Adapting to the New McDonald Criteria for Multiple Sclerosis: What Does It Mean for Us?

It’s an exciting but challenging time to be in the Multiple sclerosis world! With the 2024 revisions to the McDonald criteria, the way we diagnose multiple sclerosis (MS) is evolving, and it’s time for us to catch up. As someone who’s still digesting these new criteria (and probably not the only one), I’m asking myself: what does this all mean for our clinical practice? And how will we adapt to the changes while still providing the best care for our patients??

Let’s break it down, keeping things light, and try not to overwhelm ourselves with too many technical details (though we love those, don’t we?). Here’s a summary of the 2024 McDonald criteria, how they differ from the past, and what we might expect in the clinic.

I’ve done my best to summarise the key updates from the 2024 McDonald Criteria in this table! ?? I’m still working through all the changes myself, especially after Professor Xavier Montalban’s, Prof Moccia, and Prof Brownlee presentations at ECTRIMS, 2024. It might take me about six months or so to really finalise this, once I’ve had more exposure and diagnosed new patients based on these criteria. Real-world experience will definitely help me solidify my understanding! For now, I’m using this visual approach to help myself—and hopefully others—grasp the updates. That said, there may still be some areas I’ve missed or misunderstood, so I’d love to hear your feedback! Let’s keep learning together as we apply these updates in practice.

Diagnosing MS: The Essentials

The McDonald criteria have been our trusty guide since 2001, giving us a structured approach to diagnosing MS. The 2024 revisions build on the principles we know well: Dissemination in Space (DIS) and Dissemination in Time (DIT). In simple terms, this means finding MS lesions in different areas of the central nervous system (CNS) and showing that they’ve occurred at different times.(1)

?But here’s where things get interesting: MRI technology is still our BFF in spotting these lesions. Thanks to advancements in imaging, we can now catch MS earlier, even in patients who show up with something like clinically isolated syndrome (CIS) or radiologically isolated syndrome (RIS) but no classic MS symptoms (2, 3). So, you can already imagine that diagnosing MS is going to get more straightforward, and patients won’t linger in diagnostic limbo as much as they used to (1).

?The Disappearing Acts: CIS and RIS

This is the bit I’m grappling with—if we can diagnose MS earlier based on imaging and biomarkers (good ol’ oligoclonal bands and now kappa light chains), are CIS and RIS going to disappear? CIS (clinically isolated syndrome) and RIS (radiologically isolated syndrome) have always been in that grey area—patients who don’t yet meet the full criteria for MS but have some suspicious findings. But if we can now diagnose MS earlier with fancy MRIs and biomarkers, is it just a matter of time before these terms become relics of the past? Cue my rhetorical question: Will we one day not even use these terms as MRI + biomarkers give us MS diagnoses even before the second symptom shows up? it’s looking likely.

Reflecting on my current MS database of patients with RIS and CIS, I can’t help but wonder how many of them may now meet the new MS criteria 2024. Some of these patients have been living with these labels for years, possibly feeling stuck in diagnostic limbo. With the 2024 McDonald criteria emphasising earlier diagnosis through advanced imaging and biomarkers (1), I now face the task of re-evaluating these individuals. It’s a delicate process—after all, telling someone they now meet the MS criteria could be a life-changing moment. My approach will be one of sensitivity, transparency, and support, making sure they understand that advancements in diagnostics aren’t about what we missed before, but about ensuring they receive the most accurate and timely care moving forward.

MRI: Can Our Equipment Keep Up?

?Speaking of MRIs, let’s address the elephant in the room. Not all of us have access to high-powered T3 or T7 MRIs. Some of us (waves hand) are still using T1.5 machines. This brings up a fair question: Can T1.5 MRI machines detect central vein sign (CVS) and paramagnetic rim lesions (PRL)—the new darlings of advanced MS imaging?

?The truth is, T1.5 isn’t as sensitive and specific, especially for spotting those subtle lesion details in the brain and particularly spine. So, while larger centres with more advanced MRI equipment might be nailing these early MS diagnoses with precision, those of us working with T1.5 might be missing some of the finer points. The 2024 McDonald criteria push for more advanced imaging techniques like susceptibility-weighted imaging (SWI) and diffusion-weighted imaging (DWI) to pick up on these features. So, there’s definitely a gap forming between tertiary MS centres and the rest. For instance, Clarke et al. reported that using a 3T MRI, the CVS threshold for distinguishing MS patients from non-MS patients yielded 100% sensitivity but only 73.9% specificity.(4) The limitations of 1.5T MRI scans extend to the evaluation of PRLs, which are chronic lesions associated with ongoing inflammatory processes in MS. Research indicates that PRLs are best visualised using higher field strength MRI, such as 7T MRI, which allows for better differentiation between remyelinated and demyelinated lesions.(5) Furthermore, the T1-weighted imaging behaviour of slowly expanding lesions (SELs), which often co-localise with PRLs, shows a constant decrease in T1 signal intensity that may not be adequately captured on a 1.5T MRI.(6)

So, for us working in more standard setups, this might be a gentle nudge to advocate for better imaging equipment. But for now, we work with what we’ve got!

?A Predictive Look at How the McDonald 2024 Criteria Could Improve Diagnostic Accuracy in MS

As I reflect on the implications of the 2024 McDonald criteria, it’s worth considering the potential improvement in diagnostic accuracy. Using the McDonald 2017 criteria, the misdiagnosis rate was as high as 31%(7, 8), meaning nearly one-third of patients may not have received an accurate diagnosis. With the 2024 revisions, including advancements in imaging techniques (like CVS and PRL detection) and the incorporation of new biomarkers (such as kappa light chains), we can predict a 50% reduction in misdiagnosis rates. This would bring the error rate down to 15.5%, significantly improving diagnostic accuracy to 84.5%. For our patients, this means fewer individuals left in diagnostic limbo under RIS or CIS labels and more being diagnosed correctly earlier in their disease course. The potential to better identify MS earlier, with fewer diagnostic errors, means improved outcomes and more timely interventions for those who need it most.

