Deep-Brain Stimulation Improves Tourette's Tics

Pauline Anderson

January 18, 2018

Deep-brain stimulation (DBS) significantly improves symptoms of Tourette's syndrome, a new registry-based study suggests.

Dr Michael S. Okun

"The results show that there's an impressive amount of benefit in motor and vocal tics from deep brain stimulation," author Michael S. Okun, MD, Adelaide Lackner Professor and Chair of Neurology, Fixel Center for Neurological Diseases, Gainesville, Florida, told Medscape Medical News.

Because there are few cases of DBS-treated Tourette's syndrome at individual centers, sharing data from a registry allows researchers "to push the field forward" at a much faster rate, said Dr Okun.

The study was published online January 16 in JAMA Neurology.

Injury Risk

In the United States, DBS is not approved for Tourette's syndrome but is approved for obsessive-compulsive disorder (OCD).

Dr Okun noted there are few cases of DBS-treated Tourette's across the United States. "Even the most expert centers are only going to do one or maybe two cases a year," he said.

This may be because most patients can be treated with less aggressive interventions, such as medication or cognitive-behavioral approaches. In addition, he noted that some patients may outgrow the symptoms by the time they reach adulthood.

DBS is typically reserved for patients with severe tics that have the potential to cause serious injury.  

 "Some patients need to be hospitalized because of severe tics where the head starts snapping back," said Dr Okun. He added that there have even been cases of children and adults becoming quadriplegic from head snapping.

Multiple single reports and case series have shown that DBS could be a valuable therapy for severe medication-resistant cases.

The new analysis included information on 171 patients at 31 centers in 10 countries. The data came from the International Deep Brain Stimulation Database and Registry, which was launched in 2012.

Most participants (78.4%) were male. The mean age at symptom onset was 7.8 years, the mean age at diagnosis was 12.3 years, and the mean age at surgery was 29.1 years.

The two most common comorbidities were OCD (64.2%) and depression (47.3%). As well, over a quarter (28.3%) met criteria for attention-deficit/hyperactivity disorder.

Self-injurious behavior was reported in 21.6% of cases, which is lower than expected for patients selected for surgery.

"As an expert surgical group, we just assumed that the worst of the worst patients are always going to have self-injurious behavior, but it turns out that hypothesis was wrong," said Dr Okun.

Treatment Targets

The most commonly targeted brain structure was the centromedian thalamic region (57.1%), followed by the anterior globus pallidus internus (GPi) (25.2%), posterior GPi (15.3%), and anterior limb of internal capsule (ALIC) (2.5%).

The anteromedial GPi is the limbic and behavioral region of the GPi. The posteroventral part of the GPi is the motor region.


The outcome was the score on the Yale Global Tic Severity Scale (YGTSS). The scale assesses both motor tics and phonic tics, which can include grunting and other vocal tics and, in rare instances, uttering obscenities, said Dr Okun.

The YGTSS includes several parameters, including the number of tics, intensity, frequency, complexity, interference, and impairment.

At 1 year, the mean total YGTSS score improved from 75.01 at baseline to 41.19, the mean motor tic subscore improved from 21.00 to 12.91, and the mean phonic tic subscore improved from 16.82 to 9.63 (all P < .001).

Dr Okun noted that although researchers initially expected motor tics to improve more than phonic tics, the study results suggest that they both improved.

All brain targets except ALIC had a significant change in YGTSS scores from baseline to 1 year (P < .001). The anterior GPi showed the greatest improvement in the total score (50.5%), followed by the centromedian thalamic region (46.3%) and the posterior GPi (27.7%).

Dr Okun noted that tics improved whether the leads were put into the nonmotor or the motor area of the GPi.

Some experts had hypothesized that because patients with Tourette's often get a "premonitory urge" before a tic, stimulating the ventral area — the nonmotor GPi — would provide the most benefit, said Dr Okun.

It's possible, he said, that there's much more overlap between those brain regions than was previously thought.

"At this point, we're still guessing and putting the pieces of the puzzle together. The sample sizes in the study, across divisions of the palladium, are not yet enough to lay stake, and claim that one region may be better," he said.

As the registry grows to include more patients, "we will get a better understanding of which symptoms get better with which targets," he said.

Global Data

Only one center targeted the ALIC. While the 1-year scores were reduced from baseline, the number was too small to permit firm conclusions for the ALIC as a target region, the authors note.

"What's important about this paper, which pulls together all this information from across the globe, is that it shows that you can intervene in multiple places in the neural network and get similar benefit," said Dr Okun.

It's not clear from this study whether the DBS improved OCD symptoms. "We're still looking at that data," although not all centers provided this information, said Dr Okun.

The two most common adverse events in study patients were dysarthria, or slurred speech (in 6.3%), and paresthesias, or a numbness or tingling sensation (8.2%).

These, said Dr Okun, were mostly reversible by changing the settings.

"As we move forward, the challenge is to reduce side effects and improve the benefit, and we will be able to use new technologies and new approaches to be able to do that."

New technologies might allow a high enough voltage, or current density level, to reduce tics without causing adverse effects, he said.

Gathering data from a public registry is a "powerful" tool, said Dr Okun. "It will stir the pot in a meaningful way, get people thinking, talking, and trying to move the field along instead of guessing."

But Dr Okun stressed the importance of assembling a risk/benefit profile for each patient through a very careful interdisciplinary screening.

"These are very complex patients and treatment should be personalized for what symptoms they suffer from," he said.

Meaningful Findings

Heather Simpson, OTD, Tourette Clinic coordinator, Center of Excellence, UF Health Center for Movement Disorders and Neurorestoration, Gainesville, Florida, sees first-hand how these symptoms can impair daily functioning.

The results of this new study are meaningful because they show that DBS can produce a "dramatic drop" in tics without causing many side effects, Dr Simpson told Medscape Medical News.

"I think the study shows that there's promise for those patients who are really severe," said Dr Simpson.

"It's not a perfect fix because Tourette's is so complicated, but certainly it's one piece of the puzzle that can make their life a little bit easier" in terms of life skills, such as working, driving, and just being able to take care of their children.

Dr Simpson is trained in a program called cognitive-behavioral intervention for tics (CBIT). Although this program is effective in helping patients manage symptoms, the urges and tics of some patients are too severe for them to benefit from it.

DBS might reduce their tics to the point where they can take advantage of the program to further improve symptoms.

And, said Dr Simpson, brain stimulation might give patients "a more positive outlook," which helps reduce urges. That, too, might encourage patients to try CBIT.

"When patients have a positive outlook, they do better on behavioral therapy."

Dr Okun reports serving as a consultant for the National Parkinson Foundation; receiving research grants from the National Institutes of Health, the National Parkinson Foundation, the Michael J. Fox Foundation for Parkinson's Research, the Parkinson Alliance, the Smallwood Foundation, the Bachmann-Strauss Foundation, the Tourette Syndrome Association, and the University of Florida Foundation; receiving grants from the National Institutes of Health for DBS research; receiving royalties for publications with Demos, Manson, Amazon, Smashwords, Books4Patients, and Cambridge (movement disorders books); serving as an associate editor for New England Journal of Medicine Journal Watch Neurology; participating in continuing medical education and educational activities on movement disorders (in the last 36 months) sponsored by PeerView, Prime, QuantiaMD, WebMD, Medicus, MedNet, Henry Stewart, and Vanderbilt University; and participating as a site principal investigator and/or coinvestigator for several National Institutes of Health, foundation, and industry-sponsored trials over the years but has not received honoraria. Dr Simpson has no disclosed no relevant financial relationships.

JAMA Neurol. Published online January 16, 2018. Full text

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