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May 2017; 4 (3) Clinical/Scientific NotesOpen Access

ADEM-like presentation, anti-MOG antibodies, and MS pathology: TWO case reports

Peter Körtvélyessy, Markus Breu, Marc Pawlitzki, Imke Metz, Hans-Jochen Heinze, Mike Matzke, Christian Mawrin, Paulus Rommer, Gabor G. Kovacs, Christian Mitter, Markus Reindl, Wolfgang Brück, Klaus-Peter Wandinger, Hans Lassmann, Romana Höftberger, Frank Leypoldt
First published March 14, 2017, DOI: https://doi.org/10.1212/NXI.0000000000000335
Peter Körtvélyessy
From the Department of Neurology (P.K., M.P., H.-J.H., M.M.), Institute of Neuropathology (C.M.), University Hospital Magdeburg; German Center for Neurodegenerative Diseases (DZNE) Magdeburg (P.K.), Germany; Institute of Neurology (M.B., G.G.K., R.H.), Department of Pediatric and Adolescent Medicine (M.B.), Department of Neurology (P.R.), Division of Neuroradiology and Musculoskeletal Radiology (C.M.), Department of Biomedical Imaging and Image-guided Therapy, and Department of Neuroimmunology (H.L.), Center for Brain Research, Medical University of Vienna, Austria; Department of Neuropathology (I.M., W.B.), University Medical Center Göttingen; Leibniz Institute for Neurobiology (H.-J.H.), Magdeburg; Department of Neurology (M.M.), MEDIAN NRZ Flechtingen, Germany; Clinical Department of Neurology (M.R.), Innsbruck Medical University, Austria; Neuroimmunology (K.-P.W., F.L.), Institute of Clinical Chemistry, University Hospital Schleswig-Holstein, Kiel/Lübeck; Department of Neurology (K.-P.W.), University Hospital Schleswig-Holstein, Lübeck; and Department of Neurology (F.L.), University Hospital Schleswig-Holstein, Kiel, Germany.
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Markus Breu
From the Department of Neurology (P.K., M.P., H.-J.H., M.M.), Institute of Neuropathology (C.M.), University Hospital Magdeburg; German Center for Neurodegenerative Diseases (DZNE) Magdeburg (P.K.), Germany; Institute of Neurology (M.B., G.G.K., R.H.), Department of Pediatric and Adolescent Medicine (M.B.), Department of Neurology (P.R.), Division of Neuroradiology and Musculoskeletal Radiology (C.M.), Department of Biomedical Imaging and Image-guided Therapy, and Department of Neuroimmunology (H.L.), Center for Brain Research, Medical University of Vienna, Austria; Department of Neuropathology (I.M., W.B.), University Medical Center Göttingen; Leibniz Institute for Neurobiology (H.-J.H.), Magdeburg; Department of Neurology (M.M.), MEDIAN NRZ Flechtingen, Germany; Clinical Department of Neurology (M.R.), Innsbruck Medical University, Austria; Neuroimmunology (K.-P.W., F.L.), Institute of Clinical Chemistry, University Hospital Schleswig-Holstein, Kiel/Lübeck; Department of Neurology (K.-P.W.), University Hospital Schleswig-Holstein, Lübeck; and Department of Neurology (F.L.), University Hospital Schleswig-Holstein, Kiel, Germany.
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Marc Pawlitzki
From the Department of Neurology (P.K., M.P., H.-J.H., M.M.), Institute of Neuropathology (C.M.), University Hospital Magdeburg; German Center for Neurodegenerative Diseases (DZNE) Magdeburg (P.K.), Germany; Institute of Neurology (M.B., G.G.K., R.H.), Department of Pediatric and Adolescent Medicine (M.B.), Department of Neurology (P.R.), Division of Neuroradiology and Musculoskeletal Radiology (C.M.), Department of Biomedical Imaging and Image-guided Therapy, and Department of Neuroimmunology (H.L.), Center for Brain Research, Medical University of Vienna, Austria; Department of Neuropathology (I.M., W.B.), University Medical Center Göttingen; Leibniz Institute for Neurobiology (H.-J.H.), Magdeburg; Department of Neurology (M.M.), MEDIAN NRZ Flechtingen, Germany; Clinical Department of Neurology (M.R.), Innsbruck Medical University, Austria; Neuroimmunology (K.-P.W., F.L.), Institute of Clinical Chemistry, University Hospital Schleswig-Holstein, Kiel/Lübeck; Department of Neurology (K.-P.W.), University Hospital Schleswig-Holstein, Lübeck; and Department of Neurology (F.L.), University Hospital Schleswig-Holstein, Kiel, Germany.
