Overviewing Key Updates in the 2024 McDonald Criteria for Multiple Sclerosis

In collaboration with the National MS Society, NeurologyLive^® convened a roundtable discussion featuring leading experts in multiple sclerosis to provide a clear, clinically grounded understanding of the evolving 2024 McDonald diagnostic criteria. Moderated by Marco Meglio, this series brings together Samantha Roman, MD; Adnan Subei, DO, FAAN; and Lilyana Amezcua, MD, to explore how these updates translate into real-world clinical decision-making.

As diagnostic frameworks continue to evolve alongside advances in imaging and biomarker science, the panel emphasizes a central goal: enabling earlier, more accurate diagnosis while reducing misdiagnosis and unnecessary delays in care. Throughout the discussion, the experts highlight how the revised criteria better reflect the biological reality of MS as a disease with subclinical activity that often precedes overt clinical symptoms.

In this first episode, the panel provides a high-level overview of the most notable updates to the 2025 McDonald criteria and how they differ from the 2017 iteration. The conversation touches on the inclusion of the optic nerve as a core diagnostic location, the growing role of imaging markers such as the central vein sign and paramagnetic rim lesions, and the integration of kappa free light chains as an emerging biomarker. Panelists also begin to unpack the evolving role of dissemination in time, including scenarios where this requirement may be modified or removed.

Together, these changes signal a broader shift in how clinicians conceptualize MS diagnosis, moving away from a strict reliance on clinical relapses and toward a more nuanced, biology-driven approach. For neurologists, understanding how to apply these updates in practice will be critical as the field continues to push toward earlier intervention and improved long-term outcomes.

Transcript edited for clarity.

Marco Meglio (moderator): Give a bit of an overview of this new diagnostic criteria, some of its differences from 2017, as well as some of those smaller elements like the optic nerve, CVS, PRLs, and whatnot. I'll let anybody take the floor, and we can start to mesh and flow as we get into the conversation.

Adnan Subei, DO, FAAN: I think one of the highlights, if you look at it from a high level, is what’s different about the newest diagnostic criteria. With every version that we get, what we're trying to do is improve the accuracy of the diagnosis, getting it earlier for patients so we can start treatment sooner, while also improving specificity so that fewer people are misdiagnosed with MS. We're also trying to transition away from criteria being so focused on symptoms and relapses, because as we know now, MS has more of a prodromal phase, where activity is happening in the brain subclinically before the patient's first relapse. We don’t want to delay diagnosis until that first relapse.

Samantha Roman, MD: And I think the new criteria are more aligned with what we see clinically, with the involvement of the optic nerve as the fifth location. We know that about 50 percent of patients, at some point in their MS journey, will have optic neuritis, and I think the inclusion of that reflects what we see clinically.

Lilyana Amezcua, MD: In addition, I think one of the most important aspects is that under very specific conditions, which is really clinically important, radiologically isolated syndrome may now meet MS diagnostic criteria. Again, this aligns with the fact that we see patients with abnormal MRIs that look like MS, and we give them a designation that can have important clinical implications if left untreated.

Marco: Also, let’s talk a little bit more about kappa free light chains. Can we dive into that, as well as the removal or modification of the requirement for dissemination in time, or DIT, in certain contexts? Let’s break that down a bit more for our clinical audience.

Adnan Subei, DO, FAAN: I’ll tackle the kappa free light chains. We’ve been studying them for a few years in terms of their specificity and sensitivity in MS. They are markers of immune activity, similar to how we previously assessed oligoclonal bands. Kappa free light chains can now be performed in the CSF to improve diagnostic specificity. The main challenge is availability, as not all labs have adopted this yet, and I’m sure we’re going to be talking about challenges later on, but that is one of them. There are only a handful of labs that are performing those currently.

Samantha Roman, MD: Regarding dissemination in time, this requirement previously needed to be met with changes in MRI or a new clinical relapse. The most recent criteria allowed oligoclonal bands to be used to meet that portion of the requirement. Now we can use kappa free light chains, but in certain contexts, if there are paramagnetic rim lesions or enough central vein signs, that requirement is also removed. So it has become a little bit more of a nuanced diagnostic criteria, but certainly there are ways to diagnose MS now without seeing changes over time in clinical symptoms or in the imaging itself.

Lilyana Amezcua, MD: Another aspect of kappa free light chains is that they require less staff to perform. Oligoclonal band testing requires more staff involvement, and in certain places and regions of the world, it can be difficult to perform. Kappa free light chains offer an opportunity to use another type of biomarker to assist with diagnosis where oligoclonal bands cannot be done.

Adnan Subei, DO, FAAN: Going back to dissemination in time, I believe that if patients were to fulfill four of the five topographic locations for MS, then there would not be a need for us to wait for a clinical event or even check CSF, especially if we do not have access to the central vein sign. The five topographic locations now include the optic nerve, along with juxtacortical lesions, periventricular lesions, infratentorial lesions, and spinal cord lesions.

Samantha Roman, MD: And I think that also reflects what we would see and do clinically. I think most of us who see MS patients, if we saw lesions in four different locations typical of MS, we would go ahead and initiate treatment, regardless of whether that patient strictly met the 2017 criteria. So this is reflecting what we are already doing clinically.