DBS Equally Effective in Two Sites
(This Q&A is an update to a May 2010 MJFF News in Context with Dr. Bronstein.)
On June 3, 2010, The New England Journal of Medicine published the results from the largest, randomized, controlled study of deep brain stimulation (DBS) for advanced Parkinson's disease. The study found that DBS at two different targets, the subthalamic nucleus (STN) and the globus pallidus interna (GPi), produces similar motor and quality of life improvements for Parkinson's patients.
The Michael J. Fox Foundation spoke with one of the study authors, Jeff Bronstein, MD PhD, of the University of California, Los Angeles to learn more about what the study results mean for people living with PD.
MJFF: Let's start with the study's major results. What has the study shown?
JB: The study results demonstrate that STN DBS and GPi DBS are equally good at improving motor symptoms and quality of life in advanced PD patients. But there were also some statistically significant differences between the two sites. For example, STN DBS was favorable for reducing medications but GPi DBS was better for depression and some other cognitive measures.
MJFF: In fact the study reported that depression actually became worse with STN DBS but better with GPi DBS, correct?
JB: That was one of the big differences between the two procedures and it was statistically significant. There are two possible reasons for why STN DBS may actually increase depression. The first is that, with STN DBS, PD medications must be reduced and that may contribute to depression. There have also been some reports of depression associated with stimulation of the STN region. So it may be that STN DBS contributes directly to depression. But regardless of the reason, there is a real difference between STN DBS and GPi DBS when it comes to depression. In addition, GPi DBS was also better for a few cognitive measures.
MJFF: Why do you need to lower medications with STN DBS?
JB: STN DBS can actually cause dyskinesias, the involuntary, uncontrollable movements associated with dopamine replacement therapy. So if you stimulate the STN brain region with DBS, you get worse dyskinesias. The way you deal with that is to lower the medications. With GPi DBS, it actually seems to treat dyskinesias so you don't have to lower the medications. And the fact is that some people feel better with levodopa even if DBS has improved motor symptoms.
MJFF: So if GPi DBS is just as good as STN DBS, and even better for some symptoms, why is STN DBS the standard?
Historically, there has been a general feeling that STN is better than GPi. And there is some open label anecdotal evidence to support that feeling. But there's been very few trials comparing the two procedures in any kind of randomized controlled way. The few randomized studies have produced similar results to our study, showing that there's really no difference between STN and GPi. So the purpose of this study is to help clear up the confusion and show that GPi DBS is as effective as STN DBS. And I think that GPi needs to be really looked at with more consideration and offered to patients as a treatment option.
One of the other reasons why STN has been historically favored is that it provides motor improvements pretty quickly and dramatically. With GPi the improvements happen slowly over time -- but we now know that people end up doing just as well. But for the surgeon who only sees people immediately after the procedure, the impression is that STN is better.
MJFF: What is the bottom line for patients?
All PD treatments decisions should be personalized and made in consultation with a doctor. In terms of personalizing DBS options based on these study results, one thing to consider is whether or not reducing medications is a major issue for the patient. For people who are experiencing side effects with medications or who are seeking to reduce medications for any reason, STN may be preferable. For patients who are experiencing cognitive or behavior problems, like depression, GPi should be considered.
I always like to stress that, as a group, the proper patients will get benefit from DBS. But not all DBS is created equal and even when performed at the best centers with top medical teams, there's a significant risk of complications and the benefits are often less than generally quoted. So it's a word of caution that people really need to think about.
MJFF: What are the next steps for this area of research?
Our study showed that the risk of falls was worse with STN DBS than GPi DBS and more research should be done in this area, as well as how DBS affects cognitive and behavioral problems. These are a few of the subtle things that we're starting to pick up on but that need further investigation.