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Demystifying the Diagnosis of MOGAD: Take-Home Points for Patients from the 2023 International MOGAD Panel Proposed Diagnostic Criteria

Background and importance:

While several prior publications have suggested diagnostic criteria for MOGAD, formal guidelines for diagnosis had not been proposed until March 2023 in Lancet Neurology1. In this important paper, an international panel of adult and pediatric neurologists outline key diagnostic criteria that distinguish MOGAD as a unique disease. While these diagnostic criteria require further validation, they offer the potential to improve identification of patients with MOGAD and decrease misclassification of MOGAD with its disease mimickers–MS and NMOSD. Accurate diagnosis is critical as these three disorders have differing disease causes, treatments, and outcomes. Patients struggling to reach an accurate diagnosis of their neurologic symptoms now have the following proposed MOGAD criteria to discuss with their doctor and are encouraged to bring this article with them to their appointment.

Breaking down the proposed diagnostic criteria:

In general, the following three criteria must be met for a MOGAD diagnosis:

  1. One of the following clinical demyelinating events:
    • optic neuritis, resulting in vision loss in one or both eyes.
    • transverse myelitis, often causing limb weakness, numbness, and bowel, bladder, or sexual dysfunction.
    • acute disseminated encephalomyelitis (ADEM), resulting in notable changes in behavior, mood or cognition, and changes or loss of function in specific areas of the body; ADEM can occur along with transverse myelitis and/or optic neuritis as well.
    • cerebral monofocal or polyfocal deficits, referring to demyelinating lesions in one or more areas of the brain that can cause a variety of symptoms, such as difficulty speaking, numbness, vision problems, loss of balance, or weakness in the arms, face, or legs.
    • brainstem or cerebellar deficits, often including double vision or difficulty with balance and coordination.
    • cerebral cortical encephalitis, often presenting with seizures, difficulty speaking, stroke-like episodes, headache, and fever.
  1. A positive serum MOG IgG antibody test confirmed by a doctor (live cell-based assay is the preferred method of antibody detection). To learn more about the specifics of the test, see footnote (a).
  1. The exclusion of other diagnoses (especially MS).

Keep in mind that MOG antibody testing should ideally be performed before steroids, plasmapheresis, or intravenous immunoglobulins (or IVIG) are started, as these treatments can make it more difficult to detect the antibody.

For patients who have one of the above core confirmed clinical attacks but do not have a clear positive serum MOG antibody test, further criteria must be fulfilled. Specifically, for patients with a low positive antibody test (see footnote (b)), a reportedly positive test but no quantification or documentation of the result, or a negative blood test but a positive cerebrospinal fluid test, you must:

  1. Have one of the clinical presentations listed above
  2. Have one or more supportive criteria
  3. Have a negative aquaporin-4 (AQP4)-IgG test
  4. Have better diagnoses excluded (including MS), meaning diagnoses that are a better fit considering all evidence collectively.

Interpreting the significance of the proposed diagnostic criteria:

It is important to mention that not all patients experiencing their first demyelinating attack require screening for MOGAD. While clear positive antibody results are highly associated with the above clinical features that distinguish MOGAD from NMOSD or MS, low MOG antibody titers are occasionally seen in patients with MS, rarely in patients with other neurologic diseases, and extremely rarely in healthy patients. Therefore, blood testing all patients experiencing a first demyelinating attack–particularly those with clinical or imaging findings not typical of MOGAD–would result in false positive results, meaning that the antibody test is not indicative of MOGAD.

 

Very importantly, testing patients with MS for MOG antibody is not recommended due to the chance of false positive tests. While the likelihood of obtaining low positive MOG-IgG in MS patients is around 7-10%, testing the large population of persons living with MS would lead to a large number of individuals with false positive results.

 

Current recommendations suggest the following:

  • Testing all children younger than the age of 11 with a demyelinating presentation. In this age group, approximately 50% of children with a first demyelinating attack will have clear positive MOG-IgG, and most will present with ADEM (which is much more common in young children than in teenagers or adults) or with optic neuritis. Furthermore, MS is rare in this age group, and thus the “better” or more likely diagnosis will be MOGAD. The panel therefore recommends MOG antibody testing of children under 11 presenting with their first demyelinating attack.
  • Testing adults where there is a clinical suspicion of MOGAD (refer to diagnostic criteria).

