Myelin injury without astrocytopathy in neuroinflammatory disorders with MOG antibodies

Kaneko, Kimihiko; Sato, Douglas Kazutoshi; Nakashima, Ichiro; Nishiyama, Shuhei; Tanaka, Satoru; Marignier, Romain; Hyun, Jae‐Won; Oliveira, Letycia Maria Lopes de; Reindl, Markus; Seifert-Held, Thomas; Sepúlveda, María; Siritho, Sasitorn; Waters, Patrick; Kurosawa, Kazuhiro; Akaishi, Tetsuya; Kuroda, Hiroshi; Misu, Tatsuro; Prayoonwiwat, Naraporn; Berger, Thomas; Sáiz, Albert; Kim, Ho Jin; Nomura, Kyoichi; Callegaro, Dagoberto; Fujihara, Kazuo; Akiyama, Masashi

doi:10.1136/jnnp-2015-312676

Cited by 93 publications

(83 citation statements)

References 5 publications

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“…A small number of brain‐biopsied cases with MOG‐IgG‐positive tumefactive brain lesions have been reported, and the pathological findings are characterized by so‐called MS type II pathology (active inflammatory demyelination with deposition of immunoglobulins and complements) . Our studies on cell damage markers in the CSF during acute exacerbations showed that regardless of the clinical phenotypes, the CSF MBP level was high, whereas the CSF‐glial fibrillary acidic protein level was not elevated at all, clearly showing that MOG‐IgG‐positive disease is an inflammatory demyelinating disease, even if the clinical phenotype is NMO …”

Section: Pathology and Pathomechanismsmentioning

confidence: 65%

“…41,42 Our studies on cell damage markers in the CSF during acute exacerbations showed that regardless of the clinical phenotypes, the CSF MBP level was high, whereas the CSF-glial fibrillary acidic protein level was not elevated at all, clearly showing that MOG-IgG-positive disease is an inflammatory demyelinating disease, even if the clinical phenotype is NMO. 43,44 Data on immunological abnormalities in MOG-IgG-positive disease are insufficient, but T helper cell 17, B cells and neutrophil-related cytokines seem to be upregulated in the CSF during the acute phase of the disease. 45 Although pathogenicity of MOG-IgG has not been clarified, there have been some reports supporting it.…”

Section: Pathology and Pathomechanismsmentioning

confidence: 99%

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Myelin oligodendrocyte glycoprotein immunoglobulin G‐associated disease: An overview

Fujihara

Sato

Nakashima

et al. 2018

Clinical & Exp Neuroim

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Myelin oligodendrocyte glycoprotein (MOG) is localized at the outermost layer of the myelin sheath and is accessible for autoantibodies. Although experimental autoimmune encephalitis induced with MOG immunization has been studied for 30 years, the results of previous reports on MOG immunoglobulin G (IgG) detection with enzyme-linked immunosorbent assay and Western blot are confusing. However, after the development of human MOG-transfected cell-based assay to detect conformational-sensitive MOG-IgG, unique groups of patients have been found seropositive, and MOG-IgG-associated disease has become a hot topic in clinical neuroimmunology. Currently, the clinical spectrum of MOG-IgG-associated disease includes idiopathic optic neuritis, acute disseminated encephalomyelitis, encephalitides (brainstem and cerebral cortical), idiopathic myelitis, atypical multiple sclerosis, aquaporin-4 IgG-negative neuromyelitis optica spectrum disorders and others. MOG-IgG-associated disease occurs in both children and adults, and the female:male ratio is almost 1:1. Pleocytosis in the cerebrospinal fluids during acute exacerbation is often seen, but oligoclonal IgG bands are usually negative. T helper cell 17, B cells and neutrophil-related cytokines appear to be upregulated intrathecally. The pathology of acute lesions is characterized by active inflammation demyelination with deposition of immunoglobulins and complements. Just like aquaporin 4 IgG-positive neuromyelitis optica spectrum disorders, some disease-modifying drugs for multiple sclerosis seem to be inefficacious in MOG-IgG-associated disease, and chronic immunosuppression is required to prevent relapse, especially in patients persistently positive for MOG-IgG. Our understanding of this newly recognized disease remains insufficient, and the progress of research is much expected.

