Diagnosing Clinical Subtypes of Multiple Sclerosis  

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EP: 1.Diagnosing Clinical Subtypes of Multiple Sclerosis  

EP: 2.First-Line Treatment Considerations in RRMS

EP: 3.Advantages of High-Efficacy Therapy in RRMS

EP: 4.Selecting a High-Efficacy Therapy for RRMS 

EP: 5.Monitoring Response and Sequencing Therapies in RRMS

EP: 6.Ublituximab for MS: The ULTIMATE I and II Trials

EP: 7.Evobrutinib in MS: The EVOLUTION RMS I and II Trials

EP: 8.Future Direction of MS Treatment

Lawrence Steinman, MD: The main issue about multiple sclerosis [MS] is that, historically, the classical definition of multiple sclerosis required new events occurring in different places of the brain over time. Over the years, we’ve had a couple of revisions of the McDonald criteria. Now, a second MRI lesion is enough to qualify for having multiple sclerosis. Simplistically, that’s how the diagnosis is made.

MRI gives us a deeply informative view of what’s going on in the central nervous system, including the brain and spinal cord. There are different techniques used in MRI to elucidate new lesions, older lesions, and lesions where there is a leaky blood-brain barrier, that take up an element that’s on the periodic table called gadolinium that has a magnetic spin. All of these techniques with the availability of MRI give us precision in knowing where the lesions are, how big they are, whether they’re older or newer lesions, and whether they’re active or chronic based on those different parameters.

We’re getting stronger magnets and better programs for looking at the magnetic spin and featuring some of these different types of lesions. When all of this is combined, you’ll have an exquisite picture of the anatomy and the chronicity or acute activity. MRI has been a tremendous adjunct to clinical diagnosis based on the history and neurologic examination.

Enrique Alvarez, MD, PhD: The subtypes of multiple sclerosis are an area that different providers will think about differently. There are some nice consensus criteria discussing relapsing/remitting MS, secondary progressive MS, and primary progressive MS. Providers will sometimes make adjustments. For example, in our center, we don’t like to use the word remitting, because not all attacks will get better. You’re starting to see a bit of a shift into calling it relapsing MS.

It’s also important to consider what some of these terms mean. A lot of these criteria are defined strictly on clinical criteria. A lot of us tend to think that they might include MRI criteria, but that hasn’t been the case. These were added more recently. Some providers assume you’re discussing that, and sometimes not. It’s important to understand what providers are discussing when you’re using these words.

Clinically isolated syndrome is a category that is almost becoming extinct. That has a little to do with the newer criteria. With each revision of the McDonald criteria, more and more of those patients who are presenting with a single attack are getting absorbed into full-blown MS. The idea of clinically isolated syndrome was to try to capture patients who had only had 1 clinical attack. In order to meet a diagnosis of multiple sclerosis, as the first word implies, it has to have multiple events. The McDonald criteria started including MRI in 2000. The 2005 criteria added the ability to look at lesions as they appeared on follow-up MRIs and say that those new lesions are equivalent to an attack, and therefore it now can be considered multiple sclerosis.

As we started to look at the 2010 criteria, if you had a contrast-enhancing lesion and stuff that wasn’t enhancing or active, those patients would now be classified as MS and not clinically isolated syndrome. In 2017, the newest criteria, patients who had inflammatory spinal fluid, either oligoclonal bands or an elevated IgG [immunoglobulin G] index, would now be classified as having met dissemination in time and would meet full criteria for multiple sclerosis. When we look at patients with clinically isolated syndrome who still don’t meet the full criteria for multiple sclerosis, we can identify that there are certain groups that are much more likely to go onto MS, particularly younger patients, those who have active disease at the beginning, and more disease.

With the assumption that most patients are probably going to meet the criteria of relapsing MS, this represents about 80% to 90% of patients we see at first presentation. These are patients who have had attacks. We use some terms interchangeably here, so we often will talk about relapses, bouts, attacks, flares, and exacerbations. They all mean the same thing. We frequently interchange these terms. About half of these patients will eventually have secondary progressive MS. When we look at this group, it’s important to recognize that, in the past, we’ve often said about 50% of patients develop secondary progressive for every 10 years. At 20 years, that becomes 75%. At 30 years, it’s almost 88%. That is from a time when we didn’t really have treatments. As we start having treatments for MS, we can really reduce that. There are some data now using the oral therapies and infusible therapies that those numbers might be as low as 5% for every decade. It shows the power of the treatments to reduce the patients’ chances of developing progressive MS.

There’s a subgroup of patients, about 5% to 15%, who don’t have those clinical attacks and are just in the progressive phase. We call that primary progressive MS. Those patients have had attacks, but we don’t see them clinically. You can imagine an attack that cuts out 1 IQ point may go unrecognized by the patient. Every morning, I drop a few IQ points until I have my coffee. It’s easy to see where patients may have symptoms that aren’t classic MS symptoms and recognized. About 90% to 95% of MS lesions don’t give you symptoms. It takes a fair number of lesions, on average 13 to 15, before the appearance of a lesion that lets you be diagnosed with multiple sclerosis.

There are a couple of terms that are also important to define at this point. We talk about progression, which sometimes gets confused with worsening. With worsening, we talk about patients who are developing new symptoms, but it could be from either progression in that progressive phase of MS, or getting worse from an attack from MS. It’s a bit of a bigger umbrella term. Where you can see this be an issue is sometimes patients getting worse quickly. They’re starting to get so many attacks that they don’t really have discreet events, they’re all running together. Sometimes these patients get labeled as progressive, when in reality, they are not progressive, they’re just having a lot of attacks. It’s important to try to differentiate that.

There’s also this issue of pseudo-attacks or pseudo-relapses. These are events that are real, clinically. Patients will have symptoms associated with them, but these are more driven by old symptoms returning, rather than inflammation. Sometimes we might think of, for example, pseudo-exacerbations or recrudescence of strokes, where patients who have had an old stroke, their symptoms come back after a urinary tract infection, it’s hot outside, they’ve not been sleeping well from stress, etc. You fix the infection. You cool down. You hydrate. You take care of the underlying issue, and the symptoms will go back to what they were, and they don’t cause any worse damage to the central nervous system. Understanding these terms becomes important to understand the differences between the types of MS.

Transcript Edited for Clarity