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Imke Metz
From the Department of Neurology (P.K., M.P., H.-J.H., M.M.), Institute of Neuropathology (C.M.), University Hospital Magdeburg; German Center for Neurodegenerative Diseases (DZNE) Magdeburg (P.K.), Germany; Institute of Neurology (M.B., G.G.K., R.H.), Department of Pediatric and Adolescent Medicine (M.B.), Department of Neurology (P.R.), Division of Neuroradiology and Musculoskeletal Radiology (C.M.), Department of Biomedical Imaging and Image-guided Therapy, and Department of Neuroimmunology (H.L.), Center for Brain Research, Medical University of Vienna, Austria; Department of Neuropathology (I.M., W.B.), University Medical Center Göttingen; Leibniz Institute for Neurobiology (H.-J.H.), Magdeburg; Department of Neurology (M.M.), MEDIAN NRZ Flechtingen, Germany; Clinical Department of Neurology (M.R.), Innsbruck Medical University, Austria; Neuroimmunology (K.-P.W., F.L.), Institute of Clinical Chemistry, University Hospital Schleswig-Holstein, Kiel/Lübeck; Department of Neurology (K.-P.W.), University Hospital Schleswig-Holstein, Lübeck; and Department of Neurology (F.L.), University Hospital Schleswig-Holstein, Kiel, Germany.
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Hans-Jochen Heinze
From the Department of Neurology (P.K., M.P., H.-J.H., M.M.), Institute of Neuropathology (C.M.), University Hospital Magdeburg; German Center for Neurodegenerative Diseases (DZNE) Magdeburg (P.K.), Germany; Institute of Neurology (M.B., G.G.K., R.H.), Department of Pediatric and Adolescent Medicine (M.B.), Department of Neurology (P.R.), Division of Neuroradiology and Musculoskeletal Radiology (C.M.), Department of Biomedical Imaging and Image-guided Therapy, and Department of Neuroimmunology (H.L.), Center for Brain Research, Medical University of Vienna, Austria; Department of Neuropathology (I.M., W.B.), University Medical Center Göttingen; Leibniz Institute for Neurobiology (H.-J.H.), Magdeburg; Department of Neurology (M.M.), MEDIAN NRZ Flechtingen, Germany; Clinical Department of Neurology (M.R.), Innsbruck Medical University, Austria; Neuroimmunology (K.-P.W., F.L.), Institute of Clinical Chemistry, University Hospital Schleswig-Holstein, Kiel/Lübeck; Department of Neurology (K.-P.W.), University Hospital Schleswig-Holstein, Lübeck; and Department of Neurology (F.L.), University Hospital Schleswig-Holstein, Kiel, Germany.
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Mike Matzke
From the Department of Neurology (P.K., M.P., H.-J.H., M.M.), Institute of Neuropathology (C.M.), University Hospital Magdeburg; German Center for Neurodegenerative Diseases (DZNE) Magdeburg (P.K.), Germany; Institute of Neurology (M.B., G.G.K., R.H.), Department of Pediatric and Adolescent Medicine (M.B.), Department of Neurology (P.R.), Division of Neuroradiology and Musculoskeletal Radiology (C.M.), Department of Biomedical Imaging and Image-guided Therapy, and Department of Neuroimmunology (H.L.), Center for Brain Research, Medical University of Vienna, Austria; Department of Neuropathology (I.M., W.B.), University Medical Center Göttingen; Leibniz Institute for Neurobiology (H.-J.H.), Magdeburg; Department of Neurology (M.M.), MEDIAN NRZ Flechtingen, Germany; Clinical Department of Neurology (M.R.), Innsbruck Medical University, Austria; Neuroimmunology (K.-P.W., F.L.), Institute of Clinical Chemistry, University Hospital Schleswig-Holstein, Kiel/Lübeck; Department of Neurology (K.-P.W.), University Hospital Schleswig-Holstein, Lübeck; and Department of Neurology (F.L.), University Hospital Schleswig-Holstein, Kiel, Germany.
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Christian Mawrin
