Dr Irene MalatyIrene Malaty, MD
While Tourette syndrome is a complex tic disorder to treat, sometimes requiring more than one therapeutic intervention to control can, in some cases, be addressed with surgical methods, such as deep brain stimulation (DBS). Although, these methods are still relatively new to Tourette, and are reserved mainly for the most refractory and severe cases.

Despite this, there has been a growing interest among movement disorder specialists about the possibility of developing a better method of neuromodulation for patients with Tourette. Currently, there is a need to better understand the proper areas of the brain that need to be targeted in stimulation practices.

To find out more about those targets, and the progress that has been made with DBS for Tourette syndrome, NeurologyLive sat with Irene Malaty, MD, an associate professor at the University of Florida and the director of both its Parkinson Foundation Center for Excellence and its Tourette Association of America Southeast Regional Center of Excellence. Malaty recently presented an update on neuromodulation’s use in the tic disorder at the Child Neurology Society’s annual meeting in late 2018.

NeurologyLive: You gave a presentation on neuromodulation in Tourette syndrome at the Child Neurology Society annual meeting. What did that entail?

Irene Malaty, MD: I spoke about, specifically, DBS. We're talking about in refractory tic and Tourette syndrome, the application of electrical stimulation to try to change the abnormal circuit firing in the basal ganglia to try to improve tics. In the past, lesion therapy was tried with thalamotomy, and it was able to be shown that making a lesion in the thalamus was able to improve tics.

Basically, there's a theory that abnormally firing neurons in the striatum cause the inhibition of the Globus pallidus and substantia nigra in a way that it removes the “breaks” on the thalamus so that there's this abnormal, excessive activity, and that stimulating at different points in those circuits could change the outcome and the tics. When thalamotomy was tried, the problem is that when you make a permanent lesion, there are risks involved. Then, perhaps using DBS could actually be a more modifiable way.

We were able to show the results of the International Tourette Association data registry, so that all the cases that are being done across the globe [were included]—there are few sporadic cases done at many different sites and when it's going along at that pace, it's hard to really see the field advance quickly. The idea was to pool the data and so all of these institutions across the globe are putting their data together, and we were able to show the motor outcomes and some of the adverse events that have occurred so far in this evolving therapy.

Toward the end of my talk, I was able to show some exciting work that's being done by Michael Okun, MD, with implanting stimulators that have a recording capacity, in addition to a stimulating capacity. That [allows us to] actually learn about the electrophysiological signature of what's happening when tics occur so that in the future, we can create a stimulator that's actually specific and individualized to that patient’s needs, and that might actually be able to fire just on-demand. That would extend battery life and really sort of revolutionize the way that DBS is being done.

What do the clinicians that are utilizing DBS in this patient population need to know about it?

It's important to know that it's still early and that it really should be offered by centers that have the expertise and a multidisciplinary team that is able to really manage all the complexities of it. We are still learning about the relationship with the comorbidities that are common in Tourette syndrome and the impact there, and it's always very important to manage those and to weigh the risks and benefits from considering something to contribute to, say, a surgical approach.

Are there any cautions that need to be addressed regarding the use of DBS in Tourette syndrome?

It's still an off-label application and it's still really for severe and refractory cases, but it's actually very promising. The cautions are that some patients with Tourette syndrome—in fact, the majority—experience spontaneous remission or improvement over time, and so we're still figuring out when's the right time to intervene in cases where DBS is a consideration. How early do we intervene? That's probably one of the most unclear questions so far. Also, what the optimal brain target is because the data we showed were that at least 3 different brain targets were producing similar results. We're still figuring out the optimal brain target, and the optimal stimulation settings, and the longer-term outcomes.

The most exciting part of DBS for the future is the adaptive, closed-loop systems that are actually using recordings from the patient's own brain to define their stimulation parameters. That's what I'm the most excited about now.

Will there be trials of DBS in the future to attempt to address some of these unanswered questions?

I hope there will be. It's difficult to do placebo-controlled trials with surgical therapy, so there are a lot of challenges there. The second-best thing, or the alternative that's being employed now, is just collecting data from what's been done. But I would like to see rigorous trials going forward. I'm not sure if there's anything that's already being planned to my knowledge. Although, there is ongoing research with a closed-loop system, but it's being done on a slow pace.

It's interesting that a recent survey done by the Tourette Association showed that, despite trying multiple medications, about 45% of patients report feeling that their symptoms aren't adequately controlled by the medicines and therapies we currently have. So, there's definitely a need for something better than what we currently have, and I'm hopeful that DBS could be part of that for some of the more severe, refractory, and malignant cases of Tourette syndrome.

Is there a specific patient age group that DBS would be best used within?

The Tourette Association convened a panel of experts to put forth guidelines on patient selection, and the first set of guidelines recommended the youngest age being 25. But, the most recent revision to those guidelines removed a lower age limit from a specific age and instead suggested that individual and careful consideration be used to make the decision, but that if a patient is under 18 years old, there should be involvement with an ethics committee or institutional review board. Rather than a hard and fast bottom number, it's just recommended that there's a team approach and careful consideration.

Transcript edited for clarity.