A Simple Score (MOG-AR) to Identify Individuals at High Risk of Relapse After MOGAD Attack.

BACKGROUND AND OBJECTIVES: To identify predictors for relapse in patients with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and to develop and validate a simple risk score for predicting relapse. METHODS: In China National Registry of Neuro-Inflammatory Diseases (CNRID), we identified patients with MOGAD from March 2023 and followed up prospectively to September 2023. The primary endpoint was MOGAD relapse, confirmed by an independent panel. Patients were randomly divided into model development (75%) and internal validation (25%) cohorts. Prediction models were constructed and internally validated using Andersen-Gill models. Nomogram and relapse risk score were generated based on the final prediction models. RESULTS: A total of 188 patients (comprising 612 treatment episodes) were included in cohorts. Female (HR: 0.687, 95% CI 0.524-0.899, p = 0.006), onset age 45 years or older (HR: 1.621, 95% CI 1.242-2.116, p < 0.001), immunosuppressive therapy (HR: 0.338, 95% CI 0.239-0.479, p < 0.001), oral corticosteroids >3 months (HR 0.449, 95% CI 0.326-0.620, p < 0.001), and onset phenotype (p < 0.001) were identified as factors associated with MOGAD relapse. A predictive score, termed MOG-AR (Immunosuppressive therapy, oral Corticosteroids, Onset Age, Sex, Attack phenotype), derived in prediction model, demonstrated strong predictive ability for MOGAD relapse. MOG-AR score of 13-16 indicates a higher risk of relapse (HR: 3.285, 95% CI 1.473-7.327, p = 0.004). DISCUSSION: The risk of MOGAD relapse seems to be predictable. Further validation of MOG-AR score developed from this cohort to determine appropriate treatment and monitoring frequency is warranted. TRIAL REGISTRATION INFORMATION: CNRID, NCT05154370, registered December 13, 2021, first enrolled December 15, 2021.

[Progress in clinical application of humoral biomarkers for central nervous system inflammatory demyelinating diseases].

Central nervous system idiopathic inflammatory demyelinating diseases (CNS-IIDD) is an autoimmune disorder characterized by inflammatory demyelination. The disease follows a course of recurrent attacks and remission, with some cases displaying continuous progression, often resulting in disability. The incidence of CNS-IIDD has been increasing, imposing a substantial burden on both patients' families and society in recent years. A promising strategy for disease management involves the identification of humoral biomarkers to diagnose CNS-IIDD and predict disease attack and progression. Such biomarkers could aid in identifying individuals at high risk of disability, enabling targeted preventive interventions. This study summarizes advancements in the identification of humoral biomarkers and their potential for predicting disease activity and progression to offer novel insights into the management of CNS-IIDD.

MOG CNS Autoimmunity and MOGAD.

At one time considered a possible form of neuromyelitis optica (NMO) spectrum disorder (NMOSD), it is now accepted that myelin oligodendrocyte glycoprotein (MOG) antibody (Ab)-associated disorder (MOGAD) is a distinct entity from either NMO or multiple sclerosis (MS) and represents a broad spectrum of clinical phenotypes. Whereas Abs targeting aquaporin-4 (AQP4) in NMO are pathogenic, the extent that anti-MOG Abs contribute to CNS damage in MOGAD is unclear. Both AQP4-specific Abs in NMO and MOG-specific Abs in MOGAD are predominantly IgG1, a T cell-dependent immunoglobulin (Ig) subclass. Key insights in neuroimmunology and MOGAD pathogenesis have been learned from MOG experimental autoimmune encephalomyelitis (EAE), described 2 decades before the term MOGAD was introduced. MOG-specific T cells are required in MOG EAE, and while anti-MOG Abs can exacerbate EAE and CNS demyelination, those Abs are neither necessary nor sufficient to cause EAE. Knowledge regarding the spectrum of MOGAD clinical and radiologic presentations is advancing rapidly, yet our grasp of MOGAD pathogenesis is incomplete. Understanding both the humoral and cellular immunology of MOGAD has implications for diagnosis, treatment, and prognosis.

The burden of psychiatric morbidity in Multiple Sclerosis, AQP4-antibody NMOSD and MOGAD before and after neurological diagnosis.

