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Updates to the McDonald diagnostic criteria for MS · VJNeurology Podcast

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  Hello, and welcome to today's podcast from the Video Journal of Neurology.
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  We are an open access video journal sharing the latest news in neurology across all major disciplines.
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  Our regular podcast will bring you exclusive insights from renowned experts
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  on hot topics in their fields.
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  This episode will focus on the 2024 revised McDonald criteria for the diagnosis
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  of multiple sclerosis, which was presented at the 40th ECTRIMS meeting this September.
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  The main updates to the criteria involve the inclusion of optic nerve lesions,
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  the use of CSF kappa-free light chain as a diagnostic biomarker,
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  and the addition of central vein sign and paramagnetic rim lesions as imaging markers.
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  First, you will hear from Marcello Moccia, who speaks about the update.
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  He gives some background for the process used to develop the new criteria,
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  with a focus on improving its global applicability.
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  He then goes on to discuss the updates, including a shift from clinical to biological
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  definitions of MS and the new inclusions in the criteria.
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  The last update of the criteria was in 2017, so it's more than seven years ago,
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  because it was discussed and published in 2017, so basically a lot of time has moved.
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  And this time, for the criteria, rather than an agreement, we followed a consensus process.
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  That means that about 55 or 56 people in the same room, at the same time,
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  voted and found an agreement on some specific evidence-based statements.
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  And to be honest, we had the opportunity to revise, to have a look at studies
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  that came from all over the world.
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  So, for instance, we had studies coming from South America,
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  from Asia, from Africa, and to see if criteria, if the new criteria can be actually
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  applied anywhere in the world.
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  That means whether we try to examine all accumulating evidence from around the
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  world, from centers who are specialized in CSF analysis and from centers who
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  are specialized in MRI analysis.
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  And I think this is a huge change in the overall approach of the criteria.
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  Also, in the way that we try to make the diagnosis of MS with the tools that you have.
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  So again, here it was not only a matter of assessing evidence,
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  but also making sure that the available evidence is something that can make
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  the difference in making the diagnosis of MS all over the world.
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  So with the latest updates of the diagnostic criteria for multiple sclerosis,
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  we will be seeing a lot of changes, which can be scaring somehow,
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  but it's honestly very much pragmatic change.
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  So first of all, we are trying to change from clinical definitions of MS to
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  biological definitions of MS,
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  which means that with a new set of criteria,
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  it will be possible making the diagnosis of MS, even if the person has not experienced
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  any symptoms, but if you are able to measure disease-specific mechanisms.
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  And speaking of which, we increased the number of disease-specific mechanisms.
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  In the past, we only had oligoclonal bands in the CSF and lesions on MRI,
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  either T2 lesions or gad-enhancing lesions.
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  Now, we have the key oligoclonal bands and MRI lesions,
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  but we also include the central vein sign for better defining to increase the
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  specificity of our detection of MS lesions and paramagnetic rim lesions,
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  so MS-specific lesions with the border of activity.
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  Plus, in the CSF, we also include the kappa-3-light chain index that is fairly
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  more sensitive in detecting compartmentalized inflammation in the brain.
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  With the 2017 revision of the criteria, the optic nerve was left out.
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  However, about 20-30% of people with MS present with optic nerve involvement.
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  So it's sort of atypical that we keep something so typical out of the diagnostic criteria.
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  So now the optic nerve is an additional MS region.
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  And we also give the opportunity to study the optic nerve through different
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  modalities, OCT, MRI, and visual evoked potentials.
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  And that we believe that this is an addition to the global applicability of the criteria.
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  Again, each center will use the tool that they feel is much better,
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  that they feel it more accessible for each specific person.
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  Serena Borrelli will now speak about her research that supports the recent updates.
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  She speaks about a study that analyzed the diagnostic performance of MRI biomarkers,
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  particularly paramagnetic rim lesions, central vein sign, and cortical lesions.
