title: MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 2: Epidemiology, clinical presentation, radiological and laboratory features, treatment responses, and long-term outcome.
abstract: A subset of patients with neuromyelitis optica spectrum disorders (NMOSD) has been shown to be seropositive for myelin oligodendrocyte glycoprotein antibodies (MOG-IgG).
  
  
  
  To describe the epidemiological, clinical, radiological, cerebrospinal fluid (CSF), and electrophysiological features of a large cohort of MOG-IgG-positive patients with optic neuritis (ON) and/or myelitis (n = 50) as well as attack and long-term treatment outcomes.
  
  
  
  Retrospective multicenter study.
  
  
  
  The sex ratio was 1:2.8 (m:f). Median age at onset was 31 years (range 6-70). The disease followed a multiphasic course in 80 % (median time-to-first-relapse 5 months; annualized relapse rate 0.92) and resulted in significant disability in 40 % (mean follow-up 75 ± 46.5 months), with severe visual impairment or functional blindness (36 %) and markedly impaired ambulation due to paresis or ataxia (25 %) as the most common long-term sequelae. Functional blindess in one or both eyes was noted during at least one ON attack in around 70 %. Perioptic enhancement was present in several patients. Besides acute tetra-/paraparesis, dysesthesia and pain were common in acute myelitis (70 %). Longitudinally extensive spinal cord lesions were frequent, but short lesions occurred at least once in 44 %. Fourty-one percent had a history of simultaneous ON and myelitis. Clinical or radiological involvement of the brain, brainstem, or cerebellum was present in 50 %; extra-opticospinal symptoms included intractable nausea and vomiting and respiratory insufficiency (fatal in one). CSF pleocytosis (partly neutrophilic) was present in 70 %, oligoclonal bands in only 13 %, and blood-CSF-barrier dysfunction in 32 %. Intravenous methylprednisolone (IVMP) and long-term immunosuppression were often effective; however, treatment failure leading to rapid accumulation of disability was noted in many patients as well as flare-ups after steroid withdrawal. Full recovery was achieved by plasma exchange in some cases, including after IVMP failure. Breakthrough attacks under azathioprine were linked to the drug-specific latency period and a lack of cotreatment with oral steroids. Methotrexate was effective in 5/6 patients. Interferon-beta was associated with ongoing or increasing disease activity. Rituximab and ofatumumab were effective in some patients. However, treatment with rituximab was followed by early relapses in several cases; end-of-dose relapses occurred 9-12 months after the first infusion. Coexisting autoimmunity was rare (9 %). Wingerchuk's 2006 and 2015 criteria for NMO(SD) and Barkhof and McDonald criteria for multiple sclerosis (MS) were met by 28 %, 32 %, 15 %, 33 %, respectively; MS had been suspected in 36 %. Disease onset or relapses were preceded by infection, vaccination, or pregnancy/delivery in several cases.
  
  
  