BACKGROUND: Psychiatric comorbidities are common in Multiple Sclerosis (MS) and are increasingly recognised in Aquaporin-4-Antibody Neuromyelitis Optica Spectrum Disorders (AQP4-Ab NMOSD) and Myelin Oligodendrocyte Glycoprotein-Antibody Associated Disease (MOGAD). However, it is unclear if these psychiatric comorbidities predate neurological diagnosis or classical neurological symptoms that are conventionally used to establish the onset of these central nervous system inflammatory demyelinating diseases. We sought to: (1) assess the frequency and incidence of psychiatrist-diagnosed psychiatric disorders before and after formal MS, AQP4-Ab NMOSD, and MOGAD diagnosis, and (2) identify potential factors associated with the presence of pre-existing psychiatric morbidity and depression severity at the first clinical visit for MS patients. METHODS: A retrospective observational study was performed on MS, AQP4-Ab NMOSD, and MOGAD patients seen at the National Neuroscience Institute (NNI) Singapore. Individuals with psychiatrist-diagnosed psychiatric disorders before and after neurological diagnosis were identified. Demographic, clinical data, and Patient Health Questionnaire (PHQ)-9 score at first clinic visit were collected and analysed. RESULTS: Three hundred and ninety-nine patients (249 MS, 102 AQP4-Ab NMOSD, 48 MOGAD) were included. A higher proportion of MS patients (13/249, 5.2%) had psychiatric disorders before neurological diagnosis, compared to AQP4-Ab NMOSD (1/102, 1.0%) and MOGAD (0/48, 0.0%) (p = 0.054). Within MS patients, univariate logistic regression revealed that age, sex, race, MS subtype, initial MRI lesion load, and interval between classical MS symptom onset to MS diagnosis were not associated with pre-existing psychiatric disorders. Mean PHQ-9 score for MS patients at their first MS consult was 4.4 (cut-off for no/minimal depression is ≤4); no clinical factors were predictive of higher PHQ-9 scores on univariate linear regression. The proportion of MS patients (29/236, 12.2%) who developed psychiatric illness after neurological diagnosis was not different from AQP4-Ab NMOSD (9/101, 8.9%) (p > 0.999), while this was significantly higher compared to MOGAD (0/48, 0.0%) (p = 0.021). The incidence rate of psychiatric diseases after neurological diagnosis, accounting for follow up time, was also similar between MS and AQP4-Ab NMOSD (incidence rate ratio 1.2; 95% confidence interval 0.54 - 2.8; p = 0.689). CONCLUSION: There is a significant psychiatric burden prior to MS diagnosis compared to AQP4-Ab NMOSD and MOGAD. The increased frequency of psychiatric comorbidity after NMOSD diagnosis merits further study to investigate the determinants of this phenomenon.

Applicability of the New Myelin Oligodendrocyte Glycoprotein Antibody-associated Disease Diagnostic Criteria in an Israeli Cohort.

BACKGROUND: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a rare autoimmune demyelinating disorder of the central nervous system. Optic neuritis (ON) is the most common clinical manifestation of MOGAD in adults. In 2023, new MOGAD diagnostic criteria were proposed, highlighting the importance of supplemental criteria when MOG-immunoglobulin G (IgG) titers are unavailable. OBJECTIVES: To investigate the applicability of the 2023 MOGAD criteria in patients diagnosed with MOGAD and treated before the availability of MOG-IgG titers. METHODS: We conducted a retrospective chart review of patients classified as MOGAD between 2010 and 2023 at Rabin Medical Center. Patient demographics as well as clinical and imaging data were collected, including visual acuity, expanded disability status score, core demyelinating events, antibody status, and brain and optic nerve magnetic resonance imaging data. Patients fulfilling the 2023 MOGAD criteria were reported as definite MOGAD. RESULTS: Fifteen patients met the 2023 MOGAD diagnostic criteria despite lack of MOG-IgG titer. The most common supplemental criterion meeting the 2023 MOGAD criteria was optic disc edema (n=12, 80%), followed by longitudinal optic nerve involvement (53%), bilateral ON (40%), and perineural optic sheath enhancement (33%). CONCLUSIONS: All patients with a clinical diagnosis of MOG-ON in our cohort fulfilled the 2023 MOGAD criteria despite the lack of antibody titers. The 2023 MOGAD criteria can be reliably applied to Israeli cohorts, prior to availability of MOGAD IgG titers, with particular attention to additional supplemental criteria. Since the 2023 MOGAD criteria were published, MOGAD IgG titers have been added to routine testing at our facility.

