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March 2019; 6 (2) ArticleOpen Access

Cranial nerve involvement in patients with MOG antibody–associated disease

Alvaro Cobo-Calvo, Xavier Ayrignac, Philippe Kerschen, Philippe Horellou, Francois Cotton, Pierre Labauge, Sandra Vukusic, Kumaran Deiva, Ché Serguera, Romain Marignier
First published February 1, 2019, DOI: https://doi.org/10.1212/NXI.0000000000000543
Alvaro Cobo-Calvo
From the Service de neurologie (A.C.-C., S.V., R.M.), sclérose en plaques, pathologies de la myéline et neuroinflammation and Centre de référence pour les maladies inflammatoires rares du cerveau et de la moelle (MIRCEM)– Hôpital Neurologique Pierre Wertheimer Hospices Civils de Lyon, France; Lyon Neuroscience Research Center (A.C.-C., R.M.), U1028 INSERM, UMR5292 CNRS, FLUID Team, Lyon, France; Service de sclérose en plaques (X.A., P.L.), Hôpital Universitaire de Montpellier, France; Service de Neurologie (P.K.), Centre hospitalier de Luxembourg; Inserm (P.H.), U 1184, Center for Immunology of Viral Infections and Autoimmune Diseases, Université Paris-Sud 11, CEA, DSV/iMETI, Division of Immuno-Virology, IDMIT, Faculté de médecine, Le Kremlin-Bicêtre Cedex, France; Service de Radiologie (F.C.), Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Pierre-Bénite, France; Université Claude Bernard Lyon 1 (F.C., S.V., R.M.), F-69100 Villeurbanne, France; Lyon's Neuroscience Research Center (S.V.), Observatoire Français de la Sclérose en Plaques, INSERM 1028 et CNRS UMR5292, Lyon, France; Service de neurologie pédiatrique (K.D.), Centre de référence pour les maladies inflammatoires rares du cerveau et de la moelle, Le Kremlin-Bicêtre, France; and INSERM US27 MIRCen (C.S.), CEA, Fontenay-aux-Roses, France.
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Xavier Ayrignac
From the Service de neurologie (A.C.-C., S.V., R.M.), sclérose en plaques, pathologies de la myéline et neuroinflammation and Centre de référence pour les maladies inflammatoires rares du cerveau et de la moelle (MIRCEM)– Hôpital Neurologique Pierre Wertheimer Hospices Civils de Lyon, France; Lyon Neuroscience Research Center (A.C.-C., R.M.), U1028 INSERM, UMR5292 CNRS, FLUID Team, Lyon, France; Service de sclérose en plaques (X.A., P.L.), Hôpital Universitaire de Montpellier, France; Service de Neurologie (P.K.), Centre hospitalier de Luxembourg; Inserm (P.H.), U 1184, Center for Immunology of Viral Infections and Autoimmune Diseases, Université Paris-Sud 11, CEA, DSV/iMETI, Division of Immuno-Virology, IDMIT, Faculté de médecine, Le Kremlin-Bicêtre Cedex, France; Service de Radiologie (F.C.), Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Pierre-Bénite, France; Université Claude Bernard Lyon 1 (F.C., S.V., R.M.), F-69100 Villeurbanne, France; Lyon's Neuroscience Research Center (S.V.), Observatoire Français de la Sclérose en Plaques, INSERM 1028 et CNRS UMR5292, Lyon, France; Service de neurologie pédiatrique (K.D.), Centre de référence pour les maladies inflammatoires rares du cerveau et de la moelle, Le Kremlin-Bicêtre, France; and INSERM US27 MIRCen (C.S.), CEA, Fontenay-aux-Roses, France.
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Philippe Kerschen
From the Service de neurologie (A.C.-C., S.V., R.M.), sclérose en plaques, pathologies de la myéline et neuroinflammation and Centre de référence pour les maladies inflammatoires rares du cerveau et de la moelle (MIRCEM)– Hôpital Neurologique Pierre Wertheimer Hospices Civils de Lyon, France; Lyon Neuroscience Research Center (A.C.-C., R.M.), U1028 INSERM, UMR5292 CNRS, FLUID Team, Lyon, France; Service de sclérose en plaques (X.A., P.L.), Hôpital Universitaire de Montpellier, France; Service de Neurologie (P.K.), Centre hospitalier de Luxembourg; Inserm (P.H.), U 1184, Center for Immunology of Viral Infections and Autoimmune Diseases, Université Paris-Sud 11, CEA, DSV/iMETI, Division of Immuno-Virology, IDMIT, Faculté de médecine, Le Kremlin-Bicêtre Cedex, France; Service de Radiologie (F.C.), Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Pierre-Bénite, France; Université Claude Bernard Lyon 1 (F.C., S.V., R.M.), F-69100 Villeurbanne, France; Lyon's Neuroscience Research Center (S.V.), Observatoire Français de la Sclérose en Plaques, INSERM 1028 et CNRS UMR5292, Lyon, France; Service de neurologie pédiatrique (K.D.), Centre de référence pour les maladies inflammatoires rares du cerveau et de la moelle, Le Kremlin-Bicêtre, France; and INSERM US27 MIRCen (C.S.), CEA, Fontenay-aux-Roses, France.
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Philippe Horellou