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  So as you probably may know, the diagnosis of multiple sclerosis can be challenging
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  in clinical practice since its presentation can be sometimes atypical or can
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  be mimicked by other conditions.
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  Current diagnostic criteria enable for sure an early diagnosis and also an early treatment initiation.
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  But the problem is that the specificity is not so high and the risk of misdiagnosis is quite high.
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  So, to enhance diagnostic accuracy in multiple sclerosis, we,
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  but also other researchers, have been focusing on studying new advanced MRI biomarkers.
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  And in this study, I focus in particular on the central vein sign,
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  the paramagnetic rim lesion, and the cortical lesion.
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  They are a specific feature of MS.
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  They reflect a specific pathologic feature of MS.
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  And in this study, we focus on studying the diagnostic performance of these
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  three biomarkers, alone and in combination, but also the association with the clinical outcome.
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  So what we found in this study is that the central vein sign yielded the best
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  diagnostic performance, followed by cortical lesion and then paramagnetic rim lesion.
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  And that the combination of these three biomarkers improved the diagnostic performance
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  of the three biomarkers alone.
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  Regarding the correlation with clinical outcome, we found that PRL,
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  the paramagnetic rim lesion, and cortical lesion, both correlated with MS severity
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  and disability scales, while the central vein sign did not.
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  And in particular, PRL also were able to predict what we call PIRA,
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  the progression independent of relapse activity, over the two years following the study entry.
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  So we really think that those three biomarkers are very helpful,
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  not only for the diagnostic workup of MS, because they can reliably improve
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  diagnostic accuracy in MS,
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  but also because they can give very important prognostic information,
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  in particular for PRL and cortical lesion.
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  So advanced MRI protocols should really be implemented in clinical practice,
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  probably because for the next and upcoming revision of MS diagnostic criteria,
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  we will hear about those advanced biomarkers.
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  You will now hear from Celia Oreja-Guevara, whose focus is on the diagnostic
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  value of the central vein sign, highlighting specific quantities of CVS-positive
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  lesions that are indicative of having MS.
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  Yes, that is very important because the central vein sign, only one vein is
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  crossing through the lesion, through the white matter lesion.
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  And that is very important because there will be now in the new McDonald criteria,
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  there will be a sign to decide if a patient has multiple sclerosis or not.
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  So that when a patient has more than six lesions with the central vein.
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  It will be a very, it means that it's very probably that this patient has multiple sclerosis.
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  The other way is when a patient has many different white lesions in the brain,
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  and 40% of these lesions, they have this central vein sign, it means this patient
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  has a big probability to have MS.
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  So that the central vein sign, there will be a way to have a better diagnosis
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  for the multiple sclerosis.
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  And in our work, we present patients that they have, we don't know the diagnosis,
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  we look at the central vein sign, and when they have less than 40%, they have no MS.
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  And in our case they have MOGAD or they have NMO or perhaps only headache.
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  And when the patients have more than 40, normally most of them have MS.
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  That is important because more and more patients, they go to the private hospitals
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  or private practise and they have a headache or dizziness and they have an MRI
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  of the head and later they have some lesions and the people they say, okay, you have an MS.
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  But now with this central vein sign, we can differentiate between headache
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  and MS, only we are looking after these lesions.
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  And when you have more than 40% of these lesions with the central vein sign,
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  or you have more than six, you will have an MS. Otherwise, you have no MS.
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  They say, okay, they will be in the new criteria. And it's very important because
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  when you have a patient that you don't know the diagnosis, and you have more
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  than 40% of the lesions with the central vein sign, the probability to have MS is more than 90%.
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  So that we use the central vein sign in the clinical practice for the differential
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  diagnosis between MS, NMO and MOGAD and between MS and headache.
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  Next Giancarlo Comi speaks about optical nerve lesions in MS,
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  highlighting that although these are common in patients with MS,
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  the optic nerve was not included in the 2017 McDonald criteria.