Assessment of international MOGAD diagnostic criteria in patients with overlapping MOG-associated disease and multiple sclerosis phenotypes.

BACKGROUND: The clinical spectrum and diagnosis of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) has evolved in the setting of an optimized anti-MOG-IgG cell-based assay and expert consensus. The McDonald criteria for MS have been revised multiple times to improve the accuracy and specificity of diagnosis on a framework based on clinical presentation, MRI findings, and CSF results. While the uses of MS and MOGAD diagnostic criteria are helpful for typical cases, such utility for patients with overlapping clinical, laboratorial, and imaging features is unknown, posing diagnostic and management uncertainties. OBJECTIVES: To report a multicenter cohort of patients with overlapping phenotypic features of MOGAD and MS and evaluate the application of new MOGAD diagnostic criteria. METHODS: A collaborative retrospective cohort study was performed to identify patients with both positive serum anti-MOG-IgG and fulfillment of the MS revised 2017 McDonald criteria. Clinical and radiographic features of patients fulfilling inclusion criteria were reviewed longitudinally, including relapses, repeated MRI, and MOG-IgG testing in detail to allow the panel of expert opinion to assign to each case. The International MOGAD Panel proposed criteria were applied at onset and last follow-up to each case and compared to the expert author diagnosis assignment based on presentation, clinical and imaging features, and response to treatment. RESULTS: Ten of 225 (4%) MOG-IgG seropositive cases met study inclusion criteria [seven of 10 were female; age at initial event: eight adults (mean age 26.8 years), two adolescents (mean age 14.5 years)]. AQP4-IgG was negative for all. Apart from serum titers of MOG-IgG, distinguishing clinical and radiographic features [i.e., clinical severity of the initial demyelinating event, radiographic features (optic nerve/spine/brain), and presence/absence of lesion normalization on serial scans] led to consensus of three separate classifications differing by degrees of shared features of MOGAD and MS. Patients were classified by expert panel into (1) Classic MOGAD even with MS-like, well-defined brain lesions, when severe events and most T2 lesions normalized (n = 5; MOG-IgG titers 1:100, 1:20, 1:160, 1:40, 1:200); (2) Classic RRMS included cases thought to have likely false positive or clinically irrelevant MOG-IgG, due to mild clinical events and no radiographic normalization of well-defined MS-like lesions (n = 3; MOG titers 1:20, 1:100, 1:40); (3) MOGAD and MS overlapping phenotype was defined by those with a combination of mild and severe clinical events, partial T2 lesion normalization, both well- and ill-defined lesions (n = 2; MOG titers 1:20, 1:100). The application of the International MOGAD Panel criteria categorized five patients (50%) in agreement with expert assignment. One additional patient was classified in agreement to assignment when MOGAD criteria were applied after serial MOG-IgG titers testing. DISCUSSION: While the International MOGAD Panel diagnostic criteria have helped with accuracy for the diagnosis of this condition, in a group of patients seropositive for MOG-IgG with overlapping clinical and imaging features of RRMS criteria review may lead to increased accuracy. Serial serologies, repeated imaging, close attention to clinical course, and response to therapy are possible variables to consider for further refinement of MOGAD diagnostic criteria.

Frequency of Asymptomatic Optic Nerve Enhancement in 203 Patients With MOG Antibody-Associated Disease.

BACKGROUND AND OBJECTIVES: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a distinct CNS demyelinating disease. The rate of asymptomatic optic nerve enhancement on MRI has not been explored in patients with MOGAD. An improved understanding of this would guide clinical practice and assessment of treatment efficacy. We aimed to determine the frequency of asymptomatic optic nerve enhancement in MOGAD. METHODS: This was a retrospective review of patients evaluated at Mayo Clinic with MOGAD between January 1, 2000, and August 1, 2021 (median follow-up 1.6 [range 1-19] years). MRI studies were reviewed by masked neuroradiologists. Scans performed within 30 days of ON attack were classified as attack scans. Images obtained for routine surveillance, before ON attack, or at the time of non-ON attack were classified as interattack scans. RESULTS: Five hundred sixty-six MRIs (203 unique patients, 53% female) were included. Interattack MRIs represented 341 (60%) of the scans (median 36 days post-ON [range -1,032 to 6,001]). Of the interattack scans, 43 of 341 (13%), 30 unique patients, showed optic nerve enhancement. The enhancement was located at prior sites of ON in 35 of 43 (81%). Among the 8 patients with enhancement in new optic nerve areas, 6 had acute disseminated encephalomyelitis without an eye examination at the time of the MRI and 2 had preceding ON without imaging. Long-term visual outcomes showed no significant difference between those with and without asymptomatic enhancement, with improved visual acuity in most patients. DISCUSSION: Asymptomatic optic nerve enhancement occurred in 13% of interattack MRIs, the majority in patients with prior ON and occurring at prior sites of optic nerve enhancement. New asymptomatic optic nerve enhancement in areas without prior ON was rare. These findings are important for understanding the natural history of MOGAD, the interpretation of symptoms or response to treatment, and the adjudication of attacks in clinical trials.

