Leptomeningeal Enhancement, a Phenotype of Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease With Caudate Nucleus Involvement: A Case Report and Literature Review.
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SUBMITTER: Kim S
PROVIDER: S-EPMC9982174 | biostudies-literature | 2023 Mar
REPOSITORIES: biostudies-literature
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Leptomeningeal Enhancement, a Phenotype of Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease With Caudate Nucleus Involvement: A Case Report and Literature Review.
Kim Seondeuk S Kim Seoyeon S Jang Yoonhyuk Y Chu Kon K
Journal of clinical neurology (Seoul, Korea) 20230301 2
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Project description:Background 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. Methods 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. Results 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). Conclusion 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.
| S-EPMC10318903 | biostudies-literature
Project description:IntroductionOptic neuritis (ON) is a common neuro-ophthalmological condition and remains a significant indicator of inflammatory conditions affecting the central nervous system. Varying etiologies exist for ON including multiple sclerosis, NMOSD, and MOGAD. Differential diagnosis is achieved using both radiological and serological testing. MRI characteristics of MOG-ON include T2 hypersensitive lesions, nerve swelling, and gadolinium enhancement of the affected optic nerve. While acute MOG-ON usually presents with optic nerve enhancement, recognizing atypical presentations is critical in accurate diagnosis and effective management.Case presentationWe herein present a case of a 67-year-old woman presenting with sudden decrease in vision in the right eye. The patient underwent a 3T MRI of the orbits and brain 5 days post vision loss which returned normal right optic nerve appearance at presentation (no edema, enhancement or increased T2 signal). Further serological testing of the MOG antibody returned positive (1:100) while APQ4 antibodies were negative. This yielded a diagnosis of MOG-IgG-ON. Subsequently, the patient was treated with IV methylprednisolone 1 g daily for 5 days followed by prednisone 1 mg/kg, resulting in marked improvement in vision.ConclusionThis case highlights the complexity involved in diagnosing ON, especially in the context of MOGAD. Absence of optic nerve enhancement in this patient calls attention to the possibility of subclinical inflammation and/or detectable enhancement later in clinical course. Our findings, along with existing literature, highlight the need for clinicians to consider atypical MRI presentations in MOG-ON cases. Recognizing that normal MRI does not exclude MOG-ON is important for optimizing diagnostic accuracy and effective treatment interventions.
| S-EPMC11703545 | biostudies-literature
Project description:Myelin oligodendrocyte glycoprotein antibody-associated disease is an immune-mediated demyelinating disease of the central nervous system that is present in both adults and children. The most common clinical manifestations are optic neuritis, myelitis, acute disseminated encephalomyelitis, and brainstem syndrome. Cerebral cortical encephalitis (CCE) is a rare clinical phenotype of myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD), which usually begins with seizures, headaches, and fever, and may be misdiagnosed as viral encephalitis in the early stages. Herein, we report two typical MOG antibody (MOG-Ab)-positive patients presenting with CCE, both of whom presented with headache, fever, seizures, and who recovered completely after immunotherapy. In addition, we performed a systematic review of the present literature from the perspectives of population characteristics, clinical symptoms, MRI abnormalities, treatments, and prognosis. Among the patients reported in 25 articles, 33 met our inclusion criteria, with the age of onset ranging from 4 to 52 years. Most of the patients had seizures, headache, fever, and unilateral cortical lesions on brain MRI. For acute CCE, 30 patients were treated with high-dose intravenous methylprednisolone, and the symptoms of most patients were completely relieved after immunotherapy. This study reported our experience and lessons learned in the diagnosis and treatment of MOG-Ab-positive CCE and provides a systematic review of the literature to analyse this rare clinical phenotype.
| S-EPMC8762331 | biostudies-literature
Project description:Cortical T2-weighted fluid-attenuated inversion recovery (FLAIR)-hyperintense lesions in anti-myelin oligodendrocyte glycoprotein (MOG)-associated encephalitis with seizures (FLAMES) are mostly unilateral and rarely spread to the bilateral cortex and meninges. We describe a case of MOG-immunoglobulin G (IgG) associated disorder (MOGAD) in a 39-year-old male with bilateral meningo-cortical involvement. The patient was hospitalized for epilepsy, fever, and headache. The initial MRI revealed abnormalities in the sulci of the bilateral frontal, temporal, and parietal lobes. He was considered to have infectious encephalitis and given empiric antibiotic and antiviral therapy, which were ineffective. His condition rapidly improved after the patient was switched to high-dose immunoglobulin therapy. No tests supported the presence of central nervous system (CNS) infections or autoimmune encephalitis. The second and third MRI scans showed reduced but still clearly observable meningo-cortical lesions. The patient was discharged without a definite diagnosis, but reported severe left vision impairment 25 days later. A fourth MRI showed signs typical of demyelinating CNS disease in addition to the original meningo-cortical lesions. The patient's symptoms were initially relieved by low-dose corticosteroid therapy, but they eventually returned, and he was re-admitted. The original lesions were diminished on the fifth MRI scan, but new lesions had developed in the deep white matter. A positive cell-based assay for MOG-IgG in serum confirmed MOGAD. The patient received high-dose corticosteroid treatment followed by an oral methylprednisolone taper, and his visual acuity gradually improved. The sixth and final MRI showed substantial decreases in the original lesions without new lesion formation. This unique case presents the complete diagnosis and treatment process for MOGAD with bilateral meningo-cortical involvement and may provide a reference for prompt diagnosis.
