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

J Neuroinflammation. 2016 Sep 27;13(1):280. doi: 10.1186/s12974-016-0718-0.


Background: A subset of patients with neuromyelitis optica spectrum disorders (NMOSD) has been shown to be seropositive for myelin oligodendrocyte glycoprotein antibodies (MOG-IgG).

Objective: 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.

Methods: Retrospective multicenter study.

Results: 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.

Conclusion: 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.

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.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Distribution
  • Aged
  • Anti-Inflammatory Agents / therapeutic use*
  • Aquaporin 4 / immunology
  • Autoantibodies / cerebrospinal fluid*
  • Brain / diagnostic imaging
  • Cardiolipins / immunology
  • Child
  • Cohort Studies
  • Female
  • HEK293 Cells
  • Humans
  • Male
  • Middle Aged
  • Myelin-Oligodendrocyte Glycoprotein / genetics
  • Myelin-Oligodendrocyte Glycoprotein / immunology*
  • Neuromyelitis Optica* / cerebrospinal fluid
  • Neuromyelitis Optica* / diagnostic imaging
  • Neuromyelitis Optica* / epidemiology
  • Neuromyelitis Optica* / therapy
  • Optic Nerve / diagnostic imaging
  • Sex Factors
  • Treatment Outcome*
  • Vaccination / methods
  • Vision Disorders / etiology
  • Young Adult


  • Anti-Inflammatory Agents
  • Aquaporin 4
  • Autoantibodies
  • Cardiolipins
  • Myelin-Oligodendrocyte Glycoprotein