Adding deep brain stimulation to medical therapy for Parkinson's disease improved symptoms and physical function, though the required surgery had adverse effects for nearly 20 percent of patients, including one death.
After a year, "clinically meaningful" and statistically significant improvements in mobility and activities of daily living were seen in 183 patients who received the deep brain stimulation device in addition to medical therapy, compared with the same amount who had only medical therapy in an open-label trial, reported Dr. Adrian Williams of Queen Elizabeth Hospital in Birmingham, England, and colleagues.
"But surgery is not without risk and targeting of patients most likely to benefit might be warranted," the researchers wrote online in Lancet Neurology.
They also suggested the risk-benefit balance in deep brain stimulation could improve even more with better understanding of its therapeutic mechanism and optimizing the details of electrode placement and other parameters.
Deep brain stimulation involves implanting a device similar to a cardiac pacemaker in the chest, with electrodes running up the neck, through the skull, and into certain locations in the brain. Delivery of small currents to these regions has been shown to improve some symptoms of Parkinson's disease, although the surgery is necessarily invasive and difficult.
In this trial, Williams and colleagues randomized 366 patients with advanced Parkinson's disease from 2000 to 2006 to receive "best medical therapy" with or without deep brain stimulation.
Patients had baseline scores on the 39-item Parkinson's Disease Questionnaire (PDQ-39), the study's primary outcome measure, of about 38. Average duration of symptoms was about 11 years.
After one year in the study, average PDQ-39 scores across all domains were 32.5 in the surgery group compared with 38.7 in the patients receiving only medical therapy, for a mean difference of 5.6 points.
However, of the eight domains included in the PDQ-39, a significant advantage for surgery was seen for only four:
Mobility: mean difference 12.0 points;
Activities of daily living: mean difference 14.0 points;
Stigma: mean difference 9.5 points;
Bodily discomfort: mean difference 10.9 points.
For the other domains -- emotional well-being, social support, cognition and communication -- outcomes did not differ between groups, although there was no sign that patients receiving surgery fared worse in these measures.
Results were similar when patients were evaluated with the Unified Parkinson's Disease Rating Scale. In all evaluations, benefits of surgery were mainly in domains related to motor control; cognition, communication and social function were about the same in both groups.
About 13 percent of patients reported no dyskinesia -- a form of movement disorder -- at baseline. In the medical therapy-only group, that figure was the same after one year. But 48 percent of patients who received deep brain stimulation reported no dyskinesia at the one-year assessment.
On the other hand, 36 patients in the surgical group experienced 43 discrete, serious complications related to the implantation or the device itself. These included four cases of hemorrhage -- one fatal -- and 16 infections.
There were also 13 events related to the deep brain stimulation, including five cases of postoperative confusion and other problems such as neck pain, seizures, and psychosis. In one case, the device was accidentally switched off.
Worsening or uncontrolled Parkinson's disease symptoms were also seen more commonly in the surgery group.
In an accompanying editorial, Dr. Maria Rodriguez-Oroz of the University of Navarra in Pamplona, Spain, raised a number of methodological complaints about the study: its open-label design, lack of patient diaries on motor abilities, and definitions of the "on" state that were left to individual clinicians' judgment.
She also lamented that the report only mentioned serious adverse effects. "Information on non-serious adverse events would have been relevant for neurologists in their day-to-day treatment of patients with Parkinson's disease," she wrote, especially with respect to the apomorphine infusions that many patients in both groups relied on during the study.
On the other hand, she noted that the study was larger than other trials of deep brain stimulation in Parkinson's disease.
The trial's real value, Rodriguez-Oroz suggested, may emerge with additional follow-up of the patients, which Williams and colleagues plan to continue for nine years.
"This will provide invaluable information about the long-term benefit of surgery, especially in different subgroups of patients" defined by age, disease severity, and other parameters that could influence outcomes, Rodriguez-Oroz wrote.