Randomized trial of deep brain stimulation for Parkinson disease: Thirty-six-month outcomes.
Weaver FM, Follett KA, Stern M, Luo P, Harris CL, Hur K, Marks WJ Jr, Rothlind J, Sagher O, Moy C, Pahwa R, Burchiel K, Hogarth P, Lai EC, Duda JE, Holloway K, Samii A, Horn S, Bronstein JM, Stoner G, Starr PA, Simpson R, Baltuch G, De Salles A, Huang GD, Reda DJ; For the CSP 468 Study Group. Randomized trial of deep brain stimulation for Parkinson disease: Thirty-six-month outcomes. Neurology, 2012 Jul 3;79(1):55-65. Epub 2012 Jun 20.
Intro: There are numerous studies that have shown effectiveness of deep brain stimulation (DBS) for the treatment of Parkinson’s disease (PD). However, there are few long-term studies and even fewer that have looked at DBS subthalamic nucleus (STN) vs. DBS globus pallidus interna (GPi). The authors of this study wanted to add such information to the literature so they created a well-designed study looking at the effectiveness of DBS for these two brain structures and compared the outcomes against each other.
Methods: One hundred and fifty-nine people with Parkinson’s disease (PWP) from 13 different medical centers in the United States (Veteran’s Affairs Medical Centers and affiliated Universities) were followed for 36 months after DBS implantation. The PWP were randomly assigned to either the DBS STN (N=70) or DBS GPi (N= 89) groups. Each group was given baseline motor, cognitive, and mood measures before surgery as well as follow up evaluations at months “3, 6, 12, 18, 24, and 36” in combinations of the on/off medications stage and the on/off stimulator stage. Each group also kept “motor diaries” to track their impression of motor abilities throughout the time of the study.
Findings: Baseline Data: The STN and GPi groups were not significantly different from each other in terms of demographic information (e.g. age, sex, marital status) at baseline (prior to surgery). However, the STN group reported more difficulties prior to surgery with mobility, mood, feeling stigmatized in public or in relationships, receiving support from others, and communicating with others. The GPi group also did better prior to surgery on a task requiring them to come up with words in specific categories, as quickly as they could as well as on a task where they had to learn verbal information.
Post-surgical data: Motor: Both groups had stable improvements in formally tested motor functioning from surgery through the end of the study. It is notable that there was not a significant difference between the groups. Both groups also had improvement in “tremor, rigidity, akinesia, postural stability, and gait.” The DBS STN group was found to have worsened motor function in the off medication/off stimulator setting than the DBS GPi group at the 36-month evaluation. Interestingly, in the on medication/on stimulator settings at the 36 month mark, the DBS STN group was not as stable as the DBS GPi group. However, both groups had a reduction in medication, although greater for the DBS STN group. The PWP in both groups noticed an improvement in their motor function as measured by their motor diaries of over 5 hours per day by the 6 month mark, which was generally sustained at the 36 month mark (STN: 4.1 and GPi: 4.6 hrs/day gain in functioning). Off time and dyskinesias were reduced for both groups throughout the 3-year study.
Sleep and Quality of Life: Both groups had an increase of hours asleep per night, sustained over the three-year mark. Additionally, both groups reported a decline in the support/assistance received from others at the end, as compared to the beginning, of the study.
Cognition: The DBS STN group experienced slightly more cognitive decline (memory and executive tasks) as compared to the DBS GPi group, but both groups had evidenced cognitive decline over time.
Mood: Neither group had significant changes in mood when comparing the scores at the beginning to the end of the three-year study.
Conclusion: The authors previously reported that the DBS STN and DBS GPi groups both generally experienced sustained improvement in motor abilities after a two-year period. This study continues to show sustainable findings for both targets after a three-year period. However, there were some mild differences between the two targets as it relates to medications and stimulation effects. The authors hypothesized that the medications were not as effective at the end of the study for the DBS STN group, which is thought to be due to the greater reduction in medications after surgery. In contrast, the medications in the DBS GPi group were increased over time. As the DBS STN group had less stable motor functioning at the end of the study as discussed above, it was unclear to the authors if the DBS GPi or the higher medication dosages may have contributed to a more stable progression of PD for that group. Both groups were found to have decline in cognitive functioning likely related to progression of their PD, but the DBS STN group evidenced slightly more cognitive decline in aspects of memory and executive functioning. The two groups had comparable mood scores. Quality of life and ability to complete activities of daily living scores initially showed improvements, but these improvements were not sustained at the end of the study. The scores at the end of the study were comparable to the PWP scores prior to surgery, which was likely due to the progression of PD. Previous research had suggested that DBS GPi was not as sustainable as DBS STN, but this study suggests both targets are sustainable over time although there may be some differences with progression of the disease due to possible medication effects or the targets. The authors conclude that there is more consensus of sustainability for both targets and that previous studies may have different findings due to different patient characteristics as well as advancements in the techniques/knowledge of the therapies. This study nicely showed that both targets are beneficial in improving motor functioning in PWP, but further intervention to improve quality of life and nonmotor symptoms as it relates to PD appears indicated.