Monitoring Disease Worsening in Multiple Sclerosis

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The MD Magazine Peer Exchange “Strategies in the Management of Relapsing-Remitting Multiple Sclerosis” features a panel of physician experts discussing the importance of early therapy in multiple sclerosis treatment, factors that affect choice of management strategy, the need for ongoing monitoring, and other aspects of treating patients with multiple sclerosis.

This Peer Exchange is moderated by Fred D. Lublin, MD, FAAN, FANA, Saunders Family Professor of Neurology and director of the Corinne Goldsmith Dickinson Center for Multiple Sclerosis at Icahn School of Medicine at Mount Sinai, New York.

The panelists are:

• Patricia K. Coyle, MD, professor and vice chair (Clinical Affairs) and director of the Multiple Sclerosis Comprehensive Care Center at Stony Brook University Medical Center, New York
• Clyde E. Markowitz, MD, associate professor of neurology and director of the Multiple Sclerosis Comprehensive Care Center at Perelman School of Medicine, University of Pennsylvania, Philadelphia,
• Claire S. Riley, MD, assistant professor of neurology and director of the Columbia University Multiple Sclerosis Clinical Care and Research Center, Department of Neurology, Columbia University, New York

Fred D. Lublin, MD, FAAN, FANA: Clyde, how about monitoring? Not patients on therapy, because we’ll come back to that, but monitoring individuals where you’re not sure yet what you’re going to do.

Clyde E. Markowitz, MD: Most of the time I will look at them about every 3 to 6 months. I just saw somebody yesterday with this exact scenario. And the idea for me is that I’m looking for what is the earliest time point I could see changes clinically or radiologically. So, I see them every 3 months, maybe 6 months, depending upon where things are at. They’ll get scanned.

For some of these patients who might present with a kind of initial symptom, I don’t have enough data to support an actual diagnosis at this point. I will offer them a spinal fluid analysis, which could be very useful. But let’s say at the end of the day they’re not ready to be on therapy or I’m not ready to put them on therapy. I just set up an every 6-month assessment for that. They get scanned every 6 months and we just monitor to see whether or not there’s any ongoing evidence by scans or clinically. That’s what I do.

Fred D. Lublin, MD, FAAN, FANA: And Claire, what about looking at that brain volume? Do you do it in the clinic?

Claire S. Riley, MD: I look at every scan and make an assessment of their ventricular width, but this is not a metric that we’re getting quantitatively from our radiologist. So, I think that brain volume probably is extremely important. Probably the way that I’m looking at it is pretty insensitive.

Occasionally I see people who really seem to be dropping off from a brain volume standpoint, and that does worry me. But I think I have less confidence in, for example, making a therapeutic change based on volume that appears to be slipping versus new contrast enhancing lesions or newer enlarging T2 lesions. What so you guys do in the clinic?

Fred D. Lublin, MD, FAAN, FANA: I think there’s too much variability so our radiologist won’t give it to us. I think that if you look, you can eyeball over years and see the changes. But it’s not yet ready, at least I think, for prime time. Monitoring of individuals—there’s too much variability.

Claire S. Riley, MD: I don’t find that I’m making clinical changes based on it.

Patricia K. Coyle, MD: I think the most important thing is that we’ve acknowledged how important surveillance or monitoring brain MRI is. We should make sure we are using a facility that does a competent study and a comparable study. You can’t have patients going to different machines, different facilities, and different magnet strength. You want a uniform protocol done for MS, and there have been recommended MS protocols for imaging brain and spinal cord.

I think right now, our efforts should be at maximizing the clinical MRIs that we do to make sure they’re really comparable. If we say there’s enhancement or not, it’s valid we waited at least 5 minutes. If there’s a new T2 lesion or an enlarging T2 lesion, that’s an accurate statement. You don’t have skips or gaps. You have really good quality studies.

Claire S. Riley, MD: It’s such a challenge in the current insurance environment. Patients are being told, “Okay, if you want to get your study at the university, it’s going to cost you $600. If you get it done at the place down the road, it’s 40 bucks.”

I understand people’s limitations and barriers, but I think for best care, I absolutely agree with you, Pat. We need consistency in order to make valid comparisons.

Patricia K. Coyle, MD: Absolutely. That practice is an abomination. We need to get that changed.

Fred D. Lublin, MD, FAAN, FANA: How about distinguishing in older patients? So, one of the things that we’ve seen—especially since MRI has become popularized—is MS presenting in older individuals, where before, they may have been told they’ve had strokes. How much of a challenge is this?

Claire S. Riley, MD: I think it’s hard at times to really distinguish between ischemic disease and myelinating lesions. I always look, first, at the patient and say, “Okay, what’s the likelihood this person has ischemic white matter disease?” “What risk factors do they have?” “What’s the background of the patient?” “What are the symptoms that he or she is presenting with?” And then, radiographically, I try to look for distinguishing characteristics of MS lesions and ovoid extending out from the callosum.

I’m particularly moved by spinal cord lesions, which you shouldn’t see in ischemic disease. But I agree, it’s absolutely a challenge and there’s the dogma of, “Well, this person is 65, she can’t have MS.” Well, she can, and it can be diagnosed.

Clyde E. Markowitz, MD: Spinal fluid is particularly useful in that setting, right?

Patricia K. Coyle, MD: Thank you Clyde.

Clyde E. Markowitz, MD: You’re welcome.

Patricia K. Coyle, MD: So, only 10% of MS will have onset after the age of 50. But clearly, you can see it in the 60’s and in the 70’s. One important point is the brain MRI shouldn’t be the lynchpin of the diagnosis in this case because you begin to see the lesions with aging, but not true for the spinal cord, Claire, as you pointed out. And I think spinal fluid becomes even more important. There is an enrichment in a primary progressive onset with older age onset MS.

Clyde E. Markowitz, MD: I just saw somebody yesterday with this exact case—60 years old, a woman, had 3 or 4 lesions in her cord, many lesions in her brain, all on periventricular distribution. She has bands in her spinal fluid. This is her first presentation, slow progression from onset.