Can the revised 2024 McDonald Diagnostic criteria solve the misdiagnosis problem in multiple sclerosis?

A- and then you talk about the incorporation of the central vein sign, or CVS, and the paramagnetic rim lesions, or PRLs, and that feels like, you know, almost the initial and the centerpiece of your initial argument.

Can you explain maybe why these biomarkers are different, and why do you think they matter so much?

You know, I think as our criteria have been, uh, revised over time, the aim has really been to incorporate more patients with different presentations in sort of the diagnostic algorithm.

Or rather, to improve their sensitivity, uh, so that we could diagnose patients earlier, particularly as we've got all this compelling data that early treatment can have short and long-term, uh, consequences for patients and, and improve outcomes.

But I think this is really the first criteria where there have been some efforts to ameliorate this problem of, of misdiagnosis.

I, I hope everybody agrees that it's a problem.

I think-There have been maybe twelve or thirteen studies, they're all imperfect in terms of their methodology, but that have been published since two thousand and nineteen or so that have shown that we do see a significant number of patients who are given a diagnosis of MS in our clinics who, who wind up having something else.

So perhaps in response to that, you know, there were some efforts on the part of the committee to, uh, incorporate some elements in the criteria that could prevent misdiagnosis.

So I, I can talk about some of those specifically later, but those in partic-- you know, approaches to particular patients, uh, uh, with specific characteristics, um, you know, age, for instance.

So central vein sign is emerging now after almost a decade of data as a highly specific biomarker for MS, that it, it seems to perform pretty well when you look across all of the studies, and it's something that's based on the pathobiology of MS, uh, which makes it, you know, a, a very strong candidate, uh, diagnostic biomarker, of course.

It's not an epiphenomenon or, or something of that sort.

The criteria incorporates it as a substitute for dissemination in time, so, um, in that function on its own, it doesn't ne-- it may just improve sensitivity in some circumstances rather than specificity.

But inherently by using it, you are making a more accurate diagnosis given that, you know, enhancing lesions or positive CSF are, are actually pretty non-specific, you know, if you have other neuroinflammatory disorders.

So it's sort of a step in the right direction and, uh, you know, similarly, paramagnetic rim lesions, although they're used only in a, a small number of patients in the criteria potentially who have a, a single CNS anatomical location, also appear very likely highly specific to MS and reflect pathobiology that, that, you know, is unique to the disorder.

So in those circumstances where those are, um, incorporated, you know, a part of making the diagnosis is ruling other-- out other disorders and, and this idea of better explanation.

Uh, no better explanation.

So incorporating those biomarkers really will help us with some specificity.

Yeah.

So it really sort of, you know, incorporates some of the biologic framework around MS diagnosis and increases confidence of your diagnosis if they're present.