Medical Device Daily

More evidence has emerged this week that mechanical intervention – specifically deep brain stimulation (DBS) – in Parkinson's disease (PD) to quell the debilitating symptoms outweighs the benefits from currently available medication therapies.

In the largest study to date exploring the use of DBS in patients who span a wide age range, DBS is compared with medication therapy over a six-month period.

The current medication of choice, levodopa, works for most of the 1.5 million PD patients in the U.S., in early stages of the disease. After time passes, drug loses its effectiveness for most.

"Our patients were averaging six to seven hours a day of good time," the study's primary author, Frances Weaver, PhD, told Medical Device Daily. "Our DBS patients gained an average of 4.6 hours per day in good time. The patients on medication alone didn't improve at all."

"Good time" means that these folks don't experience shaking while a limb is at rest, slowness of movement, rigidity of the limbs or poor balance.

Weaver, who is director of the Center for Management of Complex Chronic Care at Hines Veterans Affairs Hospital (Hines, Illinois), said the study also was significant because the benefits were similar for younger and older patients, although adverse events were higher in older patients.

"For the first time, our study included 25% older sample – patients who are age 70 and older," she said. "They are often excluded from these studies, so our study is more generalizable because it includes older patients. The fact that they did almost as well as younger patients is a positive finding."

However, 40% of patients experienced adverse events. Despite that, the study authors still believe the treatment is a best choice when medication isn't used or becomes ineffective.

Results of the 255-patient study, conducted at seven Veterans Affairs and six university hospitals, were published Wednesday in the Journal of the American Medical Association.

"Deep brain stimulation was more effective than best medical therapy in alleviating disability in patients with moderate to severe PD with motor complications responsive to levodopa and no significant cognitive impairment," the study authors wrote. "The extent of benefit was similar for younger and older patients, although adverse events were higher in older patients."

"Whether or not to use DBS is a decision that has to be carefully weighed by a patient and their provider; the benefits vs. risks," Weaver said.

The data specifically revealed that, compared to patients receiving best medical therapy after six months, patients receiving bilateral DBS of the subthalamic nucleus or globus pallidus with Medtronic's (Minneapolis) Activa DBS Therapy plus medication had increased daily time spent in the "on" state (which means good symptom control and unimpeded motor function), increased time spent without troubling dyskinesia (unintentional movements), increased motor function scores, increased overall quality of life scores and decreased time spent in the "off" state (defined as poor symptom control and motor impairment).

The Activa was first cleared for the treatment of advanced-stage Parkinson's disease in January 2002 (MDD, Jan 16, 2002) and is the only brain stimulation therapy currently commercially available in the U.S. That original system used two pacemaker-like devices implanted on each side of the chest with leads implanted in the brain. The newer neurostimulator, cleared by the FDA in January 2004 (MDD, Jan. 23, 2004), is a single device that accommodates two Medtronic DBS leads carrying precisely controlled, electrical impulses to both the left and right sides of the brain, thus reducing surgical incisions.

DBS has become the treatment of choice when Parkinson's disease patients' motor function is no longer well-controlled with medications, but typical DBS candidates are younger and have fewer co-morbidities than many of the patients in this new study.

"These data show that DBS patients consistently score higher on quality of life measures than patients receiving the best medical therapy, even for the oldest subset of patients in the study," said William Marks Jr., MD, associate professor of neurology at the University of California, San Francisco, director of the Parkinson's Disease Center at the San Francisco Veterans Affairs Medical Center, and a principal investigator in the study. "I anticipate that the DBS benefits demonstrated in this large-scale study will be very compelling to the neurology community as physicians consider DBS as a treatment option for future patients."

Regarding the adverse events, Weaver and team reported that 49 DBS patients experienced 82 serious adverse events serious adverse events, which were attributed to the surgical procedure, stimulation device or stimulation therapy. Two deep brain stimulation patients died - one was secondary to cerebral hemorrhage that occurred a day after lead implantation. The second death was due to lung cancer and that patient withdrew prior to DBS implantation.

"Ten percent had infections either at the site of the battery pack or where stimulators went in and required treatment of the infection and removal of part or all of the device," Weaver said. "Then, a second surgery to re-implant was required. That's a significant consideration, but the number of infections is within the realm of other published studies."

Another concern noted among DBS recipients was a slight decrease in cognitive abilities.

"The decrease in cognitive performance is statistically significant to mention it in the study, but clinically it's hard to say how significant that decrease was. Because the quality of life was so good, the small decrements in cognitive function were more than outweighed by the benefits."

Weaver described the cognitive decrements as being a slowing in the ability to process information.

"I heard some anecdotal evidence that came from patients. Overall the feeling was the benefits outweighed the potential risks," she said.

A second phase of this study is ongoing and will focus on the best place in the brain to give stimulation.

Weaver added some thoughts about what Medtronic could do to improve its Activa device. Longer-lasting or rechargeable batteries rank as a No. 1 request, reducing the need for future surgeries along with the risks and costs.

"Our estimation is that the current batteries last two to five years, depending on the levels of stimulation," she told MDD. "During the course of the study we also saw some changes to the electrodes. The wires are thinner. You definitely want these devices to be as small as possible."