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MDS Criteria for the diagnosis of Multiple System Atrophy: New features and implications

July 18, 2022
Dr. Eduardo de Pablo-Fernández interviews Dr. Iva Stankovic and Prof. Gregor Wenning on the newly published MDS Criteria for the Diagnosis of Multiple System Atrophy. Read the article.
Journal CME will be available for this article until June 17, 2023.

Dr. Eduardo de Pablo-Fernández:
So hello and welcome everyone to a new episode of the MDS Podcast, the official podcast of the International Parkinson's and Movement Disorders Society. Today, we are going to discuss the recently published diagnostic criteria for multiple system atrophy. And I have the pleasure to welcome, not just one, but two experts in multiple system atrophy who were members of the task force for the development of these diagnostic criteria and who have ample experience and expertise on the topic.

They are Dr. Eva Stankovich from the Neurology Clinic, the University Clinical Center of Serbia in Belgrade, and professor Gregor Wenning of the Department of Neurology Innsbruck Medical University.

Welcome, and thank you for joining us today.

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So first of all, the previous diagnostic criteria were published in 2008. I think a lot has happened on the research side of things of multiple system atrophy. So my first question would be, why do we need this criteria now?

[00:01:13] Dr. Gregor Wenning:
We need the criteria because the sensitivity of the revised consensus criteria have always been sub-optimal. At first neurological visit, probable criteria was satisfied just by 18% in the order of 18%. And at this last neurological visit, this increased to like 40, 50%. So the majority of patients were missed because of these criterias. So the new criteria, we're aiming at trying to improve this deficiency in early diagnostic sensitivity.

[00:01:59] Dr. Eduardo de Pablo-Fernández:
And there has been an incredible amount of work behind this criteria over the last few years. In the paper is described a bit, but would you like to expand a bit on all the work behind the scenes?

[00:02:12] Dr. Eva Stankovich:
Thank you for that question. So we started within the task force in 2018. The task force was established, but actually this work started a few years earlier with these large literature reviews on diagnostic tests and their utility in multiple system atrophy. So these two papers are later published in Movement Disorders Clinical Practice. Those are systematic review papers. And then once the task force was established, we first define these clinical questions that were actually the questions that were related to the diagnosis of MSA, they're clinical or laboratory based. And then we, again, perform literature search to answer to these questions.

Once we had this literature evidence base prepared, then we had two Delphi rounds within the task force. And these were related to every single item of the criteria actually. What was not resolved within the group in the first round was then subjected to the second Delphi round. And then we came up with some criteria version that was later subjected to this MDS survey, which was open for MDS membership. And we received about, I think 450 responses from really all over the world and comments. And based on that, we had the consensus conference where the final criteria version was defined. And yeah, of course later the writing committee wrote this paper that was published in Movement Disorders journal just recently.

[00:03:50] Dr. Eduardo de Pablo-Fernández:
You mentioned briefly one of the critiques that can be made about a diagnostic criteria is that because NSA's is a very complex entity with a lot of clinical vulnerabilities, it's maybe difficult to apply or not very clear, but part of the process of developing this diagnostic criteria, there was survey for MDs members to discuss the clarity and applicability of the criteria in clinical practice or clinical trials.

[00:04:22] Dr. Gregor Wenning:
As Eva mentioned already, more than 400 replies out of 80 countries. So it was really a successful membership survey. And, we went through all these comments and some of them were then incorporated into the kind of pre-final version of the criteria. So it was a good mix of task force work, engaging the membership that resulted in these new criteria, hopefully increasing the level of acceptance and of these criteria.

[00:05:01] Dr. Eduardo de Pablo-Fernández:
I think you can notice that in the results of the criteria. Let's now focus on the criteria themselves. So the format is similar to the previous criteria and similar to other clinical diagnostic criteria with some essential features that are essentially change from the previous criteria and some exclusion criteria, and then some core clinical features and supportive clinical features.

There is different categories of certainty for the diagnosis of multiple system atrophy. Focusing on the clinically established and clinically probable multiple system atrophy, what are the main changes respecting comparison with the previous set of criteria and what's new?

[00:05:46] Dr. Gregor Wenning:
Well, we proposed this new category of established to indicate that these patients are clinically definite patients with MSA, because there was some feeling that the previous criteria that have probable MSA as the highest level of likelihood, are unsatisfactory to communicate the diagnosis to the patients by saying, you know, I think you have probable MSA. There should be this category of being clinically absolutely certain that patient has MSA. So we introduced this category of established MSA. And it is overlapping partly with the probable criteria of the previous revised consensus in that it includes either from the motor standpoint, levodopa refractory Parkinsonism or cerebellar ataxia or both in conjunction with autonomic dysfunction, which is now slightly differently defined for established MSA. This includes neurogenic orthostatic hypotension, 2010 blood pressure drop within three minutes of standing or tilt. Previously, the probable criteria stipulated 30 over 15, but there has been some data accumulating and suggesting that this difference doesn't really lead to a greater specificity or sensitivity of the criteria. So we basically define NOH as 2010 blood pressure drop. That or, urinary disturbance like, post-void residual volume indicating urinary retention with a volume of a hundred milliliters or more, or urinary urge incontinence. And those are the three components of autonomic dysfunction according to established MSA. You have to have autonomic dysfunction plus one of the other motor features, either poorly Levadopa responsive Parkinsonism, ataxia, or both.

