Myelin Oligodendrocyte Glycoprotein Antibody Disorders

Q: What is myelin oligodendrocyte glycoprotein antibody disease?

A: Myelin oligodendrocyte glycoprotein antibody disorders (MOGAD) is an idiopathic, inflammatory, demyelinating disease of the central nervous system (CNS). MOG is a glycoprotein uniquely expressed in oligodendrocytes in the CNS. MOG antibodies were originally thought to be involved in multiple sclerosis (MS), but subsequent studies found it to be a distinct disease. MOGAD have many similarities to neuromyelitis optica but several studies have demonstrated they have unique clinical features, treatment response, and prognosis. MOGAD were initially identified in NMOSD antibody negative patients. Pathologically NMOSD is classified as am astrocytopathy, while MOGAD are classified as oligodendrogliopathies.

Q: How common is MOGAD and who gets it?

A: The exact incidence and prevalence of MOGASD is not known. The typical age of onset is in the 20-30s, but it can occur in both pediatric and older patents. Recent studies  show an equal prevalence in males and females.1 Most patients are Caucasian. MOG IgG associated disorders are generally regarded as a non-familial disease.

Q: How do patients with MOGAD present?

A: MOGAD have several clinical presentations. One of the most common presentations is similar to neuromyelitis spectrum disorder (NMOSD) with recurrent optic neuritis, transverse myelitis, or both. In one adult clinical cohort study the combination of optic nerve, spinal cord, or a combination accounted for >90% of cases.2  The associated optic neuritis can be unilateral or bilateral.

Another common presentation is that of acute disseminated encephalomyelitis (ADEM). ADEM can present with typical symptoms of encephalitis including decreased consciousness, headache, and behavioral changes. Seizures can also occur in the context of MOGAD associated ADEM presentations and occur at varying rates.1 Other presentations include brainstem syndrome and short segment transverse myelitis.2,3

In general, older patients are more likely to present with optic neuritis and younger patients are more likely to present with encephalomyelitis.

Q: What are the MRI features of MOGAD?

A: In patients that present with an isolated myelitis many have a longitudinally extensive lesions (≥3 contiguous vertebral segments). Longitudinally extensive lesions were seen in 84.4% of patients with isolated myelitis and 55.6% of patients with myelitis plus optic neuritis at MOGAD presentation.2 There is no known unique radiographic pattern for MOG, but leptomeningeal enhancement, thalamic lesions, pontine lesions, deep white matter lesions, tumefactive, poorly defined lesions, and cortical lesions were more common in MOGAD than NMOSD or non-MOG antibody cases.2 The lesions also typically have dramatic improvement or resolution over time.

The MRI findings in the setting of ADEM are the typical diffuse signal changes in the cortical and deep grey matter and subcortical and deep white matter on T2-weighted and FLAIR images. There have also been reports of scattered linear or nodular enhancement in active lesions with restricted diffusion.

Q: How are MOGAD different than NMOSD?

A: There is significant clinical overlap  with NMOSD. MOGAD has been reported to account for 40% of seronegative NMOSD.4,5 Compared to NMO aquaporin 4 IgG (AQP4-IgG) patients, MOG patients are younger, lack the female predominance, more frequently have a monophasic course, more often present with ADEM and often have a better outcome.1,6 The optic nerve is more commonly affected in MOG disease and more likely to have simultaneous affection of both optic nerves.7 In a UK series seizures were more frequently observed in MOG (14.7%) compared to AQP4 IgG patients (1%).8 Pathologically NMOSD is classified as an astrocytopathy, while MOG IgG associated disorders are classified as oligodendrogliopathies.

Q: How are MOGAD different than MS?

A: Although the clinical presentation is closer to NMOSD there still is overlap with MS as optic neuritis and myelitis are common in all three conditions. The underlying immunopathological features of MOGAD are more closely related to MS than NMO. Since MOG is a more ubiquitous protein than AQP4 and expressed on CNS myelin sheaths there is more associated demyelination similar to MS.5,9 MOGAD patients are slightly younger and have less of a female predominance than MS. Although MOG patients often will have abnormalities on brain MRI these lesions have a distinct appearance that is different from MS lesions.6

Q: What are the unique features in pediatric patients with MOGAD?

A: In the pediatric population, MOG IgG is often associated with an ADEM presentation preceded by infection. Pediatric patients are also more likely to have transient titer elevation which predicts a monophasic course.7,10 Persistent elevation predicts a recurrent course; therefore pediatric patients should be monitored.

Q: What are the laboratory findings in MOGAD?

A: Recently developed cell based assays are available to test for the presence of immunoglobulin G (IgG) targeting MOG. Specifically a live cell-based methodology is preferred because it was shown to have a superior positive predictive value to the fixed cell assays.11 The exact sensitivity and specificity depends on the assay and are still being defined.

CSF can have lymphocytic pleocytosis, normal or mildly elevated protein, and rare oligoclonal bands.1  It is not helpful to test for MOG in the CSF.

Q: How are MOGAD diagnosed?

A: Recently proposed diagnostic criteria for MOG IgG associated disorders must meet the 3 following criteria:10

  • Laboratory finding: serum positive MOG-IgG by cell based assay
  • Clinical findings of any of the following presentations:
    1. ADEM
    2. Optic neuritis, including chronic relapsing optic neuropathy (CRION)
    3. Transverse myelitis (short or long segment)
    4. Brain or brainstem syndrome compatible with demyelination
    5. Any combination of the above
  • Exclusion of alternative diagnosis

Q: Whom do we test for MOGAD?

