Stephen Krieger, MD: Let’s think a little bit about the symptoms of relapse. One of the things, of course, you always hear about MS [multiple sclerosis] is that no 2 people with MS are the same. And you said it, there’s no average MS. There’s no average MS relapse, either because they can take such a variety of forms, and we really must be good clinicians in order to recognize the hallmarks of an MS relapse. Joe, maybe you can take us through a little bit of the characteristic symptoms of relapse. What do we look for? What gets our attention?
Joseph R. Berger, MD: Again, this gets to the capricious nature of this illness, because it can really take many different forms. To begin with, it may be monosymptomatic or polysymptomatic. So the patient may present with just 1 isolated event confined to a particular area of the brain, or it may be something that encompasses more than 1 symptom. And the things that we often see are changes in vision. So it’s not uncommon for somebody to tell you that they have pain behind an eye, their vision is blurred, or they’re losing vision, symptomatic of optic neuritis. Paresthesia, numbness, and sensory complaints are quite common as a manifestation of a relapse. It could be a motor feature. It could be weakness of 1 side or both sides, of both legs for instance, difficulty with gait. It may be in coordination or double vision, and it may be some of these things in combination with another.
There’s really no simple way of defining relapse by symptoms. It could be virtually anything. There are certain things, though, that are quite unlikely to be relapses. It’s unusual. It may occur, but it’s unusual for somebody to come in and, say, have new severe cognitive complaints as a relapse. It’s unusual for them to come in with any cortical features. There are certain things that you can distinguish, and the clinician must bear in mind that even in individuals who have defined, well-recognized multiple sclerosis, the symptoms that they’re presenting with may not be related to multiple sclerosis.
Stephen Krieger, MD: I think that’s a very important point. Any additional thoughts from both of you about the kinds of symptoms that get your attention or that you would pursue as a possible MS relapse?
Amy Perrin Ross, APN, MSN, CNRN, MSCN: Well, 1 of the things, I think, that’s really important in terms of diagnosis of MS is to listen to the patient. I do a lot of phone management in a very large academic practice, and very often people will call in. And they’re telling me things over the phone, and it’s really important to listen to what they say and how they say it and then ask appropriate questions to tease out things. I usually wind up in that call asking if they have any infections, fevers, or anything that maybe changed abruptly, even something as simple as a change in their exercise routine—perhaps they’re doing more cardio now than they were in the past, building up core body temperature and having symptoms come and go that might be very different for them. If you listen and ask the appropriate questions, you get that gut feeling and then, as Joe said, go with it.
Stephen Krieger, MD: I think that’s a great point. Sam, any other great questions you like to ask to tease out relapses?
Samuel F. Hunter, MD, PhD: I always ask, “Have you had this before?” Because I think it’s very easy to problem solve if you’ve already gone through it. And many times, these contacts are outside office hours, or they’re calling from an emergency department or urgent care. If this is a problem you’ve dealt with, then there’s a problem. And I like to know what medicines they’re on because usually it tells me a lot about how I’ve been managing them, even if I don’t have medical record in front of me.
Stephen Krieger, MD: That’s a good point.
Joseph R. Berger, MD: I think Sam makes a very important point that I think needs to be expanded on a little bit. When a patient calls and says, “Yes, I’ve had this symptom before,” 1 of the things I always ask is, “Well, how long has that symptom been present?” Because it’s not uncommon for individuals who’ve had symptoms to have transient manifestations of the same symptoms as a consequence of physiological changes. So there’s a phenomenon called Uhthoff’s syndrome, described well over 100 years ago by a German neurologist, of people who would exercise and have recurrence of their symptoms, but they’d be short lived—10 minutes, 15, 20 minutes—and then it would be gone. And we hear this all the time from people who’ve been in either hot environments. Prior to the MRI [magnetic resonance imaging], we had something called the hot-bath tests, where we’d put people in a hot bath. Medical students are very intrigued when we tell them that we actually did this to people. They think it’s barbaric, but we would raise their core body temperature, and we’d examine them before and after because they’d have transient manifestations. These are symptoms as well as signs.
Stephen Krieger, MD: This was in the era before hot yoga, also.
Joseph R. Berger, MD: That’s true. So the question when somebody tells you, “I’ve had this symptom before,” is how long is it lasting? If it’s something that is short lived, if it’s less than 24 hours, we generally don’t regard it as a relapse.
Robert Bermel, MD: I would say the other big thing that I encounter is patients who call in, and everything is worse. Across every domain of function you can think of, they have blurry vision, they have foggy thinking, they’re dropping things, their legs feel weak, and they feel numb all over. And in these people, who have global decompensation of neurological function, my suspicion that there’s a focal bona fide relapse at play is actually low. It’s more likely a secondary factor that’s involved. And if you ask enough questions, sure enough, you end up finding out that this person has an upper-respiratory tract infection that they’re recovering from, has not been getting sleep recently because they changed shifts at their job, or has been under a tremendous amount of stress—something like this. I think that’s another piece that throws people. It often seems like very severe manifestations; therefore, people are worried about the patient, especially people in urgent care or emergency settings. But in fact, we actually go hunting for non-MS contributors to global symptom exacerbations.
Stephen Krieger, MD: I have 2 things to say about that. I know you’ve done some work with your group at Cleveland Clinic looking at that, and how when MS patients come to the emergency department, often it’s for those other things that deplete the person’s ability to compensate, such as urinary tract infections. You have a nice algorithm for that, I know, at Cleveland Clinic. It also speaks to me, and anyone who knows me in this field knows that what I’ve worked on is something called the topographical model of MS, in which the lesion burden that a patient accumulates is compensated by a reserve. And things that globally deplete reserve transiently, like overheating or superimposed infection, bring down that ability to compensate. That transiently, physiologically drains reserve. And all of a sudden, all those same symptoms are present again above the clinical threshold. So I share your view that in that setting it’s not as likely to be a relapse and more likely to be something that’s globally affecting that person’s reserve and ability to compensate.