Watch out for red flag symptoms:

The authors of this paper highlight several red flag symptoms that likely argue against a diagnosis of MOGAD. Consider talking to your doctor about the accuracy of your diagnosis if you experience any of the below red flags:

  • Little to no improvement in symptoms with high-dose steroids after a disease attack.
  • Progressive, worsening neurologic disability without experiencing an acute relapse (Disability in MOGAD ties to attacks, and failure to recover from such attacks even with treatment is not typical in MOGAD. Following a MOGAD attack, most patients will recover substantially with medication and rehabilitation. Once maximal recovery occurs (measured as sustained maximum neurological function for at least 6 months), it would be highly atypical for a MOGAD patient to then experience progressive worsening. Patients who do not improve from an attack and worsen progressively without improvement are also highly unlikely to have MOGAD).
  • Quick neurologic deterioration from onset to end of an attack within minutes to hours, which is not typical in MOGAD.

Lastly, talk to your doctor about your MRI scans:

  • Does your imaging show contrast-enhancing lesions that persist for six months or more? These might correspond to non-threatening structural differences in blood vessels, including irregular arrangements of small veins that a person may have been born with.
  • Do you have lesions that fit the typical pattern for MS? If so, this should prompt reconsideration of an MS diagnosis.
  • Are you accumulating silent lesions and keeping old lesions? This is not typical for MOGAD and should prompt consideration of other diagnoses, such as MS, sarcoidosis, or other neuroimmune diagnoses.

Conclusions:

If you are a patient experiencing your first demyelinating attack, talk to your doctor about your symptoms and imaging. If your imaging or clinical features are similar to those in the proposed MOGAD diagnostic criteria, ask your doctor to consider testing for the MOG antibody. If your clinical picture more closely aligns with that of MS, however, MOG antibody testing may not be warranted and could be misleading. Lastly, if you present with optic neuritis, transverse myelitis, or other features typical of both NMOSD and MOGAD and you have a positive serum AQP4-IgG, testing for MOG antibody is likely not appropriate for you. It is extremely rare to have BOTH MOG and AQP4 antibodies, and the presence of AQP4 antibodies (which are rarely a false positive) would indicate AQP4-NMOSD.  

Reference:

1 Banwell B, Bennett JL, Marignier R, Kim HJ, Brilot F, Flanagan EP, Ramanathan S, Waters P, Tenembaum S, Graves JS, Chitnis T, Brandt AU, Hemingway C, Neuteboom R, Pandit L, Reindl M, Saiz A, Sato DK, Rostasy K, Paul F, Pittock SJ, Fujihara K, Palace J. Diagnosis of myelin oligodendrocyte glycoprotein antibody-associated disease: International MOGAD Panel proposed criteria. Lancet Neurol. 2023 Mar;22(3):268-282. doi: 10.1016/S1474-4422(22)00431-8. Epub 2023 Jan 24. PMID: 36706773.

Index:

aA clear positive result from a live cell-based assay according to the individual assay cutoffs or a fixed cell-based assay result with a titer ≥1:100

bA low positive result from a live cell-based assay according to the individual assay cutoffs or a fixed cell-based assay result with a titre ≥1:10 and <1:100

(Please see Figure 3 in reference (1) and its index in Banwell et al. (2023) for further explanation of the supporting diagnostic feature)

By Hannah Kelly

Editorial Contributions by Melissa Lefelar

Reviewed by Brenda Banwell, MD, FRCPC, FAAN, Sudarshini Ramanathan, MD, PhD and Tanuja Chitnis, MD, FAAN

Hannah Kelly

Hannah Kelly is a fourth-year medical student at Case Western Reserve University School of
Medicine and an aspiring neuroimmunology specialist. She joined The MOG Project in May 2023 to write blog posts that convey take-home points from important research publications for MOG patients. See her full bio here.