From the Service de neurologie (A.C.-C., S.V., R.M.), sclérose en plaques, pathologies de la myéline et neuroinflammation and Centre de référence pour les maladies inflammatoires rares du cerveau et de la moelle (MIRCEM)– Hôpital Neurologique Pierre Wertheimer Hospices Civils de Lyon, France; Lyon Neuroscience Research Center (A.C.-C., R.M.), U1028 INSERM, UMR5292 CNRS, FLUID Team, Lyon, France; Service de sclérose en plaques (X.A., P.L.), Hôpital Universitaire de Montpellier, France; Service de Neurologie (P.K.), Centre hospitalier de Luxembourg; Inserm (P.H.), U 1184, Center for Immunology of Viral Infections and Autoimmune Diseases, Université Paris-Sud 11, CEA, DSV/iMETI, Division of Immuno-Virology, IDMIT, Faculté de médecine, Le Kremlin-Bicêtre Cedex, France; Service de Radiologie (F.C.), Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Pierre-Bénite, France; Université Claude Bernard Lyon 1 (F.C., S.V., R.M.), F-69100 Villeurbanne, France; Lyon's Neuroscience Research Center (S.V.), Observatoire Français de la Sclérose en Plaques, INSERM 1028 et CNRS UMR5292, Lyon, France; Service de neurologie pédiatrique (K.D.), Centre de référence pour les maladies inflammatoires rares du cerveau et de la moelle, Le Kremlin-Bicêtre, France; and INSERM US27 MIRCen (C.S.), CEA, Fontenay-aux-Roses, France.
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Francois Cotton
From the Service de neurologie (A.C.-C., S.V., R.M.), sclérose en plaques, pathologies de la myéline et neuroinflammation and Centre de référence pour les maladies inflammatoires rares du cerveau et de la moelle (MIRCEM)– Hôpital Neurologique Pierre Wertheimer Hospices Civils de Lyon, France; Lyon Neuroscience Research Center (A.C.-C., R.M.), U1028 INSERM, UMR5292 CNRS, FLUID Team, Lyon, France; Service de sclérose en plaques (X.A., P.L.), Hôpital Universitaire de Montpellier, France; Service de Neurologie (P.K.), Centre hospitalier de Luxembourg; Inserm (P.H.), U 1184, Center for Immunology of Viral Infections and Autoimmune Diseases, Université Paris-Sud 11, CEA, DSV/iMETI, Division of Immuno-Virology, IDMIT, Faculté de médecine, Le Kremlin-Bicêtre Cedex, France; Service de Radiologie (F.C.), Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Pierre-Bénite, France; Université Claude Bernard Lyon 1 (F.C., S.V., R.M.), F-69100 Villeurbanne, France; Lyon's Neuroscience Research Center (S.V.), Observatoire Français de la Sclérose en Plaques, INSERM 1028 et CNRS UMR5292, Lyon, France; Service de neurologie pédiatrique (K.D.), Centre de référence pour les maladies inflammatoires rares du cerveau et de la moelle, Le Kremlin-Bicêtre, France; and INSERM US27 MIRCen (C.S.), CEA, Fontenay-aux-Roses, France.
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Pierre Labauge
From the Service de neurologie (A.C.-C., S.V., R.M.), sclérose en plaques, pathologies de la myéline et neuroinflammation and Centre de référence pour les maladies inflammatoires rares du cerveau et de la moelle (MIRCEM)– Hôpital Neurologique Pierre Wertheimer Hospices Civils de Lyon, France; Lyon Neuroscience Research Center (A.C.-C., R.M.), U1028 INSERM, UMR5292 CNRS, FLUID Team, Lyon, France; Service de sclérose en plaques (X.A., P.L.), Hôpital Universitaire de Montpellier, France; Service de Neurologie (P.K.), Centre hospitalier de Luxembourg; Inserm (P.H.), U 1184, Center for Immunology of Viral Infections and Autoimmune Diseases, Université Paris-Sud 11, CEA, DSV/iMETI, Division of Immuno-Virology, IDMIT, Faculté de médecine, Le Kremlin-Bicêtre Cedex, France; Service de Radiologie (F.C.), Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Pierre-Bénite, France; Université Claude Bernard Lyon 1 (F.C., S.V., R.M.), F-69100 Villeurbanne, France; Lyon's Neuroscience Research Center (S.V.), Observatoire Français de la Sclérose en Plaques, INSERM 1028 et CNRS UMR5292, Lyon, France; Service de neurologie pédiatrique (K.D.), Centre de référence pour les maladies inflammatoires rares du cerveau et de la moelle, Le Kremlin-Bicêtre, France; and INSERM US27 MIRCen (C.S.), CEA, Fontenay-aux-Roses, France.
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Sandra Vukusic
From the Service de neurologie (A.C.-C., S.V., R.M.), sclérose en plaques, pathologies de la myéline et neuroinflammation and Centre de référence pour les maladies inflammatoires rares du cerveau et de la moelle (MIRCEM)– Hôpital Neurologique Pierre Wertheimer Hospices Civils de Lyon, France; Lyon Neuroscience Research Center (A.C.-C., R.M.), U1028 INSERM, UMR5292 CNRS, FLUID Team, Lyon, France; Service de sclérose en plaques (X.A., P.L.), Hôpital Universitaire de Montpellier, France; Service de Neurologie (P.K.), Centre hospitalier de Luxembourg; Inserm (P.H.), U 1184, Center for Immunology of Viral Infections and Autoimmune Diseases, Université Paris-Sud 11, CEA, DSV/iMETI, Division of Immuno-Virology, IDMIT, Faculté de médecine, Le Kremlin-Bicêtre Cedex, France; Service de Radiologie (F.C.), Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Pierre-Bénite, France; Université Claude Bernard Lyon 1 (F.C., S.V., R.M.), F-69100 Villeurbanne, France; Lyon's Neuroscience Research Center (S.V.), Observatoire Français de la Sclérose en Plaques, INSERM 1028 et CNRS UMR5292, Lyon, France; Service de neurologie pédiatrique (K.D.), Centre de référence pour les maladies inflammatoires rares du cerveau et de la moelle, Le Kremlin-Bicêtre, France; and INSERM US27 MIRCen (C.S.), CEA, Fontenay-aux-Roses, France.
