Myelin Oligodendrocyte Glycoprotein Antibody Disease (MOGAD)

Podcast Transcript

Neuro Pathways Podcast Series

Release Date: July 15, 2024

Expiration Date: July 15, 2025

Estimated Time of Completion: 20 minutes

Myelin Oligodendrocyte Glycoprotein Antibody Disease (MOGAD)

Amy Kunchok, MD, PhD

Description

Each podcast in the Neurological Institute series provides a brief, review of management strategies related to the topic.

Learning Objectives

• Review up to date and clinically pertinent topics related to neurological disease
• Discuss advances in the field of neurological diseases
• Describe options for the treatment and care of various neurological disease

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Physicians and Advanced Practice providers in Family Practice, Internal Medicine & Subspecialties, Neurology, Nursing, Pediatrics, Psychology/Psychiatry, Radiology as well as Professors, Researchers, and Students.

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Podcast Series Director

Imad Najm, MD
Epilepsy Center

Additional Planner/Reviewer

Cindy Willis, DNP

Faculty

Amy Kunchok, MD, PhD
Mellen Center

Host

Glen Stevens, DO, PhD
Cleveland Clinic Brain Tumor and Neuro-Oncology Center

Agenda

Myelin oligodendrocyte Glycoprotein Antibody Disease (MOGAD)

Amy Kunchok, MD, PhD

Disclosures

In accordance with the Standards for Integrity and Independence issued by the Accreditation Council for Continuing Medical Education (ACCME), The Cleveland Clinic Center for Continuing Education mitigates all relevant conflicts of interest to ensure CME activities are free of commercial bias.

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The following faculty have indicated they have no relationship which, in the context of their presentation(s), could be perceived as a potential conflict of interest: Cindy Willis, DNP.

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Introduction: Neuro Pathways, a Cleveland Clinic podcast exploring the latest research, discoveries, and clinical advances in the fields of neurology, neurosurgery, neuro rehab, and psychiatry.

Glen Stevens, DO, PhD: As the field of neuroimmunology continues to evolve, so does our understanding and recognition of more rare demyelinating diseases like myelin oligodendrocyte, glycoprotein antibody disorder, or MOGAD. In today's episode of Neuro Pathways, we're diving into the specifics of MOGAD presentation and detailing a practical approach to diagnosis and management.

I'm your host, Glenn Stevens, neurologist, neuro-oncologist in Cleveland Clinic's Neurological Institute. I'm very pleased to have Dr. Amy Kunchok join me for today's conversation. Dr. Kunchok is a neurologist in the Mellen Center for Multiple Sclerosis Treatment and Research within Cleveland Clinic's Neurological Institute. Amy, welcome to Neuro Pathways.

Amy Kunchok, MD, PhD: Thank you so much, Dr. Stevens.

Glen Stevens, DO, PhD: So Amy, tell us a little bit about yourself, how you've made your way to Cleveland and what you do on a daily basis over at the Mellen Center.

Amy Kunchok, MD, PhD: Sure. So I'm a neurologist. I'm originally from Australia, and I came to the United States to do fellowships in a specific area in autoimmune neurology and in clinical neuroimmunology, which I did at Mayo Clinic. And I now work at the Cleveland Clinic Mellen Center, where I specialize in autoimmune neurology as well as multiple sclerosis. And day-to-day I see patients with predominantly with antibody mediated diseases, including what we're talking about today, MOGAD, as well as NMO, autoimmune encephalitis, amongst others.

Glen Stevens, DO, PhD: So I kind of look at this as a little bit of alphabet soup. We're going to have a lot of that going on today, and hopefully we won't get lost in the weeds of it. But all this alphabet business that we're going to talk about, I assume back when I was looking at this stuff, everybody thought everybody just had multiple sclerosis, right? It was probably all lumped into the same thing, but now we're going to get into the weeds. So define for us, myelin oligodendrocyte glycoprotein antibody disease or MOGAD. What is MOGAD?