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Section: Pathology and Pathomechanismsmentioning

confidence: 65%

Section: Pathology and Pathomechanismsmentioning

confidence: 99%

Myelin oligodendrocyte glycoprotein immunoglobulin G‐associated disease: An overview

Fujihara

Sato

Nakashima

et al. 2018

Clinical & Exp Neuroim

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“…35,36 Moreover, we recently reported high CSF-MBP levels without elevated CSF glial fibrillary acidic protein levels, an astrocytic damage marker, in MOG antibody–positive patients. 37 These findings suggest that MOG antibody may directly contribute to inflammatory demyelination in anti–myelin antibody–associated CNS diseases. However, in 3 of our MOG antibody–positive cases whose CSF-MBP levels were measured during the acute phase, there was no elevation in CSF-MBP despite the extensive cortical involvement and CSF pleocytosis.…”

Section: Discussionmentioning

confidence: 88%

MOG antibody–positive, benign, unilateral, cerebral cortical encephalitis with epilepsy

Ogawa¹,

Nakashima

Takahashi

et al. 2017

Neurol Neuroimmunol Neuroinflamm

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375

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Objective:To describe the features of adult patients with benign, unilateral cerebral cortical encephalitis positive for the myelin oligodendrocyte glycoprotein (MOG) antibody.Methods:In this retrospective, cross-sectional study, after we encountered an index case of MOG antibody–positive unilateral cortical encephalitis with epileptic seizure, we tested for MOG antibody using our in-house, cell-based assay in a cohort of 24 consecutive adult patients with steroid-responsive encephalitis of unknown etiology seen at Tohoku University Hospital (2008–2014). We then analyzed the findings in MOG antibody–positive cases.Results:Three more patients, as well as the index case, were MOG antibody–positive, and all were adult men (median age 37 years, range 23–39 years). The main symptom was generalized epileptic seizure with or without abnormal behavior or consciousness disturbance. Two patients also developed unilateral benign optic neuritis (before or after seizure). In all patients, brain MRI demonstrated unilateral cerebral cortical fluid-attenuated inversion recovery hyperintense lesions, which were swollen and corresponded to hyperperfusion on SPECT. CSF studies showed moderate mononuclear pleocytosis with some polymorphonuclear cells and mildly elevated total protein levels, but myelin basic protein was not elevated. A screening of encephalitis-associated autoantibodies, including aquaporin-4, glutamate receptor, and voltage-gated potassium channel antibodies, was negative. All patients received antiepilepsy drugs and fully recovered after high-dose methylprednisolone, and the unilateral cortical MRI lesions subsequently disappeared. No patient experienced relapse.Conclusions:These MOG antibody–positive cases represent unique benign unilateral cortical encephalitis with epileptic seizure. The pathology may be autoimmune, although the findings differ from MOG antibody–associated demyelination and Rasmussen and other known immune-mediated encephalitides.

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“…In addition, only patients who were seropositive were enrolled because we did not perform the test of myelin oligodendrocyte glycoprotein (MOG) autoimmunity, a distinct spectrum differentiated from seronegative NMOSD, which can limit the generalization of our data to seronegative NMOSD. [41, 42] Finally, other factors including socioeconomic variables that can affect fatigue or QOL,[43] were not investigated in this study, although we completed the comprehensive investigations of possible contributing factors of QOL (fatigue, sleep quality, depression, and pain), in remission.…”

Section: Discussionmentioning

confidence: 99%

Fatigue in patients with neuromyelitis optica spectrum disorder and its impact on quality of life

et al. 2017

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Fatigue is a prevalent symptom and major burden in neuroimmunological diseases. In neuromyelitis optica spectrum disorder (NMOSD), a severe autoimmune central nervous system (CNS) inflammatory disease with autoantibodies reactive to aquaporin-4, there are few reports about fatigue and quality of life (QOL). We aimed to evaluate the severity of fatigue and its relationship with QOL in patients with NMOSD. We prospectively studied patients with NMOSD who were in remission and seropositive for anti-aquaporin-4 antibody, and they were divided into 2 groups based on the presence of fatigue assessed using the Functional Assessment of Chronic Illness Therapy-fatigue score. Sleep quality, depression, pain, and QOL were also evaluated. A total of 35 patients were enrolled (mean age, 46.5 ± 14.1 years; female: male = 29:6), and the median Expanded Disability Status Scale (EDSS) score was 2.0 (range, 0 to 8.0). The patients with fatigue (N = 25, 71.4%) had poorer sleep quality and more severe depression than those without fatigue (p = 0.009 and p = 0.001). Both the physical and mental QOL scores were lower in patients with fatigue than in those without fatigue (p = 0.033 and p = 0.004). Multiple linear regression analyses showed that the degree of fatigue with EDSS score and pain were independent predictors of physical aspects of QOL (B = 0.382, p = 0.001), whereas depression was the only predictor of the mental components of QOL (B = -0.845, p = <0.001). Fatigue is a common symptom and an important predictor of QOL in patients with NMOSD.

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Myelin injury without astrocytopathy in neuroinflammatory disorders with MOG antibodies

Cited by 93 publications

References 5 publications

Myelin oligodendrocyte glycoprotein immunoglobulin G‐associated disease: An overview

Myelin oligodendrocyte glycoprotein immunoglobulin G‐associated disease: An overview

MOG antibody–positive, benign, unilateral, cerebral cortical encephalitis with epilepsy

Fatigue in patients with neuromyelitis optica spectrum disorder and its impact on quality of life

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