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MOG-AD Diagnosis: Testing and Titers

MOG Project MOGCast Follow-Up. MOG-AD Diagnosis Testing and Titers with Dr. John Chen, Professor of Neuroophthalmology and Neurology and Dr. Eoin Flanagan, Professor of Neurology, both from Mayo Clinic

In June of 2021, The MOG Project was joined by Dr. John Chen and Dr. Eoin Flanagan from the Mayo Clinic in our first of the MOGCast Series called MOG-AD Diagnosis: Testing and Titers. Dr. Chen and Dr. Flanagan have answered 8 important community questions that we did not have time to ask during the MOGCast. On behalf of The MOG Project and the MOG-AD Community, we would like to thank Dr. Chen and Dr. Flanagan for taking the time to help the community understand the diagnosis of MOG-AD, how to test and treat the disease, what the titers indicate, and all the research they continue to undertake on MOG Antibody-Associated Disorder.

You can view to the entire MOGCast here.

Blog Questions

Is there any hope of new treatment in the future?

Our understanding of MOG-AD is growing. Many of our prior treatments were extensions of what we have done for NMOSD, but MOG-AD is a different disease. maintenance IVIG may be an effective treatment for MOG-AD. There are likely to be randomized clinical trials for new treatments coming soon.

If someone has MOG Optic Neuritis and they are high myopic, how does that affect the interpretation of the OCT and Visual Field Test?

High refractive error, such as high myopia, will not influence visual field tests, but can alter the interpretation of the OCTs. OCTs are color coded as green (normal), yellow (mildly thin), and red (thin) when comparing a patient’s RNFL or GC-IPL thickness against the age-matched control database. However, the database of age-matched controls are from patients without much refractive error. Therefore, if a patient is highly myopic, the numbers do not match up with the age-matched controls (high myopia tends to have thinner RNFL). For this reason, it is helpful to have a baseline OCT for an individual patient so changes can be followed over time rather than depending on a comparison of the thickness against the age-matched controls.

If you were reaching out to the public for awareness purposes, what age group would you target?

We would need to reach out to all ages because MOG-AD can affect any age. Children and parents of children would also be very important because MOG-AD likely accounts for about a quarter of demyelinating disease in children.

After stopping preventive medications and negative for the MOG antibody, how often should patients be retested in the remission phase? Do we ever stop retesting if they stop having attacks?

If a patient becomes seronegative for the MOG antibody, this suggests a lower chance of relapse. However, patients can still sometimes relapse despite becoming seronegative. We often retest MOG antibodies once a year, but part of this is for research purposes so we can get a better understanding of the importance of the MOG antibodies.

How crucial is identifying if a MOG-AD patient needs immunosuppressive treatment and an MS patient needs immunomodulatory treatment for recovery and disability outcome?

For a patient with MOG-AD, we typically start chronic immunotherapy only in patients with relapsing disease.  This is because only 50% will relapse and recovery is typically good, especially with early steroid treatment. Therefore, if we were to treat every MOG-AD patient with a single attack, we would be over-treating 50% of patients because they may not relapse even without treatment. For MS, most patients need immunomodulatory treatment because patients can accumulate disability with relapsing-remitting disease and can progress to a secondary progressive phase.

For those who are steroid dependent and cannot get below a low dose without having an attack, is there a plan to allow them to transition off the steroids? Is this answer different for children vs. adults?

For patients who continue to relapse when tapering the steroids, they will usually need chronic immunotherapy. Various medications are offered, including Rituximab, Azathioprine, Mycophenolate, Tocilizumab, and maintenance IVIG. For children, we often use IVIG as first line therapy while in adults, we typically start with one of these other medications and reserve maintenance IVIG for disease that breaks through some of these other treatments.

What studies have been done with children of MOG-AD?  Is “remission” the accurate term if they’ve been testing negative with no relapses for a few years now?

There have been several large studies on children with MOG-AD. Overall, children are more often monophasic and have a higher tendency to become seronegative. If they become seronegative and have not had relapses for a few years, they could be called in remission (or be called monophasic disease if there was only a single attack), but it is important to note that a relapse can occur many years after having quite a disease.

Thank you for your paper, “Steroid-Sparing Maintenance Immunotherapy for MOG-IgG Associated Disorder (found here).” Do you know if there is a prospective randomized controlled study planned/in progress?

There are a couple of pharmaceutical sponsored randomized placebo controlled trials that will be starting in the next 1-2 years. We hope that these will provide proven treatments for MOG-AD and a better understanding of the disease.

Key Takeaways from the MOGCast and Follow-Up Questions

  • Live or inactivated cell-based assays should be used to test for the MOG antibody as they are reliable. However, live cell-based assays tend to have more specificity and sensitivity. 
  • A greater number of 1:1000 was a strong cut off for a patient who has true MOG-AD, whilst majority of the false positives were at the 1:20 – 1:40 titer levels and a few at the 1:100 level. It’s up to the neurologist to put it all together and make sure that everything fits the diagnosis as some countries do not report titer levels but rather a positive or negative result.
  • MOG-AD patients require immunosuppressive treatment after the second attack and not the first with the exception of those who have had a severe episode and poor recovery with the first attack.
  • Due to MOG-AD being a relatively new disease, the duration of treatment is not yet understood. Patients are being weaned off treatment after the 1-2 year mark unless they have poor outcomes and/or severe disability.
  • B-cell depleting therapies such as Rituximab and Ocrelizumab are used for MOG-like MS presentations, particularly when it’s difficult for the neurologist to diagnose.
  • Patients with a negative MRI should still be treated if their symptoms match the clinical picture and this can sometimes happen especially with optic neuritis as it remains a clinical diagnosis. 
  • MS patients require immunomodulatory therapy and MOG-AD patients need immunosuppressive therapy so a correct diagnosis is very crucial, especially in regards to moving forward with the right treatment plan.