Commentary
Article
The consultant neurologist at Queen's Square MS Center in London discussed the shift in the updates to the McDonald criteria for multiple sclerosis presented at ECTRIMS 2024.
Wallace Brownlee, MBChB, PhD, FRAP
(Credit: Neurology Academy)
The 2017 McDonald criteria proceeded with the severance of diagnostic criteria for relapsing-remitting MS (RRMS) and primary progressive MS (PPMS) where reasons for this were historical instead of biological. A recent study presented at the 2024 European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) Congress, held September 18-20, in Copenhagen, Denmark, by lead author Wallace Brownlee, MBChB, PhD, FRACP, showed that the 2017 McDonald RRMS criteria displayed a high accuracy for diagnosing patients with PPMS.
Additional findings showed that the inclusion of the optic nerve as a fifth topography and multiple spinal cord lesions in dissemination in space (DIS) criteria was also shown as feasible among patients with PPMS. Thus, the findings suggested that future revisions of these criteria should potentially consider a unified set of criteria for diagnosing MS that is more closely align with biological mechanisms but also simplifies diagnosis in clinical settings.1
In this study, investigators assessed the 2017 McDonald PPMS/RRMS criteria as well as the modified DIS criteria in patients suspected of PPMS from 5 MAGNIMS centers. Among 322 patients, 282 were diagnosed with PPMS using the 2017 McDonald criteria and 40 had other disorders. Results showed that the 2017 McDonald RRMS criteria had a high sensitivity (92.9%), specificity (95%) and accuracy (93.2%) in diagnosing PPMS. The modified DIS criteria including the optic nerve (sensitivity, 93.3%; specificity, 95%; accuracy, 93.5%), or at least 2 spinal cord lesions as an alternative criterion for DIS (sensitivity, 95.4%; specificity, 95%; accuracy, 95.3%) in combination with positive cerebrospinal fluid/dissemination in time on MRI also revealed a high performance for PPMS diagnosis.
In a new iteration of NeuroVoices, Brownlee, a consultant neurologist at Queen's Square MS Center in London, United Kingdom, discussed how the updated McDonald criteria presented at ECTRIMS 2024 may impact the diagnosis of atypical or asymptomatic MS cases. He also talked about the challenges in ensuring global accessibility to MS diagnostic tools, given the varying resources across healthcare systems. Furthermore, he spoke about how the changes in criteria reflect the understanding of MS as a spectrum rather than distinct phases.
Wallace Brownlee, MBChB, PhD, FRACP: I think the update to the McDonald criteria will undoubtedly be the highlight of ECTRIMS 2024 because it’s going to immediately change everybody's practice once they return to work. Although, they did tell us yesterday to wait until the paper's published, because who knows what the final changes will be. 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. Another big change is the integration of new diagnostic biomarkers into the criteria, whether it’s optic nerve biomarkers or things like MRI, VPS, or ICT, which we’re already using to some extent. There are also imaging biomarkers, like central vein sign or paramagnetic rim lesions, that many of us, including myself, don’t have much experience with. It's going to be an interesting time ahead.
One of the aspects of the session I contributed to focused on developing a unified set of diagnostic criteria for MS. The motivation was that MS is one disease. Primary progressive MS isn’t really distinguishable from relapsing MS, except for the initial symptoms. You can’t differentiate the conditions based on MRI, lumbar puncture, evoked potentials, or genetics. We’re dealing with one disease. We presented data from the MAGNIMS network showing that the diagnostic criteria for relapsing MS work just as well in the context of primary progressive MS. This is reflected in the changes to the McDonald criteria, where we’ll be using the same criteria to diagnose both RRMS and PPMS.
Unifying the diagnostic criteria does present challenges because there can be differences in clinical presentations between the two conditions. But the MRI and lumbar puncture findings are very similar, and new diagnostic biomarkers like paramagnetic rim lesions and central vein sign are seen in both primary progressive and relapsing-remitting MS. The larger challenge is ensuring that across the world, in different healthcare settings with varying medical resources, patients have equitable access to an MS diagnosis. That remains an ongoing challenge.
I definitely think the updates to the McDonald criteria move us closer to a biological definition of MS. Rather than defining MS based on symptoms, we’re shifting to define the disease based on its biology. This includes things we’re already familiar with, like focal inflammatory disease activity, T2 lesions in the brain, spinal cord, or optic nerve, gadolinium-enhancing lesions, or body fluid biomarkers like oligoclonal bands or kappa free light chain, which help establish signs of intrathecal antibody synthesis. There are also newer imaging biomarkers that reflect specific pathological aspects of MS. For example, MS lesions tend to form around veins, and iron rim lesions with activated microglia at the edge may be more closely associated with progression and neuroaxonal damage. Moving toward a biological definition, as we’re seeing in other areas of neurology, represents a real step forward.
Education around the new diagnostic criteria will be essential because we’re about to have the most complicated set of criteria for diagnosing MS ever. There are multiple ways to diagnose MS, ranging from a patient with MS symptoms and lesions in 4 or more regions of the nervous system—where the diagnosis is straightforward—to someone with lesions in 2 or 3 regions, where further evidence of dissemination in time is needed. That could involve a follow-up scan showing new lesions, a lumbar puncture looking for kappa free light chains or oligoclonal bands, or identifying a paramagnetic rim lesion or central vein lesion in the brain. With so many potential diagnostic pathways, it could cause confusion, especially outside specialized centers. Moreover, integrating these new measures, such as susceptibility-weighted imaging, will have cost and resource implications, as this isn’t currently part of standard MS diagnostic scans, meaning radiology departments and neuroradiologists will have to adopt additional scanning sequences.
I’ve been struck by the number of abstracts presented about even earlier MS than we currently recognize. I’m talking about the MS prodrome and identifying people at risk of MS or with preclinical disease, before they have symptoms. The only strongly effective way of preventing progression is using high-efficacy drugs as early as possible. So, ideally, we want to identify people on the path to MS as soon as possible. A study presented yesterday by Enrique Alvarez, MD, PhD, from the University of Colorado, was particularly interesting. They’re recruiting asymptomatic first-degree relatives of patients with MS, starting at a pediatric age, from 10 to 18 years or 18 to 30 years, and those participants are undergoing multimodal assessments. They presented MRI findings showing a substantial number of asymptomatic first-degree relatives have changes on their MRI concerning for MS, although they don’t yet meet the definition of radiologically isolated syndrome. I think this group represents a highly interesting population to study for future prevention or early diagnosis to improve long-term outcomes.
When we diagnose a patient with MS, a common question is, “When did this start?” If someone is diagnosed at 40, MS could have started at any point in young adulthood or adolescence. But when diagnosing someone at age 12, there’s a shorter timeframe for when MS could have developed. Including children in studies of prodromal or preclinical MS is essential to understanding the full spectrum of the condition.
Transcript edited for clarity. Click here for more coverage of ECTRIMS 2024.
