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International Parkinson and Movement Disorder Society
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Highlights on Tic Disorders - Congress 2022

October 01, 2022
Series:MDS Congress 2022
As tic cases rise, Dr. Christos Ganos overviews with Dr. Hugo Morales two major treatment advancements, a growing emphasis on neurostimulation research and multidisciplinary care, and progress in the field's largest area of opportunity.

[00:00:00] Dr. Hugo Morales : Welcome to another MDS podcast episode. I'm pleased to have Christos Ganos, who is a neurologist movement disorder specialist from Charité University Medicine, Berlin. He is an expert in Tic disorders. Thank you for coming today.

[00:00:19] Dr. Christos Ganos: Yeah, thank you, Hugo. Thank you.

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[00:00:21] Dr. Hugo Morales : So one of the things I think is relevant for the audience is, what is the approach that you use when evaluating the patient with a tic disorder?

[00:00:29] Dr. Christos Ganos: Thank you. Of course it is difficult to try to sum everything up in a little time, but essentially tics, you will always need a definition. And we know that they are movements or sounds that resemble voluntary actions, but appear inopportune. So they are surprising, so to say, to the eyes of the individual who observes.

They're not surprising for the individual who experiences them, though. And that's important. So if we ask people with primary tic, like Tourette syndrome why does this happen to you? Do you experience it? Sometimes they say, 'yeah, actually I do them because my experience this premonitory urge and ...' Sometimes they say, 'Oh, I, I don't feel much, but I see that I'm blinking. Or I see that I'm doing this kind of movement.' So this is an important factor. People have a certain awareness of what is happening to their body.

And even if this awareness has been so incorporated through the years that they just accept them. When we speak to them about the certain movements, then they become aware that they do them. And they say, yes, it's part of my behavior because that, and that, and that. So this essentially distinguishes tics from all other hypokinesia that we know. So this is a basic approach.

But this is just on the movement phenomenology. And later on, we'll speak about the difficulties in distinguishing primary tics from functional tics. But of course, when we do evaluate the person with tic disorders, we should always keep in mind the neuropsychiatric comorbidities, which in many cases are the leading issue in people's quality of life.

And sometimes it goes disregarded in the clinical setting. So we always have to explore about the presence of obsessive compulsive behavior or disorder, attention deficit disorder. And then for the older individuals, of course, depression, anxiety disorders, sleep disorders, and often also sexual health disorders as well.

[00:02:05] Dr. Hugo Morales : Is there anything new in terms of how we understand the pathophysiology of tics?

[00:02:13] Dr. Christos Ganos: Yes, there are new developments and most of them have been led with probably most people know Mike Fox and this type of analysis of network mapping. So now we have good studies some led by Kara Johnson. And one we did together with Andrea's horn, Mike Fox and a series of really nice collaborators.

And now we know the central network that is associated with the presence of primary tics . I will not go into much in the digital of the studies, but what we know the key components of this network are essentially the basal ganglia input and output structure, thalamus, and then interestingly, we also have the anterior singulate cortex parts of the anterior singulate cortex and the insula as a center of interceptive awareness, probably mediating this tic execution or tic emergence, in a sense. So this is important because now that we have, for the first time, a mapped network or a network that we mapped on, then this informs us also for invasive, or in the future, perhaps noninvasive, neuromodulation treatments, because we can target this network more accurately. And this we showed already in our study for example, and other people have showed as well.

So this is important when we speak now, because I made this leap to DBS: when we think about DBS, we have to be very careful which patients we select. And led by David Martino, there is this nice international consensus paper, essentially, on which patients are deemed refractory in medical or pharmacological and behavioral treatments and should be considered for DBS.

And in this context, we should always distinguish or make sure that the patients we send for DBS do not present predominantly with tics or other movements that are of functional nature.

[00:03:45] Dr. Hugo Morales : Yeah. And Christos, is there any data that we can use in terms of how soon DBS for Tourette syndrome how restrictive these cases are? Is there any suggestions that say instead of just waiting many years to see how the disease behaves, doing early DBS?

