ARTICLE IN BRIEF
Investigators studying outcomes for deep brain stimulation in Parkinson disease patients found motor improvements can be sustained for at least a decade, but disease progression and worsening axial involvement lead to progressive patient disability.
HONOLULU—Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has become a standard treatment for advanced Parkinson disease (PD). But how long do its benefits last? According to the latest study, described here at the AAN annual meeting, motor improvements can be sustained for at least a decade, although disease progression and worsening axial involvement continue to increase patient disability.
“We are always asked by our patients, ‘If I have this surgery, how long will it last?’” said Elena Moro, MD, PhD, associate professor of neurology at the University of Toronto, and a researcher at Toronto Western Hospital. “But there are no studies with follow-up longer than eight years. Now we have information we can give them.”
Dr. Moro, who led the study, noted that Toronto Western Hospital was in an ideal position to look at the records in patients in whom DBS has been used for the longest time. She pointed out that relatively few patients received the treatment during the 1990s. Forty-one patients underwent STN DBS surgery at Toronto-Western between 1996 and 2000. But because it was one of the few centers in the world offering the procedure at the time, PD patients came from all over the world. That made the long-term follow-up study more difficult, because few of the patients were available to return for testing. Thus, only 18 of the 41 were included in the study (nine had died in the intervening years). Patients who received surgery had advanced PD with severe motor fluctuations and disabling dyskinesias, and were free of dementia or active psychiatric conditions. Seven patients had previously had a unilateral pallidotomy.
The average patient age was 53 years, which Dr. Moro said was representative of the usual age for surgery in the past, and average disease duration was 13 years.
“Now we try to operate a little earlier, for many reasons,” she said, including the growing recognition of the procedure's efficacy in earlier disease. The surgical procedure was performed, as it usually is today, with only local anesthesia, under stereotactic guidance, and with intraoperative microelectrode recording. Patients were assessed at 1, 5, and 10 years post-surgery.
For the purposes of the study, videotapes were made at the 10-year visit in four conditions: off both medication and stimulation, off medication but on stimulation, on medication but off stimulation, and on both medication and stimulation.
The blinded analysis of the videotapes showed that motor function in patients was significantly better with stimulation on than with it off. In the off-medication/off-stimulation state, the average motor UPDRS score was approximately 50, while on the off-medication/on-stimulation state it was approximately 35, an improvement of 15 points. The difference between the on-medication/on-stimulation and on-medication/off-stimulation states was only about half as large, but was nonetheless significant.
In the UPDRS motor scale, the best score is 0, while the worst is 108. Previous work has suggested that a five-point improvement on the motor subscale represents a clinically important difference of moderate size.
However, Dr. Moro said, not all motor signs improved equally. While tremor and bradykinesia remained strongly affected by stimulation even after 10 years, axial signs — gait, balance, and speech — were relatively resistant to the effect of stimulation, medication, or their combination, decreasing by only about 2 points between the off-medication and stimulation and on-medication/stimulation states.
“We believe axial signs are controlled by different regions of the brain” than those most affected by levodopa, she said. “Axial signs respond partially to levodopa, but unfortunately, Parkinson disease progresses outside the levodopa-responsive areas of the brain.” Those same areas are left largely unaffected by stimulation, as well. “Stimulation, like medication, does not really improve those in the very long term follow-up.”
Some recent studies, including those from Toronto-Western, suggest that stimulation of the pedunculopontine nucleus may improve axial signs, “but it is too early to say,” Dr. Moro noted.
Dyskinesias and motor fluctuations both remained improved by stimulation in the long term, as did the reduction in levodopa that is a key benefit of surgery in patients with severe dyskinesias. It is still unclear whether the improvement in dyskinesias is due solely to the ability to reduce levodopa, Dr. Moro said, or to a hypothesized direct anti-dyskinetic effect of surgery, “but the most important factor is the reduction in medication.”
Intriguingly, the off-medication/stimulation scores changed very little over the course of follow-up, hovering just below 50 despite 10 years of disease progression. Does this mean STN DBS is neuroprotective? “It's a nice thing to see, but I cannot say it is a neuroprotective effect,” Dr. Moro said. “The stimulation has only been off for one hour” when the testing was done, she explained. The little evidence there is suggests that patients manifest their worsened disease state more as the stimulator remains off for longer.
As for adverse events, “most of the complications are at the beginning,” Dr. Moro said. Weight gain occurred by one year in all patients, with eight still reporting it at 10 years. Impulse control disorders were not reported at one year (the recognition of this effect in PD came later on), and in three patients at both five and 10 years. Other than the expected cognitive decline in patients whose disease is progressing, “there was basically nothing between five and 10 years.”
The results from this study, Dr. Moro said, were in line with other recent long-term follow-up studies of STN DBS in Parkinson disease. “The results may be less striking than some others, but this is good data from a good center,” and, unlike most reports, from a blinded evaluation.
Based on these results, she said, she is now able to tell her patients confidently that the data “really support safety and effectiveness. When we propose this surgery to patients, I can tell the truth, it works in the long term.”
These data are becoming ever more important, Dr. Moro concluded, since the number of centers offering DBS for PD has grown into the hundreds, and the number of patients who have received the treatment is over 100,000.
“This study is important to the field, as it is critical to collect long-term outcome data on deep brain stimulation patients,” said Michael S. Okun, MD, co-director of the Movement Disorders Center at the University of Florida College of Medicine in Gainesville, in an interview with Neurology Today.
“The study offered clues as to important issues facing the field, including weight changes, need for more medications over time, and impulse control disorders,” he said. Also, he added, it highlights that “Parkinson disease will continue to progress despite DBS. However, at ten years there were still important benefits of stimulation for patients.”