Amy Kunchok, MD, PhD: MOGAD is a disorder that is associated with antibodies or IgG2, the MOG antigen. And these disorders cluster with a group of phenotypes that have been defined in a diagnostic criteria. In particular, these disorders involve optic neuritis, so inflammation of the optic nerve, myelitis, the inflammation of the spinal cord, and also inflammation of the brain, which can involve a combination of encephalitis and myelitis in some cases. So these are inflammatory and immune-mediated disorders, and they are identified by a very clear phenotype along with an antibody that's a diagnostic biomarker, and they're treated typically with immunosuppressive therapies, in a summary.

Glen Stevens, DO, PhD: Yeah. No, no, that's a good summary. So who's the patient population that's affected? Young, old, male, female?

Amy Kunchok, MD, PhD: This population is younger than what we would see for say, NMO. It can affect children, and we also see young adults being affected. So it's a younger demographic. It affects males and females roughly similarly. So we don't see the same strong female predominance that we see for NMO and for multiple sclerosis.

Glen Stevens, DO, PhD: So you kind of mentioned it in your summary a little bit, but let's go a little bit deeper. Let's go through the main clinical features of MOGAD.

Amy Kunchok, MD, PhD: Yeah, sure. The most common presentation that we see clinically would be optic neuritis. And the unique features of optic neuritis in MOGAD are that it's often bilateral. And that's distinct from multiple sclerosis where it would often be unilateral.

Another interesting thing about the optic neuritis in MOGAD is it's often anterior, and so sometimes people will actually have papillitis, and you can also in some cases see peripapillary hemorrhages. We can use different methods to diagnose optic neuritis, so we can use OCT and MRI in particular to diagnose this presentation.

Glen Stevens, DO, PhD: And for our audience out there, can you define OCT for us?

Amy Kunchok, MD, PhD: Oh, sure. Optical coherence tomography.

Glen Stevens, DO, PhD: And what does that look at specifically?

Amy Kunchok, MD, PhD: In particular for inflammatory and demyelinating diseases, we are really interested in the retinal nerve fiber layers, and we use this as a tool to evaluate for changes that might represent inflammation of the optic nerve.

And the other clinical phenotype that's quite common other than optic neuritis would be myelitis. And so this is inflammation of the spinal cord. And patients that have myelitis might present with say, numbness in their legs or ascending numbness that creeps up to their abdomen. Some people may have difficulty with walking, and in some cases they may have problems with passing urine or stool. And this disorder myelitis is typically diagnosed with an MRI of the spinal cord.

And then we also have manifestations where there's inflammation in the brain. And so for MOGAD, you can have brain lesions that sometimes very similar to ADEM, which has been described in children. So these large fluffy lesions in the brain. Sometimes we'll see brainstem lesions. So particularly of the cerebellar peduncles is a common site to see large fluffy lesions in the brainstem.

Glen Stevens, DO, PhD: And if we go back a little bit to the transverse myelitis, I mean typically I think with multiple sclerosis, you'll see it in the cervical or thoracic cord, but my understanding is in MOGAD, it can also affect the conus.

Amy Kunchok, MD, PhD: Oh, yes, very good. Thank you so much for bringing that up. There are some really key differences and the conus involvement is one of them. The other differences that we often see for myelitis in MOGAD compared to MS is the longitudinally extensive nature of the lesion. So it often extends over several vertebral segments, more often greater than three. And when you look on the axial segment on an MRI, you will often see that the lesions are more centrally located as opposed to peripheral lesions that might be more typically seen in multiple sclerosis.

Glen Stevens, DO, PhD: So I was going to ask you how MOGAD is different than NMOSD or neuromyelitis optica spectrum disorder?

Amy Kunchok, MD, PhD: A great question. There are several distinguishing clinical features, and then there are some other, I guess you could say, paraclinical differences between MOGAD and NMO. From a clinical perspective, NMO and MOG both present with optic neuritis involvement, but the main difference is that the location for the inflammation of the optic nerve is different. It's more anterior for MOGAD and more posterior for NMO. And so in NMO it also often involves the chiasm. So there are some differences in the anatomical involvement for these two diseases.

