Neurology Minute

In the last episode of this series, Dr. Justin Abbatemarco and Dr. Benjamin P. Trewin discuss how to apply this data into clinical practice.  
Read more about this abstract on the AAN website.  
Show transcript: 
Dr. Justin Abbatemarco:
Hello, and welcome back. This is Justin Abbatemarco and I'm joined by Benjamin Trewin where we're reviewing top abstracts from the AAN annual meeting in Chicago. Today we're talking about his abstract maintenance immunotherapy and MOGAD, early steroid benefit, dose thresholds, and disability risk. Ben, we've done this really great job of dissecting the data, steroids, non-steroidal agents. How do you think about the treating MOGAD cases in clinic though? How do you try to put this data and the data we've talked about into clinical practice?
Dr. Benjamin P. Trewin:
It's obviously a very good and actionable question, and our research has always tried to focus on these dilemmas facing the clinician at the bedside. And so the way that we think about this is, of course, we try to come up with some rules or some guidelines to treat all patients, as that's the most effective way of giving the message, but we need to acknowledge there is variation within MOGAD patients. There are people with low relapsing propensity who will take a very long time to relapse. You'll need to follow them for a long time. And there are ones with high relapsing propensity. So some of our previous work, we actually reviewed thousands of MOGAD patients in the literature and found that if you follow them for more than five years, over 70% actually relapse. It's just a matter of following them. So acknowledging this variation in the patients is important, but at the same time, the guideline we would probably endorse based on our research is that all patients with MOGAD after a first attack should be treated with oral corticosteroid taper, including at least five months of 12.5 milligrams per day oral corticosteroids.
Now, how does that work in practice? Well, you would probably start them, and I say probably here because we don't have the strength of evidence for the very start of the course and the very end. But what did we do? Well, we start them at about one milligram per kilogram. And over probably about two to three weeks, you can bring them down to about 12.5 milligrams per day, or in children, 0.16 milligram per kilogram per day. And then you'll do that four or five months. And then over two or three weeks after that, you would step them down. Of course, you want to be careful that you don't have any adrenal issues. You would want to go slow enough for that. But at the same time, you don't want to prolong the course too long and put yourself at risk of side effects.
Dr. Justin Abbatemarco:
I think that's really helpful and practical. And you don't need these huge doses, it looks like, to treat these patients well and trying to really be mindful of those side effects that are truly dose dependent. And then yeah, we have some really great data. We need some randomized data to help us inform next steps, but this retrospective data, we're starting to put together this picture around B-cell depleting IVIG like we talked about. So super helpful. Ben, really excited to see you at the annual meeting. And yeah, thank you for your time and expertise.

