Myelin Oligodendrocyte Glycoprotein Research Articles

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

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. This is a case report of a person with a multidisciplinary evaluation at a tertiary referral center. 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. 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.

Optic Disc Cupping in Neuromyelitis Optica Spectrum Disorder, Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease, and Multiple Sclerosis and Its Relationship With Optical Coherence Tomography Parameters: A Multicenter Study

Background: Although cupping of the optic nerve is classically a sign of glaucomatous optic neuropathy, it has been shown that cupping can sometimes occur after an episode of optic neuritis (ON). The purpose of this study was to compare cupping in patients after ON from multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), or myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and to investigate the relationship between cupping and retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) thinning. Methods: This was a retrospective cohort involving patients (≥18 years) with ON from 3 institutions. Patients were eligible if they had optical coherence tomography (Cirrus, OCT) performed ≥6 months after a single unilateral ON. The amount of thinning and cupping was estimated from the difference in the OCT parameters between affected and unaffected eyes. Univariable and multivariable regressions were used to investigate the relationship between cupping and ON etiology. Pearson correlation was used to investigate the relationship between cupping and RNFL and GCC. Results: Eighty-six subjects (MS: 35, NMOSD: 26, and MOGAD: 25) were included. There was no significant difference in gender and race between the groups, and most patients (86.1%) were female. Patients with NMOSD were significantly older than patients with MS or MOGAD (P = 0.002). In the univariate model, cupping was significantly higher in the NMOSD group (P = 0.017); however, after adjusting for age, GCC, and RNFL of the affected eye, the difference was no longer statistically significant (P = 0.949). The correlation between cupping asymmetry and RNFL and GCC of the affected eye was inversely strong in patients with MS (R = −0.60 and R = −0.64, respectively), inversely moderate in patients with MOGAD (R = −0.34 and R = −0.40, respectively), and weak in patients with NMOSD (R = −0.03 and R = −0.17, respectively). Conclusions: Our results demonstrated that cupping after ON is correlated with RNFL and GCC thinning; although cupping was overall greater in the NMOSD group, once adjusted for age, RNFL, and GCC, it did not differ among patients with MS, NMOSD, and MOGAD.

Life-Threatening MOG Antibody-Associated Hemorrhagic ADEM With Elevated CSF IL-6.

Acute disseminated encephalomyelitis (ADEM) is one characteristic manifestation of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). A previously healthy man presented with retro-orbital headache and urinary retention 14 days after Tdap vaccination. Brain and spine MRI suggested a CNS demyelinating process. Despite treatment with IV steroids, he deteriorated, manifesting hemiparesis and later impaired consciousness, requiring intubation. A repeat brain MRI demonstrated new bilateral supratentorial lesions associated with venous sinus thrombosis, hemorrhage, and midline shift. Anti-MOG antibody was present at a high titer. CSF IL-6 protein was >2,000 times above the upper limits of normal. He improved after plasma exchange, then began monthly treatment alone with anti-IL-6 receptor antibody, tocilizumab, and has remained stable. This case highlights how adult-onset MOGAD, like childhood ADEM, can rapidly become life-threatening. The markedly elevated CSF IL-6 observed here supports consideration for evaluating CSF cytokines more broadly in patients with acute MOGAD.

Imaging Biomarkers for Differential Diagnosis of Central Nervous System Inflammatory Diseases

Inflammatory diseases of the central nervous system (CNS) include multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), and acute disseminated encephalomyelitis. In addition, various rheumatoid autoimmune diseases, autoimmune encephalitis, and medications such as immune checkpoint inhibitors can cause inflammation in the CNS. Radiological findings are very useful for us in differentiating inflammatory diseases of the CNS. On MRI, the shape, location, length/size, and gadolinium enhancement pattern of the lesions as well as the recovery and atrophy of the lesions following the acute phase, serve as important biomarkers for differentiating the diseases. In this review, we will highlight the typical characteristics MRI of optic neuritis, brain lesions, and myelitis in MS, NMOSD, and MOGAD, and outline the features of other inflammatory diseases of CNS.

