Myelin Oligodendrocyte Glycoprotein Antibody Disease Research Articles

MRI features of myelin oligodendrocyte glycoprotein antibody disease: a descriptive study—how it differs from neuromyelitis optica spectrum disorders and multiple sclerosis

BackgroundMyelin oligodendrocyte glycoprotein antibody disease (MOGAD) is a novel inflammatory demyelinating disease of the central nervous system. This study aims to characterize the MRI features of MOGAD and contrast our results with the findings previously described in the literature and its close differential diagnoses.ResultsMost of the abnormal findings are in the brainstem followed by supratentorial deep/subcortical white matter and optic nerves. Brain lesions in MOGAD tend to show a pattern that is different from multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD). Orbital MRIs show features of bilateral longitudinally extensive optic neuritis predominantly involving the anterior segments. The spinal cord is the least affected and mostly shows longitudinally extensive lesions in the dorsal spine.ConclusionsWe could identify numerous characteristic radiological features that could help distinguish MOGAD from NMOSD and MS. We hope this study helps clinicians systematically evaluate and manage patients with clinical features of neuroinflammatory diseases.

Leptomeningeal enhancement of myelin oligodendrocyte glycoprotein antibody-associated encephalitis: uncovering novel markers on contrast-enhanced fluid-attenuated inversion recovery images.

Myelin oligodendrocyte glycoprotein antibody disease (MOGAD) is a newly defined autoimmune inflammatory demyelinating central nervous system (CNS) disease characterized by antibodies against MOG. Leptomeningeal enhancement (LME) on contrast-enhanced fluid-attenuated inversion recovery (CE-FLAIR) images has been reported in patients with other diseases and interpreted as a biomarker of inflammation. This study retrospectively analyzed the prevalence and distribution of LME on CE-FLAIR images in children with MOG antibody-associated encephalitis (MOG-E). The corresponding magnetic resonance imaging (MRI) features and clinical manifestations are also presented. The brain MRI images (native and CE-FLAIR) and clinical manifestations of 78 children with MOG-E between January 2018 and December 2021 were analyzed. Secondary analyses evaluated the relationship between LME, clinical manifestations, and other MRI measures. Forty-four children were included, and the median age at the first onset was 70.5 months. The prodromal symptoms were fever, headache, emesis, and blurred vision, which could be progressively accompanied by convulsions, decreased level of consciousness, and dyskinesia. MOG-E showed multiple and asymmetric lesions in the brain by MRI, with varying sizes and blurred edges. These lesions were hyperintense on the T2-weighted and FLAIR images and slightly hypointense or hypointense on the T1-weighted images. The most common sites involved were juxtacortical white matter (81.8%) and cortical gray matter (59.1%). Periventricular/juxtaventricular white matter lesions (18.2%) were relatively rare. On CE-FLAIR images, 24 (54.5%) children showed LME located on the cerebral surface. LME was an early feature of MOG-E (P = 0.002), and cases without LME were more likely to involve the brainstem (P = 0.041). LME on CE-FLAIR images may be a novel early marker among patients with MOG-E. The inclusion of CE-FLAIR images in MRI protocols for children with suspected MOG-E at an early stage may be useful for the diagnosis of this disease.

MRI to differentiate multiple sclerosis, neuromyelitis optica, and myelin oligodendrocyte glycoprotein antibody disease.

