Thomas P. Leist, MD, PhD: That’s where multiple sclerosis [MS] is obviously a very variable disease. We have individuals with relatively mild disease, and we have individuals with early presentation of great impact where the patient becomes disabled, unemployable, and a burden to the family because of care needs, in a very short order. That’s the part also where we struggle as a field.

Patricia K. Coyle, MD, FAAN, FANA: Yes.

Thomas P. Leist, MD, PhD: Because we don’t have a clear roadmap to know where an individual patient will go.

Patricia K. Coyle, MD, FAAN, FANA: This is a key feature. No two MS patients are alike.

Peter L. Salgo, MD: Yet, we do make the diagnosis. So what are the clinical symptoms of MS? How does it typically present? You’ll forgive my use of the word “typically.”

Patricia K. Coyle, MD, FAAN, FANA: The presentation of MS is most commonly with a clinically isolated syndrome, or CNS [central nervous system] inflammatory attack, like an optic neuritis, like an acute transverse myelitis involving the spinal cord, like a brain stem isolated syndrome. That’s how relapsing MS typically presents. And the unusual form of MS, progressive from onset, typically presents at midlife with a slowly worsening gait, leg weakness syndrome, a myelopathy.

Peter L. Salgo, MD: What about comorbidities? What else goes along with this?

Thomas P. Leist, MD, PhD: Well really early on, particularly the young patients, there isn’t much that goes along because the individuals are very healthy. Later on in life, old comorbid conditions that can occur can also occur in MS patients. And it becomes exceedingly clear that microvascular disease, or disease of the small blood vessels, doesn’t play nicely in an MS patient. It’s also clear that diabetes doesn’t play nicely with MS patients. And one also needs to keep in mind that patients with multiple sclerosis have about double to triple the risk of having a second autoimmune condition compared to the general population.

Peter L. Salgo, MD: And before you jump on him for saying a second autoimmune condition, because you haven’t established that the first condition is autoimmune, let’s just simply say they have a second immune issue. But that’s important. And I think the takeaway that I’ve heard from you is, any disease, like microvascular disease, that doesn’t play well with neurons is going to be worse in somebody with MS.

Patricia K. Coyle, MD, FAAN, FANA: I think a very important component is we now realize comorbidity is bad in MS. It definitely occurs. It must be treated. Maybe the neurologist doesn’t take responsibility, or you won’t get a good handle on the MS. It’s really addressing maximizing CNS reserve. You want a healthy CNS.

Peter L. Salgo, MD: Somebody comes into your office and says, “I’ve got this.” And you say, “Oh, it could be MS.” What else could it be?

Patricia K. Coyle, MD, FAAN, FANA: One of the big things is an autoimmune disorder called NMO [neuromyelitis optica] spectrum disorder. It mimics presenting an optic neuritis or a transverse myelitis, but it’s a very different neuroimmune disease to MS. I think that’s in the differential of anybody presenting with a relapsing MS type of picture.

Peter L. Salgo, MD: What are the McDonald Criteria? I’ve heard this.

Patricia K. Coyle, MD, FAAN, FANA: The McDonald Criteria are the formal diagnostic criteria for MS. They were revised in 2017. They’re very valuable because they give us some objective guidelines to see if the patient qualifies for a definite diagnosis of MS.

Peter L. Salgo, MD: And there’s something called, I’m going to read this, the Expanded Disability Status Scale, the EDSS. What the heck is that?

Thomas P. Leist, MD, PhD: That’s a way of evaluating a patient’s disability. It overestimates or overemphasizes the motoric disability of an individual, it doesn’t assess the cognitive disability. It’s a measure that we all in the field of MS like to hate, or hate to like. It is the one thing that gives medications. For example, the indication of prevention of disability progression. Because if an agent can show that it delays worsening in the EDSS, then that is an added indication for the medications as they are indicated.

Peter L. Salgo, MD: Do payers depend on that? Do they look for that?

Maria Lopes, MD, MS: We do. We heavily rely on a specialist to confirm the diagnosis. And what I’m hearing is it’s as much about ruling in MS as well as ruling out other conditions. And so the medical history, the neurologic exam, how symptoms presented—the journey, if you will, by the time you present with specialists as well as MRI [magnetic resonance imaging] findings—become critical. Because once you label that patient with MS, then there are treatments, right? But hopefully it is a correct diagnosis, and I think from the experts we’re learning about different forms of MS that have meaningful implications for what treatments are available.

Patricia K. Coyle, MD, FAAN, FANA: Right. And we know we have a 5% to 10% misdiagnosis rate of MS. So very important to make an accurate diagnosis at the beginning.

Peter L. Salgo, MD: When you say missed, you mean people come in and you misdiagnose, or you don’t diagnose it?

Patricia K. Coyle, MD, FAAN, FANA: They’re told they have MS, and they don’t have MS.

Peter L. Salgo, MD: What about the converse?

Patricia K. Coyle, MD, FAAN, FANA: That can happen.

Thomas P. Leist, MD, PhD: That happens quite often. It happens often in the community, very often when practitioners don’t review the MRIs, or an inexperienced radiologist looks at an MRI. Because very often I call the MRI reads “the IKEA moment” of the day.

Peter L. Salgo, MD: What does that mean?

Thomas P. Leist, MD, PhD: An IKEA moment is when it says on the outside of the IKEA box, “Minor assembly needed.” What does it say at the end of a radiologist report? “Clinical correlation needed.” I’m not bashing on the radiologist.

Peter L. Salgo, MD: Oh, go ahead, they’re not here.

Thomas P. Leist, MD, PhD: You have the read where it says, “Clinical correlation needed.” And above is a whole litany of what this could represent. I think coming back to the diagnostic criteria, the McDonald Criteria, it’s very important to know that, for example, in the relapsing forms of multiple sclerosis an event has to have occurred. An attack has to have occurred to apply this for the progressive, primary progressive form. There has to have been disability progression over time. So sometimes when we see patients with multiple sclerosis, the symptom complex is spelled M-E-S-S, a mess. And so they have all over the body something wrong. But MS as a diagnosis is more specific than that. We need to be able to locate the symptoms in the neurological territory. We need to be able to objectify with MRI. And when we apply the criteria, we need to be able to apply the criteria as they are meant.