From the Department of Neurology (P.K., M.P., H.-J.H., M.M.), Institute of Neuropathology (C.M.), University Hospital Magdeburg; German Center for Neurodegenerative Diseases (DZNE) Magdeburg (P.K.), Germany; Institute of Neurology (M.B., G.G.K., R.H.), Department of Pediatric and Adolescent Medicine (M.B.), Department of Neurology (P.R.), Division of Neuroradiology and Musculoskeletal Radiology (C.M.), Department of Biomedical Imaging and Image-guided Therapy, and Department of Neuroimmunology (H.L.), Center for Brain Research, Medical University of Vienna, Austria; Department of Neuropathology (I.M., W.B.), University Medical Center Göttingen; Leibniz Institute for Neurobiology (H.-J.H.), Magdeburg; Department of Neurology (M.M.), MEDIAN NRZ Flechtingen, Germany; Clinical Department of Neurology (M.R.), Innsbruck Medical University, Austria; Neuroimmunology (K.-P.W., F.L.), Institute of Clinical Chemistry, University Hospital Schleswig-Holstein, Kiel/Lübeck; Department of Neurology (K.-P.W.), University Hospital Schleswig-Holstein, Lübeck; and Department of Neurology (F.L.), University Hospital Schleswig-Holstein, Kiel, Germany.
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Paulus Rommer
From the Department of Neurology (P.K., M.P., H.-J.H., M.M.), Institute of Neuropathology (C.M.), University Hospital Magdeburg; German Center for Neurodegenerative Diseases (DZNE) Magdeburg (P.K.), Germany; Institute of Neurology (M.B., G.G.K., R.H.), Department of Pediatric and Adolescent Medicine (M.B.), Department of Neurology (P.R.), Division of Neuroradiology and Musculoskeletal Radiology (C.M.), Department of Biomedical Imaging and Image-guided Therapy, and Department of Neuroimmunology (H.L.), Center for Brain Research, Medical University of Vienna, Austria; Department of Neuropathology (I.M., W.B.), University Medical Center Göttingen; Leibniz Institute for Neurobiology (H.-J.H.), Magdeburg; Department of Neurology (M.M.), MEDIAN NRZ Flechtingen, Germany; Clinical Department of Neurology (M.R.), Innsbruck Medical University, Austria; Neuroimmunology (K.-P.W., F.L.), Institute of Clinical Chemistry, University Hospital Schleswig-Holstein, Kiel/Lübeck; Department of Neurology (K.-P.W.), University Hospital Schleswig-Holstein, Lübeck; and Department of Neurology (F.L.), University Hospital Schleswig-Holstein, Kiel, Germany.
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Gabor G. Kovacs
From the Department of Neurology (P.K., M.P., H.-J.H., M.M.), Institute of Neuropathology (C.M.), University Hospital Magdeburg; German Center for Neurodegenerative Diseases (DZNE) Magdeburg (P.K.), Germany; Institute of Neurology (M.B., G.G.K., R.H.), Department of Pediatric and Adolescent Medicine (M.B.), Department of Neurology (P.R.), Division of Neuroradiology and Musculoskeletal Radiology (C.M.), Department of Biomedical Imaging and Image-guided Therapy, and Department of Neuroimmunology (H.L.), Center for Brain Research, Medical University of Vienna, Austria; Department of Neuropathology (I.M., W.B.), University Medical Center Göttingen; Leibniz Institute for Neurobiology (H.-J.H.), Magdeburg; Department of Neurology (M.M.), MEDIAN NRZ Flechtingen, Germany; Clinical Department of Neurology (M.R.), Innsbruck Medical University, Austria; Neuroimmunology (K.-P.W., F.L.), Institute of Clinical Chemistry, University Hospital Schleswig-Holstein, Kiel/Lübeck; Department of Neurology (K.-P.W.), University Hospital Schleswig-Holstein, Lübeck; and Department of Neurology (F.L.), University Hospital Schleswig-Holstein, Kiel, Germany.
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Christian Mitter
From the Department of Neurology (P.K., M.P., H.-J.H., M.M.), Institute of Neuropathology (C.M.), University Hospital Magdeburg; German Center for Neurodegenerative Diseases (DZNE) Magdeburg (P.K.), Germany; Institute of Neurology (M.B., G.G.K., R.H.), Department of Pediatric and Adolescent Medicine (M.B.), Department of Neurology (P.R.), Division of Neuroradiology and Musculoskeletal Radiology (C.M.), Department of Biomedical Imaging and Image-guided Therapy, and Department of Neuroimmunology (H.L.), Center for Brain Research, Medical University of Vienna, Austria; Department of Neuropathology (I.M., W.B.), University Medical Center Göttingen; Leibniz Institute for Neurobiology (H.-J.H.), Magdeburg; Department of Neurology (M.M.), MEDIAN NRZ Flechtingen, Germany; Clinical Department of Neurology (M.R.), Innsbruck Medical University, Austria; Neuroimmunology (K.-P.W., F.L.), Institute of Clinical Chemistry, University Hospital Schleswig-Holstein, Kiel/Lübeck; Department of Neurology (K.-P.W.), University Hospital Schleswig-Holstein, Lübeck; and Department of Neurology (F.L.), University Hospital Schleswig-Holstein, Kiel, Germany.
