Advancing the Diagnostic Criteria for Multiple Sclerosis: A New Era of Early Detection and Precision

Fast, accurate diagnosis of multiple sclerosis (MS) can be life-changing for patients, and new updates to the existing criteria are aiming to make that possible, ensuring that those living with the condition get the treatment they need when it matters most. Building on decades of research and clinical experience, the McDonald diagnostic criteria have served as a cornerstone in diagnosing MS, evolving over the years to keep up with the advancements occurring in the field. First established in 20011 and revised most recently in 20172, the criteria aim to balance sensitivity and specificity in identifying MS.

Since 2021, a panel of experts has been refining the guidelines to integrate cutting-edge insights into the disease’s biological mechanisms. This latest update prioritizes earlier and more accurate diagnoses by incorporating advanced imaging and biomarker tools alongside clinical evaluations, enabling timely treatment and improved outcomes for patients. Earlier this year, at the 2024 European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) Congress, held September 18-20 in Copenhagen, Denmark, committee chair Xavier Montalban, MD, PhD, unveiled these newly updated criteria during a scientific session cochaired by Peter Calabresi, MD.

Overall, these revisions included the adoption of advanced diagnostic methods and the development of age-specific criteria to more accurately diagnose MS in both younger and older populations. The aim of these changes is to enhance diagnostic precision by examining biomarkers of MS-related damage that go beyond observable symptoms. The finalized guidelines are expected to be published in a peer-reviewed journal by early 2025, although delays in the review process are possible. Once released, organizations like the National MS Society and ECTRIMS plan to educate providers and patients, ensuring that clinicians effectively implement the updates into their practice.

Voices of clinicians featured in recent conversations with NeurologyLive® offer a collective and valuable perspective on how the updated McDonald criteria will influence MS diagnosis in clinical practice. Each of the insights from the experts bridge the gap between the progress made in cutting-edge research and the experiences of day-to-day patient care. As part of HCPLive’s This Year in Medicine series, these clinical views expand the conversation surrounding the new criteria beyond the guidelines themselves, highlighting their practical implications for improving outcomes in MS management overall.

Proposed New Guidelines for Diagnosing MS

"During my presentation, I realized that while they may look quite complex, they are not so. Again, I want to highlight that the criteria are very much evidence based. I think this is the first time the entire set of criteria is truly evidence-based—they are sensible, logical, and the diagnostic algorithm is very easy to follow,” Montalban, chair of neurology at Hospital Universitari Vall d’Hebron, told NeurologyLive in a recent interview. As highlighted by Montalban, the proposed new revisions to the MS diagnostic criteria aim to improve accuracy and consistency in diagnosis.

Key changes in the new criteria presented at ECTRIMS 2024 included recognizing radiologically isolated syndrome (RIS) as MS in specific cases, adding the optic nerve as a fifth anatomical location, and removing the requirement for dissemination in time (DIT). Updates to dissemination in space criteria were introduced alongside the inclusion of kappa free light chains as a diagnostic tool. Montalban also highlighted in the presentation that the same criteria can be applied to both primary progressive MS and relapsing-remitting MS, with stricter standards for diagnosing older patients or those with comorbidities like migraine or vascular disorders.

“I view this as a significant shift in how we diagnose MS, primarily because we no longer require a clinical syndrome, such as a relapse or progression. So, we’ll be diagnosing MS in patients with atypical symptoms or even no symptoms,” said Wallace Brownlee, MBChB, PhD, FRACP, consultant neurologist at Queen's Square MS Center in London, told NeurologyLive. “It's going to be an interesting time ahead.”

Additional key changes featured in the presented criteria included the recommendation of optional tools, such as the central vein sign (CVS) and paramagnetic rim lesions (PRLs), for specific cases, and myelin oligodendrocyte glycoprotein antibody tests suggested for diagnosing children and adolescents. During the presentation, Montalban emphasized using paraclinical evidence for the confirmation of MS diagnoses across different patient populations. According to the clinicians NeurologyLive spoke with, these revisions may reflect a more nuanced approach to MS diagnosis, accommodating a broader range of clinical presentations.

Calabresi, codirector of the Precision Medicine MS Center at Johns Hopkins University, shared with NeurologyLive that incorporating the optic nerve as a "fifth topology" or classic location represents a significant change in the diagnostic criteria for MS. While optic neuropathy or optic neuritis has long been recognized as a common MS manifestation, it was not previously included in the criteria.

"I think adding that will be useful," he said. He also highlighted the integration of newer imaging technologies, such as optical coherence tomography (OCT), which can now assess inter-eye differences. Specifically, an inter-eye difference of more than 6 microns in the retinal nerve fiber layer or 4 microns in the ganglion cell inner plexiform complex could help confirm a diagnosis of optic neuropathy.

