COMMENTARY

A Newly Appreciated Aspect of Multiple Sclerosis

Stephen Krieger, MD; James Sumowski, MD

Disclosures

October 19, 2018

Stephen Krieger, MD: Hi. I'm Dr Stephen Krieger. I'm here with Dr Jim Sumowski. We're both from the Icahn School of Medicine at Mount Sinai in New York. We're here in Berlin at the 2018 ECTRIMS conference, thinking about cognition and multiple sclerosis (MS). What have we learned?

James Sumowski, MD: We've learned a lot over the past few years and at this conference, too. Cognition, memory, and attention are things that patients have told us about for a long time—decades, maybe even 100 years. Ten years ago, you wouldn't have seen much on cognition at the conference, but now you see posters and talks. Everyone's interested in trying to understand it and also to measure it. So we've come a long way.

Krieger: What would you say some of the currents are in cognitive research in MS?

Sumowski: It seems simple, but one of the major accomplishments we've actually made is that everyone's on board now. We know it's an issue and we want to measure it in the clinic and follow people. People have come up with metrics like the SDMT (Symbol Digit Modalities Test) and iPad versions of that to measure cognition as part of standard of care.

So in that sense, I think patients are happy that there is this symptom that they grapple with and deal with on a daily basis that people are paying attention to.

Krieger: Sure. Seeing the amount of research that you've done and that's being done in our field, what do you think some of the advancements have been? How can we do better when assessing cognition and then ultimately thinking about treating it?

Sumowski: We identified that it's a problem. Now, I think we have to take a step back a little bit and think about what are the really core issues that patients are experiencing and how we can treat those.

Krieger: We have thought of it as processing speed for a long time. I think there's more to it.

Sumowski: Well, it's a funny thing about processing speed, because we say the words "processing speed" and we sort of get what that means. It's like you're slower at doing things. But I feel like that's more of a description of how someone does something rather than like a cognitive process itself.

Krieger: Or what they're able to do.

Sumowski: Or what they're able to do. Here's an analogy that I like to use. Imagine a patient comes to you and they're like, "Doc, I'm having some difficulty walking. Over the past 6 months or so, my walking is just not what it used to be." And you say, "Oh, well let's evaluate that. Let's figure out why." So then you do a timed 25-foot walk and then you say, "Well, the reason you have difficulty walking is because you have slow walking." And it seems silly, but that's kind of what we're doing with cognition.

Krieger: So it's not getting at the function. It's conflating the speed for the ability.

Sumowski: Exactly right. So it's any part of the process. Like in gait, if it's sensory, cerebellar, or pyramidal deficits, you'll lead to ultimately slow gait. But in cognition, what we need to figure out is, why is it slow? Is it attention? Is it an aspect of attention or is it memory? And that's going to be really key in honing our treatment efforts to try to get at the core issues and treat those.

Krieger: What has your work shown so far in this particular area? How are you moving that forward?

Sumowski: We're moving it forward by trying to rethink about where these speed deficits are coming from. Thoughts about cognition originated when we thought of MS as just a demyelinating disease. It's a white matter disease and it didn't affect gray matter or the cortex. And the reason why people had memory issues was because they were kind of slow and they had attention issues and subcortical-like deficits.

But now we know that gray matter atrophy is present right from the very beginning, progresses along, and is way more associated with cognitive issues than even the white matter, in many cases. It's changing our view on what we should be focusing on in cognition. Actually, we have some really innovative work and some of it was mentioned at this conference. In 2016 and this past year, there were papers in Brain showing that the pattern of atrophy is not random.[1,2] Some areas of the brain are more likely to atrophy in MS than others.

Krieger: What's the number-one spot?

Sumowski: The number-one spot, cortically, is the posterior cingulate. Not what you would think. People will think about cognition and the frontal lobe and attention in that sense, but it's really the posterior cingulate, which is like this hub area. It's so interconnected with the rest of the brain that if you had a lesion in any spot, it probably leads to atrophy of this hub area. And then there are these other parietal areas that atrophy, too, which is not what we think of.

Krieger: When we think of problems with multitasking, one could imagine that that's going to be a hub for that.

Sumowski: Exactly. Because these are areas, like the posterior cingulate, but then going back into parietal areas. These are multimodality areas—areas where you have to take information from auditory and visual and bring it all together and keep it online.

Krieger: People aren't just walking 25 feet; they're walking and talking.

Sumowski: Exactly. When we measure people's cognition, usually we have them sit down at a table in a quiet room. We have them do one thing at a time. But in real life, they have to come up with solutions on their own. They have to be walking and doing it. They have to cook dinner while they're talking to their kids or their spouse and be listening.

Krieger: It is preferred.

Sumowski: It is preferred. Sometimes patients say that they feel a little misunderstood or not understood. And the reason is because lots of times they can look fine physically, but then a spouse or a friend might ask, "Why don't you remember what I'm telling you?" or "Why aren't you listening to me?" And they're trying; it's just not all being processed.

Krieger: I think we, as a field, are listening to that a lot more carefully. I appreciate your taking us through your thinking on cognition.

Sumowski: Absolutely. And I'm looking forward to ECTRIMS next year and 5 years from now. I think we're going to make some progress.

Krieger: I think so, too. Well, reporting for Medscape, I'm Stephen Krieger. Jim Sumowski, thank you.

Sumowski: Thank you very much.

Krieger: And thank you for watching us.

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