Deep brain stimulation (DBS) is substantially more effective for treating advanced Parkinson’s disease than the best available nonsurgical treatments but comes with a much greater risk of serious side effects, according to a new study.
DBS, in which electrodes are implanted in the brain, has been used for more than a decade to help manage the characteristic movement problems of Parkinson’s. Though many of the details remain mysterious, the electrical stimulation somehow blocks aberrant signals thought to underlie the disease’s symptoms.
Compared with what the researchers cite as the “best medical therapy”—a regimen of medications and behavioral treatments—patients treated with DBS gained about 4.6 hours of symptom-free time each day, the scientists report in the Jan. 7 issue of the Journal of the American Medical Association.
“This is pretty significant,” says lead researcher Frances Weaver, a psychologist at the Hines Veterans Affairs Hospital in Illinois. “We’re generally awake for about 16 hours in a day. These patients had about six to seven ‘on’ hours before. If you add 4.6, it gets them through a good part of the day with good functioning.”
But at the same time, 49 of the 121 DBS patients—more than 40 percent—suffered serious side effects, versus only 15 of 134 people (11 percent) from the best-medical-therapy group. DBS side effects included cognitive and psychological problems associated with stimulation, but the majority—39, including one death from cerebral hemorrhage—resulted from the surgery itself.
The new findings highlight the stark choice facing people whose condition continues to worsen despite drug and behavioral therapies, and the work may alter how often and when DBS treatment is advised.
“You’d certainly want to weigh the benefits of improved motor function versus the very real risks of surgery,” Weaver says.
Benefits for older patients
The new research is not the first randomized clinical trial to pit DBS against less invasive therapies. A 2006 study by German researchers in the New England Journal of Medicine, for instance, also found better outcomes in 78 subjects who received DBS, compared with 78 on a standard medical treatment.
But Weaver and her team extended those findings not only with more substantive side-effect data but also by looking at elderly patients. The German group excluded anyone over the age of 75.
In total, Weaver’s team tracked their 255 patients for six months each between May 2002 and October 2005, and then conducted a lengthy and extensive analysis of the resulting data.
“We were surprised at how well our older patients did,” Weaver says. “They performed almost as well, and their complications were comparable.”
Where to operate?
Hard evidence of DBS’s benefits is valuable but is really just a first step, say outside experts.
“The study is important and replicates what is already known by the medical community: that DBS is more effective than best medical therapy but with more serious side effects,” says Harriet Smeding, a Parkinson’s researcher at the University of Amsterdam’s Academic Medical Centre who did not work on the study.
But this study, as well as its predecessor, offers information only about short-term outcomes, she says. Neither tracks how well patients are doing years down the road, something of vital importance when it can take months just to adjust the stimulator to the right frequency.
The new study also presented data about the patients as a group, she added, leaving open questions about how well each individual is doing, especially when it comes to mild cognitive side effects that can easily be missed during checkups.
But, Smeding says, experts are excited that the study looked at two different DBS surgery locations. Of the 121 patients who underwent DBS surgery, 61 had the implant placed in the globus pallidus, a component of the basal ganglia, and 60 in the subthalamic nucleus, a lens-like sliver of tissue located nearby. An analysis comparing the sites should be released later this year, Weaver says—the first “head-to-head comparison to see if there is a best site for surgery.”
“The next step is to find out what nuclei have the least side effects,” Smeding says. “I am really curious about the comparison … they are promising us for the near future. That is what the medical community—and patients—are waiting for.”