Differentiating multiple sclerosis (MS) from other relapsing inflammatory autoimmune diseases of the central nervous system such as neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is crucial in clinical practice. The differential diagnosis may be challenging but making the correct ultimate diagnosis is critical, since prognosis and treatments differ, and inappropriate therapy may promote disability. In the last two decades, significant advances have been made in MS, NMOSD, and MOGAD including new diagnostic criteria with better characterization of typical clinical symptoms and suggestive imaging (magnetic resonance imaging [MRI]) lesions. MRI is invaluable in making the ultimate diagnosis. An increasing amount of new evidence with respect to the specificity of observed lesions as well as the associated dynamic changes in the acute and follow-up phase in each condition has been reported in distinct studies recently published. Additionally, differences in brain (including the optic nerve) and spinal cord lesion patterns between MS, aquaporin4-antibody-positive NMOSD, and MOGAD have been described. We therefore present a narrative review on the most relevant findings in brain, spinal cord, and optic nerve lesions on conventional MRI for distinguishing adult patients with MS from NMOSD and MOGAD in clinical practice. In this context, cortical and central vein sign lesions, brain and spinal cord lesions characteristic of MS, NMOSD, and MOGAD, optic nerve involvement, role of MRI at follow-up, and new proposed diagnostic criteria to differentiate MS from NMOSD and MOGAD were discussed.

The Role of Microorganisms in the Etiopathogenesis of Demyelinating Diseases.

Multiple sclerosis (MS), neuromyelitis optica (NMO) and myelin oligodendrocyte glycoprotein antibody disease (MOGAD) are inflammatory diseases of the central nervous system (CNS) with a multifactorial aetiology. Environmental factors are important for their development and microorganisms could play a determining role. They can directly damage the CNS, but their interaction with the immune system is even more important. The possible mechanisms involved include molecular mimicry, epitope spreading, bystander activation and the dual cell receptor theory. The role of Epstein-Barr virus (EBV) in MS has been definitely established, since being seropositive is a necessary condition for the onset of MS. EBV interacts with genetic and environmental factors, such as low levels of vitamin D and human endogenous retrovirus (HERV), another microorganism implicated in the disease. Many cases of onset or exacerbation of neuromyelitis optica spectrum disorder (NMOSD) have been described after infection with Mycobacterium tuberculosis, EBV and human immunodeficiency virus; however, no definite association with a virus has been found. A possible role has been suggested for Helicobacter pylori, in particular in individuals with aquaporin 4 antibodies. The onset of MOGAD could occur after an infection, mainly in the monophasic course of the disease. A role for the HERV in MOGAD has been hypothesized. In this review, we examined the current understanding of the involvement of infectious factors in MS, NMO and MOGAD. Our objective was to elucidate the roles of each microorganism in initiating the diseases and influencing their clinical progression. We aimed to discuss both the infectious factors that have a well-established role and those that have yielded conflicting results across various studies.

COVID-19 and the Pandemic-Related Aspects in Pediatric Demyelinating Disorders

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as Coronavirus-19 (COVID-19) infection, has been associated with several neurological symptoms, including acute demyelinating syndromes (ADS). There is a growing body of literature discussing COVID-19 and demyelinating conditions in adults; however, there is less published about COVID-19 demyelinating conditions in the pediatric population. This review aims to discuss the impact of COVID-19 in pediatric patients with central nervous system ADS (cADS) and chronic demyelinating conditions. We reviewed PubMed, Google Scholar, and Medline for articles published between December 1, 2019 and October 25, 2022 related to COVID-19 and pediatric demyelinating conditions. Of 56 articles reviewed, 20 cases of initial presentation of ADS associated with COVID-19 were described. The most commonly described cADS associated with COVID-19 infection in children was Acute Disseminated Encephalomyelitis followed by Transverse Myelitis. Cases of Myelin Oligodendrocyte Glycoprotein Antibody Disease, Neuromyelitis Optica Spectrum Disorder, and Multiple Sclerosis are also described. The risk of severe COVID-19 in pediatric patients with demyelinating conditions appears low, including in patients on disease modifying therapies, but studies are limited. The pandemic did affect disease modifying therapies in ADS, whether related to changes in prescriber practice or access to medications. COVID-19 is associated with ADS in children and the COVID-19 pandemic has impacted pediatric patients with demyelinating conditions in various ways.

What neuropathology teaches us about autoimmune encephalitides, autoimmune epilepsies, and encephalomyelitides.