Longitudinal change of serum NfL as disease activity biomarker candidate in MOGAD: A descriptive cohort study.

BACKGROUND: Myelin oligodendrocyte glycoprotein antibody (MOG-IgG)-associated disease (MOGAD) is an autoinflammatory disease of the central nervous system. MOGAD often follows a relapsing course that can lead to severe disability, but monophasic disease is possible as well. Currently, there is an unmet clinical need for disease activity biomarkers in MOGAD. Serum neurofilament light chain (sNfL) is a sensitive biomarker for neuroaxonal damage. However, data on longitudinal change of sNfL as disease activity biomarker for MOGAD are scarce. OBJECTIVE: To describe the longitudinal course of sNfL in adult patients with MOGAD in an active as well as a stable disease state in relation to clinical parameters and serum MOG-IgG titers. METHODS: We conducted a retrospective, exploratory, monocentric cohort study of adult patients with MOGAD. Cohort 1 consisted of five patients in whom NfL was tested as part of their routine clinical workup, all of which had active disease (maximum 6 months since last attack, median 3 months). Cohort 2 comprised 13 patients, which were tested for NfL in the context of a longitudinal study at predefined time intervals, mostly during remission (median 10 months since last attack). sNfL was measured using single molecule array (Simoa) technology at least at two time points (median 3) within a median observation time of 5 months in cohort 1, and at baseline and after a median duration of 12 months in cohort 2. MOG-IgG titers were measured by a fixed cell-based assay. RESULTS: Change in sNfL correlated positively with change in MOG-IgG titers (rho=0.59, p = 0.027). The variability of sNfL (difference between highest and lowest level) during the observation period was higher in patients who had an attack within six months before baseline (median 37 [interquartile range [IQR] 10-64] pg/ml vs. 2.3 [IQR 1-5] pg/ml, p = 0.006). sNfL increased in patients with an attack during the observation period. Patients with baseline sNfL measurement within two weeks after attack symptom onset displayed relatively low initial sNfL with an increase afterwards. CONCLUSIONS: Longitudinal sNfL change correlates with MOG-IgG titer change and may be a promising biomarker candidate for disease activity in MOGAD. Increasing sNfL levels might be utilized to adjudicate suspected attacks. In acute attacks, sNfL increase may occur with a delay after symptom onset.

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

OBJECTIVE: To 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 METHODS: In 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. RESULTS: The 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. CONCLUSIONS: Pediatric 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.

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

BACKGROUND: 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. OBJECTIVE: We examined if CSF IL-6 level increase is associated with clinical parameters in MOGAD. METHODS: 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. RESULTS: 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. CONCLUSION: CSF IL-6 may play important roles in the pathogenesis of MOGAD, especially in CNS inflammation.

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

PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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.

Frequency, characteristics, predictors and treatment of relapsing myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD).