A: We consider  testing any patient with any of these clinical presentations: ADEM, optic neuritis, transverse myelitis. We will also test MOG IgG in patients with brain or brainstem lesions atypical for MS.

Q: What is the utility of re-testing for MOG-IgG?

A: In patients who test positive and presented with an optic neuritis or transverse myelitis we do not routinely re-test MOG IgG. For patients that present with an initial presentation of ADEM, especially in the pediatric population seropositivity can be transient and repeat testing may be of value. In one cohort 8 (4 adults and 4 children) of 51 patients had transient positivity and only 1 adult of those 8 patients had a relapse.10 This finding suggests that in patients with an ADEM presentation it would be reasonable to re-test for MOG IgG 6 months after initial presentation to aide with determining likelihood of recurrent disease. If a patient has an initial positive test and converts to negative this is more likely to indicate a monophasic course; whereas persistent positive results predicts recurrence.

In a patient who presented with a syndrome typical of MOG IgG disease who tested negative at presentation we often consider retesting 6 months after initial testing or in the setting of recurrent disease.

Q: What is the expected course and prognosis of MOGAD?

A: MOG IgG may present as a monophasic or relapsing condition. In the context of ADEM as the presenting symptom it can be monophasic, especially in the pediatric population. There are now many reports of recurrent disease in the setting of positive MOG IgG. High and persistent MOG antibody titers are more likely to predict a relapsing course. The rate of relapsing disease varies by series, but has been reported to be as high as 72-88%.10,12 The overall prognosis of MOG is favorable compared to AQP4 positive disease with better recovery and less disability.6,12

Q: What is the general approach to a MOGAD relapse?

A: The current approach to relapses is the same as an in NMOSD. Intravenous corticosteroids are our initial acute treatment. The typical Mellen Center regimen is methylprednisolone 1000mg IV as a single daily dose on 3-5 consecutive days followed by a prolonged steroid taper. We use varying taper regimens anywhere from 2-6 months depending on the severity of presentation and planned long term regimen. We consider plasmapheresis or IVIG as a second line treatment for patients not steroid responsive. Most reported cases showed excellent response to treatment with full recovery.

Q: How do we prevent relapses in MOGAD?

A: There is limited data on long term management of recurrent MOG IgG associated disorders and there are no randomized trials to guide therapy. As with acute treatment our approach is similar to NMOSD maintenance therapy. There have been successful reports with the use of rituximab, mycophenolate mofetil, IVIG, and azathioprine.7,8,13,14


  1. Salama, S., Khan, M., Pardo, S., Izbudak, I. & Levy, M. MOG antibody–associated encephalomyelitis/encephalitis. Mult. Scler. J. 135245851983770 (2019). doi:10.1177/1352458519837705
  2. Cobo-Calvo, A. et al. Clinical spectrum and prognostic value of CNS MOG autoimmunity in adults: The MOGADOR study. Neurology 90, e1858–e1869 (2018).
  3. Jurynczyk, M. et al. Clinical presentation and prognosis in MOG-antibody disease: a UK study. Brain 140, 3128–3138 (2017).
  4. Hamid, S. H. M. et al. What proportion of AQP4-IgG-negative NMO spectrum disorder patients are MOG-IgG positive? A cross sectional study of 132 patients. J. Neurol. 264, 2088–2094 (2017).
  5. Narayan, R. et al. MOG antibody disease: A review of MOG antibody seropositive neuromyelitis optica spectrum disorder. Mult. Scler. Relat. Disord. 25, 66–72 (2018).
  6. Höftberger, R. et al. Antibodies to MOG and AQP4 in adults with neuromyelitis optica and suspected limited forms of the disease. Mult. Scler. 21, 866–874 (2015).
  7. Weber, M. S., Derfuss, T., Metz, I. & Brück, W. Defining distinct features of anti-MOG antibody associated central nervous system demyelination. Ther. Adv. Neurol. Disord. 11, 175628641876208 (2018).
  8. Hamid, S. H. M. et al. Seizures and Encephalitis in Myelin Oligodendrocyte Glycoprotein IgG Disease vs Aquaporin 4 IgG Disease. JAMA Neurol. 75, 65–71 (2018).
  9. Kaneko, K. et al. Myelin injury without astrocytopathy in neuroinflammatory disorders with MOG antibodies. J. Neurol. Neurosurg. Psychiatry 87, 1257–1259 (2016).
  10. López-Chiriboga, A. S. et al. Association of MOG-IgG Serostatus With Relapse After Acute Disseminated Encephalomyelitis and Proposed Diagnostic Criteria for MOG-IgG-Associated Disorders. JAMA Neurol. 75, 1355–1363 (2018).
  11. Waters, P. J. et al. A multicenter comparison of MOG-IgG cell-based assays. Neurology 10.1212/WNL.0000000000007096 (2019). doi:10.1212/WNL.0000000000007096
  12. Wang, L. et al. Encephalitis is an important clinical component of myelin oligodendrocyte glycoprotein antibody associated demyelination: a single-center cohort study in Shanghai, China. Eur. J. Neurol. 26, 168–174 (2019).
  13. Ramanathan, S. et al. Clinical course, therapeutic responses and outcomes in relapsing MOG antibody-associated demyelination. J. Neurol. Neurosurg. Psychiatry 89, 127–137 (2018).
  14. Tsantes, E., Curti, E., Siena, E. & Granella, F. Successful intravenous immunoglobulin treatment in relapsing MOG-antibody-associated disease. Mult. Scler. Relat. Disord. 32, 27–29 (2019).