Delineation of the autoimmune encephalitides with antibodies against neural surface antigens (anti-N-Methyl-D-aspartate, anti-leucine-rich glioma-inactivated protein 1, and others), autoimmune-associated epilepsies (Rasmussen encephalitis, paraneoplastic encephalitides, temporal lobe epilepsy with antibodies against glutamic acid decarboxylase), and encephalomyelitides with glial antibodies (neuromyelitis optica spectrum disorder, myelin oligodendrocyte glycoprotein antibody disease) has been a major advance in neurology. But how do these inflammatory diseases "work"? What kind of interaction between elements of the immune system and brain cells leads to these conditions? The only direct way of answering these questions is to investigate affected brain tissue by neuropathological techniques. They provide morphological and, in part, temporal information on the elements and localization of the disease process. Molecular techniques broaden and support these data. Brain tissue becomes available through autopsies and brain biopsies, obtained for diagnostic or therapeutic interventions. The limitations of neuropathological pathogenic research are discussed. Finally, representative neuropathological findings in autoimmune encephalitides and related conditions are summarized.

The absence of antibodies in longitudinally extensive transverse myelitis and the impact on prognosis (P9-5.029)

<h3>Objective:</h3> Evaluation of clinical outcomes in LETM. <h3>Background:</h3> Longitudinally extensive transverse myelitis (LETM) is typically defined as spinal cord inflammation that spans 3 or more vertebral segments on MRI. It is a prototypical manifestation of neuromyelitis optica spectrum disorder (NMOSD) but is also seen in myelin oligodendrocyte glycoprotein antibody disease (MOGAD) and much less commonly multiple sclerosis. In some cases, despite extensive investigation, a definitive diagnosis cannot be reached, a condition referred to as double seronegative LETM (dsLETM). <h3>Design/Methods:</h3> Cohort study of LETM cases reviewed in NMO UK Highly Specialised Service at the Walton Centre NHS Foundation Trust between Jan 2008-March 2022. Clinical presentation, radiological characteristics, aquaporin-4 antibodies (AQP4-IgG) and MOG antibodies, relapses, treatment, and EDSS at follow-up were extracted from case records. <h3>Results:</h3> LETM=93 cases were identified; NMOSD=41 (AQP4-IgG positive; 88%), dsLETM=29, MOGAD=17, others=6. The median onset age was 46 (15–85) yrs with a median follow-up of 46 (1–144) months. EDSS at nadir was similar between subgroups (NMOSD; 7, MOGAD; 7.5, dsLETM; 6.7, p&gt;0.05) but patients with dsLETM were less likely to relapse (dsLETM; 21% vs. NMOSD; 56% vs. MOGAD; 29%, p=0.008). Long term immunosuppression was used in NMOSD (100%), MOGAD (76%) and dsLETM (34%) and was associated with a reduction in median annualised relapse rate (NMOSD; 1.65 to 0.09, MOGAD; 0.75 to 0.07, and dsLETM; 1 to 0.11). Although EDSS scores at last review were higher in NMOSD than MOGAD (6 vs. 4; p=0.018) and dsLETM (6 vs 4.5; p=0.04), dsLETM patients still reached a significant disability (EDSS&gt;6) in 35% of cases. <h3>Conclusions:</h3> Patients with dsLETM relapsed less as compared to NMOSD and MOGAD and immunosuppression reduced the risk further. Although last EDSS was lower in dsLETM as compared to NMOSD, a third of patients still suffered from significant disability. <b>Disclosure:</b> Dr. Rocchi has nothing to disclose. Dr. Forcadela has nothing to disclose. Dr. Jacob has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for ALEXION. Dr. Hamid has nothing to disclose. Dr. Huda has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Guidepoint.