BACKGROUND: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) may have a monophasic or relapsing disease course. To date, factors that may predict a relapsing disease course remain largely unknown and only limited data exist regarding the efficacy of different utilized immunotherapy regimens at preventing or reducing relapses. OBJECTIVES: To assess the characteristics, predictors, and immunotherapy of relapsing MOGAD. METHODS: This multicenter retrospective analysis included all MOGAD cases at the University of Florida, Baylor College of Medicine and the University of California San Diego with minimum follow-up time of 6 months. Cox proportional hazards regression analyses, corrected for age and sex, were performed to evaluate hazard ratios (HR) of predictors of a relapsing disease course and to compare relapse hazards for utilized immunotherapies. RESULTS: The majority of included participants (51/79 [64.6 %]) had a relapsing course, and of these individuals, 68.6 % (35/51) experienced their first relapse within the first year. However, 10/51 (19.6 %) participants experienced their first relapse ≥5 years (5-15 years) after the initial presentation. Predictors of a relapsing course were CSF pleocytosis (>150 cells/mm3; HR 3.3 [1.18 - 9.24]; p = 0.023), a pediatric disease onset at age < 9 years (HR 2.69 [1.07-6.75]; p = 0.035), and an initial presentation with the clinical syndrome of meningoencephalitis (HR 3.42 [1.28 - 9.17]; p = 0.015),. In participants with a relapsing course, 13/24 (54.2 %) patients remained relapse-free on rituximab, 4/8 (50 %) on mycophenolate mofetil, and 11/14 (78.6 %) on scheduled immunoglobulins. Patients treated with immunoglobulins had significantly fewer relapses compared to patients treated with other immunotherapies (HR: 0.1 [0.2 - 0.63]; p = 0.014). CONCLUSIONS: In our cohort, the majority of MOGAD patients relapsed. The initial relapse occurred most frequently within the first year, but first relapses also took place over a decade after the initial presentation. Prepubertal onset, severe CSF pleocytosis, and the clinical syndrome of meningoencephalitis may be predictors of a relapsing course. Of the currently available off-label steroid-sparing treatments, scheduled immunoglobulins may be the most effective in relapse prevention.

MOG Antibody-Associated Disease in the Setting of Metastatic Melanoma Complicated by Immune Checkpoint Inhibitor Use.

OBJECTIVES: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is an autoimmune demyelinating disease rarely associated with malignancy. We report the clinical, MRI, immunopathology, and treatment response in a person with MOGAD and melanoma. METHODS: This is a case report of a person with a multidisciplinary evaluation at a tertiary referral center. RESULTS: A 52-year-old man presented with progressive encephalomyelitis that led to identification of metastatic melanoma. Investigations revealed positive MOG-IgG at high titers in serum (1:1,000; normal, <1:20) and CSF (1:4,096; normal, <1:2). MRI demonstrated multifocal T2 lesions with enhancement in the brain and spine. Brain biopsy showed demyelination and inflammation. MOG immunostaining was not present in the tumor tissue. He initially improved with methylprednisolone, plasmapheresis, prolonged oral steroid taper, and cancer-directed treatment with BRAF and MEK 1/2 inhibitors, but then developed bilateral optic neuritis. IV immunoglobulin (IVIG) was initiated. Five months later, he developed metastases and immune checkpoint inhibitor (ICI) treatment was started, which precipitated optic neuritis and myelitis despite IVIG and prednisone. Tocilizumab, an interleukin-6 receptor blocker, was started with excellent and sustained clinical and radiologic response. DISCUSSION: This case revealed a presentation of MOGAD concurrent with melanoma without tumor MOG immunostaining. We highlight tocilizumab as a dual-purpose treatment of MOGAD and the neurologic immune-related adverse effect of ICI.

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

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

The Indian multiple sclerosis and allied demyelinating disorders registry and research network (IMSRN): Inception to reality.

BACKGROUND: Demyelinating disorders of the CNS are a set of chronic, inflammatory, autoimmune conditions. To improve understanding of epidemiology, population characteristics and disease behaviour, an Indian, hospital-based registry has been established to serve as a platform for fostering collaborative research. The following article outlines the development, governance and current status of the Indian Multiple Sclerosis and Allied Demyelinating Disorders Registry and Research Network (IMSRN), the country's first scientific database and dedicated expert research network of these disorders. METHODS: Multiple reviews and stakeholder meetings were held to set up the registry. The IMSRN was formally initiated in August 2021 across 26 tertiary care centres. The registry is governed by the Indian Council of Medical Research (ICMR), New Delhi and its task force committee. The online secure database captures detailed clinical and imaging patient details at baseline and periodic follow up. Periodic meetings of the task force and collaborators are held to discuss the progress, improvements and research proposals. RESULTS: The IMSRN is currently active and recruiting patients following an informed consent. As of current, more than 3336 patients including RIS (N = 8), CIS (N = 134), MS (N = 1674), NMOSD (N= 561), MOGAD (N = 404), ADEM (N = 46), CRION (N = 21), CLIPPERS (N = 2), and GFAP (N =1) have been enrolled. 340 patients, not meeting the diagnostic criteria for any of the aforementioned disease phenotypes are in the others category. Various research proposals are being developed to study different aspects of these disorders. CONCLUSION: The IMSRN has been established with a vision to strengthen our understanding about MS, NMOSD, MOGAD, and other demyelinating disorders. This would help answer important questions related to disease profiles and long-term outcomes of patients in the Indian setting. From the standpoint of clinical practice, therapeutics, patient management, research, and national policy building, IMSRN shall serve as a synergising platform for bridging the gap in the aforementioned areas and guiding future research through national and international collaboration.