Glen Stevens, DO, PhD: Now you did mention that in the spine you can have several segments affected in MOGAD, right?

Amy Kunchok, MD, PhD: Yes.

Glen Stevens, DO, PhD: I think you also see that in NMOSD. Don't you also see multiple segments?

Amy Kunchok, MD, PhD: Yes, you're right. And for myelitis, both diseases do have longitudinally extensive, and that's true. So that is a similarity, but I think that the main difference is probably in the contrast enhancement in particular. Because there's less contrast enhancement for MOGAD, we more often see T-II lesions confined to the gray matter, whereas if NMO, we often see contrast enhancement, and that's a really classical feature. And in particular we can see this elongated ring of contrast enhancement, that's a classical feature for NMO.

The other distinguishing feature in addition to the features I mentioned for optic neuritis and myelitis are that in the brain stem, the lesions also look quite different. Patients with NMO often have very discrete lesions. In particular, a classical feature for NMO is the area prostrema. And so this is in the dorsum modellor, and patients will have intractable nausea and vomiting, whereas I mentioned earlier for MOGAD patients who will often have more diffuse hazy lesions, sometimes involving the bilateral cerebellar peduncles. So the appearance is different on imaging, but also there are different clinical manifestations there.

Glen Stevens, DO, PhD: Well, I'm glad that you can keep it all together, but what about MOGAD and MS? How are they similar and different? And I know you've touched on it a little bit, but talk about the lesions.

Amy Kunchok, MD, PhD: In terms of optic neuritis, the main difference for MOGAD and MS is the unilateral versus bilateral. So bilateral being more common in MOGAD, unilateral being more common in MS. Again, the length of the lesion can be different. So MOGAD can have longitudinal extensive lesions of the optic nerve, and MS can have short segment lesions.

Similarly, in the spinal cord, you might see longitudinal extensive lesions for MOGAD, short segment for MS. And on the axial segment you can see more centrally located lesions for MOGAD and more peripherally located lesions for MS. They're probably the more classical differences between the two.

Glen Stevens, DO, PhD: And if you look at the flare hyper intensities in an MS patient, they used to talk about the Dawson's fingers coming out perpendicular and the central vein sign. Can you tell us what that is and do you see that in MOGAD?

Amy Kunchok, MD, PhD: Another great question. Yes, the Dawson's fingers are classical for MS, and we typically will not see those periventricular lesions in the same manner that we do for MS in MOGAD. The central vein sign is a very specific sign for multiple sclerosis, and there've been some studies that have looked at this in MOG patients. There are a small number of MOGAD patients that can have central vein, but it's more often associated with MS than it is with MOGAD.

Glen Stevens, DO, PhD: And the central vein is inside a white matter lesion on T-II sequence where you sort of see a hypodensity, right, a dark area?

Amy Kunchok, MD, PhD: Yeah. The optimal sequence for this is often a SWI sequence that we use to look at this in detail.

Glen Stevens, DO, PhD: So who should be tested for MOGAD? How do you determine who should be tested? I guess you would look at the clinical presentation that you've just discussed with us and you'd sort of be leaning one way or the other. Or are you testing everybody?

Amy Kunchok, MD, PhD: There is some data that suggests that if we indiscriminately test patients, we might come up with false positive or irrelevant results in patients. So we do try to tailor our testing to patients that are more likely to have MOGAD than not. And so some of the more typical features might be the clinical features I've just described in particular. The population that would be of most interest would be patients that are younger, that are presenting with bilateral optic neuritis or myelitis, or an ADEM type presentation. They would be the clinical phenotypes that we'd be most interested in testing.

Glen Stevens, DO, PhD: And can you tell our audience what ADEM stands for? I know we got back to the alphabet soup here.