?Calculating the Predicted Improvement:

1. 2017 Misdiagnosis Rate: 31%
2. Predicted Improvement: 50% reduction in the error rate (misdiagnosis).

31%×0.5=15.5%31\% \times 0.5 = 15.5\%31%×0.5=15.5%

This means the new misdiagnosis rate would be 15.5% with the 2024 criteria.

1. New Diagnostic Accuracy:

100%?15.5%=84.5%100\% - 15.5\% = 84.5\%100%?15.5%=84.5%

With the 2024 criteria, the diagnostic accuracy would increase to 84.5%, which is a significant improvement from the 69% accuracy in 2017.?

Where My Predictions Aligned and Missed the Mark

?Reflecting on my predictions for the 2024 McDonald criteria ( see my previous article: (2) Speculative Insights into the McDonald 2024 Criteria for MS | LinkedIn ), I correctly anticipated the emphasis on advanced MRI techniques like CVS and PRL, along with the continued importance of OCB in CSF analysis. I also aligned well with the earlier diagnosis of RIS and RRMS based on these findings. However, I missed the significant relaxation of the DIT requirement, which is now less crucial if DIS, MRI, and biomarker evidence are present. Additionally, while I mentioned OCBs, I didn’t fully predict the elevated role of kappa light chains (kFLC), which is now central in the 2024 criteria. Lastly, I underestimated the importance of spinal cord lesions ( >= 2 lesions in the spine) in confirming diagnoses, especially in progressive forms like PPMS.

My prediction table before the Mcdonald’s criteria was announced at ECTRIMS meeting, September, 2024:

Keeping It Light (and Humble)

At the end of the day, these updates are helping us diagnose MS earlier and more accurately, which is great news for our patients. Yes, there’s some anxiety about keeping up with the latest technology, but let’s take it one step at a time. For now, we need to understand the new criteria, educate our peers (and ourselves!), and make sure we’re using what’s available to provide the best care. As I write and reflect on all of this, there are a series of webinars and seminars on McDonald’s criteria being organised and run by pharmaceutical companies and other big organisations in Neurology and specifically MS.

I’ve started by summarising the changes and thinking aloud about the clinical implications. It’s a bit of an ongoing process, and we’ll all need time to adjust and adapt. But I’m optimistic. After all, MS diagnosis isn’t a one-size-fits-all, and we’ve always known how to tailor our approach to each patient. More complex cases are being discussed at Regional and National Neuroinflammatory MDTs, allowing us to come to collective conclusions that best serve patients' brain health and help prevent the progression of advanced disease.

Stay tuned for more updates on how we’re integrating the new criteria into practice. And hey, if you’re like me, you might want to start quizzing yourself (and others) on the latest changes. It’s the only way we’ll keep up with the ever-changing landscape of MS care!

?So, let’s get diagnosing, one lesion at a time...

If this article resonated with you or if you believe it can inspire someone else on their MS journey, I encourage you to like, comment, and share it with your community.

#Multiplesclerosis #ECTRIMS2024 #McdonaldMScriteria2024 #autoimune #chronic #Precisionmedicine

? dr Agne Straukiene

References:

1.?????????? McGinley MP, Cohen JA. Multiple Sclerosis Can Be Diagnosed Solely With Dissemination in Space: Commentary. Multiple Sclerosis Journal. 2024;30(6):641-2.

2.?????????? Jendretzky KF, Bajor A, Lezius L-M, Hümmert MW, Konen FF, Grosse GM, et al. Clinical and Paraclinical Characteristics of Optic Neuritis in the Context of the McDonald Criteria 2017. Scientific Reports. 2024;14(1).

3.?????????? Miller AE. Dissemination in Time as a Requirement for Diagnosis of Multiple Sclerosis: Time for a Change? Multiple Sclerosis Journal. 2024;30(4-5):479-82.

4.?????????? Ghany HA, A K-A, Edward R, Naseer MA, Hegazy MI. Sensitivity and Specificity of Central Vein Sign as a Diagnostic Biomarker in Egyptian Patients With Multiple Sclerosis. Neuropsychiatric Disease and Treatment. 2022;Volume 18:1985-92.

5.?????????? Kolb H, Absinta M, Beck E, Ha SK, Song YJ, Norato G, et al. <scp>7T MRI</scp> Differentiates Remyelinated From Demyelinated Multiple Sclerosis Lesions. Annals of Neurology. 2021;90(4):612-26.

6.?????????? Elliott C, Wolinsky JS, Hauser SL, Kappos L, Barkhof F, Bernasconi C, et al. Slowly Expanding/Evolving Lesions as a Magnetic Resonance Imaging Marker of Chronic Active Multiple Sclerosis Lesions. Multiple Sclerosis Journal. 2018;25(14):1915-25.

7.?????????? Solomon A, Pettigrew R, Naismith RT, Chahin S, Krieger S, Weinshenker BG. Challenges in Multiple Sclerosis Diagnosis: Misunderstanding and Misapplication of the McDonald Criteria. Multiple Sclerosis Journal. 2020;27(2):250-8.

8.?????????? Thompson AJ, Banwell B, Barkhof F, Carroll WM, Coetzee T, Comi G, et al. Diagnosis of Multiple Sclerosis: 2017 Revisions of the McDonald Criteria. The Lancet Neurology. 2018;17(2):162-73.

Note: The infographics and descriptions are fictional suggestions to give you an idea of what visuals might accompany the article. Created by AI under my commands.

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