[00:08:25] Dr. Eduardo de Pablo-Fernández:
There has been in corporations, as you mentioned, of blood pressure and the post-void residual volume that can be easily measured at the bedside.

[00:08:34] Dr. Gregor Wenning:
That's right. So these criteria are very practical and kind of bedside- oriented.

[00:08:40] Dr. Eduardo de Pablo-Fernández:
Of course, the inclusion of biomarkers, of supportive features — obviously they are not as available, some of them are also in development at the moment, but it's a very interesting area. And, hopefully these biomarkers and this research will provide a more accurate test for the diagnosis multiple system atrophy.

But there has been inclusion obviously of CSF, of nuclear medicine, test brain and cardiac level. I don't know if you would like to comment on any of these biomarkers?

[00:09:10] Dr. Gregor Wenning:
The biomarkers is a very interesting area, but we all felt that the evidence that is currently available is not sufficient to insist on the biomarkers in the criteria, except for MRI, where we kind of stipulate that there should be at least four established MSA one mRI marker present. Could be atrophy signal change or increased effusion in the putamen or MCP, for example. One of those should be present for the diagnosis of established MSA.

And I forgot to mention, in addition to the core features, there are also supportive motor or non-motor features that are basically like red flags. And you need to have two of those as well, in addition to the core features. So this is the way the established MSA criteria are kind of constructed.

[00:10:15] Dr. Eduardo de Pablo-Fernández:
So we have the clinically established MSA category that, as you mentioned, Same as having a very high specificity. And then the clinically probable MSA, which probably has a balance between sensitivity and specificity. And then there is this new category of possible prodromal MSA, which is one of the new developments of this clinical criteria.

So the clinical criteria to enter into this category is basically having REM sleep behavior disorder proven by polysomnography, neurogenic orthostatic hypotension, or urinary dysfunction. Again, this is another area of ongoing research and it is likely to develop in the future.

But I would like to hear your comments on this new category and the purpose of it.

[00:11:03] Dr. Eva Stankovich:
So actually this possible prodromal, MSA category, is the greatest novelty of the criteria because we never had this category before in any of the previous criteria. So this is a, for the time being a purely a research category that will need validation and prospective studies, for sure. And ideally in clinical pathological studies in the future. So this is kind of a separate part of the criteria and we really would like to encourage also, all the colleagues to apply these criteria as well as biomarkers to gain more data and more evidence for the future validation in particular of this research category.

[00:11:48] Dr. Eduardo de Pablo-Fernández:
Because it's clear from the paper that some aspects of this diagnostic criteria is a work in progress. So what are the next task for the task force? You have mentioned validation of the criteria. Presumably this criteria will have to be reviewed as new evidence comes along. But, I don't know if there is any plans for that at the moment?

[00:12:11] Dr. Gregor Wenning:
Well, we are in the process now of developing a protocol for the validation study of these criteria. We would like to focus initially on established and probable MSA. Prodromal is more complex and requires a larger number of patients that are recruited. And it's also a matter of funding. We are not there yet, but we are working on the protocol for the validation of established and probable MSA.

[00:12:43] Dr. Eduardo de Pablo-Fernández:
I think they will definitely add to the complex diagnosis of this condition. And as you said, hopefully we will get to validation studies that will prove that the new criteria has improved prove the accuracy of the previous set of diagnostic criteria.

Thank you very much for joining us today and discussing this paper with a new diagnostic criteria for multiple system atrophy.

And thank you everyone for listening, and I hope you enjoy this as much as I did.


If you enjoyed the conversation about this paper, you can further your experience with continuing medical credits or CME. You can find the link to the journal CME course for this paper within the episode description on the MDS website. Journal CME is planned and implemented in accordance with the accreditation requirements of the Accreditation Council for Continuing Medical Education, ACCME.

The International Parkinson and Movement Disorder Society is accredited by the ACCME to provide a continuing medical education for physicians. The International Parkinson and Movement Disorder Society designates this education activity for a maximum of 1.0 AMA PRA Category 1 Credits™.

Special thank you to:

Prof. Gregor Wenning

Iva Stankovic, MD, PhD
Neurology Clinic, Clinical Center of Serbia, Faculty of Medicine, University of Belgrade

Eduardo de Pablo-Fernández, MD, PhD 

Department of Movement and Clinical Neurosciences, UCL Queen Square Institute of Neurology, London, United Kingdom

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