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Markus Reindl
From the Department of Neurology (P.K., M.P., H.-J.H., M.M.), Institute of Neuropathology (C.M.), University Hospital Magdeburg; German Center for Neurodegenerative Diseases (DZNE) Magdeburg (P.K.), Germany; Institute of Neurology (M.B., G.G.K., R.H.), Department of Pediatric and Adolescent Medicine (M.B.), Department of Neurology (P.R.), Division of Neuroradiology and Musculoskeletal Radiology (C.M.), Department of Biomedical Imaging and Image-guided Therapy, and Department of Neuroimmunology (H.L.), Center for Brain Research, Medical University of Vienna, Austria; Department of Neuropathology (I.M., W.B.), University Medical Center Göttingen; Leibniz Institute for Neurobiology (H.-J.H.), Magdeburg; Department of Neurology (M.M.), MEDIAN NRZ Flechtingen, Germany; Clinical Department of Neurology (M.R.), Innsbruck Medical University, Austria; Neuroimmunology (K.-P.W., F.L.), Institute of Clinical Chemistry, University Hospital Schleswig-Holstein, Kiel/Lübeck; Department of Neurology (K.-P.W.), University Hospital Schleswig-Holstein, Lübeck; and Department of Neurology (F.L.), University Hospital Schleswig-Holstein, Kiel, Germany.
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Wolfgang Brück
From the Department of Neurology (P.K., M.P., H.-J.H., M.M.), Institute of Neuropathology (C.M.), University Hospital Magdeburg; German Center for Neurodegenerative Diseases (DZNE) Magdeburg (P.K.), Germany; Institute of Neurology (M.B., G.G.K., R.H.), Department of Pediatric and Adolescent Medicine (M.B.), Department of Neurology (P.R.), Division of Neuroradiology and Musculoskeletal Radiology (C.M.), Department of Biomedical Imaging and Image-guided Therapy, and Department of Neuroimmunology (H.L.), Center for Brain Research, Medical University of Vienna, Austria; Department of Neuropathology (I.M., W.B.), University Medical Center Göttingen; Leibniz Institute for Neurobiology (H.-J.H.), Magdeburg; Department of Neurology (M.M.), MEDIAN NRZ Flechtingen, Germany; Clinical Department of Neurology (M.R.), Innsbruck Medical University, Austria; Neuroimmunology (K.-P.W., F.L.), Institute of Clinical Chemistry, University Hospital Schleswig-Holstein, Kiel/Lübeck; Department of Neurology (K.-P.W.), University Hospital Schleswig-Holstein, Lübeck; and Department of Neurology (F.L.), University Hospital Schleswig-Holstein, Kiel, Germany.
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Klaus-Peter Wandinger
From the Department of Neurology (P.K., M.P., H.-J.H., M.M.), Institute of Neuropathology (C.M.), University Hospital Magdeburg; German Center for Neurodegenerative Diseases (DZNE) Magdeburg (P.K.), Germany; Institute of Neurology (M.B., G.G.K., R.H.), Department of Pediatric and Adolescent Medicine (M.B.), Department of Neurology (P.R.), Division of Neuroradiology and Musculoskeletal Radiology (C.M.), Department of Biomedical Imaging and Image-guided Therapy, and Department of Neuroimmunology (H.L.), Center for Brain Research, Medical University of Vienna, Austria; Department of Neuropathology (I.M., W.B.), University Medical Center Göttingen; Leibniz Institute for Neurobiology (H.-J.H.), Magdeburg; Department of Neurology (M.M.), MEDIAN NRZ Flechtingen, Germany; Clinical Department of Neurology (M.R.), Innsbruck Medical University, Austria; Neuroimmunology (K.-P.W., F.L.), Institute of Clinical Chemistry, University Hospital Schleswig-Holstein, Kiel/Lübeck; Department of Neurology (K.-P.W.), University Hospital Schleswig-Holstein, Lübeck; and Department of Neurology (F.L.), University Hospital Schleswig-Holstein, Kiel, Germany.
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Hans Lassmann