Most Opticospinal Demyelination is NMOSD, not MS-A 17-year UK Longitudinal Cohort Study (P5-3.003)

<h3>Objective:</h3> To evaluate clinical outcomes in a cohort of patients with Opticospinal Demyelination (OSD). <h3>Background:</h3> Classification of central nervous system inflammation has progressed with the identification of aquaporin-4 (AQP4) antibodies in neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein (MOG) antibodies in MOG antibody disease (MOGAD) in addition to multiple sclerosis (MS). However, as defined in 2003, patients with opticospinal demyelination (optic neuritis (ON), short-segment transverse myelitis (TM), and brain imaging not supportive of MS) do not fulfil internationally approved criteria for MS, NMOSD, or MOGAD. <h3>Design/Methods:</h3> Between 2003–2005, 128 cases of OSD were reported via the British Neurological Surveillance Unit. In 2011, 2015 and 2022 patients and physicians were contacted for clinical, radiological, and serological (e.g., AQP4-IgG and MOG-IgG) data as part of a prospective longitudinal cohort study. <h3>Results:</h3> Of 128 cases, 67 (52%) patients fulfilled OSD diagnostic criteria. At 17 years 39/60 patients (65%) now met NMOSD diagnostic criteria, 14 (23%) had MS and 7 (12%) had OSD. The median time to diagnosis of NMOSD was 107 months (85–261) and to MS was 189 months (79–346). The median age of OSD patients at onset was 37 (25–48) years and 5/7 were male. A relapsing course was observed in 6/7 patients with a median annualised relapse rate of 0.22 (0.13–0.49). At last follow-up the median EDSS was 2.5 (range; 1–6.5) and only 2/7 patients had an EDSS&gt;3.5. <h3>Conclusions:</h3> OSD is diagnostically distinct from MS, NMOSD, and MOGAD. However, after 2 decades most OSD patients reached a diagnosis of NMOSD or MS, so OSD may lie on a spectrum with these conditions. Of the 12% of cases that retained OSD classification, all but 1 had a relapsing course but rates of significant disability were low. Future studies should focus on characterising diagnostic and prognostic biomarkers in this unique subtype of non-MS CNS inflammation. <b>Disclosure:</b> Dr. Forcadela has nothing to disclose. Dr. Rocchi has nothing to disclose. Dr. Panicker has nothing to disclose. Kerry Mutch has nothing to disclose. Dr. Huda has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Guidepoint. Dr. Jacob has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for ALEXION. Dr. Hamid has nothing to disclose.

Predictors of Conversion from Positive to Negative Myelin Oligodendrocyte Glycoprotein (MOG) Antibody Status (P9-3.011)

<h3>Objective:</h3> The goal of this study is to characterize the clinical course of patients with Myelin Oligodendrocyte Glycoprotein Antibody Disease (MOGAD) who seroconvert from a positive to negative MOG antibody status, and to determine predictors of seroconversion. <h3>Background:</h3> MOGAD is a neuroinflammatory disorder characterized by demyelination of the optic nerve, brain, or spinal cord, and can be either relapsing or monophasic. Persistent MOG antibody positivity has been identified as a potential predictor of disease-related relapses, however there has been limited research regarding what determines whether patients remain seropositive or convert to a negative MOG antibody status. <h3>Design/Methods:</h3> The Massachusetts General Hospital Neuroimmunology Clinic maintains a list of patients with MOGAD based on queries of the Massachusetts General Brigham Research Patient Data Registry database and updated with clinic visits. Patients evaluated through July 2022 were included in a chart review focused on MOG serostatus, titer levels, and potential predictors of MOG serostatus. Data analysis was conducted in Stata/SE 17.0. <h3>Results:</h3> We identified 66 patients who had at least 2 MOG antibody tests 6 months apart (60.6% females and 39.4% males). Of these, 47 had persistently positive MOG titers, and 18 had positive titers that became negative. 5 individuals had negative titers that later converted to positive. Of the 18 patients that developed negative titers, only 1 had a subsequent documented relapse, which was associated with discontinued immunotherapy and titers which became positive again at the time of relapse. Predictors of conversion to negative IgG on multivariate logistic regression included low initial MOG titers (defined as titers &lt;1:100), male sex, and childhood onset of disease. <h3>Conclusions:</h3> Low initial MOG titers, male sex, and childhood onset of disease can help predict future conversion to negative MOG serostatus. Further analysis of this cohort will focus on the effect of various immunotherapies and their timing on MOG antibody status. <b>Disclosure:</b> Ms. Hayman has nothing to disclose. The institution of Dr. Vishnevetsky has received research support from National MS Society. The institution of Dr. Vishnevetsky has received research support from NIH (NeuroNext). Ms. Romanow has received research support from Freeman Pain Award @ Harvard Medical School. Dr. Levy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Mitsubishi Pharma. Dr. Levy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB Pharma. Dr. Levy has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi. Dr. Levy has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Levy has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon. Dr. Levy has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Levy has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. Dr. Levy has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Various law firms. The institution of Dr. Levy has received research support from National Institutes Health.