Imaging Biomarkers for Differential Diagnosis of Central Nervous System Inflammatory Diseases

Inflammatory diseases of the central nervous system (CNS) include multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), and acute disseminated encephalomyelitis. In addition, various rheumatoid autoimmune diseases, autoimmune encephalitis, and medications such as immune checkpoint inhibitors can cause inflammation in the CNS. Radiological findings are very useful for us in differentiating inflammatory diseases of the CNS. On MRI, the shape, location, length/size, and gadolinium enhancement pattern of the lesions as well as the recovery and atrophy of the lesions following the acute phase, serve as important biomarkers for differentiating the diseases. In this review, we will highlight the typical characteristics MRI of optic neuritis, brain lesions, and myelitis in MS, NMOSD, and MOGAD, and outline the features of other inflammatory diseases of CNS.

Revised Diagnosis From Histiocytic Neoplasm to Optic Chiasm Glioblastoma After Genetic Analysis.

A 46-year-old man presented with left eye blurring. Automated visual field testing showed an incongruous right hemianopia, with sparing of the lower temporal quadrant in the right eye. MRI revealed foci of gadolinium enhancement in the optic chiasm and optic tracts. Serologic testing (including myelin oligodendrocyte glycoprotein and neuromyelitis optica antibodies) and cerebrospinal fluid analysis were negative. Whole-body PET/CT scan found no malignancy. Biopsy of the optic chiasm revealed a moderately cellular neoplasm composed of atypical, discohesive cells with enlarged nuclei, prominent eosinophilic nucleoli, and abundant vacuolated cytoplasm. Immunohistochemical stains for CD68 and S100 were positive, whereas those for GFAP, OLIG2, SOX10, and multiple others were negative, supporting a diagnosis of histiocytic neoplasm. Five weeks later, results became available from next-generation sequencing targeting the coding regions of hundreds of malignancy-associated genes and select introns. Alterations associated with histiocytic neoplasms (i.e. BRAF and MAP2K1 mutations) were absent. However, there was a nonsense mutation in the PTEN gene, a hotspot mutation in the TERT gene promotor, and focal amplifications of the CDK4 and MDM2 genes. Additionally, there was chromosome 6q loss, 7 gain, and 10q loss. Based on these findings, the diagnosis was revised to glioblastoma, IDH-wildtype, CNS WHO grade 4. The patient began treatment with temozolomide while continuing radiation therapy. This case illustrates how next-generation sequencing can at times provide more accurate diagnostic information than standard tissue histopathology.

Myelin-reactive B cells exacerbate CD4+ T cell-driven CNS autoimmunity in an IL-23-dependent manner

B cells and T cells collaborate in multiple sclerosis (MS) pathogenesis. IgH[MOG] mice possess a B cell repertoire skewed to recognize myelin oligodendrocyte glycoprotein (MOG). Here, we show that upon immunization with the T cell-obligate autoantigen, MOG[35-55], IgH[MOG] mice develop rapid and exacerbated experimental autoimmune encephalomyelitis (EAE) relative to wildtype (WT) counterparts, characterized by aggregation of T and B cells in the IgH[MOG] meninges and by CD4+ T helper 17 (Th17) cells in the CNS. Production of the Th17 maintenance factor IL-23 is observed from IgH[MOG] CNS-infiltrating and meningeal B cells, and in vivo blockade of IL-23p19 attenuates disease severity in IgH[MOG] mice. In the CNS parenchyma and dura mater of IgH[MOG] mice, we observe an increased frequency of CD4+PD-1+CXCR5- T cells that share numerous characteristics with the recently described T peripheral helper (Tph) cell subset. Further, CNS-infiltrating B and Tph cells from IgH[MOG] mice show increased reactive oxygen species (ROS) production. Meningeal inflammation, Tph-like cell accumulation in the CNS and B/Tph cell production of ROS were all reduced upon p19 blockade. Altogether, MOG-specific B cells promote autoimmune inflammation of the CNS parenchyma and meninges in an IL-23-dependent manner.

A comparative study on anti-MOG and anti-AQP4 associated optic neuritis following mild COVID-19: insights from a Chinese single-center experience.