Amy Kunchok, MD, PhD: Sorry. Acute disseminated encephalomyelitis.

Glen Stevens, DO, PhD: Let's go to serologic testing or CSF testing. What's the test that we check for, for MOGAD?

Amy Kunchok, MD, PhD: So we use serum testing at present to test for MOGAD. However, there is some ongoing research into the utility of CSF testing. There have been some studies that have shown that people can be CSF positive in the absence of MOG in the serum, but more often than not when it's present in the serum, it is also present in the CSF. So usually we're able to utilize serum testing for our patients, but there may be an angle if you have a patient that you have a high suspicion for to take additional measures and test the CSF. At present that's not available at every laboratory, so it does require some specialist evaluation.

Glen Stevens, DO, PhD: And the standard IgG test is a cell-based assay, correct?

Amy Kunchok, MD, PhD: That's right.

Glen Stevens, DO, PhD: And you maybe just mentioned it, but is it more sensitive in the CSF or not?

Amy Kunchok, MD, PhD: I think this is an area of ongoing research. So, so far it doesn't look like it's more sensitive. There may be certain cases that it picks it up, and this may be related to clinical phenotypes, but I think this is an area that's of ongoing research because there are a lot of patients that are serum-only positive. So this area needs more research essentially.

Glen Stevens, DO, PhD: And checking for oligoclonal bands, does that help you differentiate this alphabet soup?

Amy Kunchok, MD, PhD: Yes, it can. So oligoclonal bands are more often present in multiple sclerosis, and so they can be a helpful distinguisher from MOGAD.

Glen Stevens, DO, PhD: So my understanding is that neuromyelitis optica spectrum disorder is more an astrocytopathy and the MOGAD is more oligodendrogliopathy. There's been some suggestion that with neuromyelitis optica spectrum disorder, that GFAP could be increased in the CSF, gliofibrillary astrocytic protein. Do you ever look at that? Do you ever measure GFAP? I mean certainly in brain tumor we look at GFAP in all of our astrocytic tumors. Do you guys look at that?

Amy Kunchok, MD, PhD: We don't as a routine thing, but this is an area of ongoing research for biomarkers, for MOGAD, and for disease activity.

Glen Stevens, DO, PhD: So you mentioned a little bit in your summary earlier, but how do we manage patients with MOGAD?

Amy Kunchok, MD, PhD: Patients with MOGAD when they are experiencing an acute attack or a relapse, we typically treat that with steroids, and that would be high dose steroids. So IV methylprednisolone a gram a day, usually for three to five days. If patients are particularly disabled, we might treat those patients additionally with plasma exchange, so five to seven cycles over two weeks. And we can also utilize IVIG, so 0.4 grams per kilogram in divided doses and also two grams per kilogram total. So usually we would give 0.4 grams daily for five days.

An area that's of ongoing research is which patients should we select to treat with ongoing immunosuppressive or maintenance immunosuppression. And again, this is an area that's evolving quite a lot in research and people are trying to study work out whether there are predictors of a relapsing course and which patients we should select.

At present, the way we decide is to evaluate whether patients have had a relapsing course so that patients that have a relapsing course generally will start immunosuppressive therapy. Patients that have had perhaps a severe relapse or are at a great risk of further disability if they experienced relapse might be another group that could be considered for immunosuppressive therapies. We also take into account the age of the patient, any comorbidities.

When it comes to selecting what we use for maintenance immunosuppression, there are several options. And again, there is research going into which is the optimal treatment for maintenance therapy. At present, we use IVIG quite frequently because there has been several studies that have shown that this is very efficacious. We also sometimes use a long corticosteroid taper. There is less data that supports treatments such as rituximab, azathioprine, and mycophenolate, but they have been used and in some patients they are effective. But there's ongoing research because we don't see necessarily the same response that we might see for NMOSD with some of these therapies.

