Diagnostic Tools Used to Identify MS

Fred D. Lublin, MD: Clyde, you mentioned something about progressive disease, and I think it’s probably the form of MS [multiple sclerosis] that’s misdiagnosed the most, in both directions. That is not realizing it’s MS and thinking it’s MS, but it’s actually something else. I think that’s one of the reasons why the McDonald criteria still require a year’s history or observation of progression before you could say that it’s primary progressive MS. Spinal fluid has consistently been a part of that diagnosis, but now, as Pat alluded to, it’s more so. Tom, are you doing more spinal taps now?

Thomas P. Leist, MD, PhD: In patients who do not meet the dissemination in time criteria, but from an MRI [magnetic resonance imaging] point of view, certainly. Also, in older patients where very often the differential diagnosis is much larger, a spinal fluid examination can help to look at it. In a young woman aged in the 20s with uncomplicated unilateral optic neuritis, I’m probably still a little bit more reluctant to do a lumbar puncture at that point if I can fulfill the diagnostic criteria in 1 fell swoop. I understand that scenario where different practices practice a little bit differently. Obviously, I also come from the thought process of, what do I need to make a decision to start or not start treatment in a patient such as that one?

If the patient has 2 or more lesions at the time of a clean, crisp clinically isolated syndrome [CIS], then for me that already fulfills the criteria that I need if these lesions are in the previously described telltale locations that I need to make a treatment decision in such a patient. And so, the point of view is, what do I need at the time to adjudicate the future of this patient in terms of going on treatment, not going on treatment? So, yes, there is a little bit more CSF [cerebral spinal fluid], but I’m not necessarily categorically doing it.

Fred D. Lublin, MD: Suhayl?

Suhayl S. Dhib-Jalbut, MD: So pretty much what Dr. Leist described. The only issue I have with the spinal fluid is, how many oligoclonal bands are considered positive? Because the reports vary from 1 laboratory to the other, and I feel there is a lack of standardization there. But if you have 5 oligoclonal bands and they’re not in the serum, then that’s safe to say it’s positive. But in the range of 2 to 3, sometimes 4 bands, there’s no standardization in terms of what’s positive and what’s not.

Fred D. Lublin, MD: So how do you view it?

Suhayl S. Dhib-Jalbut, MD: I tend to consider 1 and more that are absent in the serum to be positive.

Fred D. Lublin, MD: OK, and are you doing more taps?

Suhayl S. Dhib-Jalbut, MD: Yes. As Tom said, in a patient with CIS, and I’m looking for dissemination in time. I’m using that. The other issue I have with the criteria is, what if the patient has nonspecific symptoms that could suggest a relapse, such as increasing fatigue, or cognition changes, or depression, and then you find an enhanced lesion on the MRI? Is this a symptomatic Gad [gadolinium]-enhancing lesion or not? So there are these questions that surround the revised criteria that, in my view, need to be addressed.

Fred D. Lublin, MD: So you’ve long been a proponent of the value of analyzing CSF. Has it changed any since McDonald 2017?

Patricia K. Coyle, MD: In principle, we spinal tap everybody in a disease where you have no diagnostic biomarker. We also practice in a Lyme-endemic area. We’ve actually found spinal fluid to be very helpful with regard to how certain we can be of the diagnosis, in counseling of the patient, etcetera. So right now we standardly do it in everybody for the diagnosis.

Fred D. Lublin, MD: James?

James M. Stankiewicz, MD: At the risk of being the dissenting voice here, I would say that I don’t know that with the revision of the McDonald criteria we are doing spinal taps any more frequently. Maybe I am a little bit more permissive, or I don’t know what the right word would be, but I think that in atypical cases where the presentation, the MRI doesn’t look typical, then I think there really is a role. With progressive sort of presentations, I think there is a role to do a spinal fluid. But I also have an accumulated clinical experience, and maybe this is like a fatal hubris, but I tend to think if it looks like a duck and it walks like a duck, that it’s a duck. So I think the criteria are important, but I also think that you have to exercise some clinical judgment if you have an accumulated experience.

Fred D. Lublin, MD: And that’s a very important point. The criteria are really guidelines, right? And Clyde?

Clyde E. Markowitz, MD: It’s an interesting conversation to have with patients if they want to have it done or not. Because sometimes they’re hearing about a spinal tap being the worst thing in the world, and headaches, and everything else. But I have to be honest that when you really sit down and have that conversation with patients, a lot of times they want that additional confirmation. They say, “If you think I should get it, I’ll get it.” And you know, maybe I do or I don’t. But they kind of feel like that’s more confirmatory. I think it’s a helpful thing for them to be able to know, for sure, even though we say, “The MRI’s good enough,” or “The clinical is good enough.” That extra little piece gives them another piece of reassurance that it’s not another disease phenotype or anything like that.

There’s 1 other piece to this that I think is potentially interesting, and this is just early work that we’ve been trying to address. It is whether band number might be a predictor of severity of the disease. And, at some point, we may be able to say that everybody should get tapped because we need this information to be able to predict how this individual’s scenario is going to go. If they have more than 10 oligoclonal bands, maybe their course is going to be more aggressive and we should be more aggressive about their therapy up front. So this is a piece that’s ongoing, but I think it helps us in our ability to think about how we’re going to manage these people.

Patricia K. Coyle, MD: And it’s worthwhile mentioning that there are spinal fluid red flags against the diagnosis of MS. You don’t expect a very high cell count. You don’t expect a very high total protein. You’re accessing the central nervous system compartment. If you’re going to make a diagnosis, a life-long diagnosis, and make treatment decisions, and have the patient behind you that you’re confident, then I think with the lack of a diagnostic biomarker, why wouldn’t you want a robust evaluation of the patient?

Thomas P. Leist, MD, PhD: If I may take us back to the other biomarkers that we talked about, the MRI, I think one of the very important things that we perhaps also need to bring to the table is the fact that while the MRI has become important in the diagnosis of multiple sclerosis, the technical quality of the MRI is also important. I would like to refer to the criteria that has been proposed by the consortium of MS centers as minimal criteria, where many of the community-acquired scans still skip sequences where there are areas that are not imaged in the brain.

And I would also put in a little bit of a word to actually review the MRI scans. Because the radiologist may write that this could potentially represent multiple sclerosis, but it isn’t necessarily a diagnosis of multiple sclerosis, perhaps more of a risk management from the radiologist’s point of view. And I would think that everybody sitting at this table probably also reviews the scans of the patients where we make a diagnosis of multiple sclerosis. So I don’t think that we can rely on the radiologist’s report solely in getting to a diagnosis of MS.

Fred D. Lublin, MD: And this is a big cause for a misdiagnosis. We have our weekly case review conference and there’s just that band of white matter between the cortex and the periventricular area that we call the nonspecific zone, and it sort of follows almost like a boomerang-type shape of nonspecific lesions that frequently get sent to us that have nothing to do with MS at all. So over-reading or misreading the MRI is a big cause of difficulty.