2024 Revisions of the McDonald Diagnostic Criteria: What Neurologists Need to Know

(upbeat music) - One of the main changes is that we will have biological diagnosis, and I think this is very important. This is happening in some other neurodegenerative diseases such as Alzheimer's and Parkinson's as well. - I think MS is a rapidly changing field, and within seven to eight years, we have a wealth of evidence that accumulates, that allows us to more rapidly diagnose people who have MS, and also use some tools to prevent misdiagnosis. - The diagnosis criteria will be more easily and widely applicable in many places around the world. - It's really inspiring just because I think it shows that the field is willing to be forward-thinking, and incorporate evidence that's accumulated to actually change the lives of people living with MS. - Hello, my name is Javier Montalvan. I am the head of the Department of Neurology at the University Hospital by the Bronin Barcelona, and the Director of the MS Center of Catalonia. - Hello, my name is G1O, and I'm a neurologist, and the Director of the MS Center at St. Michael's Hospital at the University of Toronto in Canada. - And I'm Brett Crement. You're listening to the Ektrums Podcast, the official podcast from the European committee for treatment and research in multiple sclerosis. (upbeat music) - One of the biggest MS news stories recently has been there are latest revisions to the McDonald criteria used for the diagnosis of multiple sclerosis. This represents an important time point as the field continues to advance in both knowledge and technology. It is critical that our diagnostic criteria reflect this. Excitingly, there's new guidelines have now been published, and we can discuss them at length. My guests in this episode, Javier and G1, are both instrumental in helping to construct these new guidelines, which we will be discussing today. Javier and G1, thank you for joining me. Thank you. - Thank you, it's a pleasure to be here. - So I think an important place to start this episode. There's obviously been a lot of talk around these revised criteria, but perhaps to start with, there would be good from hearing from both of you. Why was there a need for revisions to the McDonald criteria to be made? So I think every five to seven, eight years, we consider that we have enough evidence to review their criteria. And the revision of their criteria has a clear impact on a number of topics. For instance, the dialogue between patient and neurosis, an impact on treatment decisions, an impact on long-term prognosis at the end. So I think that's a need, and that will be happening probably for many years until we end the disease. - I mean, I think just to echo what Javier said, I think MS is a rapidly changing field. And within seven to eight years, we have a wealth of evidence that accumulates that allows us to more rapidly diagnose people who have MS and also use some tools to prevent misdiagnosis. And so it was time that we revisited all of the evidence that's accumulated to make things better with respect to diagnosis, which obviously has a lot of treatment implications. - Excellent. As we're recording this, excitingly the publication has come out with the new guidelines are in a position now to be able to talk through exactly what is in there. So from both of you, I guess, what are some of the key changes that have been made to these criteria? - So I think one of the main changes is that we will have biological diagnosis. And I think this is very important. And that will be the first time that patients with no symptoms are all, but with a very characteristic and typical MRI and also some of them with abnormalities in the CSF, they will be considered having multiple sclerosis. This is one of the important changes. And also perhaps I will ask you one to say something about the novel MRI signals that we will be incorporating as well. - Well, I think this set of diagnostic criteria, it's really exciting. And it's kind of a profound moment in the field, just because it's the first time that more novel MRI measures have been incorporated into the diagnostic criteria, just because when you look at how the diagnostic criteria have evolved for decades, it's been based on clinical measures as well as the typical clinical MRI measures that we use in the clinic. But I think for people who do a lot of imaging research, it's a major landmark, just because enough evidence has accumulated that these relatively simple to use MRI measures specifically the central vein sign and something called paramagnetic rim lesions in certain situations will enable and facilitate the diagnosis of MS in people who we think biologically have MS. And this will again facilitate earlier treatment and appropriate people. - Okay, fantastic. Do you want to go into a little bit more detail in terms of exactly how those imaging measures will be incorporated? What are the things that people will be looking out for? - Sure, so just briefly to describe what the central vein sign and paramagnetic rim lesions are. When you use certain iron sensitive sequences, and this means that with centers around the world, when they have the capability to do this, iron sensitive sequences will now become part of routine probably diagnostic MRI protocols for MS. But when you use appropriate iron sensitive sequences, when you see white matter lesions in the brain, there's actually many reasons including MS why people may have white matter lesions. But if a white matter lesion formed around a central vein, these iron sensitive sequences allow us to visualize within the white matter lesion a clear central vein. And the reason this is so significant in MS is that's one of the pathophysiologic hallmarks of MS lesions. They form around veins because lesions related to MS are related to perivenular inflammation and demyelination. So what does this mean? It means that if