Updates of Functional Movement Disorders | Congress 2022

[00:00:43] Dr. Alberto Espay: Well, thank you, Sara. I'm happy to be with you. The study group now is one that finally reconvened for the first time in person here in lovely Madrid.

What we have been developing a lot of our effort or investing a lot of our efforts into is trying to get to what might turn to be the first outcome measures study that the NIH might fund. This is in response to an RFA by the national institutes of health through the NINDS.

And we think we have through the study group and the resources connected to it a group of committed people to helping us develop an outcome measure that will be more specific for FND that could be versatile used according to different phenotypes and eventually very useful for trials.

 This is part in fact of an effort in age is undertaking to help the FND field be trial ready. So that's one of the areas that we are investing quite a bit of time and energies into, and then the other, study group is interested in the development of biomarkers for FND. And that is an area that's difficult because that would require a separate type of investment. Also ideally from the NIH. So there is some work in a piecemeal fashion with really rather limited budgets trying to get to do genetic studies in a bio repository that at the moment has been run a few centers.

Not yet quite as universal as we think will be important for us to do, but moving in that direction,

[00:02:32] Sara Schaefer: Those both sound like really exciting things to look forward to. I know in my own practice, FMD treatment is so tailored towards functional epilepsy and it's just sort of adapted to movement disorders and being able to measure outcomes I'm sure would move the needle in terms of finding treatment strategies that are effective for this particular population of FND patients. So tell me about some of the research that you've been following in the FND over the past year and things that you're looking forward to.

[00:03:06] Dr. Alberto Espay: Yeah, so I think probably the most exciting change has been the blurring of the functional organic dichotomy or the boundary we think was neatly separating these two entities. And in fact, we're at a point where we are recognizing that what isn't functional is not necessarily organic as such functional disorders are organic themselves. And what has become quite apparent is that there are those who present with a functional phenotype that go on to develop another neurological disorder and the most poignant of those examples is the one that relates to those patients that develop functional tremor in going to develop Parkinson's disease.

We initially thought this was rather diagnostic inaccuracy in terms of defining functional tremor, perhaps inappropriately patients that in fact had a Parkinson tremor. And in reality, this was an appropriate diagnosis and when patients are followed carefully, they end up having Parkinson's.

Now who are they we don't yet know for sure. But this came to light a few years back when a large group of patients with FND were tested with DaTscan and half of the cohort had a positive DaTscan. We were quite surprised by that data. We did not think as the authors reported, then that it was an issue that related to poor diagnostic accuracy. We figured something else was happening there. And as we began to look in what, at the time we called the comorbidity between Parkinson's and functional disorders, using a case control methodology, we realize that patients that have both Parkinson's and functional disorders a third of them presented with the functional disorders years and in few cases, in fact, after a decade worth of symptoms developed in Parkinson's disease. So this particular Functional prodrome of Parkinson's is of interest, because it seems to cluster eventually with a type of Parkinson's disease that appears to be somewhat more malignant.

There is a greater tendency for dementia. There is just more rapid progression it seems. Less optimal response to levodopa. So it's throwing a bit of a range on the idea that we can say to patients. Well, this is functional and be confident that there won't be a change in the phenotype.

I think that is one of the complications that we are now having to deal with. And then the second is the emphasis, is it two diseases? Is it really called morbidity where you have two conditions in one person or as the odds would suggest perhaps one that somehow at two time points would express first as a functional disorder and later as Parkinson's.

[00:06:13] Sara Schaefer: I had no idea. That is extremely interesting. Way to muddy the waters.

[00:06:19] Dr. Alberto Espay: Exactly. No, I wish our patients were to read our textbooks that indicate that functional disorders are in these separate category compared to Parkinson's. But no, it's so interesting. So I think in the future, We will have to be mindful of that.

I also think that, and this is something that was discussed at the functional neurological disorder society Congress that took place in Boston that there may be some degree of functional nest in our patients. And I think viewing that perspective is not black or white, you have functional or not, but rather, is there any degree of a functional nest that might be expressed in a variety of patients and perhaps if we look into it maybe when we've, coming back to Parkinson's for instance, think of individuals that have certain responses we've used the term functional overlay that maybe is, as if this may be part of the spectrum of many neurological disorders. And because we're aiming for a clear black or white world, we might not really be yet prepared to speak in terms of shades of gray. But in the future, perhaps we will be able to be more comfortable attributing a percentage of the phenotype of any of the neurological conditions to perhaps a functional component whatever we might end up calling it.

Perhaps at that time, even functional itself will be differently referred to and then the other percentage to whatever that disorder may be. So I think that made more sense. In reality in general when we speak of comorbidities it is because we have different labels for phenotypes, but chances are people don't have 2, 3, 4 diseases just because in reality the odds are much more likely that they have a molecular biological disruption or abnormality that, that creates a phenotype that is diverse enough that by virtue of our current classification scheme, we just think of them as separate diseases. So that probably is something that the study of functional neurological disorders might end up helping us revisit our nosology widely.

[00:08:35] Sara Schaefer: Thank you for that very insightful overview.

[00:08:39] Dr. Alberto Espay: My pleasure, Sara, it's been great to be with you.