Research on the relationship between mild COVID-19 and the subsequent development of isolated optic neuritis (ON) with antibodies specific to myelin oligodendrocyte glycoprotein (MOG-ON) and aquaporin 4 (AQP4-ON) is limited, particularly case-control studies that directly compare these conditions within the same affected population. A retrospective analysis of initial MOG-ON and AQP4-ON cases during the COVID-19 peak and subsequent months. Patients were classified as possible COVID-19 related ON (PCRON) or non-COVID-19 related ON (NCRON). The study compared epidemiology, comorbidities, and clinical features between these groups. Patients with MOG-ON tended to develop ON symptoms closer in time to a mild COVID-19 infection compared to those with AQP4-ON (6.87 ± 6.25 weeks vs. 11.06 ± 5.84 weeks; p = 0.038), a significantly higher proportion of patients with MON-ON developing symptoms within 6 weeks after COVID-19 compared to those with AQP4-ON (15/23 [65.2%] vs. 5/17 [29.4%]; p = 0.025). Comparing MOG-ON and AQP4-ON patients, MOG-ON patients were more likely to have a recent infection before ON onset (73.1% vs. 30%; p = 0.007) and had better peak and post-treatment visual acuity (p = 0.01; p < 0.001). In contrast, AQP4-ON patients frequently showed comorbid connective tissue diseases (30.0% vs. 0%, p = 0.004) and antinuclear antibody abnormalities (40.0% vs. 7.7%, p = 0.012). Among MOG-ON patients, PCRON had increased rates of atherosclerotic vascular diseases (AVDs) (53.3% vs. 9.1%, p = 0.036), phospholipid antibody abnormalities (60.0% vs. 18.2%, p = 0.04), and bilateral visual impairment (66.7% vs. 9.1%, p = 0.005). Multivariate analysis pinpointed AVDs (OR = 15.21, p = 0.043) and bilateral involvement (OR = 25.15, p = 0.015) as independent factors related to COVID-19 associated MOG-ON, with both being good discriminators for PCRON (AUC = 0.879). No differences were found between the PCRON and NCRON groups in AQP4-ON patients. Mild COVID-19 is more likely associated with MOG-ON than AQP4-ON. MOG-ON that develops within 6 weeks following a COVID-19 infection may be associated with the COVID-19 infection. AVDs may have a synergistic effect on MOG-ON in patients with COVID-19, which warrants further investigation. COVID-19 related MOG-ON often affects both eyes, and acute visual function damage can be severe, but generally has a good prognosis.

Development and validation of a claims-based algorithm to identify patients with Neuromyelitis Optica Spectrum disorder

IntroductionNo validated algorithm exists to identify patients with neuromyelitis optica spectrum disorder (NMOSD) in healthcare claims data. We developed and tested the performance of a healthcare claims–based algorithm to identify patients with NMOSD. MethodsUsing medical record data of 101 adults with NMOSD, multiple sclerosis (MS), or myelin oligodendrocyte glycoprotein antibody–associated disease (MOGAD), we tested the sensitivity and specificity of claims-based algorithms developed through interviews with neurologists. We tested the best-performing algorithm's face validity using 2016–2019 data from IBM MarketScan Commercial and Medicare Supplemental databases. Demographics and clinical characteristics were reported. ResultsAlgorithm inclusion criteria were age ≥ 18 years and (≥1 NMO diagnosis [or ≥ 1 transverse myelitis (TM) and ≥ 1 optic neuritis (ON) diagnosis] and ≥ 1 NMOSD drug) or (≥2 NMO diagnoses ≥90 days apart). Exclusion criteria were MS diagnosis or use of MS-specific drug after last NMO diagnosis or NMOSD drug; sarcoidosis diagnosis after last NMO diagnosis; or use of ≥1 immune checkpoint inhibitor. In medical record billing data of 50 patients with NMOSD, 30 with MS, and 21 with MOGAD, the algorithm had 82.0% sensitivity and 70.6% specificity. When applied to healthcare claims data, demographic and clinical features of the identified cohort were similar to known demographics of NMOSD. ConclusionsThis clinically derived algorithm performed well in medical records. When tested in healthcare claims, demographics and clinical characteristics were consistent with previous clinical findings. This algorithm will enable a more accurate estimation of NMOSD disease burden using insurance claims datasets.

