Brain histopathological study and prognosis in <scp>MOG</scp> antibody‐associated demyelinating pseudotumor

Shu, Yaqing; Long, Youming; Wang, Shisi; Hu, Wanming; Zhou, Jian; Xu, Huiming; Chen, Chen; Ou, Yang-Mei; Liu, Zhengqi; Lau, Alexander; Yu, Xinhua; Kermode, Allan G.; Qiu, Wei

doi:10.1002/acn3.712

Cited by 24 publications

(26 citation statements)

References 11 publications

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“…Our findings support most prior MOGAD pathology cases which similarly reported no AQP4 loss [12]. However, two MOGAD pathology cases reported variable AQP4 loss [66] and a single case with dual MOG-IgG and AQP4-IgG seropositivity also reported AQP4 loss [13].…”

Section: Discussionsupporting

confidence: 89%

The pathology of central nervous system inflammatory demyelinating disease accompanying myelin oligodendrocyte glycoprotein autoantibody

et al. 2020

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We sought to define the pathological features of myelin oligodendrocyte glycoprotein (MOG) antibody associated disorders (MOGAD) in an archival autopsy/biopsy cohort. We histopathologically analyzed 2 autopsies and 22 brain biopsies from patients with CNS inflammatory demyelinating diseases seropositive for MOG-antibody by live-cell-based-assay with full length MOG in its conformational form. MOGAD autopsies (ages 52 and 67) demonstrate the full spectrum of histopathological features observed within the 22 brain biopsies (median age, 10 years; range, 1-66; 56% female). Clinical, radiologic, and laboratory characteristics and course (78% relapsing) are consistent with MOGAD. MOGAD pathology is dominated by coexistence of both perivenous and confluent white matter demyelination, with an over-representation of intracortical demyelinated lesions compared to typical MS. Radially expanding confluent slowly expanding smoldering lesions in the white matter as seen in MS, are not present. A CD4+ T-cell dominated inflammatory reaction with granulocytic infiltration predominates. Complement deposition is present in all active white matter lesions, but a preferential loss of MOG is not observed. AQP4 is preserved, with absence of dystrophic astrocytes, and variable oligodendrocyte and axonal destruction. MOGAD is pathologically distinguished from AQP4-IgG seropositive NMOSD, but shares some overlapping features with both MS and ADEM, suggesting a transitional pathology. Complement deposition in the absence of selective MOG protein loss suggest humoral mechanisms are involved, however argue against endocytic internalization of the MOG antigen. Parallels with MOG-EAE suggest MOG may be an amplification factor that augments CNS demyelination, possibly via complement mediated destruction of myelin or ADCC phagocytosis.

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Section: Discussionsupporting

confidence: 89%

The pathology of central nervous system inflammatory demyelinating disease accompanying myelin oligodendrocyte glycoprotein autoantibody

et al. 2020

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“…30,31 Unlike AQP4-Ab NMOSD, MOG-Ab disease is not an astrocytopathy and glial fibrillary acidic protein is not elevated in the CSF. 32 Although accurate quantification of astrocytes has not been performed in MOG-Ab disease in view of the small number of cases with histopathology, it is likely that extent of gliosis as seen in MS (resulting from ongoing chronic neuroinflammation) does not occur in MOG-Ab disease, 33 and this may explain the reduced levels of myoinositol with respect to MS. This needs further pathologic verification.…”