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Kumaran Deiva
From the Service de neurologie (A.C.-C., S.V., R.M.), sclérose en plaques, pathologies de la myéline et neuroinflammation and Centre de référence pour les maladies inflammatoires rares du cerveau et de la moelle (MIRCEM)– Hôpital Neurologique Pierre Wertheimer Hospices Civils de Lyon, France; Lyon Neuroscience Research Center (A.C.-C., R.M.), U1028 INSERM, UMR5292 CNRS, FLUID Team, Lyon, France; Service de sclérose en plaques (X.A., P.L.), Hôpital Universitaire de Montpellier, France; Service de Neurologie (P.K.), Centre hospitalier de Luxembourg; Inserm (P.H.), U 1184, Center for Immunology of Viral Infections and Autoimmune Diseases, Université Paris-Sud 11, CEA, DSV/iMETI, Division of Immuno-Virology, IDMIT, Faculté de médecine, Le Kremlin-Bicêtre Cedex, France; Service de Radiologie (F.C.), Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Pierre-Bénite, France; Université Claude Bernard Lyon 1 (F.C., S.V., R.M.), F-69100 Villeurbanne, France; Lyon's Neuroscience Research Center (S.V.), Observatoire Français de la Sclérose en Plaques, INSERM 1028 et CNRS UMR5292, Lyon, France; Service de neurologie pédiatrique (K.D.), Centre de référence pour les maladies inflammatoires rares du cerveau et de la moelle, Le Kremlin-Bicêtre, France; and INSERM US27 MIRCen (C.S.), CEA, Fontenay-aux-Roses, France.
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Ché Serguera
From the Service de neurologie (A.C.-C., S.V., R.M.), sclérose en plaques, pathologies de la myéline et neuroinflammation and Centre de référence pour les maladies inflammatoires rares du cerveau et de la moelle (MIRCEM)– Hôpital Neurologique Pierre Wertheimer Hospices Civils de Lyon, France; Lyon Neuroscience Research Center (A.C.-C., R.M.), U1028 INSERM, UMR5292 CNRS, FLUID Team, Lyon, France; Service de sclérose en plaques (X.A., P.L.), Hôpital Universitaire de Montpellier, France; Service de Neurologie (P.K.), Centre hospitalier de Luxembourg; Inserm (P.H.), U 1184, Center for Immunology of Viral Infections and Autoimmune Diseases, Université Paris-Sud 11, CEA, DSV/iMETI, Division of Immuno-Virology, IDMIT, Faculté de médecine, Le Kremlin-Bicêtre Cedex, France; Service de Radiologie (F.C.), Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Pierre-Bénite, France; Université Claude Bernard Lyon 1 (F.C., S.V., R.M.), F-69100 Villeurbanne, France; Lyon's Neuroscience Research Center (S.V.), Observatoire Français de la Sclérose en Plaques, INSERM 1028 et CNRS UMR5292, Lyon, France; Service de neurologie pédiatrique (K.D.), Centre de référence pour les maladies inflammatoires rares du cerveau et de la moelle, Le Kremlin-Bicêtre, France; and INSERM US27 MIRCen (C.S.), CEA, Fontenay-aux-Roses, France.
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Romain Marignier
From the Service de neurologie (A.C.-C., S.V., R.M.), sclérose en plaques, pathologies de la myéline et neuroinflammation and Centre de référence pour les maladies inflammatoires rares du cerveau et de la moelle (MIRCEM)– Hôpital Neurologique Pierre Wertheimer Hospices Civils de Lyon, France; Lyon Neuroscience Research Center (A.C.-C., R.M.), U1028 INSERM, UMR5292 CNRS, FLUID Team, Lyon, France; Service de sclérose en plaques (X.A., P.L.), Hôpital Universitaire de Montpellier, France; Service de Neurologie (P.K.), Centre hospitalier de Luxembourg; Inserm (P.H.), U 1184, Center for Immunology of Viral Infections and Autoimmune Diseases, Université Paris-Sud 11, CEA, DSV/iMETI, Division of Immuno-Virology, IDMIT, Faculté de médecine, Le Kremlin-Bicêtre Cedex, France; Service de Radiologie (F.C.), Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Pierre-Bénite, France; Université Claude Bernard Lyon 1 (F.C., S.V., R.M.), F-69100 Villeurbanne, France; Lyon's Neuroscience Research Center (S.V.), Observatoire Français de la Sclérose en Plaques, INSERM 1028 et CNRS UMR5292, Lyon, France; Service de neurologie pédiatrique (K.D.), Centre de référence pour les maladies inflammatoires rares du cerveau et de la moelle, Le Kremlin-Bicêtre, France; and INSERM US27 MIRCen (C.S.), CEA, Fontenay-aux-Roses, France.
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Citation
Cranial nerve involvement in patients with MOG antibody–associated disease
Alvaro Cobo-Calvo, Xavier Ayrignac, Philippe Kerschen, Philippe Horellou, Francois Cotton, Pierre Labauge, Sandra Vukusic, Kumaran Deiva, Ché Serguera, Romain Marignier
Neurol Neuroimmunol Neuroinflamm Mar 2019, 6 (2) e543; DOI: 10.1212/NXI.0000000000000543