From the Department of Neurology (P.K., M.P., H.-J.H., M.M.), Institute of Neuropathology (C.M.), University Hospital Magdeburg; German Center for Neurodegenerative Diseases (DZNE) Magdeburg (P.K.), Germany; Institute of Neurology (M.B., G.G.K., R.H.), Department of Pediatric and Adolescent Medicine (M.B.), Department of Neurology (P.R.), Division of Neuroradiology and Musculoskeletal Radiology (C.M.), Department of Biomedical Imaging and Image-guided Therapy, and Department of Neuroimmunology (H.L.), Center for Brain Research, Medical University of Vienna, Austria; Department of Neuropathology (I.M., W.B.), University Medical Center Göttingen; Leibniz Institute for Neurobiology (H.-J.H.), Magdeburg; Department of Neurology (M.M.), MEDIAN NRZ Flechtingen, Germany; Clinical Department of Neurology (M.R.), Innsbruck Medical University, Austria; Neuroimmunology (K.-P.W., F.L.), Institute of Clinical Chemistry, University Hospital Schleswig-Holstein, Kiel/Lübeck; Department of Neurology (K.-P.W.), University Hospital Schleswig-Holstein, Lübeck; and Department of Neurology (F.L.), University Hospital Schleswig-Holstein, Kiel, Germany.
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Romana Höftberger
From the Department of Neurology (P.K., M.P., H.-J.H., M.M.), Institute of Neuropathology (C.M.), University Hospital Magdeburg; German Center for Neurodegenerative Diseases (DZNE) Magdeburg (P.K.), Germany; Institute of Neurology (M.B., G.G.K., R.H.), Department of Pediatric and Adolescent Medicine (M.B.), Department of Neurology (P.R.), Division of Neuroradiology and Musculoskeletal Radiology (C.M.), Department of Biomedical Imaging and Image-guided Therapy, and Department of Neuroimmunology (H.L.), Center for Brain Research, Medical University of Vienna, Austria; Department of Neuropathology (I.M., W.B.), University Medical Center Göttingen; Leibniz Institute for Neurobiology (H.-J.H.), Magdeburg; Department of Neurology (M.M.), MEDIAN NRZ Flechtingen, Germany; Clinical Department of Neurology (M.R.), Innsbruck Medical University, Austria; Neuroimmunology (K.-P.W., F.L.), Institute of Clinical Chemistry, University Hospital Schleswig-Holstein, Kiel/Lübeck; Department of Neurology (K.-P.W.), University Hospital Schleswig-Holstein, Lübeck; and Department of Neurology (F.L.), University Hospital Schleswig-Holstein, Kiel, Germany.
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Frank Leypoldt
From the Department of Neurology (P.K., M.P., H.-J.H., M.M.), Institute of Neuropathology (C.M.), University Hospital Magdeburg; German Center for Neurodegenerative Diseases (DZNE) Magdeburg (P.K.), Germany; Institute of Neurology (M.B., G.G.K., R.H.), Department of Pediatric and Adolescent Medicine (M.B.), Department of Neurology (P.R.), Division of Neuroradiology and Musculoskeletal Radiology (C.M.), Department of Biomedical Imaging and Image-guided Therapy, and Department of Neuroimmunology (H.L.), Center for Brain Research, Medical University of Vienna, Austria; Department of Neuropathology (I.M., W.B.), University Medical Center Göttingen; Leibniz Institute for Neurobiology (H.-J.H.), Magdeburg; Department of Neurology (M.M.), MEDIAN NRZ Flechtingen, Germany; Clinical Department of Neurology (M.R.), Innsbruck Medical University, Austria; Neuroimmunology (K.-P.W., F.L.), Institute of Clinical Chemistry, University Hospital Schleswig-Holstein, Kiel/Lübeck; Department of Neurology (K.-P.W.), University Hospital Schleswig-Holstein, Lübeck; and Department of Neurology (F.L.), University Hospital Schleswig-Holstein, Kiel, Germany.
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Citation
ADEM-like presentation, anti-MOG antibodies, and MS pathology: TWO case reports
Peter Körtvélyessy, Markus Breu, Marc Pawlitzki, Imke Metz, Hans-Jochen Heinze, Mike Matzke, Christian Mawrin, Paulus Rommer, Gabor G. Kovacs, Christian Mitter, Markus Reindl, Wolfgang Brück, Klaus-Peter Wandinger, Hans Lassmann, Romana Höftberger, Frank Leypoldt
Neurol Neuroimmunol Neuroinflamm May 2017, 4 (3) e335; DOI: 10.1212/NXI.0000000000000335