Combined Central and Peripheral Demyelination (CCPD) Associated with MOG Antibodies: Report of Four New Cases and Narrative Review of the Literature

Background/Objectives: Myelin oligodendrocyte glycoprotein (MOG) is exclusively expressed in the central nervous system (CNS) and is found on the outer surface of oligodendrocytes. Antibodies to MOG are associated with CNS demyelination, whereas peripheral nervous system (PNS) demyelination is seldom reported to be related to MOG-IgG. Methods: The database of patients seen in our neurological academic center was searched for MOG-IgG seropositivity and concomitant demyelinating polyneuropathy. For the purpose of the review, in March 2024, we searched for case reports and case series in the following databases: PubMed, Scopus, Cochrane, and ScienceDirect. Inclusion criteria were MOG-IgG seropositivity and demyelinating polyneuropathy. Exclusion criteria were type of publication other than case reports and case series, unconfirmed diagnosis of demyelinating polyneuropathy, and other diseases causing demyelination in either the CNS or PNS. Critical appraisal of the selected case reports and case series was realized by JBI. Results: Four new cases were identified with MOG-IgG and confirmed demyelinating polyneuropathy. This review identified 22 cases that have been published since 2018. Clinical, imaging, neurophysiological, and immunological characteristics, as well as treatment options and outcomes are presented and compared to those of other cases with combined central and peripheral demyelination (CCPD). Conclusions: The pathogenetic mechanism is unclear; thus, different hypotheses are discussed. New case reporting and large cohort studies will help further the exploration of the underlying mechanism and guide more effective therapeutic interventions.

Myelin oligodendrocyte glycoprotein antibody-associated disease

Myelin oligodendrocyte glycoprotein antibody-associated disease

Identification of brain-enriched proteins in CSF as biomarkers of relapsing remitting multiple sclerosis

BackgroundMultiple sclerosis (MS) is a clinically and biologically heterogenous disease with currently unpredictable progression and relapse. After the development and success of neurofilament as a cerebrospinal fluid (CSF) biomarker, there is reinvigorated interest in identifying other markers of or contributors to disease. The objective of this study is to probe the predictive potential of a panel of brain-enriched proteins on MS disease progression and subtype.MethodsThis study includes 40 individuals with MS and 14 headache controls. The MS cohort consists of 20 relapsing remitting (RR) and 20 primary progressive (PP) patients. The CSF of all individuals was analyzed for 63 brain enriched proteins using a method of liquid-chromatography tandem mass spectrometry. Wilcoxon rank sum test, Kruskal-Wallis one-way ANOVA, logistic regression, and Pearson correlation were used to refine the list of candidates by comparing relative protein concentrations as well as relation to known imaging and molecular biomarkers.ResultsWe report 30 proteins with some relevance to disease, clinical subtype, or severity. Strikingly, we observed widespread protein depletion in the disease CSF as compared to control. We identified numerous markers of relapsing disease, including KLK6 (kallikrein 6, OR = 0.367, p < 0.05), which may be driven by active disease as defined by MRI enhancing lesions. Other oligodendrocyte-enriched proteins also appeared at reduced levels in relapsing disease, namely CNDP1 (carnosine dipeptidase 1), LINGO1 (leucine rich repeat and Immunoglobin-like domain-containing protein 1), MAG (myelin associated glycoprotein), and MOG (myelin oligodendrocyte glycoprotein). Finally, we identified three proteins—CNDP1, APLP1 (amyloid beta precursor like protein 1), and OLFM1 (olfactomedin 1)—that were statistically different in relapsing vs. progressive disease raising the potential for use as an early biomarker to discriminate clinical subtype.ConclusionsWe illustrate the utility of targeted mass spectrometry in generating potential targets for future biomarker studies and highlight reductions in brain-enriched proteins as markers of the relapsing remitting disease stage.