In the second episode of this series, Dr. Justin Abbatemarco and Dr. Benjamin P. Trewin discuss what was found in non-steroidal maintenance therapies. 
Read more about this abstract on the AAN website.  
Show transcript: 
Dr. Justin Abbatemarco:
Hello and welcome back. This is Justin Abbatemarco from the Cleveland Clinic. And we're joined by Ben Trewin on his abstract maintenance immunotherapy and MOGAD, early steroid benefit, dose thresholds and disability risk. Ben, in our first episode we really talked about corticosteroids, but your paper and abstract looked at other therapies. What did you find in those non-steroidal maintenance therapies?
Dr. Benjamin Trewin:
In addition to looking at oral corticosteroid therapies, we also looked at B-cell depleting therapies, namely rituximab and ocrelizumab, and intravenous immunoglobulin and steroid-sparing therapies, namely azathioprine and mycophenolate predominantly, I suppose a couple on methotrexate. Now, what we found, it's important to note that we were able to tease apart the effects of all these drugs with our Cox proportional hazard model chops up, follow up into distinct intervals with different combinations and permutations of these medications and their different doses in a more granular way than is allowed by previous techniques like incident rate ratios when we compare pre and post annualized relapse rate, and we think this is a strength of the study. With this methodological strength, we were able to see that steroid-sparing therapies, despite 334 patient years of data, do not appear to have any independent benefit with respect to time to next relapse.
The estimate of effect there was 1.06. And then for time to confirm sustained disability, there was also no confidence signal, the confidence interval being 0.15 to 1.4, that it actually prevented any disability despite a wealth of data, which I think is an important thing to note. And I think previous studies, particularly looking with incident rate ratios, have been a little more optimistic with that. And I think there might be misattributing some of the benefit of concomitant steroids to the steroid-sparers, but it's more complex than that, of course. And then with respect to B-cell depleting therapies, we did have 48 of 261 patients exposed, which is reasonable, but not quite enough to get the signal we're looking for. However, we found something quite interesting, because when we compared the Liverpool data to the Australasian data, the two big study groups involved, we saw that it wasn't quite as effective in Liverpool as it was in Australasia in this subgroup analysis.
And so we dug a little deeper, as one should, and found that the dosing is actually different. And in Australasia, we have a tendency to just give two grams of rituximab up front, or 600 milligrams of ocrelizumab. And then six-monthly, you give a gram of rituximab without fail, without trying to watch the B cells or trying to muck around with doses in any way. And when we looked at that, the threshold dosing, as we termed it, as compared to below threshold dosing, there actually was weak evidence at a PVA of 0.08 that threshold dosing is superior to below threshold dosing. And that needs to be reproduced, but I think that was an important signal. And finally, I would say IVIG, of course, has some very strong data in this area. And I think it's important from this study at least to remain a little agnostic on that as we only had 31 patients on IVIG, and so I absolutely wouldn't say it's not effective. I would say unfortunately, we had insufficient data to make any big claims about that.
Dr. Justin Abbatemarco:
I think some really great data to help pick apart here and help inform practice. I think your point about looking at the previous literature and trying to tease apart these steroid-sparing agents, that corticosteroids they're not uniformly addressed, and so it's difficult to think about at those previous data points, so I appreciate that. And then this dose response to the B-cell therapies, there's been questions in the literature, because I think we've gotten a lot of mixed results on B-cell therapies. And so this to me is one of the larger studies that really help answer this question that maybe B-cell therapies are effective and maybe we need to be a little more sensitive to dose, which is the same theme we saw on IVIG. IVIG, maybe at higher doses, could be more effective for MOGAD. What do you think about that comparison?
Dr. Benjamin Trewin:
I like where you're going with that because we're quite interested in these dose responses as we introduce this 12.5 milligram per day oral corticosteroid dose or 0.16 milligrams per kilograms per day in kid. And so we're quite interested. And, of course, that work by Dr. Chen and Dr. Mariner has revealed that IVIG also has quite a sensitive dose threshold there at one gram every four weeks. And we followed that precinct because that research was so strong. So it's nice to feel like we're building on previous studies and then perhaps even detecting another dose threshold with respect to rituximab. And I must say, it was a little bit of a surprise, we came in and saw why is the Liverpool data moving that way and the other one moving this way? So it was a nice data-driven evolution of our multi-variable model.
Dr. Justin Abbatemarco:
So helpful. And I'll ask everyone to come back for the final episode, where we try to put this all together. We're going to put Ben on the spot and really understand how he approaches these cases in clinical practice. Ben, thank you.
Dr. Benjamin Trewin:
Thanks very much, Justin.