A protective effect of lower MHC-II expression in MOGAD.

Myelin oligodendrocyte glycoprotein-antibody-associated disease (MOGAD) is a demyelinating central nervous system disorder. We aimed to uncover immune pathways altered in MOGAD to predict disease progression. Using nanostring nCounter technology, we analyzed immune gene expression in PBMCs from MOGAD patients and compare it with healthy controls (HCs). We found 35 genes that distinguished MOGAD patients and HCs. We then validated those results in a larger cohort including MS and NMOSD patients. Expressions of HLA-DRA was significantly lower in MOGAD patients. This reduction in HLA-DRA, correlated with a monophasic disease course and greater brain volume, enhancing our ability to predict MOGAD progression.

Validation of the international MOGAD panel proposed criteria: a single-centre US study.

BACKGROUND: Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is a demyelinating disorder of the central nervous system. We aimed to evaluate the diagnostic performance of recently proposed MOGAD diagnostic criteria in a real-world patient cohort at a tertiary referral centre. METHODS: We identified all patients who were evaluated at Johns Hopkins and were MOG-IgG seropositive by cell-based assay. We retrospectively applied the proposed MOGAD diagnostic criteria. RESULTS: Among the 122 patients included in this study, 109 fulfilled the diagnostic criteria. Of 64 patients with clear positive MOG-IgG titre, 63 patients also satisfied the supporting clinical or MRI features. Of 58 patients with low positive or unknown MOG-IgG titre, 46 met criteria by fulfilment of the supporting features. The medical records were independently reviewed by two investigators with expertise in demyelinating disease, and patients were assigned empirical clinical diagnoses, with agreement with the application of the MOGAD diagnostic criteria in the majority of cases (90%). CONCLUSIONS: Our findings support the diagnostic utility of the proposed MOGAD diagnostic criteria. Patients with MOGAD met the supporting clinical or MRI features almost universally, which suggests that the criteria can be used to accurately differentiate MOGAD from mimics with low-titre MOG-IgG seropositivity.

Clinico-radiologic Spectrum and Outcome of Pediatric Acquired Demyelinating Disorders of Central Nervous System: A Retrospective Indian Tertiary Care Hospital Cohort.

BACKGROUND: Pediatric acquired demyelinating syndrome (ADS) constitutes a group of treatable disorders with acute neurologic dysfunction. Neuroimaging has played a significant role in diagnosis of ADS. We describe clinico-radiologic spectrum, outcomes, and comparison of the groups: acute disseminated encephalomyelitis (ADEM), neuromyelitis optica spectrum disorder (NMOSD), clinically isolated syndrome (CIS), multiple sclerosis (MS), and myelin oligodendrocyte glycoprotein antibody-associated disorders (MOGAD). METHODS: Retrospective review of 70 children with ADS at a tertiary care hospital over 15 years (2008-2023) was performed. Diagnosis was assigned as per International Pediatric Multiple Sclerosis Study Group criteria 2016. Fisher's exact and chi-square tests were applied. RESULTS: Thirty-nine boys and 31 girls aged 8.2 ± 4.0 years with CIS (n = 27), ADEM (n = 16), NMOSD (n = 13), MS (n = 1), and MOGAD (n = 13) were included. Clinical syndromes with positive significant association included polyfocal symptoms, encephalopathy in ADEM, optic neuritis (ON) in MOGAD, brainstem, area postrema syndrome in NMOSD. MOGAD presented with atypical presentations like prolonged fever (PF; 76.9%) and aseptic meningitis (23%). Seropositivity for myelin oligodendrocyte glycoprotein immunoglobulin-G was 62% and for NMO-IgG 2.6%. Neuroimaging of MOGAD showed lesions predominantly in basal ganglia/thalami (69.2%), optic nerve (46.2%), and cerebellum (46.2%). Imaging patterns between ADEM and MOGAD were comparable except for more ON (p = 0.004), spinal cord (p = 0.01), and cerebellar lesions (p = 0.03) in MOGAD. Area postrema lesion was unique to NMOSD. All patients received immunotherapy, of whom 91.4% (n = 64) had good recovery, 8.6% (n = 6) had functional limitation on modified Rankin scale at discharge, and 12 (17.1%) relapsed. CONCLUSION: The largest group was CIS. Seropositivity of MOG was high with atypical presentations like PF and aseptic meningitis. Specific neuroimaging patterns correlated with ADS categories. Short-term outcome with immunotherapy was favorable in spite of relapses.

