Management of Progressive Multiple Sclerosis - Episode 2

Diagnosing SPMS

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An overview of the criteria used to diagnose relapsing-remitting multiple sclerosis when it converts to secondary progressive multiple sclerosis.

Bruce Cree, MD: I want to now turn to the topic of how to diagnose when a patient converts from a relapsing disease course to a progressive disease course. Dr Krysko, what are your criteria for making a diagnosis of secondary progressive MS [multiple sclerosis]? How do you make that determination in clinical practice?

Kristen Krysko, MD: As we’ve been talking about, generally it’s steadily worsening neurological dysfunction after someone has begun with a relapsing-remitting course. There should be worsening of disability independent of relapses. It can be pretty difficult sometimes to tell when that transition occurs because someone may continue to have relapses superimposed. There’s no specific test available clinically that we can use to say that someone’s transitioned to secondary progression. It’s really a clinical judgment, which can be difficult to make.

A study out of Mount Sinai in New York led by Aaron] Miller, MD, showed it took about 3 years to determine when that transition occurred. There was a period of uncertainty over a 3-year interval, despite being a very experienced clinician. It can be difficult to diagnose. We know relapses tend to decrease with age and over time. Development of secondary progression could be an age-dependent phenomenon, so I tend to watch more closely when someone’s in their 40s or 50s.

After they’ve had the disease for a long time, the natural history studies show a median of about 20 years from onset that a transition to progressive disease occurs. Although with new therapies, maybe that’s not as common as in the past. In the future, it’d be helpful to have specific biomarkers that might help us identify that transition better. 

Bruce Cree, MD: Do you think that transition might occur early on? Some patients have a progressive phenotype embedded within what we would normally consider a relapsing disease. If you look at the patients and carefully follow them, we sometimes see progression in terms of disability worsening that is not clinically recognized. We recognize it in retrospect when we look at things like the EDSS [Expanded Disability Status Scale] score, timed 25-foot walk, or other measures of disability. 

Do you think that these processes really are one leading to the other, or do you think that the 2 processes are superimposed on top of each other?

Kristen Krysko, MD: I think there is a lot of overlap. Some of the more recent studies, like your EPIC study, did show the term “silent progression.” There were patients who were classified as relapsing-remitting in the clinic, who did have worsening independent of relapses. We’re recognizing that more, where there could be a gradual worsening, even in the younger patients with a relapsing-remitting definition of MS. 

Fred D. Lublin, MD: There are 2 issues to think about that you’re getting at here, Bruce. One is: is progression there in everyone? I would posit no. The second is: is progression born or made? Is it there in the progressive patients from the very start, or does something happen to relapsing-remitting patients along the course of their disease that then leads them into this transition into progressive disease? I’d be interested in comments on that.

Robert Fox, MD: We know that patients who have a lot of spinal cord lesions are more likely to evolve into progressive MS than patients who don’t. That suggests that there is something back at the inception of the lesions, whenever those lesions develop, that may set into process something that leads to progressive MS. I’m not sure we know the answers to that, although they’re important questions.

Another facet is that it depends on what the patient does. I have a couple of patients who are long-distance runners who first noticed their progressive MS when they were in mile 21 or 22 of their marathon runs. Then it gradually moved back to mile 15, mile 12, then mile 8 of their long-distance runs. When they’re not running, they’re totally fine. Is that consistent with progressive MS? Absolutely. But what if they weren’t runners? If they weren’t runners, we wouldn’t know that they have progressive MS. We have patients who only notice the slowing when they do long walks around the block or when they climb stairs. What happens if they didn’t do long walks or climb stairs? We wouldn’t know they have progressive MS.

Some of progressive MS is defined based on what patients are doing, which is a pretty crummy way to make a diagnosis, but that’s what we’re stuck with. It goes back to when the system is being pushed really hard, whether it’s long distance running, climbing stairs, or long walks around the block. When the system is being pushed for a long duration, that’s when it starts breaking down and we start noticing the progressive aspects of progressive MS.

Joseph R. Berger, MD: What I would say is that the illness is extremely capricious, and every patient is different. There are individuals who have relapsing-remitting disease that looks very bad at the inception and then have nothing for extensive periods thereafter. Then there are individuals who have no evidence as best as you can tell, even people who continue to exercise vigorously without any evidence of progression. 

On the other hand, there are people who are wheelchair-bound in short periods of time. It’s very difficult to predict who is going to have that particular outcome. Perhaps we’re doing better. Maybe some biomarkers will help us. We certainly have prognostic factors that we’ve employed, such as the lesion burden in the spinal cord, but it’s extremely difficult to predict.

I would posit that whatever drives relapsing-remitting disease is probably quite different than whatever drives progressive disease. We certainly don’t find that the drugs that are so effective for relapsing-remitting disease have much of an effect in individuals with progressive disease.

Bruce Cree, MD: Thank you for watching NeurologyLive® Peer Exchange. If you enjoyed the content, please subscribe to our e-newsletters to receive upcoming Peer Exchanges and other great content right in your inbox.

Transcript Edited for Clarity