MOG and Neuromyelitis Optica

Robert C. Sergott, MD: Let’s talk about this anti-MOG variety of NMO [neuromyelitis optica]. Rod, tell us about that, especially in children.

Rod Foroozan, MD: Yeah, so the MOG story actually dates back a little earlier, when it was thought to be using antibodies against MOG that were thought to be maybe somehow protective treatment for MS [multiple sclerosis]. Actually, what was found was that MOG was found to be used in an experimental model causing experimental autoimmune encephalitis, so an animal model of MS, and subsequently the antibody became available a few years ago more commercially and for research purposes several years before that. And what was noted is a group of patients who had optic neuritis that often was very responsive to steroids were found to have these positive antibodies.

Exactly what their role is in the pathogenesis of optic neuritis is not clear, but it is a marker in a group of patients, and that includes younger patients, pediatric patients, who develop optic neuritis. In our experience, probably about one-third of patients at Texas Children’s Hospital who develop optic neuritis who are children will have MOG antibodies present. And they can signify in older patients a risk for recurrent optic neuritis or what was previously termed CRION, for chronic relapsing idiopathic optic neuritis. Now we have a spectrum of disease that initially was only considered to be MS and now it has branched into at least 2 other forms, MOG and NMO.

Robert C. Sergott, MD: One of the tip-offs for MOG disease that we’ve seen is a lot of swelling on fundoscopic examination. The old teaching about optic neuritis was that the patient couldn’t see anything, and when the doctor looked in, the optic nerve looked normal. They couldn’t see anything. But if you see a patient who fits the clinical profile of optic neuritis, and that optic nerve is swollen and there are hemorrhages, the index of suspicion for NMO goes up very high and also for anti-MOG. I admit all these patients now, so that I can get the imaging of the cord done right away, and I can see their response. If after 3 days of IV [intravenous] steroids they’re not better, I give them 2 more days. If they’re not better then, I’m looking at pheresis. How about you, Rod?

Rod Foroozan, MD: Yeah, I was going to ask you the same thing. I say after 5 days, sometimes 6. If they are not better, then we look to plasmapheresis. Especially for the pediatric cases routinely admitted, 1 of the things I’ll look for is an early response to treatment. We talked about a lack of response as being a marker maybe for NMO. One of the things that we’ll see with MOG is a very rapid response. If you’re getting a visual recovery within 24 to 48 hours with IV steroids, I’m very suspicious for MOG. The other thing is, on MRI with MOG, there is this tendency for a perineural enhancement pattern. If you’re seeing enhancement of the optic nerve that’s extending into the orbital fat or around the optic nerve sheath, rather than just the nerve itself, that’s a strong indication that you might be dealing with MOG or at least another type of inflammatory optic neuropathy.

Robert C. Sergott, MD: I predict the following: When I was in medical school, before we had MRI and before we had a lot of things—I won’t go into many more details about how long ago that was—we thought multiple sclerosis was a rare disease. That is not true. And that happened because of MRI. Anytime we get better technology, we become better clinicians and can more precisely treat patients. The teaching, 5 years ago, was that NMO and anti-MOG were rare. I think they’re common. Rod, what do you think?

Rod Foroozan, MD: Yeah, they’re certainly common in our practices. I think we didn’t even have MOG commercially available to us until a couple of years ago. I’ve seen in the past few months a handful of cases at Texas Children’s Hospital, so clearly they’re much more common than we thought. Maybe years from now we’ll be doing this again and there will be another antibody that further subdivides this group of conditions.

Robert C. Sergott, MD: And you know Rod mentioned lumpers and splitters. In the short term, the lumpers are always right. In the long term, the splitters are always right. I would take that approach, and Rod’s comments here about other antibodies is very insightful. Rod, do you have Lyme disease in Texas?

Rod Foroozan, MD: We test for it. I ordered it yesterday. But I was telling a resident who had trained in New York, and he said, “Yeah, we got it all time.” The reality is travel, setting aside COVID-19, is so common these days that you can be in an endemic area in the Northeast and come into Texas, but it’s not part of our armamentarium to look for Lyme here very often.

Robert C. Sergott, MD: Well, there’s no shortage of hunters in Texas. And although Lyme disease was first described in Connecticut, it’s now almost the state disease of New Jersey and Pennsylvania. So where you practice makes a difference. If we talk about infectious optic neuritis, Lyme is there, and we test for it all the time because the treatments are different. Penicillin and antibiotics help this. Rod, for bilateral disease we have a finding in neuro-ophthalmologists seeing cells in the vitreous. It can be easily overlooked that we thought doesn’t happen that much. But we see several cases a year that respond to penicillin.

Rod Foroozan, MD: Yep. And I would add in there cat scratch disease, especially in the pediatric population. I’m always looking for vitritis or uveitis because that really tilts your thinking. It should tilt your thinking into infectious or some other inflammatory response. We don’t see that with NMO, MOG, and typical MS for the most part.

Robert C. Sergott, MD: Of course, syphilis is in there. Again, everybody gets a test for syphilis, and if you find that, it’s obviously a different treatment. You will not hurt a patient with syphilis by treating them with steroids, but you won’t help them either, so you’ve always got to be careful about that.