MS Relapse: Supplementary Strategies to Assess Outcomes

Stephen Krieger, MD: That takes it right to Rob. What you have developed at Cleveland Clinic to capture data even beyond what the EDSS [Expanded Disability Status Scale] gives us to fill out some of the details, given that the EDSS is weighted toward gait and doesn’t capture things like cognition and mood and anterial visual system function all that well. How do you add to that, and do you also see some of the same fluctuations happening over time in your patients with the data that you’re capturing?

Joseph R. Berger, MD: Well, I think what we’re all striving for is a way to quantify how much of a deficit a patient accumulated because of a relapse and how well they’ve recovered. And as we pointed out in the beginning, degree of recovery from a relapse is a really important prognostic sign. I would probably put on a short list of 4 or 5 prognostic signs of how carefully you need to be with someone’s MS [multiple sclerosis] because they may potentially have a poor prognosis. If you don’t recover well from your first couple of relapses, you’re unlikely to recover well from subsequent ones. And so we quantify using this digital version of the MSFC [Multiple Sclerosis Functional Composite].

We sometimes will perform an EDSS. I’ll put a plug here for the visual system, and especially multimodality assessment of things, so you can assess patient-reported outcomes in the visual system. You can assess low-contrast letter acuity for a clinical measurement of how someone is doing. And then you can put an imaging biomarker to that also and measure things like the retinal nerve fiber layer or the ganglion cell layer thickness.

This is a model that, in my mind, I used to help understand the process of how we identify and treat relapses and measure recovery. I’ll give you an example of a patient who comes with optic neuritis, and it’s been severe and they still have persistent deficits, even after a course or even 2 courses of IV [intravenous] steroids. If I do an OCT [optical coherence tomography] and see that their ganglion cell layer, after 6 or 8 weeks, remains intact, it shows me that there’s potential for recovery there, and that’s a patient I would potentially refer for plasma exchange. In the visual system we actually have a marker for that. We’re measuring neuronal loss of the ganglion cell layer. And if it’s not gone yet, maybe there’s a chance for recovery. We don’t have that opportunity in any other systems using advanced MRI [magnetic resonance imaging] that’s available clinically or anything. It is useful not only for patients who have visual problems but also as a way to help understand how I make decisions in general.

Stephen Krieger, MD: That’s great. It’s such a great example of using a more nuanced biomarker that admittedly we don’t all have, but it gives us insight into what kind of things should we be looking for to assess disability and gauge response to treatment and the need for treatment. Sam, do you have other thoughts on things that you do or hope to do in your practice to look more carefully at treatment response?

Samuel F. Hunter, MD, PhD: I try to do the EDSS at a nonrelapsed point, because it’s most useful if you can actually transform that very simply with the MS severity score to tell you how your patient is doing over time. But what everybody has to do who sees MS patients is write down an accurate exam when they see the patients regularly. That’s the best way you can assess if that person is getting worse. When you see a deficit, you look back at your prior exams and identify, how long have they had this deficit? OK, well, they’ve had a hemiparesis for 6 years.

It’s not that their MS isn’t going down in a handbasket, but the first time they come in with that weak leg; it requires some real interrogation. When did this happen? What’s going on? Many times, it’s a relapse, and you’re going to treat it like a relapse because you don’t know it’s not. And it may or may not be a relapse. If it gets better, it may be progression. But it comes up on the radar screen simply because you’ve got a comparator exam in the medical record. Your pyramidal, your sensory, your cerebellar, and your visual cranial nerve exams. Watch the patient walk. I can’t tell you how often I get records from somebody with a normal template, and that person has obvious disabilities. And you ask the patient, “Did the doctor ever examine you?” They say, “Oh no, he’d pat me on my head and say ‘You look good,’ and walk out of the room.” So that shortcut is very, very bad for being able to manage MS patients. And so take history and do an exam, just as you were taught. It really pays off in medic