Major Finding: Scores on the motor subscale of the UPDRS improved from baseline by similar amounts after 2 years of DBS targeting the globus pallidus interna (from 42 to 30) or subthalamic nucleus (from 43 to about 32.5).
Data Source: Randomized, rater-blinded trial of 299 patients with idiopathic Parkinson's disease.
Disclosures: The Department of Veterans Affairs, the National Institute of Neurological Disorders and Stroke, and Medtronic, maker of a DBS device, funded the trial. Dr. Follett had no relevant financial disclosures to report.
TORONTO — Motor function in Parkinson's disease patients improved by a similar amount after 2 years of bilateral deep brain stimulation of the subthalamic nucleus or globus pallidus in the first blinded, randomized trial to compare outcomes with the two targets.
This result may free clinicians to give greater weight to the effects of deep brain stimulation (DBS) at each site on quality of life, neuropsychiatric symptoms, and medication reduction, Dr. Kenneth A. Follett said at the annual meeting of the American Academy of Neurology.
The subthalamic nucleus (STN) has become the preferred and most common target of deep brain stimulation for Parkinson's disease patients, even though “there really is a lack of high-quality evidence that STN-DBS provides clinical outcomes that are superior to outcomes with GPi [globus pallidus interna]–DBS,” said Dr. Follett, professor and chief of neurosurgery at the University of Nebraska Medical Center, Omaha.
GPi-targeted patients completed the trial with slightly better neurocognitive performance in some areas and slightly more “on” stimulation time, but also with significantly greater medication use, compared with STN-targeted patients.
“The bottom line is that given the uniformity of outcomes, clinicians may comfortably take into consideration factors other than just motor function when selecting a target. For example, you may have preferences based on what you perceive is in need of targeting one site or another, the ease of programming one site or another.
“You may decide it's prudent to select one target versus the other based on symptoms. For example, a patient with severe, dose-limiting dyskinesias may be a [slightly] better candidate for GPi. A patient who has medication side effects such as nausea or hallucinations at a low dose may be a better candidate for STN-DBS, knowing that she'll be more likely to reduce medications postoperatively,” Dr. Follett said.
Although it is unclear whether medication reduction is necessarily desirable for all patients, it “may play some role ultimately in selection of target,” he noted.
During 2002–2008, patients enrolled in the trial and underwent follow-up at 13 VA Parkinson's Disease Research, Education, and Clinical Care Centers and their affiliated universities, Dr. Follett said.
To be enrolled, patients had to be at least moderately disabled off medications (Hoehn and Yahr stage 2 or worse) and be l-dopa responsive with clearly defined “on” periods, and to have a diagnosis of idiopathic Parkinson's disease, persistent disabling symptoms such as dyskinesias, motor fluctuations, and a minimum of 3 hours per day in the “off” state or “on” with dyskinesias.
The investigators excluded patients with “Parkinson's Plus” or secondary or atypical Parkinson's syndromes, previous surgeries for Parkinson's disease, medical contraindications to surgery or stimulation, contraindications to MRI, active alcohol or substance abuse, or a Mini-Mental Status Examination score of 24 or lower or other neuropsychological dysfunction.
The randomized DBS trial was embedded within another randomized trial that compared best medical therapy (BMT) with pooled outcomes of DBS. After 6 months, clinical outcomes were examined and BMT patients were randomized to either DBS target.
In an interim analysis of the data when 134 patients had been randomized to BMT and 121 to DBS, the data safety monitoring board decided to stop randomizing patients to BMT because enough data had been gathered to compare the primary outcome.
An additional 61 patients were randomized to only one of the DBS targets, leaving a total of 316 enrolled patients. The investigators conducted follow-up with the patients for 2 years after DBS implantation, meaning that patients who had been initially randomized to BMT received 30 months of follow-up.
A total of 17 BMT patients withdrew from the trial without being randomized to DBS, leaving 152 patients in the GPi group and 147 in the STN group. These patients had a mean age of about 62 years and had been on Parkinson's disease medications for a mean of 11–12 years. Patients and the clinical raters were blinded to the target brain region.
In the “on stimulation, off medication state,” scores on the motor subscale (part III) of the United Parkinson's Disease Rating Scale (UPDRS III) at 6 months improved similarly in the GPi (from 42 at baseline to 30) and STN patients (from 43 at baseline to about 32.5). The scores at 2 years—the primary outcome of the trial—were no different. Additional longitudinal analyses with mixed-effect models that used worst-case scenarios for all incomplete data also found no difference between the groups.