someone has a lot of white matter lesions and that most of them show central veins, the likelihood of a diagnosis of MS is very high in comparison to many other diseases that can cause white matter lesions. And so within the diagnostic criteria, you'll see how they're used. But basically there's this select six criteria that means that if when you use the appropriate iron sensitive sequence, you can identify clearly six lesions that very clearly have a central vein. The diagnosis of MS is very likely and there's specific kind of criteria that need to be met. And if you have fewer than six lesions, as long as you have more lesions that demonstrate the central vein than those that do not, then again, the diagnosis of MS is very likely. And with the paramagnetic rib lesions, so these are called PRLs or pearls. Again, when you use appropriate iron sensitive sequences around some lesions, you can see this rim of iron. And the reason we care about that is because these are known as chronic active or smoldering lesions. And it turns out, again, amongst the many different diseases that cause white matter lesions, chronic active lesions are highly specific to MS. And so in certain situations, and again, there's diagnostic algorithms that you'll see in the paper. If you are able to show that somebody has a paramagnetic rim lesion, again, the likelihood of a diagnosis of MS is very high. - Fantastic, very interesting. Are there changes to the criteria that we should be aware of? - Well, I think on my hand, the criteria, some of them will allow a biological diagnosis, as I said. And I think this is a very important step. On the other hand, a set of the new criteria will make that the diagnosis criteria will be more easily and widely applicable in many places around the world. Because we are, for instance, we are incorporating the optic nerve as a fifth topography. And we will be able to measure that abnormality, not only by MRI, which maybe can be a little bit complicated in some countries, in some centers, but also by the visual potentials or OCD, which is easier. We are incorporating the cap of free light change instead, well, not instead, but apart from oligonal bands, and they are easier as well. And then we then have a number of signs or signals or criteria increasing the specificity. As you all mentioned, the CVS and the PRS, some of them, but also increasing the number of criteria in patients who are older than 55, patients who have bascular risk factors, for instance, in kits, we will be asking for anti-mog and antibodies as well. So I think the criteria meet the two components of increasing sensitivity with also maintaining the specificity or even increasing the specificity. There's one of the things that we know around diagnosis that's been made very clear with all of the data that we've established over the past few years is earlier diagnosis, getting on to highly effective therapies earlier has a big impact on long-term outcomes for people living with MS. be interested in both of you commenting on the new criteria that have now been published and your thoughts on will there be anything around this that will help aid earlier diagnosis? Absolutely. I think as Travier highlighted, even in people who do not have kind of the typical clinical symptoms of MS, if these people meet, you know, some of the criteria that we've talked about, we all know that these individuals biologically do have MS and, you know, this is an entity called radiologically isolated syndrome or RIS and it's in people like this where we know that biologically they have the same disease processes that are underlying MS and a high proportion of people with RIS over time have a high likelihood of developing MS. So these are the types of situations that will facilitate an earlier diagnosis of MS, therefore facilitating the early initiation of treatment. Absolutely agree. Perhaps we may say that the diagnostic criteria are not treatment guidelines and I think we should distinguish the two of them, but there is a clear implication and as you want to mention, it's very clear over time that when we are using new criteria, we had four revisions up to now, 2001, 5, 10, and 17 and this will be the 24th revision in 2024. The time between the first symptom and the diagnosis and the time between the first symptom and the treatment set has decreased quite a lot. And as a consequence of this, the long-term prognosis has improved very much in this. So I think this is one of the objectives of course of the new diagnostic theory as well. Fantastic. And I guess another area around that being misdiagnosis, some comments around that both in terms of I guess not missing people living with multiple sclerosis but also not diagnosing people with MS that may have another ran urological condition. You know I think with diagnostic criteria it's always tricky because you obviously want to increase the sensitivity but and diagnose people with MS who biologically have MS but then of course you want to prevent misdiagnosis. And so in terms of diagnostic terms this means ensuring that the diagnostic criteria have high specificity. And again I think this is one of the really unique aspects of this set of diagnostic criteria. Bringing in some of these measures including the central vein sign and paromagnetic rim lesions and you know the great strength of these measures are there very high specificity for MS as well as sensitivity for MS. But I think building in these mechanisms to ensure that while we want to obviously increase the sensitivity ensuring that we have ways to prevent misdiagnosis and maintain high specificity is really key. And I think again by bringing in some of these novel imaging measures this is what we've been able to do with the set of diagnostic criteria. Completely agree as always of course perhaps a couple of comments one is that with this revision the diagnosis of the MS requires to have