Myelin Oligodendrocyte Glycoprotein Antibody Disease (MOGAD) in conjunction with Allogeneic Bone Marrow Transplantation and Autoimmune Neutropenia: A study of two companion cases and institutional review of the MOGAD clinical phenotype spectrum (P13-5.031)

Myelin Oligodendrocyte Glycoprotein Antibody Disease (MOGAD) in conjunction with Allogeneic Bone Marrow Transplantation and Autoimmune Neutropenia: A study of two companion cases and institutional review of the MOGAD clinical phenotype spectrum (P13-5.031)

Spinal Glioblastoma Mimicking Myelin Oligodendrocyte Glycoprotein Antibody Disease Transverse Myelitis (P13-5.021)

<h3>Objective:</h3> To present a case of spinal glioblastoma mimicking myelin oligodendrocyte glycoprotein antibody disease (MOGAD). <h3>Background:</h3> Spinal cord lesions have a broad differential, with inflammatory, vascular, and malignant causes often misdiagnosed. MOGAD is an inflammatory disease responsive to immunosuppressant therapy, while malignancies require surgery, radiation, and chemotherapy. Positive antibody titers support the diagnosis of MOGAD, but false positive results have been reported at low titers. Studies on primary spinal glioblastoma are limited with no reported cases of positive MOG antibodies. <h3>Design/Methods:</h3> N/A <h3>Results:</h3> A 55-year old male presented with two months of leg weakness, paresthesias, and urinary retention. MR imaging showed longitudinally extensive abnormal cord signal from C3–C4 to T12 with 4.9×1.1cm rim-enhancing intramedullary lesion at T5–T6. MOG antibody titer was 1:40; other work up including cytology was negative. High dose steroids and three days of plasmapheresis (stopped due to allergic reaction) led to improved strength and cord edema regression, and the patient transitioned to a prednisone taper. Two weeks later, the patient developed arm weakness. Imaging showed progressive spinal cord edema. Additional history revealed symptoms developed a year before initially reported. Repeat testing was negative except unchanged MOG titer. After additional immunosuppressant therapy, imaging demonstrated unchanged enhancing spine lesion. Spinal biopsy revealed glioblastoma. <h3>Conclusions:</h3> Spinal cord malignancy can mimic MOGAD transverse myelitis. Chronicity and progression can aid in the diagnosis. This case highlights two atypical features for MOGAD: recurrence of cord signal changes and symptoms despite treatment, and the low elevation of MOG antibody titers, which raised suspicion for an alternative diagnosis. When atypical features are present in suspected inflammatory myelitis, a broad differential should be maintained. Studies show that patients with primary CNS malignancies can have signs of increased immune response, indicating that malignancy and autoimmune processes cause chronic immunologic dysfunction. <b>Disclosure:</b> Dr. Breitenbucher has nothing to disclose. Dr. Welsh has nothing to disclose. The institution of Dr. Robers has received research support from National Multiple Sclerosis Society. The institution of Dr. Robers has received research support from Bristol Myers Squibb Foundation. The institution of Dr. Robers has received research support from Barrow Neurological Foundation.