Neurotoxin-induced animal model of multiple sclerosis: Molecular mechanism focus

Background: Neurotoxins can alter the central nervous system. They induce severe clinical symptoms such as encephalopathy, convulsions, muscle paralysis, and respiratory failure. Hence, the neurotoxin can mimic human central nervous system disorders such as Multiple Sclerosis (MS) to study pathophysiology and drugs of development. Objective: This mini-review compared the neurotoxins for mimicking MS in animal models. Method: This study was a narrative review using the scientific electronic databases Scopus, PubMed, and Google Scholar. All related articles by keywords animal models, multiple sclerosis, and neurotoxins were collected by YP and BW. All authors contributed to manuscript development. Result: Cuprizone, ethidium bromide, lysolecithin, Myelin Oligodendrocyte Glycoprotein (MOG), and Myelin Essential Protein (MBP) are neurotoxins for MS animal models. Cuprizone is particularly relevant for use in studies addressing toxic mechanisms of the demyelination process and studies of therapeutic interventions. Ethidium bromide causes spinal cord demyelination with distinctive features in the oligodendrocytes and astrocytes. However, it is a carcinogen agent. Lysolecithin is suitable for old animal models because the duration for remyelination is relatively longer than others. MOG and MBP are preferable to resemble MS pathophysiology in humans. Conclusion: MOG and MBP are appropriate for generating animal multiple sclerosis models for further in vivo experiments.

Rituximab Therapy for Immune-Mediated Neurological Diseases: Our Experience at a Tertiary Care Centre.

Rituximab (RTX) is a monoclonal anti-CD20 chimeric antibody that inhibits B cell activity. However, it is an appealing substitute for traditional immunomodulatory drugs as a swiftly acting, targeted therapy with mounting evidence of efficacy and tolerance in numerous neuroinflammatory conditions. We discuss the scientific evidence for the use of RTX in neurological illnesses, as well as the dose, safety, and other practical elements of prescription. This study aims to assess and correlate the effects of RTX on immune-mediated neurological disorders. The primary objective of this study is to determine the outcomes in patients treated with RTX for the following conditions: myasthenia gravis (MG), autoimmune encephalitis, multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), myelin oligodendrocyte glycoprotein antibody disease (MOGAD), immune-mediated peripheral neuropathy, and inflammatory muscle disease. The secondary objective is to assess adverse drug reactions in patients treated with RTX. This is a prospective observational study conducted at a tertiary care centre. The data were analyzed for the period from May 2022 to May 2024. Approval was obtained from the institutional ethics committee before commencing the study, andwritten informed consent was obtained from all patients. A total of 56 patients were included in the study. The distribution of patients according to diseases is as follows: MG (17), MS (11), NMOSD (10), MOGAD (7), immune-mediated peripheral neuropathy (6), autoimmune encephalitis (3), and inflammatory muscle disease (2). However, one patient was lost to follow-up in the autoimmune encephalitis group. All patients experienced improvements in symptoms, and no relapse episodes have been reported except for one patient who had a relapse in the inflammatory muscle disease group. During the infusion process, some adverse drug reactions, such as chills and rigors, were observed, and two patients experienced major side effects, such as Pott's disease and cryptogenic organizing pneumonia. Nevertheless, overall, rituximab shows promise as an off-labelimmunosuppressive treatment for the aforementioned neurological immune-mediated diseases.

Long-term outcomes of ADEM-like and tumefactive presentations of CNS demyelination: a case-comparison analysis

A minority of initial multiple sclerosis (MS) presentations clinically or radiologically resemble other central nervous system (CNS) pathologies, acute disseminated encephalomyelitis (ADEM) or tumefactive demyelination (atypical demyelination presentations). With the aim of better defining the long-term outcomes of this group we have performed a retrospective cohort comparison of atypical demyelination versus ‘typical’ MS presentations. Twenty-seven cases with atypical presentations (both first and subsequent demyelinating events) were identified and compared with typical MS cases. Disease features analysed included relapse rates, disability severity, whole brain and lesion volumes, lesion number and distribution. Atypical cases represented 3.9% of all MS cases. There was considerable overlap in the magnetic resonance imaging (MRI) features of ADEM-like and tumefactive demyelination cases. ADEM-like cases tended to be younger but not significantly so. Atypical cases showed a trend towards higher peak expanded disability severity score (EDSS) score at the time of their atypical presentation. Motor, cranial nerve, cerebellar, cerebral and multifocal presentations were all more common in atypical cases, and less likely to present with optic neuritis. Cerebrospinal fluid (CSF) white cell counts were higher in atypical cases (p = 0.002). One atypical case was associated with peripheral blood myelin oligodendrocyte glycoprotein (MOG) antibodies, but subsequent clinical and radiological course was in keeping with MS. There was no difference in long-term clinical outcomes including annualised relapse rates (ARR), brain volume, lesion numbers or lesion distributions. Atypical demyelination cases were more likely to receive high potency disease modifying therapy early in the course of their illness. Despite the severity of initial illness, our cohort analysis suggests that atypical demyelination presentations do not confer a higher risk of long-term adverse outcomes.

Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD) Initially Presenting as Septic Meningoencephalitis in a 16-Year-Old Male.

We describe a case of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) in a 16-year-old patient who initially presented with clinical features of septic meningoencephalitis. This case outlines the importance of considering a diagnosis of MOGAD in patients who fail to improve with appropriate antimicrobial therapy or show a positive clinical response to glucocorticoids (often used in treatment of meningococcal meningitis). We emphasise the importance of recognising that an infectious prodrome can precede MOGAD. A 16-year-old male was admitted with vomiting, fever, headache, photophobia and altered mental state. He was treated for meningoencephalitis with initial clinical improvement. Lumbar puncture findings were suggestive of viral meningoencephalitis. During admission the patient went through several periods of transient clinical and biochemical improvement, alternating with periods of symptomatic relapse. On day 17 of admission, he was transferred to a tertiary centre for suspected autoimmune disseminated meningoencephalitis (ADEM) and two days later, he suffered a catastrophic neurological decline with new dysarthria, dysphagia, aphasia, horizontal nystagmus and facial paralysis. He made a remarkable neurological recovery after commencing treatment with IV immunoglobulin, IV methylprednisolone and plasma exchange, with complete resolution of symptoms. MOGAD can run a variable course and present soon after a central nervous system infection, making the diagnosis more challenging. Nonetheless, patients can achieve a full neurological recovery with early recognition, diagnosis and treatment of this rare entity. Autoimmune encephalitis can be preceded by an infectious prodrome which makes the diagnosis more challenging.Autoimmune encephalitis can run a subacute and fluctuating course with transient periods of symptomatic improvement preceding a rapid neurological decline.Glucocorticoids often used in treatment of patients with meningococcal meningitis may lead to transient symptomatic improvement in patients with autoimmune encephalitis, masking the diagnosis.MRI findings of demyelination in autoimmune encephalitis may lag behind clinical symptoms by days to weeks.

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

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

A comparative study of hypothalamic involvement in patients with myelin oligodendrocyte glycoprotein antibody-associated disease, neuromyelitis optica spectrum disorder, and multiple sclerosis.

We aimed to characterize hypothalamic involvement in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and compare it with neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS). A retrospective study was performed to identify hypothalamic lesions in patients diagnosed with MOGAD, NMOSD, or MS from January 2013 to May 2020. The demographic, clinical, and radiological features were recorded. Hypothalamic dysfunction and prognosis were assessed through physical examination, biochemical testing, sleep monitoring, and magnetic resonance imaging. Hypothalamic lesions were observed in seven of 96 patients (7.3%) with MOGAD, 34 of 536 (6.3%) with NMOSD, and 16 of 356 (4.5%) with MS (p = 0.407). The time from disease onset to development of hypothalamic lesions was shortest in MOGAD (12 months). The frequency of bilateral hypothalamic lesions was the lowest in MOGAD (p = 0.008). The rate of hypothalamic dysfunction in MOGAD was 28.6%, which was lower than that in NMOSD (70.6%) but greater than that in MS patients (18.8%; p = 0.095 and p = 0.349, respectively). Hypothalamic dysfunction in MOGAD manifests as hypothalamic-pituitary-adrenal axis dysfunction and hypersomnia. The proportion of complete regression of hypothalamic lesions in MOGAD (100%) was much greater than that in NMOSD (41.7%) and MS patients (18.2%; p = 0.007 and p = 0.001, respectively). An improvement in hypothalamic dysfunction was observed in all MOGAD patients after immunotherapy. MOGAD patients have a relatively high incidence of asymptomatic hypothalamic lesions. The overall prognosis of patients with hypothalamic involvement is good in MOGAD, as the lesions completely resolve, and dysfunction improves after immunotherapy.

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