In the second part of this series, Dr. Justin Abbatemarco and Dr. Paulus Rommer discuss how to apply these study results into clinical practice. 
Show citation: 
Vietzen H, Kühner LM, Berger SM, et al. Epstein-Barr Virus Antibodies to Differentiate Multiple Sclerosis From Other Neuroinflammatory Diseases. JAMA Neurol. Published online March 9, 2026. doi:10.1001/jamaneurol.2026.0240 
Show transcript:
Dr. Justin Abbatemarco:
Hello and welcome back. This is Justin Abbatemarco, and we're finishing up our interview with Paulus Rommer on his article on JAMA Neurology, Epstein-Barr Virus Antibodies that differentiate multiple sclerosis from other Neuroinflammatory Diseases. Paulus, can we talk about how we would apply your results into clinical practice right now?
Dr. Paulus Rommer:
The persistent high apnea antibody responses are a hallmark of multiple sclerosis. And in our micro center study, we found that the singular measurement is not sufficient to differentiate multiple sclerosis from other related disorders like MOGAD or NMOSD, but it's the repeated high levels over time. We see them in about 95% of our MS patients, but really rarely in MOGAD or NMOSD. So this persistent high levels is a good factor, with a high accuracy, to really diagnose multiple sclerosis and to differentiate them from MOGOD or NMOSD.
Dr. Justin Abbatemarco:
I think these are really helpful and I think a little more evolution in how we interpret these on individual patient level, like we talked about in the podcast, but more to come. Paulus, thank you again for all your work on this topic for coming on and we're excited to have you back in the future.
Dr. Paulus Rommer:
Thank you.

Dr. Zohaib Siddiqi and Dr. Laurence Poirier discuss a complex stroke case associated with systemic vasculitis, highlighting diagnostic challenges and management strategies, including the role of endovascular therapy. 
Show citation: 
Poirier L, Brissette V, Shamy MCF, Maxwell JP, Drake B, Fahed R. Clinical Reasoning: A 70-Year-Old Man With Systemic Illness Related Strokes Refractory to Medical Treatment Managed With Intracranial Stent. Neurology. 2025;104(1):e210068. doi:10.1212/WNL.0000000000210068

In part one of this series, Dr. Justin Abbatemarco and Dr. Paulus Rommer discuss the relationship between Epstein-Barr virus and multiple sclerosis, as well as the questions that still remain unanswered.
Show citation:
Vietzen H, Kühner LM, Berger SM, et al. Epstein-Barr Virus Antibodies to Differentiate Multiple Sclerosis From Other Neuroinflammatory Diseases. JAMA Neurol. Published online March 9, 2026. doi:10.1001/jamaneurol.2026.0240 
Show transcript: 
Dr. Justin Abbatemarco:
Hello and welcome. I just finished interviewing Paulus Rommer on his article published in JAMA Neurology, Epstein-Barr Virus Antibodies to Differentiate Multiple Sclerosis From Other Neuroinflammatory Diseases. Paulus, could we maybe talk about this relationship that we've understood about multiple sclerosis and Epstein-Barr virus? And maybe the points that still remain unanswered?
Dr. Paulus Romme:
There's a very long story behind this because in 1868, Pierre Marie, a student of Charcot was talking about that multiple sclerosis is a sequelae of an infection disorder. By this, we now know that there's a long story. There have been associations between infectious mononucleosis, EBV infection, multiple sclerosis. Also, the migration studies really fits very well in this. So there have been an association, but then, in 2022, there was the US Army study, Bjornevik and Ascherio, who really have shown that there is almost no multiple sclerosis without EBV infection. But still, we do not know why almost all of our patients have EBV infection, but only very small subset have multiple sclerosis. But this is very important to get a deeper understanding, but this is still unknown.
Dr. Justin Abbatemarco:
This story of EPV and multiple sclerosis continues to evolve. And your work, as we talked about on the podcast, has really helped inform that discussion as well. And we still need to understand, outside of the initiation of the disease, how it drives the pathophysiology years after that initial infection. But it's really helpful to understand this in the larger set and now maybe using it as a biomarker to help us with our other neuroinflammatory diseases, so we'll discuss that the next episode. Again, I was just speaking with Paulas Rommer on his article in JAMA Neurology, Epstein-Barr Virus Antibodies to Differentiate Multiple Sclerosis From Other Neuroinflammatory Diseases. Paulus, thank you.