[00:04:03] Dr. Christos Ganos: Yeah. This is a nice question and we have the advantage that Tourette syndrome is not a neurodegenerative disorder, right? So it's a neurodevelopmental syndrome. So either ways we have a development of the syndrome over many years. And in adults in this paper by David Martino, we established a list of things that have to happen before somebody considers DBS. And these are behavioral treatments and these are pharmacological agents that need to be tried for several weeks.

This was part of a consensus, but I would say that one needs to try pharmacological agents, at least three, for example, from the class of dopamine blocking agents, for at least eight to 12 weeks. And this was an contentious issue, but at least for this period. And then one can try also other medications or augment dopamine blocking agents with the pyramid, for example, and one can also resort to cannabinoids. This is another mm-hmm issue to discuss, but there should bea rigid protocol of how to approach this, which behavioral and pharmacological strategies have been tried, and when they fail and when we are still convinced that the main issue is tics and not other comorbidities or other diagnoses, then we can discuss with the patient that now it would be the time to think of DBS.

[00:05:12] Dr. Hugo Morales : Are there any clinical trials in the near future for new treatments for Tourette syndrome or other related disorders?

[00:05:20] Dr. Christos Ganos: So we have some nice news from the behavioral front. So there are some nice studies published that online behavioral treatments work as well. Both exposure response prevention, this is a strategy essentially when you train individuals to stop or to, to increase an Inhibitory capacity for things. So we have these behavioral studies. We know, anyway that CBIT, the comprehensive behavior intervention for tics works as well. And this can also be done in an online setting.

And now we have this news on pharmacology, about a ecopipam, a D one receptor blocker, and essentially new. This was a Gilbert study back from 2014. And since then several studies, and now we have a phase two B trial that has been concluded in children and adolescent, that saw the efficacy for ecopipam. It's still unclear how significant efficacy is for the overall quality of life of people, but there is a signal to notice there, and this will be explored further, I think.

[00:06:13] Dr. Hugo Morales : Interesting. And with the recent pandemic, with COVID 19, I remember seeing that it increased of the number of patients being diagnosed with tic disorders. It seems to be a different thing, but what is your view of these cases with emerging tic disorders, and what we can learn from them?

[00:06:31] Dr. Christos Ganos: So for our listeners, the issue of functional tics is not a new one. This has always been a difficult issue since the inception of the concept of tics as a disorder back in the 19th century, essentially. So there were two fronts: that tics are functional or tics are a primary disorder, neurological disorder.

And this has continued over time. In the eighties, nineties, where we started with primary tic disorders, the reevaluation and reappraisal of what Tourettes is essentially, then the focus was given on primary disorders. But then there were always patients that would appear like Tourettes, but they had the functional disorder, essentially. And now we see that clearly.

What you refer to is an increase in cases that has been seen in clinics all over the world with people presenting with acute onset functional tics. Some people refer to tic-like behaviors, but indeed there has been in increasing these cases and many of these cases have been using social media, like TikTok, like YouTube, but we have written commentaries on that. And many people have. It's not a one-to-one correlation that if you see a video of a certain motor phenomenon, you will catch it. It's not like that.

And people use, to my understanding, not correctly, the word echophenomenon. This is not an echophenomenon in the proper sense. But indeed, exposure and increased knowledge to Tourette syndrome and tics has led also to an increased prevalence of people with functional tics. And this is what we observe. And this is I think the most careful scientific comment to make at this time.

What is interesting, and what people are discussing is that the profile of comorbidities of these people with acute onset functional tic differs from the people with primary tics. And it might allude to more, to increased anxiety, increased depression and other issues but not so much the ADHD profile or the OCD profile that we see classically in people with Tourette's. And there are also some factors related to personality issues. But I think this is a careful topic that one wants to approach very cautiously.

[00:08:23] Dr. Hugo Morales : Yes. What do you think are the gaps in knowledge in terms of tics, and what are the future areas of research for this?