Seizures in inflammatory demyelinating disorders of the central nervous system.

BACKGROUND: Multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) may be associated with acute symptomatic seizures and chronic epilepsy as well. The clinical features of the seizures and/or accompanying epilepsy seen in each disease group may vary. In this study, we aimed to contribute to the existing literature by describing the clinical features of seizures and epilepsy in our demyelinating patient population. METHODS: We retrospectively analyzed patients who were followed up in our tertiary referral center neurology demyelinating diseases outpatient clinic between 2019 and 2024. Patients who had at least one seizure before, simultaneously, or after the diagnosis of demyelinating disease were included in the study. RESULTS: Among 1735 patients with MS, 40 had experienced at least one epileptic seizure (2.3 %). Thirty patients (1.7 %) had seizures that could not be explained by another factor than MS. When secondary progressive MS (SPMS) and relapsing-remitting MS (RRMS) were compared, the interval between MS-epilepsy diagnosis was longer and seizure recurrence was more in SPMS. However, the prognosis of epilepsy was good in both subtypes. There were 21 patients followed up with antibody-positive neuromyelitis optica spectrum disorder. No patient had a seizure during the follow-up. We identified 56 patients who fulfilled the criteria for MOGAD with high antibody titers. Seizures were observed in three of them (5.4 %). All of them had status epilepticus either at the onset or during the course of the disease. CONCLUSION: Even rare, seizures constitute one of the important clinical features of the inflammatory demyelinating disorders of the central nervous system. The pathophysiologic mechanism underlying seizures in MS is still not clear. Seizures may occur through different mechanisms in patients where seizures are the initial symptom or a sign of relapse and those that occur spontaneously during the progressive course of the disease. Prevalence of status epilepticus was common in MOGAD patients. Given the rarity of the seizures in CNS demyelinating disorders, it is difficult the define clinical and pathophysiological characteristics of accompanying seizures and epilepsy. Future studies conducted on large patient groups will contribute to the existing literature.

Cerebrospinal fluid eosinophils in pediatric myelin oligodendrocyte glycoprotein antibody-associated disease.

BACKGROUND: Eosinophils in cerebrospinal fluid (CSF) are an uncommon finding most often associated with parasitic infections, but have also been described in some neuroinflammatory disorders. Eosinophilic infiltration is not thought to be a typical feature of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). We aim to describe the rate of CSF eosinophil positivity in a cohort of pediatric MOGAD patients. METHODS: Single-center retrospective chart review of pediatric MOGAD patients. Clinical and laboratory data was collected from the electronic medical record and analyzed. RESULTS: Of 46 pediatric patients with positive serum myelin oligodendrocyte glycoprotein antibody (MOG-IgG) identified, 38 patients fulfilling internationally proposed MOGAD diagnostic criteria were included for analysis. 6 patients with MOGAD were excluded as no CSF data was available, and 2 patients with positive MOG-IgG but diagnosis more consistent with MS were excluded. Median age was 7.3 years, and 19/38 (50 %) were female. Acute disseminated encephalomyelitis (ADEM) was the most common presenting phenotype (23/38, 61 %), and other phenotypes included optic neuritis (10/38, 26 %), transverse myelitis (3/38, 8 %), and neuromyelitis optica spectrum disorder (NMOSD) (2/38, 5 %). 12 of 36 (33 %) patients with all lumbar puncture (LP) data available had CSF eosinophils present, with eosinophil mean of 3 % and range from 1 % to 18 % of CSF while blood cells. CONCLUSION: CSF eosinophils were present in one third of pediatric MOGAD patients, which is a higher rate than previously reported in either MOGAD or aquaporin-4 antibody positive NMOSD cohorts. Understanding the CSF composition of pediatric MOGAD patients helps to facilitate more prompt diagnosis and treatment and may shed light onto underlying pathologic mechanisms of disease with the goal to inform future therapeutic targets.