A huge question facing Parkinson’s disease patients and clinicians has been “What is the best target for deep brain stimulation (DBS)?” Over the years, two main brain regions have emerged as possibilities: the subthalamic nucleus (STN) and the globus pallidus interus (GPi). Though each target has had defenders, most centers have gravitated toward utilizing only STN DBS. A series of recent trials, however, will likely change this simple practice pattern into a more complex and tailored approach. In this month’s, What’s Hot in Parkinson’s Disease?, we will explore this issue and present the latest data.
Weaver and colleagues published the long-awaited three year data that was derived from the VA-NINDS STN vs. GPi DBS for Parkinson’s disease trial. Patients were randomly assigned to a GPi or a STN brain target, and though the original trial had more subjects, this long-term follow-up cohort was relatively large for a surgical trial (GPi n=89 and STN n=70). The primary outcome was “motor function on stimulation/off medication using the Unified Parkinson’s Disease Rating motor subscale,” and patients were followed for a total of 36 months. Motor function, as in the original trial, improved similarly in both groups. The surprise was that the Mattis Dementia Rating Scale and other neurocognitive/thinking measure scores such as the Hopkins memory test “declined faster for STN than GPi patients.” Overall, quality of life was improved in both groups, though it was overall diminished from the previously reported 24 month follow-up. This worsening of quality of life was thought to be due to disease progression.
The recent VA-NINDS Cooperative study focusing on STN vs. GPi DBS validated previous reports by Anderson, and also by the NIH COMPARE DBS randomized trial. All of these STN vs. GPi DBS studies have collectively demonstrated similar motor efficacy when using either brain target when applied to patients with advanced fluctuating Parkinson’s disease. Though many neurologists and neurosurgeons may have prematurely rushed to adopting STN over GPi DBS, accumulating evidence has underscored a critical importance of carefully and thoughtfully studying DBS targets through the application of appropriate clinical trials.
The results of the current study were largely forecasted by a 2005 editorial, which provided an illustrated cartoon entitled “the rematch.” The editorial compared a very popular STN DBS target against the less utilized GPi. The cartoon even went so far as to place boxing gloves on each target. There was speculation that the GPi target would “make a return,” and that in the future, DBS targets would be chosen on a symptom specific basis. If we fast-forward to the present, it seems that this projected scenario is quickly becoming a reality.
The current VA study by Weaver and colleagues revealed specific advantages of the GPi DBS target. The most important reported finding was the worsening of cognitive/thinking function in the STN group. This finding has practical implications for patients. If you are considering a DBS and you seem to have cognitive or thinking issues, you and your team should consider implantation into the GPi target. Additionally, sometimes detailed cognitive testing will uncover previously unknown but potentially important symptoms. Another important take home message is that although medication reduction occurs more commonly with the STN brain target, there seems to be more flexibility in adjusting medications if you choose the GPi target. The ability to have enhanced flexibility when making medication adjustments will likely be important as DBS patients experience natural disease progression and worsening of symptoms.
The data from the Weaver study also revealed that in STN, there was a gradual loss of the “additive effect of medication to stimulation.” This point led the accompanying editorial to question whether GPi stimulation would be more compatible with long-term medical therapy. Additionally the post-operative off medication scores remained remarkably stable in the GPi target. It is unknown whether this finding represented a failure of stimulation washout, a micro-lesional effect, or a disease modifying benefit.
The results from the study strongly suggest that clinician’s weighing the possibility of DBS for their patients should not consider STN as the sole option. All of the recently available data, inclusive of this new study, supports the notion that the future of DBS patient and target selection will require a more tailored and symptom-specific approach, and that both STN and GPi are viable options. All DBS patients should be sure that they are evaluated by an interdisciplinary team (neurologist, neurosurgeon, neuropsychologist, psychiatrist, physical therapist, occupational therapist, and speech therapist), and that the team has met and discussed the best approach (unilateral versus bilateral), the best target (STN vs. GPi) and the overall risk-benefit ratio. These types of pre-operative evaluations will facilitate the best chance to enhance the overall outcomes of DBS surgery.*
Okun MS, Fernandez HH, Wu SS, Kirsch-Darrow L, Bowers D, Bova F, Suelter M, Jacobson CE 4th, Wang X, Gordon CW Jr, Zeilman P, Romrell J, Martin P, Ward H, Rodriguez RL, Foote KD. Cognition and mood inParkinson's disease in subthalamic nucleus versus globus pallidus interna deep brain stimulation: the COMPARE trial.Ann Neurol. 2009 May;65(5):586-95. PubMed PMID: 19288469; PubMed Central PMCID: PMC2692580.
Okun MS, Foote KD. Subthalamic nucleus vs globus pallidus interna deep brain stimulation, the rematch: will pallidal deep brain stimulation make a triumphant return? Arch Neurol. 2005 Apr;62(4):533-6. PubMed PMID: 15824249.
Follett KA, Weaver FM, Stern M, Hur K, Harris CL, Luo P, 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; CSP 468 Study Group. Pallidal versus subthalamic deep-brain stimulation for Parkinson's disease. N Engl J Med. 2010 Jun 3;362(22):2077-91. PubMed PMID: 20519680.
Okun MS. Deep Brain Stimulation: Time to Change Practice. Journal Watch. June 26, 2012. *Excerpts from this short review are utilized in the above current review.
You can find out more about our National Medical Director, Dr. Michael S. Okun, by also visiting the Center of Excellence, University of Florida Health Center for Movement Disorders and Neurorestoration. Dr. Okun is also the author of the Amazon #1 Parkinson's Best Seller 10 Secrets to a Happier Life and 10 Breakthrough Therapies for Parkinson's Disease.