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Acute disseminated encephalomyelitis (ADEM) mostly occurs in children and can be triggered by infections and vaccinations. Recently, 40% of patients with ADEM were found to be seropositive for myelin oligodendrocyte glycoprotein antibodies (MOG-abs).1 Furthermore, a subgroup of adult patients negative for aquaporin-4 antibody fulfilling diagnostic clinical and radiologic criteria for neuromyelitis optica spectrum disorder (NMOSD) harbor high-titer serum MOG-abs.2 We present clinical, serologic, and histopathologic features of 2 adult patients with a clinical diagnosis of ADEM according to the diagnostic criteria3 associated with intrathecal MOG-abs synthesis. MOG-abs were determined by live-cell immunofluorescence on HEK293T cells expressing full-length human MOG-enhanced green fluorescent protein at a starting dilution of 1:20 in serum and 1:2 in CSF using an epifluorescence microscope and end-point titration as previously described.2

Case reports.

Case report 1.

A 49-year-old man developed subacute encephalopathy with bradyphrenia, dysphoria, and anhedonia together with progressive central paresis of the right leg, a sensory level below TH10, myalgia, and deteriorated to tetraparesis despite treatment with aciclovir, ceftriaxone, and methylprednisolone. No preceding infections, vaccinations, or prior neurologic symptoms were reported. MRI showed extensive spinal cord and cerebral lesions (figure 1, A and B, and figure e-1 at Neurology.org/nn). CSF analysis demonstrated pleocytosis (133 white blood cells [WBCs]/μL) and elevated protein (1,572 mg/L) without CSF-restricted oligoclonal IgG. No infectious agents were detected. Brain biopsy performed 4 weeks after the onset of symptoms showed active, confluent demyelination with IgG and complement deposition, perivascular and parenchymal B- and T-cell accumulation, parenchymal macrophage infiltration, and oligodendrocyte apoptosis associated with selective loss of minor myelin proteins consistent with overlapping features of MS patterns II and III (figure 1, C–G). Plasma exchange and intravenous cyclophosphamide led to improvement. No new clinical or radiologic activity was observed on follow-up (17 months).

Figure 1
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Figure 1 Neuropathology of MOG-antibody–associated demyelination

Case 1 (A–G): MRI showed large bilateral hazy, partly Gd-enhancing lesions in the deep white matter and periventricular zone (A, left axial-fluid-attenuated inversion recovery (FLAIR), right Gd-enhanced axial T1) that regressed partially during follow-up (B, axial-FLAIR). Histopathology showed a demyelinating lesion (C, Luxol fast blue) and inflammatory infiltrates mainly composed of CD8-positive T cells (D, CD8; arrow). The lesion showed deposits of activated complement complex C9neo on degenerating fibers and in macrophages (E). In early active demyelinating lesion zones, MOG was still present (F; MOG), while myelin-associated glycoprotein (MAG) was lost (G; MAG). Case 2 (H–N): MRI showed large bilateral hazy lesions in the deep white matter and periventricular zone as well as gadolinium rim-enhancing, well-demarcated lesions in the deep white matter (H, left axial-FLAIR, right Gd-enhanced axial T1) that regressed on follow-up (I, axial-FLAIR). Biopsy of a ring-enhancing lesion revealed a well-demarcated demyelinating lesion (J, Luxol fast blue), T-cell dominated inflammation (K, CD8), and mild perivascular complement deposition (L, C9neo; arrows) reminiscent of MS pattern II. Numerous remyelinating oligodendrocytes were encountered (M, tubulin polymerization promoting protein/p25) that were partly MOG positive (N; MOG; arrows). Magnification: C–G; L–N: ×400; J, K: ×100 (MRIs [A, B] from the Institute of Neuroradiology, Magdeburg, Germany). Further panels are provided in figure e-1. MOG = myelin oligodendrocyte glycoprotein.

