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Dr. Okun

Post of the Week: STN and GPi DBS Motor Outcomes Similar: NEJM

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Dear forum members,


Two important trials are out concerning DBS and PD.


More Evidence and More Choices for DBS Therapy: The Time Has Come to Tailor Surgical Therapies


In the May 2010 issue of the Lancet Neurology, the PD SURG trial results (conducted by a multicenter team of collaborative investigators from all over Britain) are including a one year follow-up of Parkinson’s disease deep brain stimulation (DBS) patients. The trial was randomized, and it compared DBS to best medical therapy. The primary outcome variable was quality of life, and interestingly, patients in the best medical therapy arm had access to apomorphine pumps. Though sites were allowed to use the subthalamic nucleus target, the globus pallidus interna target, and even lesion therapy (e.g. pallidotomy), 174/178 (98%) of patients in the surgery group were implanted with subthalamic nucleus DBS. There was a five point improvement noted in quality of life scores in the surgical compared to medical group. Although compared to other studies the quality of life improvement was less robust, this may have reflected a longer study duration, or potentially even disease progression. There were unmistakable improvements in dyskinesias, and on time in the surgical group, although diaries were not utilized.


Though, not a perfect trial, its large size and use of a medical control group along with unique access to apomorphine made it unique among available DBS publications. The results underscored the powerful influence that DBS can have on motor fluctuations. Additionally, these SURG investigators plan in the future a long term (9 year) follow-up, and this will surely enlighten the field as to disease progression, and other issues potentially important to DBS cohorts.


One unique and hidden aspect of this trial was the report of the “reasons why patients sought DBS surgery.” Severe off periods, dyskinesia and tremor were far and away the most common indications cited for DBS therapy. As DBS moves into a tailoring phase (the right target and approach for a particular symptom or symptom cluster) this type of information will be very useful to clinicians.


People may criticize the lower total motor change scores reported in PD SURG when comparing pre- and post-operative operative outcomes to other trials, however they must remember that as many randomized blinded DBS trial results emerge from international centers (VA PADRECC study, Cleveland Clinic/Emory Study, UF COMPARE trial), than the open label improvements previously documented will almost certainly be shown to be a study bias. The results of the PD SURG trial may offer a look at what DBS outcomes may realistically look like as the therapy migrates to centers with less expertise (remember they used a multitude of centers all over Britain).


It is fascinating to see that 98% of implants were placed in the subthalamic nucleus in this study, despite the option for surgeons to use a different target. Though the subthalamic target has many strengths, it also has relative weaknesses. Emerging data is now strongly suggestive that the motor outcomes in pallidum and subthalamic nucleus are actually similar, and that targets in the future should be tailored for individual patients and individual symptoms. The results of the long-awaited VA Randomized STN versus GPi DBS were announced shortly after the PD SURGE trial (New England Journal of Medicine). Two hundred and ninety-nine patients were randomized and patients were followed carefully for two years post-implantation. The results of this study, like the NIH COMPARE trial which was published in 2009, confirmed that motor outcomes were equivalent whether implanted in STN or in GPi. There were however, subtle differences between brain targets, and as more data emerges we will hopefully be able to start matching patient profiles to specific brain targets.


Can we say the PD SURG trial and the VA DBS trials were a surge forward for the PD community? The answer is certainly yes, as the publication of more carefully controlled DBS trials will be important in guiding the therapy . There is now solid evidence supporting the efficacy of DBS in select patient populations, and emerging data that may help us in selecting the right target for the right patient- “A Truly Tailored Approach.”


N Engl J Med. 2010 Jun 3;362(22):2077-91.

Pallidal versus subthalamic deep-brain stimulation for Parkinson's disease.

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.


Collaborators (129)

Iowa City Veterans Affairs Medical Center, Iowa City, USA.


BACKGROUND: Deep-brain stimulation is the surgical procedure of choice for patients with advanced Parkinson's disease. The globus pallidus interna and the subthalamic nucleus are accepted targets for this procedure. We compared 24-month outcomes for patients who had undergone bilateral stimulation of the globus pallidus interna (pallidal stimulation) or subthalamic nucleus (subthalamic stimulation). METHODS: At seven Veterans Affairs and six university hospitals, we randomly assigned 299 patients with idiopathic Parkinson's disease to undergo either pallidal stimulation (152 patients) or subthalamic stimulation (147 patients). The primary outcome was the change in motor function, as blindly assessed on the Unified Parkinson's Disease Rating Scale, part III (UPDRS-III), while patients were receiving stimulation but not receiving antiparkinsonian medication. Secondary outcomes included self-reported function, quality of life, neurocognitive function, and adverse events. RESULTS: Mean changes in the primary outcome did not differ significantly between the two study groups (P=0.50). There was also no significant difference in self-reported function. Patients undergoing subthalamic stimulation required a lower dose of dopaminergic agents than did those undergoing pallidal stimulation (P=0.02). One component of processing speed (visuomotor) declined more after subthalamic stimulation than after pallidal stimulation (P=0.03). The level of depression worsened after subthalamic stimulation and improved after pallidal stimulation (P=0.02). Serious adverse events occurred in 51% of patients undergoing pallidal stimulation and in 56% of those undergoing subthalamic stimulation, with no significant between-group differences at 24 months. CONCLUSIONS: Patients with Parkinson's disease had similar improvement in motor function after either pallidal or subthalamic stimulation. Nonmotor factors may reasonably be included in the selection of surgical target for deep-brain stimulation. (ClinicalTrials.gov numbers, NCT00056563 and NCT01076452.) 2010 Massachusetts Medical Society


PMID: 20519680 [PubMed - indexed for MEDLINE]

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