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  I think that about 20-25% of MS patients have the disease that starts with an optic nerve attack.
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  So one out of four.
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  So how can we leave out the optic nerve as a site that may contribute to demonstrate,
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  the spatial dissemination of deletion?
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  Today, if a person has an optic neuritis attack
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  you perform brain MRI, a spinal cord MRI, and you see a lesion in the spinal cord,
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  or might be three lesions in periventricular areas, or might be two lesions
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  on subcortical, just a cortical area.
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  Well, this is not classifiable as an MS because the optic nerve is not one of
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  the four sites that are considered for the spatial dissemination,
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  which is really quite strange.
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  It's not an atypical presentation, it's probably one of the most typical presentations. So why [inaudible]?
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  Well, the main reason when we discussed in 2017 in the committee for the diagnostic
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  criteria, the real way we, at the end,
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  rejected the idea to have optic nerve as the fifth nerve was that at that time,
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  the evidences of good sensitivity of brain MRI and particularly orbital MRI
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  to detect lesions in the optic nerve was considered not so good, not so high.
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  But in the last five years, we had a lot of advances in terms of MRI techniques.
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  And now, with the double inversion recovery, particularly the 3D double inversion
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  recovery, we have quite substantially increased our sensitivity.
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  That is of the order of 93%, 94%.
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  So, now if a person has a suspicion of an optic neuritis, we can demonstrate
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  that there is a damage in the optic nerve.
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  Of course, we have also for the optic nerve an advantage that we don't have for other locations.
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  Again, that's very strange because for the other locations, we do not have a
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  quite strong neurophysiological evidence.
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  Of course, in a spinal cord lesion, if the posterior pathways are affected,
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  we can have evoked potential that reveal damage there.
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  But of course, it's not really always the case.
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  So here now we have also optic nerve and evoked potential that may contribute to reveal the damage.
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  And for this reason, I think today it is really unreasonable not to add the [inaudible] optic nerve.
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  Finally, we go back to Marcello Moccia, who gives advice for the implementation
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  of the new criteria into clinical practice.
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  The new criteria are very easy to implement. To be honest, after the meeting,
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  we have all been trying to implement the criteria in our clinical practice,
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  comparing the past criteria and the new criteria.
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  It's very easy if you accept, and to be honest, this is the case,
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  that not every person with MS needs, with suspected MS, needs to do everything.
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  You do what is more reasonable for each case. If in a specific moment you
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  have difficulties accessing MRI or some specific MRI sequences, you can do CSF analysis.
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  If there are some reasons contradicting or if the person does not want to do
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  CSF analysis, then you can do more thorough MRI studies.
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  So it's a matter of getting used to new possibilities.
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  I mean, science and MS research are advancing, so we need to follow what's going on.
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  We can't speak on something that stays the same.
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  We need to make sure that scientific advances and clinical practice go in the same direction.
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  So here, the key point is making sure that there is a set of tests that can be widely available.
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  And then each center will implement the tests that are needed on a specific case.
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  Of course, there will be a limited number of people who are suspected of MS
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  where center might not be 100% sure about the final diagnosis.
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  But honestly, this is a very little
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  minority of people with suspected MS, and in this case,
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  they can refer to other centers who have access to other methods.
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  But to be honest, with the previous set of criteria, we already had the same
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  problem with some people that we were unable to make the diagnosis.
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  Now we are adding additional tools that can improve our sensitivity and our
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  specificity in making the diagnosis.
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  We are aware that there is the risk of increasing complexity,
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  but to be honest, medicine is increasing complexities in any field of medicine
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  and any field of neurology.
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  So I don't think this is something MS-specific.
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  What we are doing, though, is not increasing overall complexity.
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  It's increasing the number of possibilities to make the diagnosis of MS.
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  So here it's more a matter of mix and match whatever you need to do for each single person.
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  That's all the updates we have for you today. Thanks so much for tuning in.
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  conferences. Until next time!