasional disappearance of lesions within a single attack suggest MOGAD diagnosis over MS and AQP4+NMOSD. These findings have implications for clinical practice, clinical trial attack adjudication, and understanding of MOGAD pathogenesis.

MOG Antibody Disease: Nuances in Presentation, Diagnosis, and Management.

Myelin oligodendrocyte glycoprotein antibody disease (MOGAD) is a distinct neuroinflammatory condition characterized by attacks of optic neuritis, transverse myelitis, and other demyelinating events. Though it can mimic multiple sclerosis and neuromyelitis optica spectrum disorder, distinct clinical and radiologic features which can discriminate these conditions are now recognized. This review highlights recent advances in our understanding of clinical manifestations, diagnosis, and treatment of MOGAD. Studies have identified subtleties of common clinical attacks and identified more rare phenotypes, including cerebral cortical encephalitis, which have broadened our understanding of the clinicoradiologic spectrum of MOGAD and culminated in the recent publication of proposed diagnostic criteria with a familiar construction to those diagnosing other neuroinflammatory conditions. These criteria, in combination with advances in antibody testing, should simultaneously lead to wider recognition and reduced incidence of misdiagnosis. In addition, recent observational studies have raised new questions about when to treat MOGAD chronically, and with which agent. MOGAD pathophysiology informs some of the relatively unique clinical and radiologic features which have come to define this condition, and similarly has implications for diagnosis and management. Further prospective studies and the first clinical trials of therapeutic options will answer several remaining questions about the peculiarities of this condition.

MOG antibody-associated optic neuritis.

Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is a demyelinating disorder, distinct from multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). MOGAD most frequently presents with optic neuritis (MOG-ON), often with characteristic clinical and radiological features. Bilateral involvement, disc swelling clinically and radiologically, and longitudinally extensive optic nerve hyperintensity with associated opticperineuritis on MRI are key characteristics that can help distinguish MOG-ON from optic neuritis due to other aetiologies. The detection of serum MOG immunoglobulin G utilising a live cell-based assay in a patient with a compatible clinical phenotype is highly specific for the diagnosis of MOGAD. This review will highlight the key clinical and radiological features which expedite diagnosis, as well as ancillary investigations such as visual fields, visual evoked potentials and cerebrospinal fluid analysis, which may be less discriminatory. Optical coherence tomography can identify optic nerve swelling acutely, and atrophy chronically, and may transpire to have utility as a diagnostic and prognostic biomarker. MOG-ON appears to be largely responsive to corticosteroids, which are often the mainstay of acute management. However, relapses are common in patients in whom follow-up is prolonged, often in the context of early or rapid corticosteroid tapering. Establishing optimal acute therapy, the role of maintenance steroid-sparing immunotherapy for long-term relapse prevention, and identifying predictors of relapsing disease remain key research priorities in MOG-ON.

Contributions of CSF interleukin-6 elevation to the pathogenesis of myelin oligodendrocyte glycoprotein antibody-associated disease.

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a rare neuroinflammatory disorder characterized by acute episodes of central nervous system (CNS) demyelination. Previous studies have reported elevated interleukin (IL)-6 in cerebrospinal fluid (CSF) of MOGAD patients. We examined if CSF IL-6 level increase is associated with clinical parameters in MOGAD. IL-6 levels were measured using 44 CSF samples during the acute phase and 6 samples during recovery from 34 MOGAD patients, as well as 65 CSF samples from 45 aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4Ab + NMOSD), 107 samples from 76 multiple sclerosis patients, and 45 samples from neurodegenerative disease patients. Associations between IL-6 levels and clinical parameters in MOGAD were also evaluated. CSF IL-6 levels were significantly comparably elevated during acute-phase in MOGAD and AQP4Ab + NMOSD, but declined following the acute phase. Among MOGAD patients, CSF IL-6 level was significantly correlated with CSF cell count, greater in patients with brain lesions than spinal cord lesions, and higher in CSF than serum, suggesting that excessive IL-6 is produced predominantly in CNS. Neurological recovery was tended to be poorer in MOGAD patients with higher CSF IL-6 level. CSF IL-6 may play important roles in the pathogenesis of MOGAD, especially in CNS inflammation.

Grey Matter Atrophy and its Relationship with White Matter Lesions in Patients with Myelin Oligodendrocyte Glycoprotein Antibody-associated Disease, Aquaporin-4 Antibody-Positive Neuromyelitis Optica Spectrum Disorder, and Multiple Sclerosis.

To evaluate: (1) the distribution of gray matter (GM) atrophy in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4+NMOSD), and relapsing-remitting multiple sclerosis (RRMS); and (2) the relationship between GM volumes and white matter lesions in various brain regions within each disease. A retrospective, multicenter analysis of magnetic resonance imaging data included patients with MOGAD/AQP4+NMOSD/RRMS in non-acute disease stage. Voxel-wise analyses and general linear models were used to evaluate the relevance of regional GM atrophy. For significant results (p < 0.05), volumes of atrophic areas are reported. We studied 135 MOGAD patients, 135 AQP4+NMOSD, 175 RRMS, and 144 healthy controls (HC). Compared with HC, MOGAD showed lower GM volumes in the temporal lobes, deep GM, insula, and cingulate cortex (75.79 cm3); AQP4+NMOSD in the occipital cortex (32.83 cm3); and RRMS diffusely in the GM (260.61 cm3). MOGAD showed more pronounced temporal cortex atrophy than RRMS (6.71 cm3), whereas AQP4+NMOSD displayed greater occipital cortex atrophy than RRMS (19.82 cm3). RRMS demonstrated more pronounced deep GM atrophy in comparison with MOGAD (27.90 cm3) and AQP4+NMOSD (47.04 cm3). In MOGAD, higher periventricular and cortical/juxtacortical lesions were linked to reduced temporal cortex, deep GM, and insula volumes. In RRMS, the diffuse GM atrophy was associated with lesions in all locations. AQP4+NMOSD showed no lesion/GM volume correlation. GM atrophy is more widespread in RRMS compared with the other two conditions. MOGAD primarily affects the temporal cortex, whereas AQP4+NMOSD mainly involves the occipital cortex. In MOGAD and RRMS, lesion-related tract degeneration is associated with atrophy, but this link is absent in AQP4+NMOSD. ANN NEUROL 2024;96:276-288.