WASHINGTON (FRONTLINE MEDICAL NEWS) – Scheduled administration of bilateral deep brain stimulation of the centromedian thalamus for less than 2 hours a day resulted in a significant reduction in tics in several patients with Tourette syndrome over 2 years in a proof-of-concept study presented at the annual meeting of the American Academy of Neurology.

Of the four patients who completed the 24-month study, three experienced significant improvements, said Justin Rossi, an MD-PhD candidate at the University of Florida in Gainesville.

Instead of using the standard continuous deep brain stimulation (DBS), Mr. Rossi and colleagues at the university’s Center for Movement Disorders and Neurorestoration evaluated a scheduled, personalized stimulation approach, with stimulation of the centromedian thalamus (bilaterally) tailored to the times of the day when patients experienced the most sequelae from the tics, such as when they were driving, exercising, or working, and when the intensity of the tics was the greatest.

The rationale for investigating this approach is that instead of using the “classical continuous approach” to DBS, a tailored approach might be effective in these patients, with the potential benefits of increasing battery life (and delaying another surgical procedure to replace the battery) and reducing side effects associated with stimulation, Mr. Rossi said.

Many studies have found that DBS is effective in “select medication-refractory cases of Tourette syndrome,” he noted. “However, in contrast to Parkinson’s disease, essential tremor, and other movement disorders for which DBS has been commonly used as a therapy, Tourette syndrome is a paroxysmal disorder,” and the frequency of tics can vary from patient to patient, with individual patients reporting that the intensity of tics “waxes and wanes throughout the day, often predictably.”

The study enrolled five patients; responses were evaluated with two rating scales, the Yale Global Tic Severity Scale (YGTSS) and the Modified Rush Video-Based Tic Rating Scale (MRTRS). A patient was considered a responder if there was more than a 40% improvement in the YGTSS or MRTRS from the preoperative baseline level, at 24 months, the primary outcome. (One patient was lost to follow-up after 18 months because the center was too far away.) Patients had the opportunity to modify the schedule at each 6-month visit.

At 24 months, the YGTSS total scores improved by 46%, 58%, and 17% and the MRTRS total scores improved by 79%, 81%, and 44% in the three responders. These patients had a mean stimulation time of 1.85 hours a day, ranging from 47 to 186 minutes per day. The one patient who did not meet the primary endpoint – with a 10% response on the YGTSS and a 21% response in the MRTRS – had the greatest amount of stimulation per day (4 hours a day). At 24 months, the responders had statistically significant improvements from baseline in components of the two scales, including the number of phonic tics per minute, motor tic severity, and phonic tic severity, Mr. Rossi said.

This is a proof-of-concept study and the results and conclusions are preliminary, but the results “warrant larger studies,” he concluded.

More research is needed to understand this mechanism on a more physiological level, which is being pursued at his center, he added. The results shed some light on whether the mechanism of DBS in Tourette syndrome is a cumulative effect of stimulation over time or whether DBS has an effect around the time the tics occur, and these results support the latter explanation, Mr. Rossi speculated.

He had no disclosures. The study was sponsored by the National Institutes of Health.


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