Paediatric MOG-antibody disease presenting with intracranial hypertension and unilateral vision loss without radiological evidence of optic neuritis

Intracranial hypertension (IH) is poorly described in paediatric myelin oligodendrocyte glycoprotein antibody disease (MOGAD). We describe a unique case of seropositive MOGAD in an obese 13-year-old boy who presented with an isolated IH, bilateral optic disc swelling and sudden-onset complete vision loss in one eye without radiological evidence of optic nerve involvement. Treatment with intravenous methylprednisolone combined with an emergency shunt fully restored vision and resolved the optic disc swelling. This report adds to the growing body of evidence suggesting that obese children presenting with isolated IH should be investigated for MOGAD, and the importance of managing IH during MOGAD.

Pathophysiology of myelin oligodendrocyte glycoprotein antibody disease.

Myelin Oligodendrocyte Glycoprotein Antibody Disease (MOGAD) is a spectrum of diseases, including optic neuritis, transverse myelitis, acute disseminated encephalomyelitis, and cerebral cortical encephalitis. In addition to distinct clinical, radiological, and immunological features, the infectious prodrome is more commonly reported in MOGAD (37-70%) than NMOSD (15-35%). Interestingly, pediatric MOGAD is not more aggressive than adult-onset MOGAD, unlike in multiple sclerosis (MS), where annualized relapse rates are three times higher in pediatric-onset MS. MOGAD pathophysiology is driven by acute attacks during which T cells and MOG antibodies cross blood brain barrier (BBB). MOGAD lesions show a perivenous confluent pattern around the small veins, lacking the radiological central vein sign. Initial activation of T cells in the periphery is followed by reactivation in the subarachnoid/perivascular spaces by MOG-laden antigen-presenting cells and inflammatory CSF milieu, which enables T cells to infiltrate CNS parenchyma. CD4+ T cells, unlike CD8+ T cells in MS, are the dominant T cell type found in lesion histology. Granulocytes, macrophages/microglia, and activated complement are also found in the lesions, which could contribute to demyelination during acute relapses. MOG antibodies potentially contribute to pathology by opsonizing MOG, complement activation, and antibody-dependent cellular cytotoxicity. Stimulation of peripheral MOG-specific B cells through TLR stimulation or T follicular helper cells might help differentiate MOG antibody-producing plasma cells in the peripheral blood. Neuroinflammatory biomarkers (such as MBP, sNFL, GFAP, Tau) in MOGAD support that most axonal damage happens in the initial attack, whereas relapses are associated with increased myelin damage.

Low mortality rate in a large cohort of myelin oligodendrocyte glycoprotein antibody disease (MOGAD).

The mortality rates of individuals with myelin oligodendrocyte glycoprotein antibody disease (MOGAD) are currently unknown. This study aimed to assess the mortality rate in a large cohort of patients with MOGAD. Since none of the patients in our cohort died, we estimated the upper limit of a 95% confidence interval of the crude mortality rate in the cohort to be 2.1%. These data suggest that mortality in MOGAD is lower than that reported in other neuroinflammatory diseases and comparable to the age-adjusted mortality rates of the general population in the United States. Additional studies are warranted to confirm this observation.

Retinal structural and microvascular changes in myelin oligodendrocyte glycoprotein antibody disease and neuromyelitis optica spectrum disorder: An OCT/OCTA study.

To compare the optical coherence tomography (OCT)/OCT angiography (OCTA) measures in patients with neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody disease (MOGAD). Twenty-one MOG, 21 NMOSD, and 22 controls were enrolled in our study. The retinal structure [retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GCIPL)] was imaged and assessed with the OCT; OCTA was used to image the macula microvasculature [superficial vascular plexus (SVP), intermediate capillary plexus (ICP), and deep capillary plexus (DCP)]. Clinical information such as disease duration, visual acuity, and frequency of optic neuritis and disability was recorded for all patients. Compared with NMOSD patients, MOGAD patients showed significantly reduced SVP density (P = 0.023). No significant difference (P > 0.05) was seen in the microvasculature and structure when NMOSD-ON was compared with MOG-ON. In NMOSD patients, EDSS, disease duration, reduced visual acuity, and frequency of ON significantly correlated (P < 0.05) with SVP and ICP densities; in MOGAD patients, SVP correlated with EDSS, duration, reduced visual acuity, and frequency of ON (P < 0.05), while DCP density correlated with disease duration, visual acuity, and frequency of ON. Distinct structural and microvascular changes were identified in MOGAD patients compared with NMOSD patients suggesting that the pathological mechanisms are different in NMOSD and MOGAD. Retinal imaging via the SS-OCT/OCTA might have the potential to be used as a clinical tool to evaluate the clinical features associated with NMOSD and MOGAD.