  Our findings from a predominantly Caucasian cohort strongly argue against the concept of MOG-IgG denoting a mild and usually monophasic variant of NMOSD. The predominantly relapsing and often severe disease course and the short median time to second attack support the use of prophylactic long-term treatments in patients with MOG-IgG-positive ON and/or myelitis.
authors: Molecular Neuroimmunology Group, Department of Neurology, University of Heidelberg, Heidelberg, Germany. sven.jarius@med.uni-heidelberg.de.
authors: Sven
authors: S
authors: Jarius
authors: Department of Neurology, Charité University Medicine Berlin, Berlin, Germany.
authors: Klemens
authors: K
authors: Ruprecht
authors: Department of Neurology, Ruhr University Bochum, Bochum, Germany.
authors: Ingo
authors: I
authors: Kleiter
authors: NeuroCure Clinical Research Center and Clinical and Experimental Multiple Sclerosis Research Center, Department of Neurology, Charité University Medicine, Berlin, Germany.|Experimental and Clinical Research Center, Max Delbrueck Center for Molecular Medicine and Charité University Medicine Berlin, Berlin, Germany.
authors: Nadja
authors: N
authors: Borisow
authors: Department of Neurology and Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
authors: Nasrin
authors: N
authors: Asgari
authors: Department of Neurology, Ruhr University Bochum, Bochum, Germany.
authors: Kalliopi
authors: K
authors: Pitarokoili
authors: NeuroCure Clinical Research Center and Clinical and Experimental Multiple Sclerosis Research Center, Department of Neurology, Charité University Medicine, Berlin, Germany.|Experimental and Clinical Research Center, Max Delbrueck Center for Molecular Medicine and Charité University Medicine Berlin, Berlin, Germany.
authors: Florence
authors: F
authors: Pache
authors: Department of Neurology, Albert Ludwigs University, Freiburg, Germany.
authors: Oliver
authors: O
authors: Stich
authors: Department of Neurology, Albert Ludwigs University, Freiburg, Germany.
authors: Lena-Alexandra
authors: LA
authors: Beume
authors: Department of Neurology, Hannover Medical School, Hannover, Germany.
authors: Martin W
authors: MW
authors: Hümmert
authors: Department of Neurology, Heinrich Heine University, Düsseldorf, Germany.
authors: Marius
authors: M
authors: Ringelstein
authors: Department of Neurology, Hannover Medical School, Hannover, Germany.
authors: Corinna
authors: C
authors: Trebst
authors: Department of Neurology, University of Rostock, Rostock, Germany.
authors: Alexander
authors: A
authors: Winkelmann
authors: Molecular Neuroimmunology Group, Department of Neurology, University of Heidelberg, Heidelberg, Germany.
authors: Alexander
authors: A
authors: Schwarz
authors: Department of Neurology, Julius Maximilians University, Würzburg, Germany.
authors: Mathias
authors: M
authors: Buttmann
authors: Department of Neurology, Charité University Medicine Berlin, Berlin, Germany.
authors: Hanna
authors: H
authors: Zimmermann
authors: Department of Neurology, Charité University Medicine Berlin, Berlin, Germany.
authors: Joseph
authors: J
authors: Kuchling
authors: IRCCS, C. Mondino National Neurological Institute, Pavia, Italy.
authors: Diego
authors: D
authors: Franciotta
authors: Centro di Riferimento Regionale SM, Azienda Ospedaliero Universitaria San Luigi Gonzaga, Orbassano, Italy.
authors: Marco
authors: M
authors: Capobianco
authors: Department of Neuroradiology, Charité University Medicine - Berlin, Berlin, Germany.
authors: Eberhard
authors: E
authors: Siebert
authors: Department of Neuroradiology, Ruhr University Bochum, Bochum, Germany.
authors: Carsten
authors: C
authors: Lukas
authors: Molecular Neuroimmunology Group, Department of Neurology, University of Heidelberg, Heidelberg, Germany.
authors: Mirjam
authors: M
authors: Korporal-Kuhnke
authors: Molecular Neuroimmunology Group, Department of Neurology, University of Heidelberg, Heidelberg, Germany.
authors: Jürgen
authors: J
authors: Haas
authors: Institute of Experimental Immunolog, affiliated to Euroimmun AG, Lübeck, Germany.
authors: Kai
authors: K
authors: Fechner
authors: Department of Neurology, Charité University Medicine Berlin, Berlin, Germany.
authors: Alexander U
authors: AU
authors: Brandt
authors: Department of Neurology, Medical University Innsbruck, Innsbruck, Austria.
authors: Kathrin
authors: K
authors: Schanda
authors: Department of Neurology, Hannover Medical School, Hannover, Germany.
authors: Orhan
authors: O
authors: Aktas
authors: NeuroCure Clinical Research Center and Clinical and Experimental Multiple Sclerosis Research Center, Department of Neurology, Charité University Medicine, Berlin, Germany.|Experimental and Clinical Research Center, Max Delbrueck Center for Molecular Medicine and Charité University Medicine Berlin, Berlin, Germany.
authors: Friedemann
authors: F
authors: Paul
authors: Department of Neurology, Medical University Innsbruck, Innsbruck, Austria.
authors: Markus
authors: M
authors: Reindl
authors: Molecular Neuroimmunology Group, Department of Neurology, University of Heidelberg, Heidelberg, Germany.
authors: Brigitte
authors: B
authors: Wildemann
mesh_terms: D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D051401:Aquaporin 4 / Q000276:immunology; D001323:Autoantibodies / Q000134:cerebrospinal fluid*; D001921:Brain / Q000000981:diagnostic imaging; D002308:Cardiolipins / Q000276:immunology; D002648:Child; D015331:Cohort Studies; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D008875:Middle Aged; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000235:genetics / Q000276:immunology*; D009471:Neuromyelitis Optica / Q000134:cerebrospinal fluid / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000628:therapy; D009900:Optic Nerve / Q000000981:diagnostic imaging; D012737:Sex Factors; D016896:Treatment Outcome; D014611:Vaccination / Q000379:methods; D014786:Vision Disorders / Q000209:etiology; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; D051401:Aquaporin 4; D001323:Autoantibodies; D002308:Cardiolipins; D063308:Myelin-Oligodendrocyte Glycoprotein
keywords: Aquaporin-4 antibodies (AQP4-IgG, NMO-IgG); Autoantibodies; Azathioprine; Barkhof criteria; Cerebrospinal fluid; Electrophysiology; Evoked potentials; Glatiramer acetate; IPND criteria; Infections; Interferon beta; International consensus diagnostic criteria for neuromyelitis optica spectrum disorders; Longitudinally extensive transverse myelitis; Magnetic resonance imaging; McDonald criteria; Methotrexate; Multiple sclerosis; Myelin oligodendrocyte glycoprotein antibodies (MOG-IgG); Natalizumab; Neuromyelitis optica spectrum disorders (NMOSD); Ofatumumab; Oligoclonal bands; Optic neuritis; Outcome; Pregnancy; Rituximab; Therapy; Transverse myelitis; Treatment; Vaccination; Wingerchuk criteria 2006 and 2015