[00:08:31] Dr. Christos Ganos: It's a beautiful question. And let's, let's celebrate a gap that has been closed now. So we now speak so much about TikTok tics and this phenomena, but I think we don't have such a brief memory to have forgotten, like PANDAS. And tics associated with Streptococcal infections. And there are these wonderful studies done from a consortium of colleagues that looked whether CCAL infects a group, a CCAL infections are associated with exacerbation of tics in people with primary tics and new onset tics in people who did not show tics before. And there is no data to support this.

So I think first of all, one knowledge gap that was still entering many people's thinking, like this PANDAS issue, has been now closed. So we have no evidence to support antibiotics in people which have new onset tic anticipations. This is one.

For me, the most troubling issue is the issue of terminology. Perhaps the most important issue is the issue of definition.

And we did start this conversation by defining what tics are. But actually, this is a difficult issue because this definition is very broad and it allows people to subsume different phenomena under the tic rubric. But this phenomena of repetitive behaviors do not all actually pinpoint what we see in people with primary tic disorders. And therefore we have the problem to say, is this a repetitive behavior? Is it a tic? Is it a tic like behavior? What is it when somebody, for example, hits somebody else and says, I, I cannot control it. Is it a tic? Is it tic-like? Is it other aggression? Is it something that's just a behavioral phenomenon?

And I think the main issue now for us, is to better define what a tic is so we can characterize our populations. And do essentially better trials with these populations that will also lead to better results — more signal than noise, essentially.

And in order to achieve this, I would like to celebrate the fact and thank the Movement Disorder Society for allowing us to begin a new Task Force On Tic Disorders, whose mandate is essentially, ideally within one year's time, we'll see if this is feasible, to provide a new consensus definitions of tics and also split phenomenology from etiology.

So we don't have to speak of a tic of a tic-like behavior of a non-tic behavior that looks like a tic or this complic complicated issues. But essentially we can define better what a tic is separated from etiology. And so then we speak of functional tics. And then if people would like to use a term of tic- like behavior, who would try to also find a definition for that. So essentially we achieve a global consensus on the phenomena. That's very important.

And it's really important because last year also through the Movement Disorder Society, the Tic Disorders and Tourette Syndrome Study Group, we did this study that we, the survey among movement disorders, experts who see people with tics. And essentially we saw that it is really important to achieve the consensus. And the majority of people reported that their knowledge and pathophysiology and phonology of tic is insufficient. And I think this is a domain that, with the help of the Movement Disorders Society, we can increase knowledge and education about.

Another issue that we'll see will be the rise of the cases that receive noninvasive neurostimulation. This is in the near future. And indeed, hopefully with the data that we have provided and are published non literature, we'll see also better applicability and better efficacy of the applied deep brain stimulation strategies in people.

This augmented with pharmacology, this augmented with concepts of clinics that do not focus only on the motor phenomena, but we have interdisciplinary clinics where we have movement disorder specialists, but psychiatry, psychologists, social workers. It's very important to be in discussion with all these colleagues of ours in order to provide our patients who do not have only a motor phenotype, but also behavioral phenotype and many issues to deal with, all the support they need. I think this is very important.

I will use Mike Okun's beautiful sentence that the patient is the son, and this is a guiding light also for us. Because we should put this patient in the center and all of us are trying to, form our different disciplines and capacities and, and our talent to speak with each other, the goal should be to, to help the patient.

[00:12:32] Dr. Hugo Morales : Thank you, crystal, for your wonderful overview and keeping us abreast with Tourette syndrome , tics, and letting us know there's room for improvement. And I will invite all our listeners to check. Christos Ganos's research. And thank you, Christos, again for coming.

[00:12:48] Dr. Christos Ganos: And many other people's, please, many other people's research.

Thank you. Good. Yeah.

Special thank you to:

Christos Ganos
Neurologist movement disorder specialist
Charité University Medicine, Berlin

Hugo Morales Briceño, MD 

Neurology and Movement Disorders Unit, Westmead Hospital

NSW, Australia

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