Goals of Treating Relapse in Multiple Sclerosis

Stephen Krieger, MD: We want to treat relapses. What are our goals when we are doing that? A patient comes to us, and we assess that they’re having a relapse. What’s the treatment goal with that initial response to an MS [multiple sclerosis] relapse?

Samuel F. Hunter, MD, PhD: We see the patient at the time of symptoms that they notice. Or much less commonly, we see them incidentally because they were scheduled to and we wonder what’s going on here. We have what is obviously some kind of objective change, whether or not it’s a sensory event that’s more subjective for the patient. It’s clear that something has changed. And our goal is to assess: When did this start? Is it getting worse still? How bad is it going to get? What’s the prior history? And how can we appropriately treat it? What have we done before? How have we managed this person’s relapses? Were we successful?

Younger people tend to come on faster and resolve faster from when we treat them, presumably because of the nature of the inflammation. With older people, it can be much more gradual. It can be very gradual in onset in people who are on therapy as well. What I have to ask myself is: How bad is this going to get? Is this something where patients have a very great deal of discomfort because of the nature of the event? It’s really not a disabling sensory event. It might be painful. It might require symptomatic treatment. But to resolve the event unless it’s really quite exclusively painful, you may need to do nothing except to treat it symptomatically. And similarly, some very unpleasant symptoms can be very benign relapses with vision or vertigo.

But you also have relapses that mean a lot, like if the legs and the bladder aren’t working, if there’s a really big liability here for other things happening—for injury, for occupational disability—that you want to not only treat but make sure you’re assessing that person, that the treatment was enough and it’s effective.

Joseph R. Berger, MD: I’d like to pick up on what Sam said. When you walk down the center of the campus at the University of Pennsylvania, you find the aphorisms of Benjamin Franklin. Why? Because Franklin started the University of Pennsylvania, and among his sayings is “An ounce of prevention is worth of a pound of cure.” What is a relapse telling us? A relapse is telling us that this disease is still active, and that’s why it’s critically important, I think, for us to identify the relapses, because that disease is still active. Whether you treat the relapse or not, you know that disease is active, and you know whatever you’re doing for the patient at that point in time is simply not working. And it may lead to a change in the disease-modifying therapy that you’re using.

And I’d also like to add that we think individuals, just because they seem to improve very often following the relapse, have gone back to their baseline. But generally, they don’t. It’s probably 50% who may. If you look at the optic neuritis treatment trial, which I think is quite informative in this regard, they found that at 6 months, everybody who had optic neuritis still had impaired visual acuity in some way, shape, or form. And when they looked at them 15 years later, a quarter of them still had significant visual acuity, and the patient may not recognize it. How often do we see patients who have had optic neuritis and say, “Well, which eye did you have the optic neuritis in?” And they say, “I don’t know, Doc, it was 5 years ago. I can’t tell you.”

But if you look hard enough, you find that there’s an abnormality. If the treatments that we have for relapses are effective in eliminating that inflammation, it likely has a role in decreasing whatever permanent damage is left.

Stephen Krieger, MD: I think that’s a great point, and the idea about being even more sensitive to subtle findings, either of a relapse or from a relapse, is a direction our field is moving in to try to develop more sensitive ways of measuring some of these things. Rob, maybe you can speak a little bit to how the Cleveland Clinic uses its infrastructure for early identification of relapse or looking for subtle consequences and prognostic implications of a relapse.

Robert Bermel, MD: Sure. I think if we’re talking about identifying relapses, 1 of the most important points is providing something that pediatricians are always really good at, and that’s anticipatory guidance to our patients. One of the questions that many patients have and only a few of them ask is, what should I call the doctor for? What sorts of symptoms should worry me? And so I think even just a minute or so of conversation with a patient who’s newly diagnosed in an exam room is important, to reassure them and tell them that most patients’ relapses do not occur 3 times a week, do not occur once a month. They’re an infrequent event, and they’re neurological symptoms that last longer than 24 hours, and we need to tell them that we’re available. And if they’re having any symptom that lasts longer than 24 hours, they should call us about it.

The first thing we do is instruct the patients about what to call about, basically. And at Cleveland Clinic, we monitor patients’ neuro performance. That means checking different domains of neurological function quantitatively over time. That includes cognition, it includes low-contrast letter acuity vision, it includes manual dexterity and walking speed, and we also have patient-reported outcomes that we collect at each office visit. We can literally plot those out over time, and if we’ve had a history on a patient for a while, you can see whether those numbers are stable or changed. If there’s been a deviation from things, if all the numbers are off, if you’re suspicious that maybe there’s something else going on—especially the depression measure potentially or anxiety measure that we collect on patients at every visit. And if you see that the walking speed is off and they’re having these lower-extremity symptoms, it helps to have the neuro performance and the patient reported outcomes monitored.

And so instruct the patient to call when they have symptoms that we would worry about. Have these numbers on file for the patients and the ability to plot them over time. And then get them checked out, as Amy said. Our options have really expanded a little bit, whereas the options used to be just talk to them by phone and figure something out, or we’ll bring them in for a visit. There’s an in-between option now at a lot of places called virtual visits, where you can see a person via a video link from their smartphone, and you can actually talk to them face to face with a provider and assess them. And that’s become an increasingly common way for us to assess patients with new symptoms at our center.

Stephen Krieger, MD: It’s a good middle ground between the phone call—where you can’t always get a full sense—and having the person come in geographically might be difficult for them.