| S-EPMC8160241 | biostudies-literature
Project description: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.
| S-EPMC10011114 | biostudies-literature
Project description:Myelin oligodendrocyte glycoprotein-associated disorders (MOGAD) are autoimmune diseases that often manifest in the context of infections. They can also arise less commonly following vaccination but even more rarely in a paraneoplastic context. Herein, we will report a patient presenting with subacute inflammatory myelopathy after a fourth dose of the mRNA COVID-19 vaccine. Concurrently, a diagnosis of MOGAD was made with a metastatic abdominal seminoma. The patient was acutely treated with high-dose steroids followed by plasma exchange therapy and was subsequently started on a chemotherapy regimen for the underlying germ cell tumor. The patient had a complete resolution of neurological symptoms upon the last follow-up. Overall, 72 cases of COVID-19 vaccination associated with MOGAD were analyzed (median age at onset 39 years old; female to male ratio = 1.2:1). All cases occurred in adults except for an adolescent, with the majority occurring after vaccination with ChAdOx nCoV-19 (87%), and an average temporal profile between vaccination and symptom onset of 19 days. There were no reported cases after the third or fourth doses, and most patients were diagnosed with new-onset MOGAD after their first vaccine (76%). Although COVID-19 vaccination could be a potential causality, there are significant discrepancies between the reported cases and this patient, alongside the unlikely causality assessment obtained with the Bradford Hill criteria. Vaccination could unmask potential pre-existing autoimmune diseases, such as in this patient, where myelopathy was most likely part of a paraneoplastic syndrome associated with a newly diagnosed seminoma.
| S-EPMC11559457 | biostudies-literature
Project description:Multiple sclerosis is a chronic disease of the central nervous system (CNS) characterized by inflammation, demyelination, and axonal loss. The immunopathogenesis of demyelination in multiple sclerosis involves an autoantibody response to myelin oligodendrocyte glycoprotein (MOG), a type I transmembrane protein located at the surface of CNS myelin. Here we present the crystal structures of the extracellular domain of MOG (MOGIgd) at 1.45-A resolution and the complex of MOGIgd with the antigen-binding fragment (Fab) of the MOG-specific demyelinating monoclonal antibody 8-18C5 at 3.0-A resolution. MOGIgd adopts an IgV like fold with the A'GFCC'C" sheet harboring a cavity similar to the one used by the costimulatory molecule B7-2 to bind its ligand CTLA4. The antibody 8-18C5 binds to three loops located at the membrane-distal side of MOG with a surprisingly dominant contribution made by MOG residues 101-108 containing a strained loop that forms the upper edge of the putative ligand binding site. The sequence R101DHSYQEE108 is unique for MOG, whereas large parts of the remaining sequence are conserved in potentially tolerogenic MOG homologues expressed outside the immuno-privileged environment of the CNS. Strikingly, the only sequence identical to DHSYQEE was found in a Chlamydia trachomatis protein of unknown function, raising the possibility that Chlamydia infections may play a role in the MOG-specific autoimmune response in man. Our data provide the structural basis for the development of diagnostic and therapeutic strategies targeting the pathogenic autoantibody response to MOG.