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    Figure 1 Radiologic features of human myelin oligodendrocyte glycoprotein immunoglobulin G–positive patients with cranial nerve involvement

    Patient Id.1 (A–D). (A) Bilateral upper cerebellar peduncle. (B and C) Left and right trigeminal nerve gadolinium enhancement on T1W postcontrast sequence. (D) Complete resolution of the lesions on T1 postgadolinium. Patient Id. 2 (E–H). (E) White matter cerebral lesions on FLAIR sequences. (F, a–c), Bilateral oculomotor nerve gadolinium enhancement in the cisternal part of the nerve on T1W postcontrast sequence with fat saturation. (G) Focal cervical T2 lesion on spinal cord MRI. (H) Resolution of oculomotor gadolinium enhancement on T1W postcontrast sequence with fat saturation. Patient Id.3 (I–L). (I) Brainstem asymmetric FLAIR hyperintensities and dorsal pontine tegmentum hyperintensity. (J and K) Bilateral trigeminal nerve gadolinium enhancement on FLAIR postcontrast sequence. (L, a and b), Bilateral vestibulocochlear nerve gadolinium enhancement on FLAIR postgadolinium sequence.

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    Figure 2 Nonhuman primate brain immunohistochemistry

    (A) Purified IgG-AF594 from patients (A.a) and from controls (A.b). (B) Brain and cerebellum nonhuman primate myelin staining with commercial monoclonal MOG 8–18C5. (C) Purified IgG-AF594 from patients colocalized with commercial anti-MBP. An example of patient Id.1. hMOG = human MOG; MBP = myelin basic protein; MOG = myelin oligodendrocyte glycoprotein; NHP = nonhuman primate.

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    Figure 3 Nonhuman primate peripheral nerve immunohistochemistry

    Purified IgG-AF594-IgG from patients staining in (A) trigeminal, (B) sciatic, and (C) oculomotor nerves. *Staining labeling MOG protein at the CNS region. MOG = myelin oligodendrocyte glycoprotein.

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