Retrospective analysis of the initial CSF and serum confirmed MOG-abs (IgG1, IgG3, and IgM) in the CSF (IgG 1:64, follow-up 17 months later 1:2) and serum (IgG 1:160, follow-up 17 months later 1:40). Initial intrathecal MOG-abs-IgG index was 22.3 (<4, total IgG-CSF 0.143 g/L, serum 8.0 g/L).

Case report 2.

A 34-year-old man presented with aphasia and somnolence followed by hypesthesia and paresis of lower extremities, bladder dysfunction, and ataxia. MRI showed multiple cerebral and spinal lesions (figures 1, H and I and e-1). CSF studies revealed pleocytosis (151 WBCs/μL), elevated protein (1,260 mg/L), and CSF-restricted oligoclonal bands. Biopsy 6 weeks after symptom onset showed a confluent, well-demarcated demyelinating lesion with a rim of parenchymal macrophages, T-cell–dominated inflammation, and mild complement deposition, reminiscent of MS pattern II (figure 1, J–N). The patient responded well to treatment with methylprednisolone, IV immunoglobulin (IVIG), and plasma exchange. Three-month follow-up showed regression of MRI lesions. CSF-restricted oligoclonal bands were still present. Last follow-up 9 months after the onset did not reveal any new clinical or radiologic activity.

Retrospective serum and CSF analyses confirmed IgG and IgM MOG-abs (initial serum 1:80, CSF 1:16; 3-month follow-up serum <1:40, CSF <1:2). Initial intrathecal MOG-abs-IgG index was 32.4 (<4, total IgG-CSF 0.073 g/L, serum 1.2 g/L).

Discussion.

We report 2 adult patients with a subacute, multifocal clinical presentation with encephalopathy and MRI features fulfilling clinical diagnostic criteria of ADEM,3 who both had (1) an MS-like histopathology on brain biopsy and (2) intrathecal MOG-abs synthesis.

Pathologically, ADEM is distinct from MS with minor perivascular demyelination in ADEM vs confluent plaque–like demyelination in MS while both conditions share perivascular inflammation. Neuropathologic reports of MOG-abs–associated demyelination are scarce and show MS typical confluent demyelination with astrocyte preservation in a patient with a clinical syndrome of NMOSD,4 MS pattern II–like pathology in a patient with a clinically isolated syndrome,5 a patient fulfilling criteria for relapsing MS,6 and an overlap of pathologic MS and NMOSD features in a patient clinically classified as ADEM, who also had anti–aquaporin-4 antibodies.7

Our cases imply that, although clinically and radiologically presenting as ADEM-like syndrome, MOG-abs–associated demyelinating disorders could pathologically resemble MS.

MOG-abs are increasingly recognized in adult patients with inflammatory CNS demyelination with a yet-to-be-defined spectrum encompassing NMOSD, ADEM, and uni- or bilateral isolated optic neuritis (ON).1 They are considered as highly sensitive and specific when tested with appropriate methods using live (unfixed) cell-based assays. MOG-abs are more consistently detected in the serum than in the CSF, and intrathecal MOG-abs synthesis is unusual.2 While CSF MOG-abs in children with ADEM are unusual, future systematic examination of adults with multifocal demyelinating CNS syndromes with MOG-abs will hopefully elucidate, whether our observation of intrathecal MOG-abs synthesis is a coincidental or causal association. Our observations (1) indicate that MOG-abs–associated inflammatory demyelination independent of clinical presentation histopathologically resembles MS and (2) should encourage clinicians to test for MOG-abs in inflammatory CNS diseases suggestive of ADEM, ON, or NMOSD in the serum and CSF using appropriate test methods.

Footnotes

  • ↵* These authors contributed equally to this work as co-first authors.

  • ↵‡ These authors contributed equally to this work as co-last authors.