Glen Stevens, DO, PhD: So if I come to see you and I have MOGAD and you give me steroids and maybe some IVIG or PLEXME, and the decision is not to put me on a maintenance immunosuppressant medication, what's the general natural course? Is this a one and done? Am I likely to relapse? 50% of people do. What's the numbers? Because MS, very different disorder. But what do MOGAD patients do?

Amy Kunchok, MD, PhD: Most of patients that are relapsing differs by reported cohorts, and that probably is skewed by the fact that a lot of the data comes from tertiary centers that see a high proportion of relapsing patients due to referral bias. So in a lot of studies there have been cohorts that have been reported to be 50 to 60% of tertiary cohorts that are relapses. But again, is that the natural history, are not certain and because there's probably is referral bias. And that matches very similarly to what we see at Cleveland Clinic where we receive a greater proportion of patients that do have a relapsing course.

Glen Stevens, DO, PhD: So it sounds like we need to have a much bigger database that we draw on to sort of determine the natural history even of this disorder.

Amy Kunchok, MD, PhD: Yeah. Looking at long-term outcomes is I think a really huge priority for patients of MOGAD because it's been a fairly... although there's been research going on in this area for several years, it's only been more recently recognized and the testing's only been available more widely to clinicians over the last few years. So that limits our ability to fully understand the natural history and the prognosis for these patients. But this is an area that people are actively researching across the United States.

Glen Stevens, DO, PhD: So what about research in the field? Where's the research going?

Amy Kunchok, MD, PhD: I think in some of the areas we've just covered, there is a lot of interest in observational research in looking at optimal treatment regimens, optimal immunosuppressive therapies. Along with that, there are clinical trials. We are doing a clinical trial here looking at satchelizumab in MOGAD patients, but there are other clinical trials around, including rosanelixizumab is another therapy that's in clinical trials at present. So I think there'll be more emerging therapies in the clinical trial space. That's one area of research growth.

Neuroimaging, which we've touched on some of the key easily recognizable radiological features of MOGAD, but this is an area, again, that's evolving. Imaging biomarkers for MOGAD, trying to understand further the evolution from an imaging perspective is an area of research. I think the testing, and again, we covered some of these areas today, understanding the role of CSF testing, optimizing assays for sensitivity and specificity. This is another area of research.

And then I think what we covered at the end of this talk, looking at outcomes and prognostication, and using longitudinal data is another area that's coming from observational cohorts as we begin to accumulate patients and understand better the disease course.

Glen Stevens, DO, PhD: So it sounds like if I'm out in the community seeing one of these patients, maybe not a bad idea to send them to a tertiary center?

Amy Kunchok, MD, PhD: I think so. I think the advantages of going to a tertiary clinic focused on MOGAD is that you can have access to the testing, to the imaging, to clinical care, multidisciplinary care, and also access to the latest treatments through clinical trials and research. So yes, I think that would be the optimal management strategy for patients with MOGAD.

Glen Stevens, DO, PhD: Any final takeaways for the audience?

Amy Kunchok, MD, PhD: I think that it's an emerging disease and it's something that general neurologists are probably going to encounter more and more. It is more frequent than NMO, and I think it's a disorder to think about, particularly if you come across patients of optic neuritis, which is the most common presentation. When you see this presentation, I think this is a good scenario where you would think about referring to a tertiary center and arranging testing for MOG.

Glen Stevens, DO, PhD: Well, Amy, thanks for joining me today. Certainly been a lot of developments in the demyelinating field since I started many, many years ago, and I appreciate your bringing us up to speed on what's going on and look forward to continued understanding of the field. Thank you.

Amy Kunchok, MD, PhD: Thank you, Glen.

Closing: This concludes this episode of Neuro Pathways. You can find additional podcast episodes on our website, clevelandclinic.org/neuropodcast, or subscribe to the podcast on iTunes, Google Play, Spotify, or wherever you get your podcasts. And don't forget, you can access real-time updates from experts in Cleveland Clinic's Neurological Institute on our Consult QD website. That's @CleClinicMD, all one word. And thank you for listening.