Deciphering anti-MOG IgG antibodies: Clinical and radiological spectrum, and comparison of antibody detection assays

Tzartos, John; Karagiorgou, Katerina; Tzanetakos, Dimitrios; Breza, Marianthi; Evangelopoulos, Maria-Eleftheria; Pelidou, Sygkliti-Henrietta; Bakirtzis, Christos; Nikolaidis, Ioannis; Notas, Konstantinos; Chroni, Elisabeth; Markakis, Ioannis; Grigoriadis, Nikolaos; Anagnostouli, Maria; Orologas, Anastasios; Parisis, Dimitrios; Karapanayiotides, Theodoros; Papadimitriou, Dimitra; Kostadima, Vasiliki; Elloul, John; Xidakis, Iosif; Maris, Thomas G.; Zisimopoulou, Paraskevi; Tzartos, Socrates J.; Kilidireas, Constantinos

doi:10.1016/j.jns.2020.116673

Cited by 12 publications

(16 citation statements)

References 35 publications

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“…Two of these studies 23 , 26 were prospective observational studies, while the remaining nine being retrospective studies. 16 – 22 , 24 , 25 Three of these studies 18 , 24 , 26 focused on adults, three studies 19 , 20 , 23 on children, and the remaining five studies 16 , 17 , 21 , 22 , 25 on both adults and children. The quality score of each study were assessed by AHRQ checklist, indicating all included studies were identified as being high quality as shown in Table 1 .…”

Section: Resultsmentioning

confidence: 99%

“…In 4 of 11 included studies, 18 , 21 , 22 , 26 a varied proportion of patients had received other immunotherapies prior to RTX, MMF, or AZA, while patients received RTX, MMF, and AZA as first immunosuppressants to prevent relapses in the other studies. 16 , 17 , 19 , 20 , 23 , 24 , 25 With regard to concomitant maintenance corticosteroids, some patients received concomitant corticosteroids in two studies, 17 , 21 meanwhile, patients in seven studies 18 – 20 , 22 – 25 did not, and data were not available in the remaining two studies. 16 , 26 A certain proportion of patients received concomitant intravenous immune globulins or plasma exchange in three studies, 17 , 19 , 21 while patients in other studies 16 , 18 , 20 , 22 – 26 did not.…”

Section: Resultsmentioning

confidence: 99%

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Efficacy and safety of immunosuppressive therapy in myelin oligodendrocyte glycoprotein antibody–associated disease: a systematic review and meta-analysis

Lai

Zhang

Cai

et al. 2021

Ther Adv Neurol Disord

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Background: A considerable number of patients with myelin oligodendrocyte glycoprotein antibody–associated disease (MOGAD) will experience a relapse, but the effect of maintenance therapies on re-attack rates is currently unknown. Objective: To investigate the efficacy and safety of immunosuppressive therapy for preventing disease relapses in patients with MOGAD, including rituximab (RTX), mycophenolate mofetil (MMF), and azathioprine (AZA). Methods: English-language studies published prior to August 31, 2020, were searched in the NCBI (PubMed), ISI Web of Science, and the Cochrane Library databases. Patient characteristics, treatment regimens, outcome measures, and adverse effects were retrieved. Results: We enrolled 11 studies in the final meta-analysis, including 346 patients with MOGAD. RTX therapy was demonstrated to result in reduced mean annualized relapse rate (ARR) by 1.35 (95% confidence interval (CI): 0.85–1.85) and reduced mean Expanded Disability Status Scale score by 0.80 (95% CI: 0.53–1.08) in patients with MOGAD. MMF therapy was associated with the mean ARR decreasing by 0.83 (95% CI: 0.31–1.35), and AZA was related to the mean ARR decreasing by 1.71 (95% CI: 0.83–2.58). The reported discontinuation rates of RTX, MMF, and AZA therapy due to adverse effects were 3/197 (1.52%), 3/39 (7.69%), and 4/37 (10.81%), respectively. Conclusion: The study provided evidence to support the efficacy of RTX, MMF, and AZA on the preventive treatment in patients with MOGAD. However, large randomized controlled trials are still needed in the future.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Efficacy and safety of immunosuppressive therapy in myelin oligodendrocyte glycoprotein antibody–associated disease: a systematic review and meta-analysis

Lai

Zhang

Cai

et al. 2021

Ther Adv Neurol Disord

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“…Nevertheless, TDL might occur in patients with other atypical demyelinating syndromes such as Acute Disseminated Encephalomyelitis (ADEM), AQ4 IgG seropositive or MOG-seropositive Neuromyelitis Optica Spectrum Disorders (NMOSD), as well as other neuroinflammatory disorders, such as Neurosarcoidosis or Behçet's disease (4). Of note, the spectrum of MOG antibodyassociated encephalomyelitis the last years has expanded to involve cases with TDL and ADEM-like presentation, clinical presentations that could fit to our patient history (11,16). Nevertheless, our patient was negative for both MOG and AQ4 autoantibodies.…”

Section: Discussionmentioning

confidence: 99%

“…Spine MRI was normal. Evaluation of serological parameters, including AQ4 (Euroimmun, Lübeck, Germany) and MOG abs (live cell-based assay), was negative, except for the presence of serum monoclonal IgA (k) type paraprotein ( 11 ). Bone marrow examination revealed findings compatible with MGUS (less that ~5% were CD138+ plasma cells).…”