  • Supplemental data at Neurology.org/nn

  • Author contributions: Péter Körtvélyessy and Markus Breu have access to all the data and take responsibility for the data, accuracy of the data analysis, the conduct of the research design and conceptualization of the study and analysis and interpretation of the data, and drafting of the manuscript for intellectual content. Marc Pawlitzki: design and conceptualization of the study and revising the manuscript for intellectual content. Imke Metz: accuracy of the data analysis, the conduct of the research design, analysis and interpretation of the data, and drafting of the manuscript for intellectual content. Mike Matzke, Hans-Jochen Heinze, and Christian Mawrin: design and conceptualization of the study and revising the manuscript for intellectual content. Paulus Rommer, Gabor G. Kovacs, and Christian Mitter: accuracy of the data analysis and revising the manuscript for intellectual content. Hans Lassmann. Wolfgang Brück, Klaus-Peter Wandinger, and Markus Reindl: accuracy of the data analysis, the conduct of the research design analysis and interpretation of the data, and drafting of the manuscript for intellectual content. Romana Höftberger and Frank Leypoldt have access to all the data and takes responsibility for the data, accuracy of the data analysis, the conduct of the research design and conceptualization of the study and analysis and interpretation of the data, and drafting of the manuscript for intellectual content.

  • Study funding: This study was supported by a research grant from the “Medizinisch-Wissenschaftlicher Fonds des Bürgermeisters der Bundeshauptstadt Wien, Project 15022,” the “Jubiläumsfonds der Österreichischen Nationalbank, Project 16919,” and the Austrian Federal Ministry of Science and Economy (grant BIG WIG MS).

  • Disclosure: P. Körtvelyessy received travel funding from Eisai gGmbH. M. Breu reports no disclosures. M. Pawlitzki served on the scientific advisory board for Novartis and received travel funding from Novartis. I. Metz served on the advisory board for Roche; received travel funding and/or speaker honoraria from BiogenIdec, Bayer Healthcare, TEVA, Serono, Novartis, and Genzyme; and received research support from BiogenIdec and German Ministry for Education and Research. H.-J. Heinze served on the scientific advisory board for UKE Hamburg Eppendorf, Hertie Institute for Clinical Brain Research, and Neuro-Nielsen; served on the editorial board for Frontiers in Human Neuroscience; is vice-speaker for German Centre for Neurodegenerative Diseases; and received research support from Deutsche Forschungs Gemeinschaft, DFG, BMBF, Bundesministerium für Bildung und Forschung, SFB 779, and Excellence initiative of the state Saxony-Anhalt. M. Matzke received travel funding and speaker honoraria from Bayer-Schering, Merck Serono, Novartis, Sanofi-Aventis, Biogen, and TEVA; received research support from Novartis and Merck Serono. C. Mawrin reports no disclosures. P. Rommer consulted for Teva and received speaker honoraria from Merck and Roche. G.G. Kovacs served on the scientific advisory board for Gedeon Richter Plc. Pharmaceutical Company; is on the editorial board for Acta Neuropathologica, Neuropathology and Applied Neurobiology and Clinical Neuropathology; holds a patent for Anti-alpha-synuclein; receives publishing royalties from Cambridge University Press; received research support from Federal Ministry of Health, FP7 EU Project Develage. C. Mitter reports no disclosures. M. Reindl is an academic editor for PLoS One, The University Hospital, and Medical University of Innsbruck (Austria, Markus Reindl); receives payments for antibody assays (NMDAR, AQP4, and other autoantibodies) and for MOG and AQP4 antibody validation experiments organized by Euroimmun (Luebeck, Germany). W. Brück served on the advisory board for Genzyme, Novartis, Biogen, and Teva; received speaker honoraria from Teva, Sanofi, Genzyme, Novartis, Merck Serono, Biogen, Roche, and Bayer; is on the editorial board for Acta Neuropathologica, Therapeutic Advances in Neurological Disorders, Multiple Sclerosis International and Neuropathology, and Applied Neurobiology; received research support from Teva Pharma, Novartis, Biogen, Genzyme, German Research Foundation, German Ministry for Education and Research, Tschira Foundation, and German Multiple Sclerosis Foundation; and was an expert witness for Teva. K.-P. Wandinger reports no disclosures. H. Lassmann received travel funding and speaker honoraria from BiogenIdec, Novartis, Roche, and Teva; is on the editorial board for journals in the fields of Neurology and Neuroscience; has consulted for BiogenIdec and AMGEN; and received research support from Austrian Science Fund and European Union PITN. R. Höftberger reports no disclosures. F. Leypoldt served on the scientific advisory board for Roche; received travel funding and/or speaker honoraria from Grifols, Teva, Biogen, Fresenius, and Bayer; and does commercial antibody testing service for 20% of his time. Go to Neurology.org/nn for full disclosure forms. The Article Processing Charge was paid by the authors.

  • Received November 13, 2016.
  • Accepted in final form January 3, 2017.
  • Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology

This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

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