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Advances in Early Treatment Approaches in Multiple Sclerosis - Episode 1

Updated McDonald Criteria for Diagnosing MS

Fred D. Lublin, MD: Multiple sclerosis [MS] is an inflammatory demyelinating progressive disease that affects the central nervous system. There is no cure for multiple sclerosis, but advances in early treatment are available, which can modify the course of the disease. In this Neurology Live® Peer Exchange discussion entitled, “Advances in Early Treatment Approaches in Multiple Sclerosis,” I am joined by a panel of my colleagues, all experts in the field of multiple sclerosis. Together we’re going to discuss the use of new therapeutic options. We will review the latest clinical trials and provide practical perspective on how the recent data apply to your clinical practice.

I’m Dr Fred Lublin, the Saunders Family Professor of Neurology and the director of the Corinne Goldsmith Dickinson Center for Multiple Sclerosis at Mount Sinai Medical Center in New York.

Today I’m joined by Dr Amit Bar-Or, the chief of the Multiple Sclerosis Division in the Department of Neurology of the Perelman School of Medicine at the University of Pennsylvania in Philadelphia, and the director of the Center for Neuroinflammation and Experimental Therapeutics.

Dr Peter Calabresi, the director of the Division of Neuroimmunology and a professor of neurology at Johns Hopkins Medicine in Baltimore, Maryland.

Dr Patricia K. Coyle, the director of the MS Comprehensive Care Center and a professor of neurology and interim chair at the Stony Brook Neurosciences Institute in Stony Brook, New York.

And Dr Stephen Krieger, an associate professor of neurology at the Corinne Goldsmith Dickinson Center for Multiple Sclerosis at Mount Sinai Medical Center in New York.

Thank you for joining us, so let’s begin.

We’re going to start with discussing diagnostic issues of multiple sclerosis. We’ve changed the criteria for diagnosis, the guidelines, several times since 2001. The first McDonald Criteria came out in 2001. We modified them in 2005, again in 2010. And then the last time was in 2017, and that’s been published in The Lancet Neurology. We’re going to discuss a bit, Stephen will take the lead on this, on what’s new in McDonald Criteria 2017.

Stephen C. Krieger, MD: I think the goal of the McDonald Criteria, as you said, has been to define a gold standard by which we can diagnosis this disease. And that’s been incredibly important since MS is, of course, so heterogeneous; it’s important to have criteria that we can use that we’re all in a sense speaking the same language about what constitutes defined multiple sclerosis.

The 2010 McDonald Criteria I think simplified matters, particularly pertaining to the MRI [magnetic resonance imaging] scan. It allowed us to use really any 2 lesions and any new lesions, as I like to think of them, in their characteristic locations, as being able to diagnose MS on the basis of dissemination in space, and dissemination in time in the right clinical circumstances.

The 2017 criteria moved us a little bit further, and I think, again, this makes it a bit easier to diagnose MS in some cases. The real additions of the 2017 criteria are that if you have a patient who has a classic clinically demyelinating syndrome presentation—optic neuritis, a brain stem episode or a partial myelitis—we can use the MRI scan to make that diagnosis. And now the presence of, again, lesions in the characteristic places, periventricular, infratentorial, juxtacortical, are essential, and to that we’ve now added that cortical and juxtacortical lesions both count.

I think that’s a reflection of the fact that we understand that MS is not just a white matter disease, but it principally involves grey matter, and so looking for those cortical and juxtacortical lesions, lesions that touch the cortex, now both count.

On the other side, we had not used spinal fluid all that often in making an MS diagnosis for the past, I don’t know, decade or so. And the 2017 McDonald Criteria promoted spinal fluid findings back into the pantheon, if you will, for MS diagnosis. And so now the presence of oligoclonal bands, unique to the central nervous system, on spinal fluid analysis can be an important part of the MS diagnosis; it can substitute for dissemination in time. 