Joseph Kuchling, MD, a postdoctoral research assistant at Charité University Berlin, also highlighted an important update to the diagnostic criteria: the inclusion of specific markers like the CVS and PRLs. "These additions could help improve the specificity of diagnoses," Kuchling told NeurologyLive, noting that although the 2017 McDonald criteria were highly sensitive, they lacked specificity in real-world practice.

With the new criteria, there is hope for greater confidence in diagnosing MS and initiating treatment earlier in patients presenting with strong indicators such as CVS, without needing to consider other differential diagnoses like sarcoidosis or neuromyelitis optica spectrum disorder. However, Kuchling emphasized the importance of observing how the new criteria perform in clinical practice.

Marcello Moccia, MD, PhD, assistant professor at the University of Naples, explained to NeurologyLive that a major advancement in the updated criteria is the transition from viewing MS as a purely clinical diagnosis to recognizing it as a biological disease. "This shift is evident in two key aspects of the criteria," he said. The first involves RIS, which was previously described as a set of MRI findings but can now be diagnosed as MS in specific cases where biological evidence of the disease is present. Additionally, the criteria for relapsing and progressive forms of MS have been unified.

"In the past, we used two separate criteria for different clinical presentations, but biologically, the disease is the same," Moccia explained. He added that although this change may have a minimal impact on clinical practice, it significantly advances the understanding and interpretation of MS.

Potential Areas for Future Revisions

As the revised MS diagnostic criteria continue to evolve, several open questions remain for clinicians to take into future consideration. According to Montalban’s presentation, one area that may require further investigation could be the demonstration of DIT using advanced techniques such as visual evoked potentials (VEP) and OCT, which could offer more precise diagnostic insights. Additionally, the refinement of using PRLs and CVS as diagnostic tools in specific contexts may need further exploration according to Montalban and colleagues.

The criteria’s application to cases of solitary sclerosis and other atypical MS presentations also could warrant further study to ensure broader applicability. Another key question presented at ECTRIMS 2024 on future revision is how the criteria perform across diverse populations, particularly in regions like Asia and Latin America, where MS presentations and risk factors may differ. Finally, Montalban highlighted the integration of other emerging biomarkers for MS diagnosis, beyond the currently accepted standards, that could be an essential consideration in the future revisions.

"A lot of the discussion hinged on what we should do for the next round of criteria. Another point is that we change the criteria every few years, right? That's the model we've been using. But is there a different model that might work better, where we adjust the criteria more frequently as data is produced? We heard some of that,” said Daniel Ontaneda, MD, PhD, associate professor of neurology at the Cleveland Clinic Lerner College of Medicine, told NeurologyLive. “So, definitely, I think just because we have a new set of diagnostic criteria doesn't mean we've solved all the problems. We need to continue working on things and evolving how we make a diagnosis of MS."

Next Steps

The development of the revised McDonald diagnostic criteria represents a significant milestone in the field of MS for both clinicians and patients receiving care, supported by a forthcoming publication of a paper and diagnostic algorithm. As highlighted in the ECTRIMS 2024 presentation by experts, these updates are the result of extensive consultation with the wider MS community and are designed to address both current challenges and emerging insights.

Based on Montalban’s presentation, clinicians can expect additional papers planned to expand on specific aspects such as imaging advancements, visual system assessments, and the role of biomarkers. Overall, experts recognize that the implementation of these changes globally will possibly require careful consideration of resources, education for providers, and patient accessibility. Thus, a global education campaign may be essential to ensure that MS clinicians worldwide can adopt these criteria effectively into their practice, improving diagnostic accuracy and patient outcomes as well as addressing the unique challenges and perspectives of patients living with MS.

“In essence, the disease hasn’t changed but every few years, new criteria are introduced. The question is, what are these criteria really for? I think they serve several purposes. One is for non-specialists who need help in defining what the disease might be. I believe some of the additions to the new criteria—partly based on new technologies—have genuinely improved the criteria,” said David A. Hafler, MD, FANA, the William S. and Lois Stiles Edgerly Professor of Neurology at Yale School of Medicine, in a recent interview with NeurologyLive. “But ultimately, I should point out that the diagnosis of MS is a pathological diagnosis, and what we do clinically is add various measurements that increase the probability of making an accurate diagnosis.”

References:

1. McDonald WI, Compston A, Edan G, et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol. 2001;50(1):121-127. doi:10.1002/ana.1032
2. Thompson AJ, Banwell BL, Barkhof F, et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol. 2018;17(2):162-173. doi:10.1016/S1474-4422(17)30470-2
3. Montalban X. 2024 Revisions of the McDonald Criteria. Presented at ECTRIMS Congress; September 18-20, 2024; Copenhagen, Denmark. Scientific Session 1: New diagnostic criteria.
4. European Committee for Treatment and Research in MS. McDonald Diagnostic Criteria. Accessed November 12, 2024. https://ectrims.eu/mcdonald-diagnostic-criteria#