From Trial to Practice: How the 2024 Criteria Perform in Real-World Settings

In collaboration with the National MS Society, NeurologyLive^® convened a roundtable discussion bringing together leading multiple sclerosis experts to examine the evolving 2024 McDonald diagnostic criteria and their implications for clinical practice. Moderated by Marco Meglio, assistant managing editor of NeurologyLive, the panel features Samantha Roman, MD; Adnan Subei, DO, FAAN; and Lilyana Amezcua, MD, who offer perspectives grounded in both academic and real-world care environments.

As updates to diagnostic criteria aim to enable earlier and more precise identification of MS, understanding how these changes perform outside of controlled settings is critical. The panel emphasizes that beyond theoretical improvements, real-world validation through clinical studies and registry-based analyses is essential to ensuring that earlier diagnosis does not come at the cost of reduced specificity or increased misdiagnosis.

In this episode, the discussion focuses on emerging data supporting the application of the updated criteria, including findings from recent presentations at the 2025 ECTRIMS Congress led by Luca Bollo, PhD, and Wallace Brownlee, PhD, FRACP, MBChB. Panelists highlight how these analyses compare the 2017 and updated criteria across different clinical environments, including both resource-rich and more limited settings. Key findings include increased rates of MS diagnosis, a reduction in radiologically isolated syndrome classifications, and overall maintenance of high diagnostic accuracy.

The conversation also explores the clinical implications of these findings, including how earlier diagnosis may translate to earlier treatment initiation and improved long-term outcomes. At the same time, panelists address ongoing concerns around misdiagnosis and overdiagnosis, emphasizing the importance of advanced imaging markers, biomarker integration, and careful clinical interpretation to ensure appropriate application of the criteria.

Transcript edited for clarity.

Marco Meglio (moderator): These diagnostic criteria were first introduced at ECTRIMS 2024 and were officially published later that year. Since then, we have seen some real-world data supporting the guidelines. This includes studies such as the CAVS-MS trial, as well as two notable presentations at ECTRIMS, one led by Dr. Bollo and one by Dr. Brownlee. Can you talk about some of the data we have seen so far, what it shows, and what stands out from a clinical perspective?

Lilyana Amezcua, MD: I think those two presentations were designed to show how the criteria perform in different settings. The Bollo group in Barcelona compared the 2017 criteria with the 2024 criteria and found that they were able to diagnose more patients using the updated criteria, about 71% versus 47%. That is a significant difference. At follow-up, the difference remained, with about 83% diagnosed under the updated criteria compared with 60% using the 2017 criteria.

In contrast, the Brownlee group in the United Kingdom applied the criteria in a more real-world setting. They did not have access to kappa free light chains or the central vein sign but did use other components of the 2024 criteria. Even without those elements, they were able to diagnose more cases of MS, 121 compared with 97 using the 2017 criteria. They also observed a reduction in radiologically isolated syndrome, meaning more of those patients were reclassified as MS.

In both studies, sensitivity and specificity remained high, and overall diagnostic accuracy was preserved. These findings suggest that the updated criteria are performing well and may be more effective than the 2017 criteria in identifying MS earlier.

Samantha Roman, MD: I think that is an excellent summary. It is exciting to be able to diagnose MS earlier, because as we know, earlier treatment can reduce long-term disability. This gives us an opportunity to intervene sooner in the disease course.

Lilyana Amezcua, MD: It is also important to recognize that behind these criteria is the CAVS study, which is the central vein sign multicenter NIH-supported study. This work helped validate the central vein sign as an imaging biomarker for MS and contributed significantly to where we are today.

Adnan Subei, DO, FAAN: I also want to mention paramagnetic rim lesions, which represent iron deposition within chronically active lesions where microglia and macrophages are present. The presence of at least one paramagnetic rim lesion is highly specific for MS and adds another layer of diagnostic confidence.

Marco Meglio: I am also curious about whether there is concern around overdiagnosing patients. These updated criteria expand the ability to diagnose MS earlier, including in patients without symptoms. How much of a concern is overdiagnosis at this point?

Adnan Subei, DO, FAAN: There is certainly a concern. In clinical practice, I see a number of patients who were misdiagnosed with MS, often due to nonspecific white matter lesions on MRI. Even for MS specialists, these cases can be challenging to interpret. In community settings, there is a higher risk of misinterpretation, which makes access to advanced diagnostic tools even more important.

Lilyana Amezcua, MD: In cases where advanced imaging such as central vein sign or paramagnetic rim lesions is not available, additional testing can help. For example, evaluating optic nerve involvement through OCT or visual evoked potentials can provide supporting evidence. If we see thinning of the retinal nerve fiber layer, that may indicate prior optic nerve involvement.

In terms of misdiagnosis, it is always a concern, but we have made progress. Compared with 2017, we now have better understanding and access to testing for conditions such as MOG antibody disease and aquaporin-4 related disease, which are important mimickers of MS. This should help reduce misdiagnosis. At the same time, the addition of more specific imaging markers, such as central vein sign and paramagnetic rim lesions, may help reduce overdiagnosis by improving our ability to distinguish MS from other causes of white matter lesions, including vascular disease.