Hereditary optic neuropathy associated with demyelinating diseases of the central nervous system

Demyelinating optic neuritis and hereditary optic neuropathy (HON) take a leading place among the diseases, the leading clinical syndrome of which is bilateral optic neuropathy with a simultaneous or sequential significant decrease in visual acuity. Optic neuritis can occur at the onset or be one of the syndromes within multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD), and myelin oligodendrocyte glycoprotein (MOG) antibody disease (MOGAD). HON are a group of neurodegenerative diseases, among which the most common variants are Leber's hereditary optic neuropathy (LHON), associated with mitochondrial DNA (mtDNA) mutations, and autosomal recessive optic neuropathy (ARON), caused by nuclear DNA (nDNA) mutations in DNAJC30. There are phenotypes of LHON «plus», one of which is the association of HON and CNS demyelination in the same patient. In such cases, the diagnosis of each of these diseases causes significant difficulties, due to the fact that in some cases there are clinical and radiological coincidences between demyelinating and hereditary mitochondrial diseases.

Clinical features and modern diagnostic criteria of the disease associated with myelin oligodendrocyte glycoprotein antibody disease

Demyelinating disease of the central nervous system associated with antibodies to myelin oligodendrocyte glycoprotein (MOGAD) has been proposed to be distinguished from neuromyelitis optica spectrum disorders (NMOSD) into a separate nosological form. The basis for the recognition of nosological independence was the presence of clinical features of this disease and the detection of a specific biomarker in the blood serum of patients - IgG class antibodies to MOG. The article summarizes the current data on the clinical and radiological phenotypes of MOGAD in children and adults and the features of the course of the disease. The requirements for the laboratory diagnosis of the disease and diagnostic criteria for MOGAD proposed by an international group of experts in 2023 are given.

Evidence for and Against Subclinical Disease Activity and Progressive Disease in MOG Antibody Disease and Neuromyelitis Optica Spectrum Disorder

Objective To investigate the evidence for and against relapse-independent clinical progression and/or subclinical disease activity in patients with Myelin Oligodendrocyte Glycoprotein Antibody Disease (MOGAD) and Aquaporin-4 IgG Seropositive Neuromyelitis Optica Spectrum Disorder (AQP4-IgG+ NMOSD). Background MOGAD and AQP4-IgG+ NMOSD are generally relapsing disorders, without clinical progression or subclinical disease activity outside of relapses. With advances in the diagnosis and treatment of these conditions, prolonged periods of remission without relapses can be achieved, and the question of whether progressive disease courses can occur has re-emerged. Design/Methods We conducted a narrative literature review in Ovid MEDLINE and Embase, exploring the evidence for and against relapse-independent progression in MOGAD and AQP4-IgG+ NMOSD. We classified the results in four categories : 1)Clinical observations, 2)MRI findings, 3)Retinal imaging, and 4)Fluid-based biomarkers. Results As the optic nerve is the major site of involvement in MOGAD and AQP4-IgG+ NMOSD, much of the data comes from the visual pathway studies. Possible pathophysiologic mechanisms of the OCT abnormalities in the absence of symptomatic optic neuritis are: 1) primary neurodegenerative process in retina, 2) subclinical inflammation of the optic nerve, 3) chiasmal involvement leading to abnormal findings in the unaffected eye, and 4)trans-synaptic retrograde degeneration originating from inflammatory lesions in the posterior visual pathway. Except for chiasmal involvement, these mechanisms are not specific to the visual pathway, and are considered as potential explanations for subclinical disease activity outside of the retina. Outside of the visual pathway, there is a lack of sufficient evidence to support the existence of subclinical disease activity and/or relapse-independent clinical progression in MOGAD and AQP4-IgG+ NMOSD, although recent fluid-based biomarker data (serum NfL and GFAP) support that neuro-axonal and/or astrocytic damage may be ongoing between attacks in these diseases. Conclusions This review highlights the many unknowns that remain in our understanding of the pathophysiology and clinical course of MOGAD and AQP4-IgG+ NMOSD.