| S-EPMC170938 | biostudies-literature
Project description:ImportanceMyelin oligodendrocyte glycoprotein-IgG1-associated disorder (MOGAD) is a distinct central nervous system-demyelinating disease. Positive results on MOG-IgG1 testing by live cell-based assays can confirm a MOGAD diagnosis, but false-positive results may occur.ObjectiveTo determine the positive predictive value (PPV) of MOG-IgG1 testing in a tertiary referral center.Design, setting, and participantsThis diagnostic study was conducted over 2 years, from January 1, 2018, through December 31, 2019. Patients in the Mayo Clinic who were consecutively tested for MOG-IgG1 by live cell-based flow cytometry during their diagnostic workup were included. Patients without research authorization were excluded.Main outcomes and measuresMedical records of patients who were tested were initially reviewed by 2 investigators blinded to MOG-IgG1 serostatus, and pretest probability was classified as high or low (suggestive of MOGAD or not). Testing of MOG-IgG1 used a live-cell fluorescence-activated cell-sorting assay; an IgG binding index value of 2.5 or more with an end titer of 1:20 or more was considered positive. Cases positive for MOG-IgG1 were independently designated by 2 neurologists as true-positive or false-positive results at last follow-up, based on current international recommendations on diagnosis or identification of alternative diagnoses; consensus was reached for cases in which disagreement existed.ResultsA total of 1617 patients were tested, and 357 were excluded. Among 1260 included patients tested over 2 years, the median (range) age at testing was 46 (0-98) years, and 792 patients were female (62.9%). A total of 92 of 1260 (7.3%) were positive for MOG-IgG1. Twenty-six results (28%) were designated as false positive by the 2 raters, with an overall agreement on 91 of 92 cases (99%) for true and false positivity. Alternative diagnoses included multiple sclerosis (n = 11), infarction (n = 3), B12 deficiency (n = 2), neoplasia (n = 2), genetically confirmed adrenomyeloneuropathy (n = 1), and other conditions (n = 7). The overall PPV (number of true-positive results/total positive results) was 72% (95% CI, 62%-80%) and titer dependent (PPVs: 1:1000, 100%; 1:100, 82%; 1:20-40, 51%). The median titer was higher with true-positive results (1:100 [range, 1:20-1:10000]) than false-positive results (1:40 [range, 1:20-1:100]; P < .001). The PPV was higher for children (94% [95% CI, 72%-99%]) vs adults (67% [95% CI, 56%-77%]) and patients with high pretest probability (85% [95% CI, 76%-92%]) vs low pretest probability (12% [95% CI, 3%-34%]). The specificity of MOG-IgG1 testing was 97.8%.Conclusions and relevanceThis study confirms MOG-IgG1 as a highly specific biomarker for MOGAD, but when using a cutoff of 1:20, it has a low PPV of 72%. Caution is advised in the interpretation of low titers among patients with atypical phenotypes, because ordering MOG-IgG1 in low pretest probability situations will increase the proportion of false-positive results.
| S-EPMC8077043 | biostudies-literature
Project description:ObjectivesGlobal brain volume changes in patients with myelin oligodendrocyte glycoprotein antibody-associated disease compared with healthy controls (HC) could be revealed by magnetic resonance imaging, but specific atrophy patterns of cortical structures and relation to cognitive impairment are not yet comprehensively known. Thus, we aimed to investigate cortical thickness differences in patients with myelin oligodendrocyte glycoprotein antibody-associated disease compared with HC.Methods3-Tesla brain magnetic resonance imaging was performed in 23 patients with myelin oligodendrocyte glycoprotein antibody-associated disease and 49 HC for voxel-wise group comparisons and neuropsychological testing in patients. Surface-based morphometry with region of interest-based surface analysis and region of interest-based extraction of cortical thickness was performed in patients compared with HC and in patient subgroups with and without cognitive impairment.ResultsComparing patients with myelin oligodendrocyte glycoprotein antibody-associated disease with HC, exploratory surface-based morphometry demonstrated cortical volume reduction in pericalcarine and lingual cortical regions. Region of interest-based surface analysis specified reduced cortical thickness in the adjacent pericalcarine and orbitofrontal regions in myelin oligodendrocyte glycoprotein antibody-associated disease, as well as reduced temporal cortical thickness in patients with cognitive impairment (n = 10). Patients without cognitive impairment (n = 13) showed only circumscribed cortical brain volume loss compared with HC in the pericalcarine region.InterpretationIn conclusion, cortical atrophy in myelin oligodendrocyte glycoprotein antibody-associated disease was characterized by cortical thickness reduction in the adjacent pericalcarine and orbitofrontal regions, with a tendency of temporal thickness reduction in cognitively impaired patients.
| S-EPMC11330211 | biostudies-literature
Project description:BackgroundThe autoantibody to myelin oligodendrocyte glycoprotein (MOG), a component of the central nervous system myelin, has been identified in a subset of demyelinating diseases. However, there is no convincing evidence to support the direct pathogenic contribution of this autoantibody.ObjectiveTo elucidate the role of anti-MOG autoantibodies in human demyelinating disorders, we assessed the effect of autoantibodies on MOG-expressing cells.MethodsMammalian cells expressing the human MOG protein reacted with human anti-MOG autoantibodies in the presence or absence of complement. Sera from 86 patients and 11 healthy sera were used. We analyzed anti-MOG antibody titers, IgG subclass, and their cytotoxic ability in sera from patients with various neurological diseases. Membrane attack complex (MAC) formation was examined by detection of complement C9 or C9neo with western blot or flow cytometry.ResultsAmong 86 patients, 40 were determined to be MOG-IgG-positive and 46 were negative. Anti-MOG-positive sera, but not -negative sera, caused cell death in MOG-expressing cells. This cytotoxic effect was disappeared after heat inactivation of sera. Importantly, anti-MOG IgG and externally added complement were necessary for sufficient cytotoxic effects. Anti-MOG autoantibodies were histologically colocalized with complement and formed a membrane attack complex consisting of anti-MOG IgG and complement factors.ConclusionThe human MOG antibody specifically killed MOG-expressing cells in vitro in the presence of externally added complement. Membrane attack complexes were formed on the cells, indicating that this autoantibody activated complement-mediated cytotoxicity. Further studies in larger numbers of patients are needed to characterize the role of complement in MOGAD.
| S-EPMC9930155 | biostudies-literature