So in essence if you have a patient who has 1 attack whose MRI doesn’t meet criteria for both dissemination in space and time, doing a spinal tap, finding unique oligoclonal bands, can allow us to make a McDonald Criteria diagnosis of MS in that patient.

Fred D. Lublin, MD: Patricia, you’ve been a proponent of CSF [cerebrospinal fluid] analysis for a long time. Any changes that you’ve made since this came out?

Patricia K. Coyle, MD: Absolutely none, because we routinely looked at spinal fluid in all the patients. We are missing a diagnostic biomarker. We’re trying to make the diagnosis as early as possible. Therefore, we want to be critically correct. And my concept of a work-up, and I don’t think this should be a clinical diagnosis, it should be a laboratory-based diagnosis, is a judicious choice of blood work; brain MRI with and without contrast; cervical and thoracic MRI scan going down to the conus, so you completely image the central nervous system; and evaluating spinal fluid; and the single best test, oligoclonal bands. Now that preempts the IgG [immunoglobulin G] Index. I think every patient deserves that. We’re tending to do optical coherence tomography also routinely. And let me make a bold statement. I believe if you’re working up somebody for relapsing MS, we should be routinely checking IgG to aquaporin-4 and MOG [myelin oligodendrocyte glycoprotein].

Fred D. Lublin, MD: Let’s hold that thought for a minute and let’s get back to spinal fluid. Has this changed? Has McDonald Criteria 2017 changed your approach?

Amit Bar-Or, MD, FRCP: We’ve been relatively proactive in terms of getting spinal fluid, so this is not radically changing the way that we approach it. But I think it is an important reminder that the spinal fluid does add a layer of added value and is particularly important to keep in mind in the context of those presentations that are not going to be particularly typical of standard relapsing-remitting forms of MS.

Peter A. Calabresi, MD:I’ll say it hasn’t changed my approach too much either. I would agree with everyone. I think 1 point that I would like to emphasize is that the McDonald Criteria were not designed to discriminate MS from other syndromes. They’re mostly to increase our confidence that a patient with a clinically isolated syndrome really has definite MS. And so I would urge caution in the differential diagnosis. We see a lot of people for second or third opinions who have been misdiagnosed, and now with MRI we can usually count up white spots that are not necessarily demyelinating lesions. So I think it’s important to seriously consider alternatives.

Fred D. Lublin, MD: That raises 2 things. But first I’m going to finish up with spinal fluid, because I am doing more spinal taps. How about you Stephen?

Stephen C. Krieger, MD: I think we are doing more of them; and in particular, for the reason that you said. The McDonald Criteria, it doesn’t give us a differential, we have to still think about that. That’s the place where you said MS needs to be a laboratory diagnosis, not a clinical one. But I do still think the clinical judgment of what to look for in that differential diagnosis and when to look at spinal fluid to pursue some of those things remains really important. The laboratory tests can’t be done without the clinical judgment that chooses them.

Patricia K. Coyle, MD: Obviously the clinical is key. But what I’m saying is every patient deserves a laboratory work-up.

Fred D. Lublin, MD: They deserve the work-up they need depending on their history and physical. But 2 points that Stephen and Peter made are worth repeating. McDonald Criteria is for diagnosing MS, not differentially diagnosing MS. And the second is that the criteria that were developed for McDonald Criteria were based on classical CIS [clinically isolated syndrome]—optic neuritis, a partial myelitis, or a brain stem cerebellar syndrome. And anything outside of that, one has to be much more cautious, which is what I think you were alluding to.

The other is that McDonald Criteria 2017, for the first time I believe, brought up the issue of misdiagnosis. There’s been a lot of interest in that because there ends up being a lot of misdiagnosis out there. So a big part of our education activity is making sure people are diagnosing this correctly. Also we’re going to discuss this, we’ve stressed treating early, because treating early, people do better. But there’s also the risk of treating someone before they have the right diagnosis. And we have people on agents, and any adverse effects on an agent that are not going to do you any good, are intolerable.