Acute Central Nervous System Demyelination Following COVID-19 Vaccination

Objective To describe features of central nervous system (CNS) demyelinating events following vaccination against coronavirus disease 19 (COVID-19). Background Several reports suggest a potential association between COVID-19 vaccines and acute CNS inflammation. Design/Methods A case series was performed at the BARLO MS Centre in Toronto, Ontario, Canada. Clinicians reported patients who experienced an acute CNS demyelinating event within 60 days after receiving at least one COVID-19 vaccination from March 2021 to January 2022. Clinical characteristics were evaluated. Results Twenty patients were identified (median age 39 years (range 25-82); 13 (65.0%) female). Two had pre-existing multiple sclerosis (MS). Individuals received the Pfizer (n = 14), Moderna (n = 5) or Astrazeneca (n = 1) COVID-19 vaccines. Within 1-53 days (median 12) of the first (n = 8) or second (n = 12) vaccine dose, patients developed transverse myelitis (TM) (n = 15), optic neuritis (n = 4) or brain demyelination (n = 4). Diagnoses at last follow up (median 114 days (range 39-255)) were relapsing remitting MS (n = 8), post-vaccine TM (n = 5), clinically isolated syndrome (n = 3), myelin oligodendrocyte glycoprotein antibody disease (n = 2), MS relapse (n = 1) and neuromyelitis optica spectrum disorder (n = 1). Thirteen patients received pulse corticosteroids, and of these, 4 received plasma exchange. Seven did not receive acute treatment. 20.0% returned to baseline (n = 4), 75.0% partially recovered (n = 15) and 5.0% worsened (n = 1). At last follow up, 11 were on disease modifying therapy and 9 were not. Nine patients received a subsequent COVID-19 vaccine. Of these, one experienced symptom recrudescence without radiologic evidence of a new demyelinating attack. Conclusions To our knowledge, this is the largest series to date describing acute CNS demyelination after vaccination against COVID-19. The rate of vaccination in the eligible general population was high during the time of the cases and we could not determine whether the number of demyelinating events was higher than expected. Repeat vaccination was not associated with recurrent adverse events in this small observational series.

High levels of cerebrospinal fluid soluble triggering receptor expressed on myeloid cells 2 might be a biomarker of activity in pediatric patients with MOG-AD.

Myelin oligodendrocyte glycoprotein antibody disease (MOG-AD) is characterized by its monophasic or relapsing course and inflammatory demyelinating condition which is unable to be classified in typical multiple sclerosis (MS) or other known neuroinflammatory conditions. In the condition of neuroinflammatory, activated microglia are essential for demyelination. The secreted ectodomain of soluble triggering receptor expressed on myeloid cells 2 (sTREM2), expressed by microglial cells, is associated with abnormal biological pathways. It is known that the cerebrospinal fluid (CSF) sTREM2 concentration is much higher in neuroinflammatory and neurodegeneration diseases. However, the role of activated microglia has not been reported in MOG-AD pediatric patients. For the first time, the increased CSF and serum sTREM2 concentration in pediatric patients with MOG-AD is investigated in this work, showing evidence of microglia activation in MOG-AD. CSF sTREM2 levels significantly correlated with clinical inflammatory indexes and adapted modified Rankin Scale score, indicating the potential value of sTREM2 as a severity biomarker.