Section: Discussionmentioning

confidence: 99%

Classifying the antibody-negative NMO syndromes

Yeo

Probert

Juryńczyk

et al. 2019

Neurol Neuroimmunol Neuroinflamm

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ObjectiveTo determine whether unsupervised principal component analysis (PCA) of comprehensive clinico-radiologic data can identify phenotypic subgroups within antibody-negative patients with overlapping features of multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSDs), and to validate the phenotypic classifications using high-resolution nuclear magnetic resonance (NMR) plasma metabolomics with inference to underlying pathologies.MethodsForty-one antibody-negative patients were recruited from the Oxford NMO Service. Thirty-six clinico-radiologic parameters, focusing on features known to distinguish NMOSD and MS, were collected to build an unbiased PCA model identifying phenotypic subgroups within antibody-negative patients. Metabolomics data from patients with relapsing-remitting MS (RRMS) (n = 34) and antibody-positive NMOSD (Ab-NMOSD) (aquaporin-4 antibody n = 54, myelin oligodendrocyte glycoprotein antibody n = 20) were used to identify discriminatory plasma metabolites separating RRMS and Ab-NMOSD.ResultsPCA of the 36 clinico-radiologic parameters revealed 3 phenotypic subgroups within antibody-negative patients: an MS-like subgroup, an NMOSD-like subgroup, and a low brain lesion subgroup. Supervised multivariate analysis of metabolomics data from patients with RRMS and Ab-NMOSD identified myoinositol and formate as the most discriminatory metabolites (both higher in RRMS). Within antibody-negative patients, myoinositol and formate were significantly higher in the MS-like vs NMOSD-like subgroup; myoinositol (mean [SD], 0.0023 [0.0002] vs 0.0019 [0.0003] arbitrary units [AU]; p = 0.041); formate (0.0027 [0.0006] vs 0.0019 [0.0006] AU; p = 0.010) (AU).ConclusionsPCA identifies 3 phenotypic subgroups within antibody-negative patients and that the metabolite discriminators of RRMS and Ab-NMOSD suggest that these groupings have some pathogenic meaning. Thus, the identified clinico-radiologic discriminators may provide useful diagnostic clues when seeing antibody-negative patients in the clinic.

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“…A systematic literature search identified a limited number of pathology studies of MOGAD cases who presented with large demyelinating lesions. All patients were positive for MOG antibodies confirmed by cell-based assays and their diagnoses varied, including ADEM-like presentation (50,86), tumefactive MS-like lesions (87)(88)(89), NMOSD-like phenotype (90,91), and large white matter lesions with MOG+ antibodies (92). Less than 10 cases found in the literature strictly presented with TDLs.…”

Section: Tdls In the Spectrum Of Mog-related Demyelinationmentioning

confidence: 97%

Immunopathology of Tumefactive Demyelinating Lesions-From Idiopathic to Drug-Related Cases

et al. 2022

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Tumefactive demyelinating lesions (TDL) represent a diagnostic dilemma for clinicians, and in rare atypical cases a collaboration of a neuroradiologist, a neurologist, and a neuropathologist is warranted for accurate diagnosis. Recent advances in neuropathology have shown that TDL represent an umbrella under which many different diagnostic entities can be responsible. TDL can emerge not only as part of the spectrum of classic multiple sclerosis (MS) but also can represent an idiopathic monophasic disease, a relapsing disease with recurrent TDL, or could be part of the myelin oligodendrocyte glycoprotein (MOG)- and aquaporin-4 (AQP4)-associated disease. TDL can appear during the MS disease course, and increasingly cases arise showing an association with specific drug interventions. Although TDL share common features with classic MS lesions, they display some unique features, such as extensive and widespread demyelination, massive and intense parenchymal infiltration by macrophages along with lymphocytes (mainly T but also B cells), dystrophic changes in astrocytes, and the presence of Creutzfeldt cells. This article reviews the existent literature regarding the neuropathological findings of tumefactive demyelination in various disease processes to better facilitate the identification of disease signatures. Recent developments in immunopathology of central nervous system disease suggest that specific pathological immune features (type of demyelination, infiltrating cell type distribution, specific astrocyte pathology and complement deposition) can differentiate tumefactive lesions arising as part of MS, MOG-associated disease, and AQP4 antibody-positive neuromyelitis optica spectrum disorder. Lessons from immunopathology will help us not only stratify these lesions in disease entities but also to better organize treatment strategies. Improved advances in tissue biomarkers should pave the way for prompt and accurate diagnosis of TDL leading to better outcomes for patients.

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Brain histopathological study and prognosis in MOG antibody‐associated demyelinating pseudotumor

Cited by 24 publications

References 11 publications

The pathology of central nervous system inflammatory demyelinating disease accompanying myelin oligodendrocyte glycoprotein autoantibody

The pathology of central nervous system inflammatory demyelinating disease accompanying myelin oligodendrocyte glycoprotein autoantibody

Classifying the antibody-negative NMO syndromes

Immunopathology of Tumefactive Demyelinating Lesions-From Idiopathic to Drug-Related Cases

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