Clinical Subtypes of MS


A panel of experts led by Bruce Cree, MD, highlight the clinical subtypes of multiple sclerosis including presentation and prevalence.

Bruce Cree, MD: Hello and welcome to this NeurologyLive® Peer Exchange titled, “Management of Progressive Multiple Sclerosis.” I’m Dr Bruce Cree from the University of California San Francisco Multiple Sclerosis Center. 

Joining me today in this virtual discussion are my colleagues, Dr Joseph Berger from the MS [multiple sclerosis] Division at the University of Pennsylvania, in Philadelphia; Dr Robert Fox from the Cleveland Clinic in Ohio; Dr Kristen Krysko from St. Michael’s Hospital-Unity Health Toronto, in Canada; and Dr Fred Lublin from the Corinne Goldsmith Dickinson Center for Multiple Sclerosis at Mount Sinai Medical Center in New York. 

Today, we’re going to discuss a number of topics pertaining to the diagnosis and treatment of secondary progressive and primary progressive multiple sclerosis. Let’s get started on our first topic.

I’d like to begin with an overview of relapsing-remitting MS, secondary progressive MS, primary progressive MS, and the clinical subtypes of MS, including the presentation and prevalence. Joe, would you like to go ahead and start our discussion on that? 

Joseph R. Berger, MD: Sure. I’d be delighted. Traditionally, we’ve divided multiple sclerosis into different clinical subtypes. The one that is most prevalent is the relapsing-remitting form of the disease, where an individual has an event that occurs with resolution of those symptoms—maybe not in their entirety—and then a second event and a third event. It’s called relapsing-remitting for that reason.

It is the type that is seen most commonly. Of all the individuals who present, around 80% present with relapsing-remitting disease. However, at the initial presentation before you can define it as relapsing-remitting disease, they may present with an isolated event without having anything before that could be recognized as a clinical event related to multiple sclerosis. We refer to that as the clinically isolated syndrome. 

As many as 50% of individuals who have had this disease for 10 or 15 years, at least prior to the availability of disease-modifying therapies, would enter a phase of the illness that has been classified as secondary progressive multiple sclerosis, where they have a slow progression of the disease without there necessarily being clinically identified relapses superimposed on it. 

Those individuals generally have increasing difficulty with their gait, balance, and cognition. You may see other manifestations as well. In my opinion, the frequency with which that is seen has decreased very considerably with the availability of disease-modifying therapies. In years past, the data suggested that 50% of people within 10 to 15 years of onset of their disease would evolve to a secondary progressive form. I don’t think that’s necessarily the case any longer. 

About 10% of the people we see present with what is referred to as a primary progressive MS subtype or phenotype. That’s the individual who slowly gets worse over time. It’s generally an individual who comes in with spinal cord manifestations, worsening gait, and worsening balance. It is sometimes an extraordinarily difficult diagnosis to confirm. Sometimes it’s quite easy, but sometimes it can be quite difficult. There are other things that can appear similar. Those individuals tend to be older than the individuals who present with relapsing-remitting disease. Those are the 4 subtypes that we generally classify MS into. 

Bruce Cree, MD: Joe, I’m going to follow that up with a question. For clarity, does secondary progressive MS, which is going to be one of the key topics we review today, always begin with a relapsing-remitting onset?

Joseph R. Berger, MD: Not necessarily. There are individuals who will come in with a progressive phenotype when they present to you. When you question them very carefully, they’ll say, “You know, 5 years ago, I had numbness on the right side of my body. It lasted for 3 days. I thought I slept on it funny.” Or they’ll say, “I had some problems with my vision and it went away.” They often get classified as primary progressive disease, but there’s evidence in their history that there are preceding events that were misclassified. 

A number of people we label with primary progressive disease have actually had an active component, a relapsing-remitting component, sometime in the past.

Fred D. Lublin, MD: Everything Joe just said was true, except for his answer to your question, where he said, “Not necessarily.” Necessarily by definition, they have to start with a relapse. Sometimes the relapse wasn’t recognized at the time.

Joseph R. Berger, MD: Well, yes. I would agree with that.

Bruce Cree, MD: Yes, I think that’s what Joe was getting at, and that’s exactly right. Sometimes you do get remote histories reported by the patients, and we don’t necessarily have medical records from those events from 10 or 20 years ago. There may not even be a medical record. Sometimes people will relay an episode of monocular vision loss that clears up spontaneously after a few days, and we don’t exactly know what that event was. 

Joseph R. Berger, MD: I’d like to comment on that. It’s the rare individual who comes into the office and when you look at their MRIs, you don’t see evidence of their having had past disease. Almost invariably, you’ll see evidence of there having been disease that they were totally unaware of. We have no idea when the disease starts in the vast majority of our patients. This is an ongoing process.

Robert Fox, MD: It’s important to recognize some of these episodes are really hard to know. A patient may say, “I had some numbness in my leg 5 years ago, but I also had some back pain, and I’d just been lifting,” so we’re not sure. Was it sciatica? Was it a partial transverse myelitis? They might say, “I had a couple of days of some difficulties with my vision,” but it’s hard to tell if it was optic neuritis, irritation, or conjunctivitis. Oftentimes, it’s very fuzzy to know if this was an undiagnosed relapse in the past or some other neurologic symptom unrelated to MS. 

Bruce Cree, MD: The diagnosis of MS is not always entirely straightforward, nor is the classification. When we can make those classifications, it’s great.

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Transcript Edited for Clarity

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