Section: Case Presentationmentioning

confidence: 99%

Recurrent Fulminant Tumefactive Demyelination With Marburg-Like Features and Atypical Presentation: Therapeutic Dilemmas and Review of Literature

et al. 2020

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Atypical forms of demyelinating diseases with tumor-like lesions and aggressive course represent a diagnostic and therapeutic challenge for neurologists. Herein, we describe a 50-year-old woman presenting with subacute onset of left hemiparesis, memory difficulties and headache. Brain MRI revealed a tumefactive right frontal-parietal lesion with perilesional edema, mass effect and homogenous post-contrast enhancement, along with other small atypical lesions in the white-matter. Brain biopsy of cerebral lesion ruled out lymphoma or any other neoplastic process and patient placed on corticosteroids with complete clinical/radiological remission. Two years after disease initiation, there was disease exacerbation with reappearance of the tumor-like mass. The patient initially responded to high doses of corticosteroids but soon became resistant. Plasma-exchange sessions were not able to limit disease burden. Resistance to therapeutic efforts led to a second biopsy that showed perivascular demyelination, predominantly consisting of macrophages, with a small number of T and B lymphocytes, and the presence of reactive astrocytes, typical of Creutzfeldt-Peters cells. The patient received high doses of cyclophosphamide with substantial clinical/radiological response but relapsed after 7-intensive cycles. She received 4-weekly doses of rituximab with disease exacerbation and brainstem involvement. She eventually died with complicated pneumonia. We present a very rare case of recurrent tumefactive demyelinating lesions, with atypical tumor-like characteristics, with initial response to corticosteroids and cyclophosphamide, but subsequent development of drug-resistance and unexpected exacerbation upon rituximab administration. Our clinical case raises therapeutic dilemmas and points to the need for immediate and appropriate immunosuppression in difficult to treat tumefactive CNS lesions with Marburg-like features.

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“… 1 The predominant subtype IgG1 antibodies to MOG initiate CNS demyelinating process via T cell-mediated cytotoxicity and B cell-mediated immune responses with complement activation. 1 , 13 As part of VGKC complex, Caspr2 is located in the juxtaparanodal region of myelinated fibers in both CNS and peripheral nervous system (PNS), and participates in synapse synthesis and construction of central neural network. 2 , 3 , 14 , 15 Non-complement-activating IgG4 antibodies dominate in anti-Caspr2 antibody-associated autoimmune encephalitis.…”

Section: Discussionmentioning

confidence: 99%

Possible coexistence of MOG-IgG-associated disease and anti-Caspr2 antibody-associated autoimmune encephalitis: a first case report

Liu

Bai²,

et al. 2020

Ther Adv Neurol Disord

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Myelin oligodendrocyte glycoprotein antibody-associated disease has been proposed as a separate inflammatory demyelinating disease of the central nervous system (CNS) since the discovery of pathogenic antibodies against myelin oligodendrocyte glycoprotein (MOG-IgG). Antibodies targeting contactin-associated protein-like 2 (Caspr2), a component of voltage-gated potassium channel (VGKC) complex, have been documented to be associated with a novel autoimmune synaptic encephalitis with a low incidence. Herein, we reported an adult female with initial presentation of decreased vision in the right eye and subsequent episodes of neuropsychiatric disturbance including hypersomnia, agitation, apatheia, and memory impairment. Magnetic resonance imaging (MRI) revealed multiple lesions scattered in brain, brainstem, and cervical and thoracic spinal cord, showing hypointensity on T1-weighted images, hyperintensity on T2-weighted and fluid attenuated inversion recovery (FLAIR) images. Heterogenous patchy or ring-like enhancement was observed in the majority of lesions. The detection of low-titer MOG-IgG exclusively in cerebrospinal fluid (CSF; titer, 1:1) and Caspr2-IgG in both serum and CSF (titers, 1:100 and 1:1) led to a possible diagnosis of coexisting MOG-IgG-associated disease (MOGAD) and anti-Caspr2 antibody-associated autoimmune encephalitis. The patient was treated with immunosuppressive agents including corticosteroids and immunoglobulin, and achieved a sustained remission. To the best of our knowledge, this is the first report on the possible coexistence of MOGAD and anti-Caspr2 antibody-associated autoimmune encephalitis, which advocates for the recommendation of a broad spectrum screening for antibodies against well-defined CNS antigens in suspected patients with autoimmune-mediated diseases of the CNS.

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Deciphering anti-MOG IgG antibodies: Clinical and radiological spectrum, and comparison of antibody detection assays

Cited by 12 publications

References 35 publications

Efficacy and safety of immunosuppressive therapy in myelin oligodendrocyte glycoprotein antibody–associated disease: a systematic review and meta-analysis

Efficacy and safety of immunosuppressive therapy in myelin oligodendrocyte glycoprotein antibody–associated disease: a systematic review and meta-analysis

Recurrent Fulminant Tumefactive Demyelination With Marburg-Like Features and Atypical Presentation: Therapeutic Dilemmas and Review of Literature

Possible coexistence of MOG-IgG-associated disease and anti-Caspr2 antibody-associated autoimmune encephalitis: a first case report

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