an abnormal MRI. This never happened before. You were able to make a clinical diagnosis basis some clinical grounds and I think in 2024 this is not possible at all. Of course we have a plan also to disseminate the knowledge to disseminate the criteria among general neurologists among you know patients as well etc and I think this is important. Of course you need to know neurology to apply the diagnosis criteria correctly. I mean you touch on an interesting point there that I'm keen to get both of your thoughts on as well around what would your messaging be now to neurologists MS specialists around the world about adopting these criteria. I think the criteria they don't look easy right? They don't look easy I have to say. But then when you when you read them carefully you realize that they are very easy and they're very easily applicable. So at the end in the future will be easier to make the diagnosis of multiple sclerosis in most cases and as G1 mentioned we will be able to diagnose MS in few patients who otherwise will not be completely in the criteria. So read the criteria easily and don't worry they will not make mistakes at all. I don't know you are well perhaps you can explain this better. I mean I think with any sort of diagnostic criteria you know Chavuja said this earlier but it needs to be done by an experienced and trained neurologist and I think some of the mechanisms that have now been built into the diagnostic criteria facilitates the diagnosis but again has these you know fail safe mechanisms to hopefully you know prevent misdiagnosis and so I would say to the general neurology community you know carefully apply the diagnostic criteria and they're pretty easy to use but when in doubt use some of these built-in mechanisms that we have in the in the new versions of the diagnostic criteria that allow us to ensure specificity and make sure we prevent misdiagnosis and so you know when in doubt just make sure you follow the diagnostic criteria and also get the opinions of other people and then use some of these mechanisms that we have. Lastly now that we're sort of at the the end stage of this and the guidelines are out as two people who were instrumental in being a part of this process we're talking about this is this has been an easy change this has obviously been a lot and a lot of hard work and meetings and discussions that have gone into that how do you both feel now that this has happened it's obviously a landmark moment and anything or do you want to say around the other people who also participated in this process and helped make these changes. Well perhaps I can share with you that the meeting we had in Barcelona and you one was a fundamental part of that meeting was very special I would say so people people felt that we were doing a great job and we were modifying the knowledge of multiple sclerosis quite a lot and with a number of positive consequences so I think we enjoyed the process was a carefully planned meeting with a clear methodology that was the first time ever we were 55 experts in multiple sclerosis from different areas of knowledge and the female male ratio was quite similar that was the first time again so I think could be as an example for future revisions that do one we'll be leaving. I think it was I think there was a huge amount of work that went into preparing for the meeting Chavier and his team really put in kind of you know actually almost two years of work leading into this meeting so I think it was really dense but we covered a lot of ground there was a very clear process and as Chavier said I think there was very good representation from you know different say scientific specialties and global representation and gender representation too so overall a really informative meeting it was exhausting but I think we came out of it having moved the field forward and you know for me personally seeing some of these novel imaging measures being incorporated for the first time it it makes me really optimistic about the field because the fact that you know this group of experts from around the world is willing to embrace how quickly the science in MS is changing and that actually it makes a a clear tangible change in kind of one of the most basic clinical principles diagnosis it's really inspiring just because I think it shows that the field is willing to be forward thinking and incorporate evidence that's accumulated to actually change the lives of people living with MS so overall it's just really positive and it was a lot of work and we have Chavier to thank for all of the blood sweat and tears that for years you know he's put into it but it's I think a really really positive change and I'm excited that this is taking place well Chavier she wanted thank you for both for your hard work in terms of getting these new diagnostics criteria out and the hard work of the rest of the team that was involved in this and thank you both for sharing this with us today on the podcast I'm sure it's going to be met with a lot of excitement thank you very much for inviting us thank you very much and thank you all for listening once again I'm Brett Drummond host of this podcast episode and co-founder of MS Translate an independent resource center that aims to simplify the complex wealth of information about MS for the greater MS community the Oktron's podcast is produced and hosted in collaboration with two key partners MS Translate and the MS Journal appear reviewed international journal that focuses on MS Neuromilitis Optica and other related autoimmune diseases of the central nervous system the 2024-25 Oktron's podcast series is supported by educational grants from Alexian AstraZeneca rare disease and Novartis educational grant providers have no input in the podcast content you can read more about the top of this latest podcast episode and more on the ACTROMS website. 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